Chronic kidney disease is a progressive condition characterized by a sustained reduction in glomerular filtration rate (GFR < 60 mL/min/1.73 m²) or evidence of kidney damage persisting for three or more months, leading to irreversible loss of renal function.

Exam domain	One-glance essentials
Definition / diagnosis	*CKD = kidney structure/function abnormality persisting > 3 months with health implications* ^[1] Diagnose with eGFR < 60 mL/min/1.73 m² and/or a marker of kidney damage (especially albuminuria); classify by Cause–GFR–Albuminuria (CGA).
Epidemiology / risks	*Diabetes, hypertension, glomerular disease, inherited disease, obstruction, recurrent AKI, and nephrotoxins are key causes/risks* ^[1] Faster progression: heavy albuminuria, poor BP/glycaemic control, smoking, recurrent AKI, and cardiovascular disease.
Core mechanism	Nephron loss → single-nephron hyperfiltration and intraglomerular hypertension → proteinuria, sclerosis, and further nephron loss. Reduced endocrine/excretory function causes EPO deficiency, phosphate retention, impaired calcitriol activation, acid retention, and K⁺ retention.
Clinical picture	Often asymptomatic until advanced; detect by reduced eGFR or albuminuria. Later: fatigue/pallor, oedema, pruritus, nocturia, anorexia, nausea, neuropathy, restless legs, dyspnoea, or uraemic features.
Investigations	Repeat creatinine/eGFR and urine ACR to establish chronicity; urinalysis/microscopy and renal ultrasound define cause/structure. Monitor K⁺, HCO₃⁻, Ca²⁺, phosphate, ALP/PTH, FBC, iron studies, BP, glucose/HbA1c, and lipids. Small echogenic kidneys support chronicity; normal-sized kidneys do not exclude CKD.
Management	*Control BP and albuminuria with ACEI/ARB when indicated; use an SGLT2 inhibitor in eligible patients; treat diabetes and cardiovascular risk* ^[1]^[2] Correct iron deficiency/anaemia, acidosis, hyperkalaemia, fluid overload, and CKD-mineral bone disorder; a bicarbonate of 20 mmol/L is an exam cue to consider oral bicarbonate ^[3]. Plan transplant/dialysis conservatively and early by symptoms, trajectory, and complications—not eGFR alone ^[4].
Complications	*Cardiovascular disease is the major cause of morbidity and death* ^[1] Anaemia, hyperkalaemia, metabolic acidosis, fluid overload, CKD-MBD/secondary hyperparathyroidism, malnutrition, neuropathy, and uraemia ^[2].
Prevention / follow-up	Screen high-risk patients with eGFR + urine ACR; optimise BP, diabetes, weight, exercise, and smoking cessation. Avoid NSAIDs and unregulated remedies; dose-adjust renally cleared drugs and prevent/review AKI episodes.
Exam traps	Creatinine alone is not CKD staging: use eGFR and albuminuria, and prove > 3-month chronicity. Do not stop ACEI/ARB for a small expected creatinine rise without assessing volume status, K⁺, and the magnitude/trend. Do not start dialysis for eGFR alone; refractory complications and uraemic symptoms drive initiation.

References

^[1] Lecture slides: GC 034. Chronic Kidney Disease & Its Complications_Update 2025.pdf (pp3–4, 7 — definition, causes, progression, complications, renoprotection) ^[2] Senior notes: Block A 2017 Chronic Kidney Disease Its complications.pdf (pp8, 12 — CKD complications and nephrotoxic-drug risks) ^[3] Past paper: 2020 Fourth Summative Assessment MCQ paper.pdf (p19, Question 47 — stage 4 CKD with bicarbonate 20 mmol/L) ^[4] Lecture slides: GC080: Renal Replacement Therapy.pdf (pp8–10 — indications and modality planning)

Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for > 3 months, with implications for health (KDIGO 2012) ^[1]^[2]^[3].

Let's break that down:

"Chronic" → persisting > 3 months (this is what separates it from AKI)
"Kidney disease" → can be structural (e.g. albuminuria, abnormal histology, imaging abnormalities) OR functional (e.g. decreased GFR)

Two readings of GFR < 60, at least 3 months apart, confirm CKD ^[4]. A single low GFR reading could be AKI or a lab artefact — you need chronicity.

Quantitatively, CKD is defined as > 3 months of either ^[1]^[2]:

GFR < 60 mL/min/1.73m² (i.e. Stage 3–5), OR
ACR > 3 mg/mmol (or equivalently > 30 mg/g) or other markers of kidney damage (even if GFR ≥ 60)

CKD with Normal GFR

If GFR is ≥ 60, an individual can still be classified as CKD (Stage 1 or 2) if there is concomitant presence of some other kidney abnormality — blood/protein in urine, or structural kidney issues on imaging ^[1]. This is a commonly examined point: CKD is not just about GFR.

The "markers of kidney damage" include:

Albuminuria (ACR ≥ 3 mg/mmol)
Urine sediment abnormalities (e.g. haematuria, RBC casts)
Electrolyte or other abnormalities due to tubular disorders
Abnormalities detected by histology (renal biopsy)
Structural abnormalities detected by imaging (e.g. polycystic kidneys, small kidneys)
History of kidney transplantation

Global prevalence: approximately 10–15% of the general adult population ^[5]
US prevalence: ~14.8% ^[5]
In Hong Kong (2013 data): 8,510 patients on renal replacement therapy (RRT) — 3,501 transplant, 1,192 haemodialysis (HD), 3,817 peritoneal dialysis (PD) ^[5]
- Hong Kong has the highest utilisation of peritoneal dialysis worldwide — this is a PD-first policy unique to HK and is frequently examined
CKD prevalence increases with age — as GFR naturally declines by ~1 mL/min/1.73m² per year after age 30–40 ^[6]^[7]
CKD is a major risk factor for cardiovascular morbidity and mortality — in fact, most CKD patients die of cardiovascular disease before they ever reach dialysis

High Yield — Causes of Death in CKD

Causes of death in CKD: Vascular (50%), Infection (30%), Termination of dialysis (7%) ^[3]. Cardiovascular disease is the leading killer — not kidney failure itself.

Understanding risk factors for CKD matters both for prevention and for identifying patients who need screening:

Category	Risk Factors
Non-modifiable	Age > 50, male sex, family history of kidney disease (e.g. ADPKD, Alport syndrome, IgA nephropathy), ethnicity (African, Asian), low birth weight (fewer nephrons)
Modifiable — metabolic	Diabetes mellitus (single most important risk factor worldwide and in HK), hypertension, obesity, dyslipidaemia, hyperuricaemia
Modifiable — renal insults	Previous AKI (AKI → CKD progression is well-established), recurrent UTIs, nephrolithiasis, urinary tract obstruction (e.g. BPH)
Modifiable — drugs/toxins	NSAIDs (chronic use), calcineurin inhibitors (ciclosporin, tacrolimus), lithium, aminoglycosides, contrast nephropathy
Systemic diseases	SLE, vasculitis, amyloidosis, multiple myeloma, sickle cell disease
Lifestyle	Smoking, high-sodium diet, sedentary lifestyle

Pre-existing CKD is itself a risk factor for AKI — and AKI accelerates CKD progression. This bidirectional relationship is frequently examined ^[8].

4. Anatomy and Function of the Kidney (Review)

Understanding CKD requires understanding what the kidneys do, because each function that fails produces a specific clinical feature.

Paired retroperitoneal organs, approximately 10–12 cm in length
Located at T12–L3 level, right kidney slightly lower than left (displaced by liver)
Each kidney receives ~20–25% of cardiac output via the renal arteries (branches of the aorta)
Blood supply: renal artery → segmental → interlobar → arcuate → interlobular → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries/vasa recta → renal vein

The nephron is the functional unit of the kidney. There are approximately 1 million nephrons per kidney at birth ^[9].

Each nephron consists of:

Glomerulus (in the cortex): the filtration unit
- Bowman's capsule surrounding the glomerular capillary tuft
- Produces an ultrafiltrate of plasma (~180 L/day of primary filtrate)
- Normally no plasma protein or red cells in the urine ^[9]
Proximal convoluted tubule (PCT): reabsorbs ~65% of filtered Na⁺, water, glucose, amino acids, phosphate, bicarbonate
Loop of Henle: countercurrent multiplier for urine concentration; thick ascending limb reabsorbs Na⁺/K⁺/Cl⁻ (site of action of loop diuretics)
Distal convoluted tubule (DCT): fine-tuning of Na⁺ reabsorption (thiazide-sensitive NCC channel), Ca²⁺ reabsorption (PTH-dependent)
Collecting duct: final Na⁺/K⁺ exchange (aldosterone-dependent ENaC), water reabsorption (ADH-dependent aquaporin-2)

Function	Mechanism	What Fails in CKD
Excretion of waste	GFR-dependent clearance of urea, creatinine, uremic toxins	Uraemia → nausea, encephalopathy, pericarditis
Fluid/volume regulation	Tubular Na⁺/H₂O reabsorption	Early: salt wasting/nocturia; Late: fluid overload/oedema
Electrolyte homeostasis	K⁺ secretion (collecting duct), PO₄ excretion, Ca²⁺/Mg²⁺ balance	Hyperkalaemia, hyperphosphataemia, hypocalcaemia
Acid-base balance	HCO₃⁻ reabsorption (PCT), H⁺/NH₄⁺ excretion (collecting duct)	Metabolic acidosis (HAGMA ± NAGMA component)
Endocrine — EPO	Peritubular interstitial fibroblasts produce erythropoietin	Normocytic normochromic anaemia
Endocrine — Vitamin D	1α-hydroxylation of 25(OH)D₃ → active 1,25(OH)₂D₃ in PCT	↓Active vitamin D → hypocalcaemia → secondary hyperparathyroidism → renal osteodystrophy
Endocrine — Renin	JGA produces renin → RAAS	Hypertension, disturbed Na⁺ balance
Drug/toxin metabolism	Renal clearance of drugs	Drug accumulation, need for dose adjustment

5. Aetiology (with Hong Kong Focus)

The aetiology of CKD varies by age and geography. The distribution in Hong Kong adults differs somewhat from Western populations.

Cause	Approximate %	Notes
Diabetic nephropathy	20–40% (up to 51% in some HK series)	Most common cause of CKD and ESRD ^[3]^[5]^[10]
Glomerulonephritis	10–25%	IgA nephropathy is the most common primary GN worldwide and in HK ^[3]^[5]
Hypertensive nephrosclerosis	5–20%	Causality controversial — renal disease can itself cause HTN ^[5]
Interstitial/tubulointerstitial diseases	20–30%	Often drug-induced (NSAIDs, analgesics, lithium) ^[5]
Polycystic kidney disease	~5%	Autosomal dominant (ADPKD) most common inherited cause
Systemic diseases	5–10%	SLE, vasculitis, amyloidosis
Renovascular disease	~5%	Mostly atheromatous → chronic ischaemic nephropathy ^[5]
Congenital/hereditary	~5%	Alport syndrome, congenital anomalies
Unknown	5–20%	May be due to genetic mutations ^[3]

High Yield — HK Aetiology

In Hong Kong, diabetic nephropathy is the most common cause of ESRD requiring RRT. However, glomerulonephritis (especially IgA nephropathy) remains proportionally more common in HK/Asia than in Western populations. Always think of IgA nephropathy when you see an Asian patient with haematuria and slowly progressive CKD ^[10].

In children, the causes of CKD are very different from adults ^[11]:

Congenital anomalies of kidney and urinary tract (CAKUT): 53% — most common cause
Glomerular diseases: 19%
Familial/hereditary: 13%
Systemic disease (~5%): SLE, vasculitis
Tubulointerstitial diseases (~5%)
Others (~5%): PKD, metabolic

This is the standard approach for thinking about causes systematically ^[12]:

6. Pathophysiology

This is the most important concept in CKD pathophysiology. Here's the story:

Initial insult (e.g. diabetes, GN, hypertension) damages and destroys some nephrons
Remaining nephrons compensate by increasing their individual GFR (hyperfiltration) — this is driven by:
- Afferent arteriole dilatation + efferent arteriole constriction (via angiotensin II)
- Increased glomerular capillary pressure
- Increased single-nephron GFR (SNGFR)
This compensatory hyperfiltration initially maintains total GFR — which is why patients can lose up to 50% of nephron mass before GFR drops significantly
However, hyperfiltration is maladaptive in the long term:
- Increased glomerular pressure → glomerular hypertension → endothelial injury → mesangial expansion → glomerulosclerosis
- Increased filtration of proteins → proteinuria → tubular reabsorption of protein → tubulointerstitial inflammation and fibrosis
- Progressive loss of more nephrons → more hyperfiltration → vicious cycle

This is exactly why ACEI/ARBs are renoprotective — they dilate the efferent arteriole, reducing glomerular capillary pressure and slowing hyperfiltration-mediated damage. This initially causes a small rise in creatinine (which is expected and acceptable up to ~30%), but in the long run preserves nephrons.

Regardless of the original aetiology, CKD converges on a final common pathway of tubulointerstitial fibrosis and glomerulosclerosis:

Chronic inflammation → myofibroblast activation → collagen deposition
Loss of peritubular capillaries → chronic ischaemia
Tubular atrophy
End result: small, scarred, shrunken kidneys with loss of corticomedullary differentiation on ultrasound

6.3 Pathophysiology of CKD Complications (Mechanism by Mechanism)

Each complication of CKD arises logically from loss of specific kidney functions:

Early CKD (tubular dysfunction predominates):

As nephrons are lost, each remaining nephron must handle a larger solute load
This causes an osmotic diuresis per nephron → nocturia is often the earliest symptom
Salt wasting can occur, particularly in tubulointerstitial diseases → may even cause volume depletion and thirst

Late CKD (loss of total nephron mass):

Total capacity for Na⁺ and H₂O excretion is overwhelmed
Fluid retention → oedema, hypertension, pulmonary oedema ^[5]
Oliguria in late stages (but never anuria in CKD alone — anuria always indicates AKI or acute-on-chronic kidney disease) ^[13]

K⁺ is excreted primarily by the collecting duct (principal cells, driven by aldosterone)
As GFR falls, K⁺ excretion capacity diminishes
Hyperkalaemia typically becomes significant at GFR < 20–25 mL/min
Particularly problematic in patients on ACEI/ARB/spironolactone (which inhibit K⁺ secretion)
Clinical effects: muscle weakness (LL > UL), cardiac arrhythmias
ECG changes: peaked T waves → widening of QRS → loss of P waves → sine wave → asystole ^[14]

Rate Matters

The rate of rise of K⁺ is as important as the absolute level. Chronic hyperkalaemia is more tolerable than acute rises because cells have time to adapt their membrane potentials ^[14].

The kidney normally excretes ~1 mmol/kg/day of H⁺ (as titratable acid and NH₄⁺) and regenerates HCO₃⁻
In CKD:
- ↓ Nephron number → ↓ excretion of organic acids → high anion gap metabolic acidosis (HAGMA) ^[11]
- ± RTA component → normal anion gap metabolic acidosis (NAGMA) (especially in tubulointerstitial disease)
Consequences:
- Kussmaul's respiration (deep, sighing breathing — respiratory compensation)
- ↓ Myocardial contractility, vasodilation
- Muscle wasting (acidosis promotes protein catabolism)
- Bone disease (chronic acidosis buffers H⁺ against bone mineral)

This is a complex and frequently examined cascade. Let's trace it step by step:

↓ GFR → ↓ phosphate excretion → hyperphosphataemia
↓ Functioning renal mass → ↓ 1α-hydroxylase activity → ↓ active vitamin D [1,25(OH)₂D₃] → ↓ intestinal Ca²⁺ absorption → hypocalcaemia
Hyperphosphataemia directly suppresses 1α-hydroxylase (worsening vitamin D deficiency) and also directly binds Ca²⁺ (further lowering ionised Ca²⁺)
Hypocalcaemia + ↓ vitamin D + hyperphosphataemia → stimulates PTH secretion → secondary hyperparathyroidism
PTH tries to restore Ca²⁺ by:
- Increasing bone resorption → renal osteodystrophy (osteitis fibrosa cystica)
- Increasing renal PO₄ excretion (but this is limited in CKD)
- Stimulating 1α-hydroxylase (but substrate is limited in CKD)
Over time, chronic stimulation of the parathyroid glands causes parathyroid hyperplasia → eventually autonomous (tertiary) hyperparathyroidism where PTH is secreted independently of Ca²⁺ levels

Clinical consequences of CKD-MBD:

Renal osteodystrophy: bone pain, pathological fractures, proximal myopathy
Vascular calcification: calcium-phosphate product deposition in vessel walls → accelerated atherosclerosis (this is a major contributor to the cardiovascular mortality in CKD)
Calciphylaxis: rare but devastating condition with ischaemic skin necrosis due to arteriolar calcification
Hypocalcaemia symptoms: tetany, Chvostek/Trousseau signs, paraesthesia, seizures

The kidney produces ~90% of erythropoietin (EPO) from peritubular interstitial fibroblasts
As functioning renal mass decreases → ↓ EPO production → normocytic normochromic anaemia (anaemia of CKD) ^[3]^[11]
Typically becomes clinically significant at GFR < 30–45 mL/min (Stage 3b–4)
Other contributing factors in CKD:
- Iron deficiency (from chronic blood loss in dialysis, poor absorption)
- Uraemic toxins suppressing erythropoiesis
- Shortened RBC lifespan in uraemic milieu
- Functional iron deficiency (iron is trapped in stores by hepcidin, which is elevated in CKD due to chronic inflammation)

"Uraemia" literally means "urea in the blood" (Greek: ouron = urine, haima = blood). But it refers broadly to the clinical syndrome caused by accumulation of nitrogenous waste products and other toxins that the kidneys normally clear.

Uraemic symptoms usually become apparent at GFR < 15 mL/min (Stage 5 / ESRD) ^[5]^[11]:

System	Manifestations	Mechanism
General	Anorexia, nausea (most specific symptom), malaise, weight loss	Uraemic toxin accumulation, gastroparesis
Skin	Café au lait complexion, pruritus, scratch marks, uremic frost	Retained urochrome pigments + ↓melanin metabolism; pruritus from Ca²⁺-PO₄ deposition & uraemic toxins; uremic frost = urea crystallisation on skin (very late)
CVS	Uremic pericarditis (at BUN > 60 mg/dL), accelerated atherosclerosis, cardiomyopathy	Serosal inflammation from uraemic toxins; vascular calcification
Neuro	Uremic encephalopathy (confusion, ↓memory, seizures, coma), peripheral neuropathy (glove-and-stocking)	Neurotoxic effect of uraemic toxins
Haematological	Uraemia-induced platelet dysfunction → bleeding tendency; EPO deficiency → anaemia	Uraemic toxins interfere with platelet adhesion/aggregation
Immunological	↑ Risk of infection	Uraemic toxins impair leukocyte function; immunocompromised state
GI	Metallic taste, fetor uremicus (ammonia-like breath)	Urea breakdown by oral flora → ammonia
Endocrine	Sexual dysfunction, amenorrhoea, infertility	Disturbed HPG axis from uraemic toxins

CKD is an independent risk factor for cardiovascular disease, and this is the leading cause of death:

Hypertension (fluid retention + RAAS activation)
Left ventricular hypertrophy (pressure and volume overload)
Accelerated atherosclerosis (vascular calcification, dyslipidaemia, chronic inflammation)
Uraemic cardiomyopathy
Uraemic pericarditis

Present in > 80% of CKD patients
Mechanisms: Na⁺/H₂O retention → volume expansion; RAAS activation; ↓ renal vasodilator production (PGE₂, NO); sympathetic activation
HTN both causes and accelerates CKD — bidirectional relationship ^[5]

7. Classification / Staging

CKD is staged by GFR (G stages) AND albuminuria (A stages) — this is the "heat map" system. Both dimensions independently predict prognosis.

GFR Categories:

Stage	GFR (mL/min/1.73m²)	Description
G1	≥ 90	Normal or high (requires other evidence of kidney damage)
G2	60–89	Mildly decreased (requires other evidence of kidney damage)
G3a	45–59	Mildly to moderately decreased
G3b	30–44	Moderately to severely decreased
G4	15–29	Severely decreased
G5	< 15	Kidney failure (ESRD)

Albuminuria Categories:

Stage	ACR (mg/mmol)	ACR (mg/g)	Description
A1	< 3	< 30	Normal to mildly increased
A2	3–30	30–300	Moderately increased (formerly "microalbuminuria")
A3	> 30	> 300	Severely increased (formerly "macroalbuminuria")

The combination of G and A categories produces a risk matrix (green → yellow → orange → red → deep red) that guides monitoring frequency and intervention intensity.

High Yield — GFR Estimation

Equation	Parameters	Use	Limitations
CKD-EPI	Age, sex, race, Cr	Recommended equation: performs better at normal/low-normal GFR	Unaccounted: Chinese race, muscle mass ^[3]
MDRD	Age, sex, race, Cr	Most commonly used historically	Underestimates GFR when > 60 (derived from CKD patients) ^[3]
Cockcroft-Gault	(1.23)(140-age)(weight)/Cr, ×0.85 if female; not adjusted for BSA	Drug dosing	Overestimates GFR; depends on body weight ^[3]

At ESRD (GFR < 15): eGFR and 24h CrCl are not accurate in estimating renal function → take average of both ^[3].

This is a critical clinical skill — you must distinguish chronic from acute kidney injury:

Feature	CKD	AKI
Duration	> 3 months	Hours to days
Kidney size on USS	Small, atrophic kidneys	Normal or enlarged
Corticomedullary differentiation	↓ (lost)	Preserved
Calcium	↓ (hypocalcaemia)	Usually normal
Phosphate	↑ (hyperphosphataemia)	May be normal or ↑
ALP	↑ (secondary hyperparathyroidism → bone turnover)	Normal
Anaemia	Present (anaemia of chronic disease / EPO deficiency)	Usually absent (unless bleeding)
Urine output	Oliguria (rarely anuria)	May be anuric
Previous bloods	Often previous abnormal creatinine results	Normal baseline creatinine

Features suggesting CKD but not AKI: ↓Ca, ↑PO₄, ↑ALP, anaemia of chronic disease, small atrophic kidneys with ↓ corticomedullary differentiation on USS ^[3].

Anuria in CKD

Anuria is NEVER observed in CKD alone and always indicates AKI. It may be present with acute on chronic kidney disease ^[13]. This is a common exam trap — if the question describes anuria, think AKI or obstruction, not CKD.

8. Clinical Features

CKD produces few symptoms and signs early on — many patients will present with creatinine of 200–300 without even knowing they have a kidney problem. Generalised symptoms increase at GFR < 15–20 ^[1]^[5]^[11].

Symptom	GFR Stage	Pathophysiological Basis
Nocturia	Early (G2–3)	↓ Nephron function → ↑ solute load per remaining nephron → osmotic diuresis → inability to concentrate urine at night ^[5]
Thirst	Early–Mid	Acidosis → hyperventilation → insensible fluid loss; also osmotic diuresis → volume depletion ^[1]
Fatigue / malaise	Mid–Late (G3–5)	Anaemia (↓ EPO), uraemia, acidosis, muscle wasting
Anorexia, nausea, vomiting	Late (G4–5)	Nausea is the most specific symptom of uraemia ^[3]^[11]; uraemic toxins cause gastroparesis and direct chemoreceptor trigger zone stimulation
Pruritus (itch)	Late (G4–5)	Uremic pruritus — multifactorial: Ca²⁺-PO₄ deposition in skin, uraemic toxins, dry skin, neuropathy, elevated PTH, systemic inflammation ^[1]
Poor appetite / weight loss	Late	Uraemic anorexia → protein-energy wasting (malnutrition is extremely common in ESRD) ^[1]
Metallic taste	Late	Urea breakdown → ammonia in oral cavity
Dyspnoea / orthopnoea	Late	Fluid overload → pulmonary oedema; anaemia → ↓ oxygen carrying capacity; metabolic acidosis → Kussmaul's breathing
Oedema (ankle swelling)	Late	Na⁺/H₂O retention → volume overload; ± nephrotic-range proteinuria → hypoalbuminaemia → ↓ oncotic pressure
Muscle weakness	Variable	Hyperkalaemia (LL > UL), uraemic myopathy, proximal myopathy from vitamin D deficiency
Bone pain	Late	Renal osteodystrophy (secondary hyperparathyroidism → osteitis fibrosa cystica)
Paraesthesia / numbness	Late	Uraemic peripheral neuropathy (axonal degeneration from uraemic toxins); hypocalcaemia
Impaired concentration / confusion	Very late (G5)	Uraemic encephalopathy
Seizures	Very late	Severe uraemia, electrolyte disturbances (hypoCa²⁺, hypoNa⁺)
Amenorrhoea / sexual dysfunction	Late	HPG axis disruption by uraemic toxins, hyperprolactinaemia
Easy bruising / bleeding	Late	Uraemia-induced platelet dysfunction (impaired adhesion and aggregation)

Sign	Pathophysiological Basis
Café au lait complexion	Combination of pallor (anaemia) + yellow-brown discolouration (retained urochrome pigments that are normally excreted by the kidney) ^[1]^[3]^[11]
Pallor	Anaemia (↓ EPO) ^[11]
Scratch marks (excoriations)	Chronic pruritus from uraemic toxins, Ca²⁺-PO₄ deposition
Uremic frost	Crystallised urea on skin surface — very late, rarely seen now with modern dialysis
Peripheral oedema (bilateral pitting)	Na⁺/H₂O retention ± hypoalbuminaemia ^[12]
Elevated JVP	Volume overload
Hypertension	Na⁺/H₂O retention, RAAS activation, sympathetic overactivity. Present in > 80% of CKD patients
Pulmonary crepitations	Pulmonary oedema from fluid overload
Pericardial friction rub	Uraemic pericarditis (fibrinous pericarditis from uraemic toxin deposition on pericardial surfaces)
Kussmaul's respiration	Metabolic acidosis → respiratory compensation (deep, regular breathing)
Peripheral neuropathy	Glove-and-stocking sensory loss; uraemic toxin-mediated axonal damage
Proximal myopathy	Vitamin D deficiency → impaired calcium handling in muscle
Fetor uremicus	Ammonia-like breath from urea breakdown by oral bacteria
Asterixis (flapping tremor)	Uraemic encephalopathy (similar to hepatic flap) — indicates severe toxin accumulation
Small kidneys on ballottement	Chronic scarring, fibrosis, and atrophy — cannot be felt (normal kidneys are usually not palpable either, but in CKD they are definitively shrunken) ^[8]
AV fistula (or PD catheter)	Evidence of RRT — look for thrill and bruit in the non-dominant arm
Fundoscopy: hypertensive retinopathy, diabetic retinopathy	Underlying aetiology (HTN, DM); also look for silver wiring, AV nipping ^[10]

Clinical Approach to a CKD Patient — History and Examination

History is often non-specific ^[1]^[4]:

Swelling, malaise, fatigue
If advanced, may develop nausea and vomiting
Ask about: fluid intake/output, colour of urine (haematuria/frothy urine), nocturia, pruritus
Drug history: NSAIDs, analgesics, herbal medicines (common in HK!)
Family history: PKD, Alport syndrome, IgAN
Co-morbidities: DM, HTN, SLE, recurrent UTIs

Physical examination ^[4]^[12]:

Café au lait complexion, fluid overload
BP measurement (both arms)
Ballottement of kidneys
Bilateral pitting ankle oedema
Fundoscopy
Cardiovascular examination (pericardial rub, JVP)
Look for AV fistula or PD catheter

Diabetic nephropathy is the most common cause of renal impairment (~51% in some series) ^[10]. However, it is crucial to identify non-diabetic nephropathy cases. Red flags include:

Gross haematuria (DM nephropathy typically causes proteinuria, NOT haematuria)
Sudden/rapid reduction in GFR (DM nephropathy is slowly progressive)
Short duration / recent diagnosis of diabetes (e.g. 2–3 years — need 15–20 years for T2DM to cause nephropathy, although many are undiagnosed for years)
Absence of other microvascular complications (no diabetic retinopathy → less likely diabetic nephropathy)

High Yield Exam Point

Unfortunately, good glycaemic control in DM patients will NOT completely prevent development of diabetic nephropathy — it merely delays and slows progression ^[10]. This is because genetic susceptibility, haemodynamic factors, and epigenetic changes also drive nephropathy.

Proteinuria is both a marker of kidney damage and an independent driver of CKD progression (tubulotoxicity from protein reabsorption).

Method	Description	Use
Urine dipstick	Semiquantitative (trace to 4+); detects albumin primarily	Screening; can miss non-albumin proteins (e.g. Bence Jones)
24-hour urine protein	Gold standard for quantification	Cumbersome; used mainly in research now ^[4]
Spot urine protein-to-creatinine ratio (uPCR)	Correlates with 24h protein; done on first morning void	Used in QMH/HK clinical practice ^[4]
Spot urine albumin-to-creatinine ratio (uACR)	Especially for diabetic patients and CKD staging	Major protein in urine is albumin anyway; there are formulas to convert uPCR ↔ uACR ^[4]

Modality	Findings in CKD	Significance
USS kidneys	Small kidneys (< 9 cm), ↓ corticomedullary differentiation, ↑ echogenicity	Hallmark of chronicity ^[3]^[4]
USS kidneys	Large kidneys in CKD	Think: ADPKD (bilateral enlarged cystic kidneys), diabetic nephropathy (early), amyloidosis, HIV-associated nephropathy
KUB X-ray	Renal calcification, renal stones	Obstructive causes, nephrocalcinosis
CT/MRI	Structural detail, vascular anatomy	Renovascular disease (CT/MR angiography); avoid contrast if possible (contrast nephropathy risk)

Contrast in CKD

GFR < 30: contrast is generally contraindicated. GFR 30–60: adequate hydration (IV NS), N-acetylcysteine, avoid ACEI/ARB/diuretics/NSAIDs periprocedurally ^[3]. Gadolinium MRI contrast is also risky in severe CKD — causes nephrogenic systemic fibrosis (NSF).

A systematic workup for CKD includes ^[3]^[4]^[12]:

Bloods:

CBC → look for anaemia (normocytic normochromic)
RFT (creatinine, urea, eGFR) → assess severity and stage
Bone profile (Ca²⁺, PO₄, ALP, PTH) → CKD-MBD
Electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻) → hyperkalaemia, metabolic acidosis
LFT → baseline, hepatorenal syndrome
Fasting glucose, HbA1c → DM screening/control
Fasting lipids → cardiovascular risk
Tests for aetiology: HBV/HCV serology, ANA/anti-dsDNA (SLE), ANCA (vasculitis), complement levels, serum/urine protein electrophoresis (myeloma), anti-GBM antibodies

Urine:

Dipstick (protein, blood, glucose, nitrites, leukocytes)
Microscopy → RBC casts (glomerular disease), WBC casts (interstitial nephritis), muddy brown casts (ATN)
Quantify proteinuria (uACR or uPCR)
Urine culture if infection suspected
24h urine protein and CrCl → used in research and ESRD estimation

Imaging:

USS kidneys → size, echogenicity, corticomedullary differentiation, obstruction, cysts

Special:

Renal biopsy → when aetiology is unclear and would change management; especially in unexplained progressive CKD, nephrotic/nephritic syndrome, suspected GN ^[9]

High Yield Summary

Definition: CKD = kidney structure/function abnormality > 3 months; diagnosed by GFR < 60 OR ACR > 3 mg/mmol (with confirmatory repeat at ≥ 3 months)
Commonest cause in HK adults: Diabetic nephropathy (~40–51%); in children: CAKUT (53%)
Commonest GN in HK/Asia: IgA nephropathy
Key pathophysiology: Nephron loss → compensatory hyperfiltration → glomerulosclerosis → more nephron loss (vicious cycle); ACEI/ARB breaks this cycle
Few symptoms early — nocturia is often earliest. Late symptoms: nausea (most specific), pruritus, anorexia, café au lait complexion
Anuria is NEVER seen in CKD alone — always think AKI or acute-on-chronic
Features distinguishing CKD from AKI: ↓Ca²⁺, ↑PO₄, ↑ALP, anaemia, small kidneys on USS
CKD-MBD cascade: ↓PO₄ excretion + ↓vitamin D activation → hypoCa → secondary hyperparathyroidism → renal osteodystrophy + vascular calcification
Most CKD patients die of CVD (50%), not ESRD
GFR estimation: CKD-EPI recommended; Cockcroft-Gault for drug dosing; at ESRD take average of eGFR and 24h CrCl
HK PD-first policy: HK has highest PD utilisation worldwide
Red flags for non-diabetic nephropathy in a diabetic: haematuria, rapid GFR decline, short DM duration, absence of retinopathy

Active Recall — Chronic Kidney Disease: Definition, Epidemiology, Pathophysiology and Clinical Features

^[1] Lecture slides: Block A - Chronic Kidney Disease and its Complications.pdf ^[2] Lecture slides: GC 034. Chronic Kidney Disease and its Complications [update 2025].pdf ^[3] Senior notes: Maksim Medicine Notes.pdf (Section 10.5 - Chronic kidney disease) ^[4] Senior notes: Block A - Introduction to Renal Investigations (RFT, urine tests and US kidneys).pdf ^[5] Senior notes: Ryan Ho Urogenital.pdf (Section 5.2 - Chronic Kidney Disease) ^[6] Lecture slides: Introduction-kidney-Ix.pdf (p2) ^[7] Lecture slides: Nephrology - ntroduction to Renal Investigation.pdf (p2) ^[8] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (Chronic GN section) ^[9] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf ^[10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (Case P2) ^[11] Senior notes: Adrian Lui Pediatrics Notes.pdf (Section 9.3.2 - CKD) ^[12] Senior notes: Block A – Nephrology Data Interpretation.pdf ^[13] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (CKD section) ^[14] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (Hyperkalemia section)

Differential Diagnosis of Chronic Kidney Disease

When a patient presents with elevated creatinine or reduced eGFR, the clinical task is two-fold:

Is this AKI, CKD, or acute-on-chronic kidney disease? (Chronicity)
What is the underlying aetiology of the CKD? (Cause)

These are fundamentally different questions but are worked through simultaneously. Let's tackle both.

Before you can generate a differential for the cause of CKD, you must first establish that you are indeed dealing with a chronic process. An elevated creatinine could represent:

Diagnosis	Key Features	Why
AKI	Normal previous RFT (< 3 months ago); normal-sized kidneys on USS; normal bone profile; no anaemia (usually); may have anuria/marked oliguria; progressive daily ↑Cr	Acute insult → tubular/glomerular injury is recent; kidney hasn't had time to shrink or develop endocrine failure
CKD	Abnormal RFT > 3 months ago (diagnostic); small atrophic kidneys with ↓ corticomedullary differentiation on USS; ↓Ca²⁺, ↑PO₄, ↑ALP; normocytic normochromic anaemia ^[3]^[5]	Chronic nephron loss → endocrine failure (EPO, vitamin D), bone mineral disorder; scarring shrinks kidneys
Acute-on-chronic	Known CKD baseline with acute deterioration in creatinine; may have anuria (which is never seen in CKD alone); superimposed reversible cause	Pre-existing damaged kidneys with less reserve → more vulnerable to acute insults (infection, dehydration, nephrotoxins, obstruction)

High Yield — Distinguishing CKD from AKI

Features suggesting CKD but NOT AKI ^[3]^[5]:

↓Ca, ↑PO₄, ↑ALP
Anaemia of chronic disease
USS: Small atrophic kidneys, ↓ corticomedullary differentiation

Marked oliguria (< 500 mL/day) rarely occurs in CKD — this favours AKI ^[5]. Anuria is NEVER observed in CKD alone ^[13].

However, note that anaemia is NOT always helpful as many diseases cause AKI + anaemia (e.g. HUS/TTP, massive haemorrhage), and hyperphosphataemia is NOT specific as it also occurs in AKI (from cell lysis, rhabdomyolysis) ^[5].

2. Second-Level Differential: What Is the Cause of the CKD?

Once chronicity is established, you must determine the aetiology. This is critical because some causes are treatable or at least modifiable. The GC lecture slide ^[2] lists the major CKD causes as a key learning objective.

The causes of CKD can be classified anatomically ^[6]^[7]^[12]:

Anatomical Category	Specific Causes	Key Distinguishing Features
Vascular	Hypertensive nephrosclerosis; bilateral renal artery stenosis (atheromatous or fibromuscular dysplasia); ischaemic nephropathy; HUS/TTP; vasculitis	Severe/resistant HTN; renal bruit; diminished peripheral pulses; flash pulmonary oedema; bland urinalysis (no haematuria/proteinuria in RAS); ↓GFR > 30% after starting ACEI/ARB (classic for RAS) ^[5]^[15]^[16]
Glomerular — Primary	IgA nephropathy (most common primary GN); FSGS; membranous nephropathy; MPGN; minimal change disease (rare cause of CKD)	Haematuria (especially synpharyngitic in IgAN); proteinuria; RBC casts; nephrotic or nephritic picture ^[17]^[18]
Glomerular — Secondary	Diabetic nephropathy (most common overall); lupus nephritis; HBV/HCV-associated GN; amyloidosis; light chain deposition disease; post-streptococcal GN (rarely chronic)	Long DM history with retinopathy (for DMN); systemic features (rash, arthralgia for SLE); hepatitis serology; serum/urine protein electrophoresis for myeloma/amyloid ^[5]^[10]^[18]
Tubulointerstitial	Drug-induced (NSAIDs, analgesics, lithium, cisplatin, calcineurin inhibitors, PPIs); chronic pyelonephritis; reflux nephropathy; radiation; TB; sarcoidosis; Sjögren's	Prominent tubular dysfunction (hyperK, acidosis, polyuria, salt wasting, pronounced anaemia out of proportion to GFR); sterile pyuria; WBC/tubular casts; prior drug/toxin exposure; classical triad for acute TIN: fever + rash + eosinophilia ^[1]^[5]^[9]^[19]
Obstructive	BPH; bilateral kidney stones; bladder neck tumour; retroperitoneal fibrosis; neurogenic bladder	Bilateral hydronephrosis on USS; LUTS; palpable bladder; history of stone disease
Congenital/Hereditary	Polycystic kidney disease; Alport syndrome; thin basement membrane disease; congenital renal anomalies	FHx of renal disease; bilateral large cystic kidneys on USS (PKD); sensorineural hearing loss + anterior lenticonus (Alport); young age of onset ^[1]^[3]^[5]
Systemic/Autoimmune	SLE, ANCA-associated vasculitis, Goodpasture syndrome, amyloidosis, scleroderma renal crisis	Multisystem features; specific autoantibodies (ANA, anti-dsDNA, ANCA, anti-GBM) ^[8]^[9]
Neoplastic/Paraprotein	Myeloma (CRAB); monoclonal gammopathy of renal significance (MGRS)	Bone pain, anaemia, hypercalcaemia; serum/urine protein electrophoresis; Bence Jones proteinuria (not detected by dipstick!) ^[1]
Metabolic	Obesity-related glomerulopathy; hyperuricaemic nephropathy	BMI > 30; gout history ^[1]

GC Lecture — Causes of CKD (Exam-Critical List)

From the GC 034 lecture and Block A CKD notes, the differential for the cause of CKD ^[1]^[2]:

Diabetes
Hypertension / vascular
Chronic glomerulonephritis e.g. IgA GN
Chronic pyelonephritis
Polycystic kidney disease
Drug induced, TIN, TCM (traditional Chinese medicine — particularly relevant in HK!)
Myeloma (CRAB), monoclonal gammopathy
Vasculitis, SLE, other autoimmune diseases
Obstruction, kidney stones
Alport's or other hereditary or rare diseases
Obesity

In Hong Kong: Diabetes is by far the #1 cause (~51%), followed by hypertension/vascular causes ^[1].

This is an extremely practical and commonly examined approach. USS is the best, most non-invasive way to assess and visualise kidneys ^[1]. Normal kidney size on USS: 10–12 cm, symmetrical ^[1].

USS Finding	Differential	Why
Small kidneys (< 9 cm)	CKD — dysplastic, scarred, or shrunken kidney ^[1]	Chronic fibrosis, nephron loss, and atrophy → kidneys shrink over time
Normal-sized kidneys + high creatinine	AKI (parenchymal, vascular, GN problems) — will require kidney biopsy ^[1]	Acute process → not enough time for kidneys to atrophy; biopsy needed to guide specific treatment
Large kidneys	Polycystic kidney disease; infiltration (amyloidosis — rarer); obstruction (post-renal, hydronephrosis) ^[1]; also: early diabetic nephropathy (nephromegaly); HIV-associated nephropathy	PKD: cysts expand kidney volume; Amyloid: protein deposition expands interstitium; Obstruction: back-pressure dilates pelvis/calyces
Asymmetric kidneys	Renovascular disease (unilateral RAS); reflux nephropathy (unilateral scarring); congenital unilateral renal agenesis/dysplasia	Unilateral ischaemia or scarring → asymmetric atrophy

The urine sediment is your best friend for narrowing the differential of CKD cause — it tells you which compartment of the kidney is affected:

Urinalysis Finding	Points Towards	Reasoning
RBC casts, dysmorphic RBCs	Glomerulonephritis (IgAN, lupus nephritis, ANCA vasculitis, anti-GBM disease)	RBCs squeeze through damaged glomerular basement membrane → become dysmorphic; they then get trapped in Tamm-Horsfall protein in tubules → RBC casts ^[17]
Heavy proteinuria (> 3.5 g/day) with bland sediment	Nephrotic-pattern GN (diabetic nephropathy, membranous nephropathy, FSGS, amyloidosis, minimal change)	Podocyte injury → loss of charge/size selectivity → massive albumin leak; no cellular proliferation → no haematuria
WBC casts, sterile pyuria, tubular epithelial casts	Tubulointerstitial nephritis (drug-induced, chronic pyelonephritis, reflux nephropathy) ^[5]^[19]	Inflammation centred on interstitium and tubules → WBCs accumulate in tubular lumen
Bland sediment (no casts, minimal protein/blood)	Vascular causes (HTN nephrosclerosis, RAS); obstructive uropathy	These conditions damage vessels/stroma rather than glomeruli/tubules → urine is relatively "clean"
Broad waxy casts	Chronic kidney disease (end-stage)	Formed in dilated, atrophic tubules with very slow flow — indicates chronicity

Clinical Clue	Most Likely Aetiology	Why
Long-standing DM (> 10–15 years) + progressive proteinuria + diabetic retinopathy	Diabetic nephropathy ^[5]^[10]	Need long duration of hyperglycaemia for glomerular basement membrane thickening → Kimmelstiel-Wilson nodules; retinopathy presence supports microvascular aetiology
Young woman + malar rash + arthralgia + haematuria/proteinuria	Lupus nephritis ^[10]	Immune complex deposition in glomeruli; check ANA, anti-dsDNA, C3/C4
Episodic macroscopic haematuria concurrent with URTI ("synpharyngitic")	IgA nephropathy ^[17]	Mucosal infection → ↑ IgA production → mesangial IgA deposition → glomerular inflammation; classically within 1–2 days of URTI (cf. post-streptococcal GN which has 1–3 week latency)
Family history of kidney disease + bilateral large cystic kidneys on USS	Autosomal dominant polycystic kidney disease (ADPKD) ^[1]^[3]	PKD1/PKD2 mutations → defective polycystin → abnormal tubular cell proliferation → cyst formation
Family history of deafness + haematuria in young male	Alport syndrome	X-linked COL4A5 mutation → defective type IV collagen in GBM, cochlea, and lens ^[17]
Elderly + bone pain + anaemia + hypercalcaemia + elevated creatinine	Multiple myeloma (CRAB: Calcium, Renal, Anaemia, Bone) ^[1]	Light chain deposition/cast nephropathy; Bence Jones proteins are NOT detected by urine dipstick → need urine protein electrophoresis
Refractory HTN + renal bruit + flash pulmonary oedema + AKI after ACEI/ARB	Renal artery stenosis ^[15]^[16]	Atherosclerotic narrowing → ↓ renal perfusion → RAAS activation → HTN; ACEI removes efferent tone → GFR crashes
Drug exposure (NSAIDs, analgesics, lithium, PPIs, TCM) + tubular dysfunction	Drug-induced chronic TIN ^[1]^[19]	Direct tubular toxicity or chronic allergic interstitial inflammation → interstitial fibrosis
Elderly Chinese patient + herbal medicine (TCM) use	Aristolochic acid nephropathy (Chinese herb nephropathy)	Aristolochic acid (found in some TCM formulations) → direct tubulotoxicity + carcinogenicity (↑ risk of urothelial carcinoma); HK-relevant! ^[1]
Obesity (BMI > 35) + proteinuria + FSGS on biopsy	Obesity-related glomerulopathy ^[1]	Hyperfiltration from ↑ metabolic demand → glomerular hypertrophy → secondary FSGS
Gout history + CKD	Hyperuricaemic/gouty nephropathy	Chronic urate crystal deposition in medullary interstitium → inflammation → fibrosis

Red Flags for Non-Diabetic Nephropathy in a Diabetic Patient

Diabetic nephropathy is the most common cause of renal impairment (~51%) ^[10]. But your job is to identify the non-diabetic cases. Red flags include ^[10]:

Gross haematuria (DM nephropathy = proteinuria, NOT haematuria)
Sudden/rapid reduction in GFR
Short duration / recent diagnosis of DM (e.g. 2–3 years) — need 15–20 years for T2DM (though many are undiagnosed for years)
Absence of other microvascular complications (no diabetic retinopathy)

If any of these are present → renal biopsy is indicated to look for superimposed GN, TIN, or other pathology ^[5]^[10].

The GC 057 lecture slide explicitly lists the differential diagnosis of haematuria ^[20]:

Urologic conditions: stones, tumour Renal conditions: glomerulonephritis, acute interstitial nephritis, polycystic kidney disease Infection: cystitis, TB, schistosomiasis

This is important because haematuria in a CKD patient may represent the underlying cause (GN) or a superimposed new pathology (bladder cancer, stones). You must exclude urological causes in any patient with haematuria, especially if it is non-glomerular (no RBC casts, isomorphic RBCs, presence of clots).

Factor	Relevance
Traditional Chinese medicine (TCM)	Drug-induced TIN / aristolochic acid nephropathy — always ask about TCM use in HK patients ^[1]
IgA nephropathy prevalence	Higher in Asian populations than Western; most common primary GN in HK ^[3]
Hepatitis B/C	HBV-associated membranous nephropathy and MPGN; HCV-associated cryoglobulinaemic GN; HK has intermediate HBV endemicity
Diabetes epidemic	Rising prevalence in HK → increasing burden of diabetic nephropathy ^[1]^[10]
Peritoneal dialysis first policy	Once ESRD is reached, HK's PD-first policy means the differential should also consider PD-related complications as causes of acute-on-chronic deterioration

The initial evaluation should include ^[5]:

Investigation	What It Tells You
History	DM duration, HTN, drug exposure (NSAIDs, TCM, lithium), FHx (PKD, Alport), systemic symptoms (SLE, vasculitis), haematuria episodes
Urine dipstick + microscopy	Glomerular vs tubular vs bland pattern
Urine protein quantification (uACR or uPCR)	Severity of proteinuria; nephrotic range?
USS kidneys	Size, symmetry, corticomedullary differentiation, cysts, obstruction
Bloods — RFT, bone profile, CBC	Stage CKD; differentiate from AKI
HbA1c, fasting glucose	DM as cause
Autoimmune screen	ANA, anti-dsDNA, C3/C4 (SLE); ANCA (vasculitis); anti-GBM (Goodpasture) ^[5]^[13]
Serology	HBV/HCV (GN association)
Serum/urine protein electrophoresis + free light chains	Myeloma, amyloidosis ^[13]
Renal duplex USS	RAS (if refractory HTN, bruit, AKI post-ACEI) ^[5]^[15]
Renal biopsy	When cause is unclear and would change management; atypical features in a diabetic; suspected GN; unexplained progressive CKD with normal-sized kidneys ^[1]^[4]^[5]

When Is Renal Biopsy Indicated in CKD?

Someone with high creatinine and normal-sized kidneys → worried about AKI or a treatable intrinsic renal disease → will require kidney biopsy ^[1].

Biopsy is contraindicated in: contracted/small kidneys (just get fibrous tissue), large cysts (cannot stop bleeding), solitary kidney (no backup if complication occurs) ^[4].

In diabetic patients, biopsy is only indicated in atypical situations ^[5]:

Haematuria or active sediment
Absence of other microvascular complications
Acute or too-early onset of proteinuria
Features of systemic disease
Significant ↓GFR > 30% after ACEI/ARB (think RAS)

Rank (HK)	Aetiology	Key Clues	Key Investigation
1	Diabetic nephropathy	Long DM history, retinopathy, progressive proteinuria, no haematuria	HbA1c, uACR, fundoscopy
2	Hypertensive nephrosclerosis	Long HTN history, LVH, bland urinalysis	ECG/Echo, USS
3	Chronic GN (esp. IgAN)	Haematuria ± proteinuria, RBC casts	Autoimmune screen, renal biopsy
4	Chronic TIN / drug-induced	Drug history (NSAIDs, TCM, analgesics), tubular dysfunction	Drug history, urine WBC casts
5	ADPKD	FHx, bilateral large cystic kidneys	USS, genetic testing
6	Systemic (SLE, vasculitis)	Multisystem features, active sediment	ANA, ANCA, C3/C4, biopsy
7	Renovascular (RAS)	Refractory HTN, bruit, AKI post-ACEI	Duplex USS, CTA/MRA
8	Obstructive	LUTS, bilateral hydronephrosis	USS, CT KUB
9	Myeloma / paraprotein	Elderly, bone pain, anaemia, hypercalcaemia	SPEP/UPEP, free light chains, bone marrow biopsy
10	Hereditary (Alport)	FHx deafness + renal failure, young male	Audiometry, genetic testing, biopsy

High Yield Summary — Differential Diagnosis of CKD

Always first establish chronicity (AKI vs CKD vs acute-on-chronic) using previous RFT, USS kidney size, bone profile, and anaemia status
Anatomical classification: Vascular / Glomerular / Tubulointerstitial / Obstructive / Congenital-Hereditary
#1 cause in HK: Diabetic nephropathy (~51%); #2: Hypertension/vascular
IgA nephropathy is the most common primary GN in HK/Asia
USS kidney size is crucial: Small = CKD; Normal + high Cr = AKI (consider biopsy); Large = PKD, amyloid, obstruction
Urinalysis pattern guides compartment: RBC casts = glomerular; WBC casts = TIN; bland = vascular/obstructive
Always ask about TCM/herbal medicine use in HK — aristolochic acid nephropathy
Red flags in diabetic CKD for non-diabetic cause: haematuria, rapid GFR decline, short DM duration, absent retinopathy → biopsy indicated
Myeloma is a must-not-miss: CRAB features; Bence Jones protein NOT detected by dipstick
Renal biopsy when cause is unclear and kidneys are normal-sized and result would change management

Active Recall — Differential Diagnosis of CKD

References

^[1] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf ^[2] Lecture slides: GC 034. Chronic Kidney Disease and its Complications [update 2025].pdf ^[3] Senior notes: Maksim Medicine Notes.pdf (Section 10.5) ^[4] Senior notes: Block A - Introduction to Renal Investigations (RFT, urine tests and US kidneys).pdf ^[5] Senior notes: Ryan Ho Urogenital.pdf (Section 5.2) ^[6] Lecture slides: Introduction-kidney-Ix.pdf (p2) ^[7] Lecture slides: Nephrology - ntroduction to Renal Investigation.pdf (p2) ^[8] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf ^[9] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf ^[10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (Case P2) ^[12] Senior notes: Block A – Nephrology Data Interpretation.pdf ^[13] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (CKD section) ^[15] Senior notes: Block A - High blood pressure_ hypertension.pdf ^[16] Senior notes: Ryan Ho Cardiology.pdf (Secondary HTN) ^[17] Senior notes: Ryan Ho Fundamentals.pdf (Isolated Glomerular Haematuria) ^[18] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (Glomerular disease classification) ^[19] Senior notes: Maksim Medicine Notes.pdf (TIN section) ^[20] Lecture slides: GC 057. Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p16)

Diagnostic Criteria, Diagnostic Algorithm and Investigations for CKD

1. Diagnostic Criteria for CKD

CKD is not diagnosed by a single test — it requires demonstrating persistence (chronicity) and characterising severity (staging). The KDIGO 2012 criteria remain the standard in 2025/2026.

CKD is diagnosed when EITHER of the following is present for > 3 months ^[1]^[2]^[13]:

Criterion	Definition	Notes
Decreased GFR	GFR < 60 mL/min/1.73m²	Alone sufficient for diagnosis (Stage G3a–G5) regardless of other markers
Markers of kidney damage	ACR > 3 mg/mmol (> 30 mg/g) OR other markers	Required if GFR ≥ 60 (Stage G1–G2); "other markers" include haematuria, structural abnormalities, electrolyte disturbances from tubular disorders, abnormal histology, history of kidney transplantation

The key word is > 3 months. Two readings below 60, at least 3 months apart, confirm CKD ^[4]. A single abnormal reading could represent AKI, a lab error, or a transient insult.

GC Lecture High Yield — Defining CKD

Greater than 3 months of: GFR less than 60 mL/min/1.73m² OR ACR > 3 mg/mmol or other markers of kidney damage ^[1].

If GFR is greater than 60, an individual can still be classified as CKD (Stage 1 and 2) if there is concomitant presence of some other kidney abnormality — blood/protein in urine, or structural kidney issues ^[1].

Staging uses two independent axes — both predict prognosis ^[1]^[5]:

GFR Categories (G):

Stage	GFR (mL/min/1.73m²)	Description
G1	≥ 90	Normal or high
G2	60–89	Mildly decreased
G3a	45–59	Mildly to moderately decreased
G3b	30–44	Moderately to severely decreased
G4	15–29	Severely decreased
G5	< 15	Kidney failure

Albuminuria Categories (A):

Stage	ACR (mg/mmol)	ACR (mg/g)	Description
A1	< 3	< 30	Normal to mildly increased
A2	3–30	30–300	Moderately increased
A3	> 30	> 300	Severely increased

Report CKD stage in terms of GxAy — e.g. "G3aA3 CKD" ^[1]. The colours in the KDIGO guideline represent the likelihood of progressing to ESRD — red worst, green best ^[1].

Why two axes? Because a patient with GFR 50 and ACR 500 has a far worse prognosis than a patient with GFR 50 and ACR 10 — proteinuria is both a marker and a driver of progressive nephron loss (tubulotoxicity from protein reabsorption).

eGFR normally falls with age ^[1]:

Age	Expected eGFR
20–29	~116
30–39	~107
40–49	~99
50–59	~93
60–69	~85
70+	~75

So if an 85-year-old grandmother presents with an eGFR of 75, this is actually in keeping with physiological age-related decline — less concerning if she is otherwise well, has no proteinuria, and has no structural kidney disease ^[1]. Clinical context always matters.

The approach to a patient with newly discovered elevated creatinine / low eGFR follows three key steps ^[5]:

Establish chronicity → AKI vs CKD vs acute-on-chronic
Determine the cause
Evaluate complications

GC Lecture — Approach to Evaluation of CKD

Three-step approach ^[2]^[5]:

Establishing diagnosis and staging: chronicity, GFR, albuminuria
Evaluation of cause
Evaluation of complications

AKI is potentially reversible — must be ruled out ^[5].

3. Investigation Modalities — Detailed Breakdown

3.1 Blood Tests

Component	What It Measures	Interpretation in CKD	Pitfalls
Serum creatinine	By-product of creatine phosphate metabolism in muscle; freely filtered, minimally secreted	Rises inversely with GFR; the primary input for eGFR equations	Insensitive: GFR can drop ~40–50% before plasma Cr is raised ^[4]^[5]. Also varies with muscle mass, age, sex, protein intake, race
Serum urea (BUN)	End-product of protein metabolism; freely filtered, partially reabsorbed (40–60%) in PCT	Rises in renal failure; also rises with high protein intake, GI bleeding, catabolic states, dehydration	Less specific than creatinine — affected by many non-renal factors
Urea:Creatinine ratio	Differential between pre-renal and intrinsic renal disease	> 100 (in μmol/μmol) suggests pre-renal (disproportionate urea reabsorption in dehydration); < 40 suggests intrinsic renal disease (ATN) ^[3]	Mainly useful in AKI differentiation
eGFR	Estimated from serum Cr using equations	The standard for staging CKD	See equation comparison below

GFR estimating equations ^[1]^[3]^[5]:

Equation	Parameters	Role	Limitations
CKD-EPI	Age, sex, race, Cr	Recommended: performs better at normal/low-normal GFR; can ↓ overdiagnosis of CKD ^[5]	Chinese race and muscle mass not fully accounted for
MDRD	Age, sex, race, Cr	Most commonly used (equation of choice in HA laboratories) ^[5]	Derived from CKD patients → tends to underestimate eGFR when > 60 ^[3]^[5]
Cockcroft-Gault	(1.23)(140−age)(weight)/Cr, ×0.85 if female; NOT adjusted for BSA	Drug dosing ^[3]	Overestimates GFR; depends on body weight (body weight data often not available to lab → not used routinely in RFT) ^[5]

At ESRD (GFR < 15): eGFR and 24h CrCl are both not accurate in estimating renal function → take the average of both ^[3].

Why Is Serum Creatinine a Poor Early Marker?

When creatinine rises, GFR has already been reduced by at least 50% ^[10]. This is because of the inverse, hyperbolic relationship between GFR and Cr:

At GFR 120 → Cr might be 80 μmol/L
At GFR 60 (50% loss) → Cr might only be 130 μmol/L (looks "mildly elevated")
At GFR 30 → Cr jumps to ~250+ μmol/L

The early, critical loss of nephrons is "silent" on blood tests. This is why screening with uACR in at-risk populations (diabetics, hypertensives) catches damage much earlier than waiting for Cr to rise ^[10].

Finding	Significance	Mechanism
Normocytic normochromic anaemia	Supports chronicity (CKD) ^[1]^[3]^[13]	↓ EPO production from loss of peritubular interstitial fibroblasts; also uraemic suppression of erythropoiesis, shortened RBC lifespan, functional iron deficiency (↑ hepcidin)
Leukocytosis / eosinophilia	May indicate acute TIN (drug reaction) or infection	Eosinophilia seen in ~40% of drug-induced acute interstitial nephritis ^[9]
Thrombocytopenia	Consider HUS/TTP (microangiopathic haemolytic anaemia)	Platelet consumption in thrombotic microangiopathy

Note: Anaemia is NOT helpful for differentiating CKD from AKI as many diseases cause AKI + anaemia ^[5]. However, normocytic normochromic anaemia combined with other chronic features (small kidneys, abnormal bone profile) strongly supports CKD ^[13].

Parameter	Expected in CKD	Mechanism	Clinical Significance
↓ Ca²⁺	Hypocalcaemia	↓ 1α-hydroxylase → ↓ active vitamin D → ↓ intestinal Ca²⁺ absorption	Supports chronicity (rarely seen in AKI) ^[3]^[13]
↑ PO₄	Hyperphosphataemia	↓ Renal PO₄ excretion	Also seen in AKI (cell lysis), so NOT specific for CKD alone ^[5]
↑ ALP	Raised alkaline phosphatase	Secondary hyperparathyroidism → ↑ bone turnover → osteoblast activity releases ALP	Suggests renal osteodystrophy — supports CKD ^[3]^[13]
↑ PTH	Secondary hyperparathyroidism	Chronic hypocalcaemia + hyperphosphataemia + ↓ active vitamin D → parathyroid gland stimulation	Confirms CKD-MBD; guides treatment with phosphate binders, vitamin D analogues

The classic "CKD bone profile" is: ↓Ca, ↑PO₄, ↑ALP, ↑PTH ^[1]^[3]^[8]. This constellation, when combined with small kidneys and anaemia, is virtually diagnostic of CKD (not AKI).

Test	Expected Finding	Mechanism
Serum K⁺	Hyperkalaemia (especially GFR < 20–25)	↓ Distal tubular K⁺ secretion; worsened by ACEI/ARB/MRA
Serum HCO₃⁻ / ABG	Metabolic acidosis (HAGMA ± NAGMA component)	↓ Nephron mass → ↓ H⁺/NH₄⁺ excretion → ↑ organic acid retention; ± RTA in tubulointerstitial disease
Serum Na⁺	Variable (may be normal, low in dilutional states)	Depends on fluid balance

Test	What You're Looking For	When to Order
HbA1c, fasting glucose	Diabetes mellitus as cause of CKD	All CKD patients (DM is #1 cause) ^[1]^[3]
Fasting lipids	Cardiovascular risk assessment; dyslipidaemia	All CKD patients ^[3]^[12]
HBV/HCV serology	Hepatitis-associated GN (membranous nephropathy, MPGN, cryoglobulinaemia); urgent HBsAg if haemodialysis is anticipated ^[13]	All CKD patients
ANA, anti-dsDNA, C3/C4	SLE / lupus nephritis	Suspected autoimmune disease (young female, multisystem)
ANCA	ANCA-associated vasculitis (GPA, MPA, EGPA)	Rapidly progressive GN, pulmonary-renal syndrome
Anti-GBM antibodies	Goodpasture syndrome	Pulmonary haemorrhage + AKI/RPGN
Serum / urine protein electrophoresis + immunofixation	Myeloma, monoclonal gammopathy, amyloidosis	Elderly with bone pain, anaemia, hypercalcaemia, unexplained CKD ^[13]^[21]
Serum free light chain level and ratio	Light chain myeloma, MGRS	Suspected paraprotein-related disease ^[21]
Complement levels (C3, C4)	Low in SLE, MPGN, post-infectious GN, cryoglobulinaemia	Suspected immune complex-mediated GN
ASOT / anti-DNase B	Post-streptococcal GN	Recent pharyngitis/skin infection → acute nephritic syndrome
Anti-PLA2R	Primary membranous nephropathy	Nephrotic syndrome with suspected MN

Myeloma — A Must-Not-Miss Diagnosis

Bence Jones proteins (free light chains) are NOT detected by urine dipstick — dipstick detects albumin, not light chains ^[16]. You need urine protein electrophoresis (UPE) and serum free light chain assays to diagnose myeloma kidney ^[21]. If an elderly patient has unexplained CKD with bland urinalysis but high uPCR → think myeloma.

In myeloma, the dipstick may show "undetectable" urine protein but the uACR will be markedly elevated ^[16] — this discrepancy is a classic exam clue.

3.2 Urine Tests

Urine tests are critical and should always be performed alongside blood tests ^[4]^[12].

Parameter	Significance	Mechanism / Notes
Protein	Albuminuria (screening)	Semiquantitative (trace to 4+); detects albumin primarily; misses Bence Jones proteins
Blood	Haematuria	Can be glomerular or non-glomerular; false positives with myoglobinuria, haemoglobinuria
Glucose	Glycosuria	DM, proximal tubular dysfunction (Fanconi syndrome), SGLT2i use
Leukocyte esterase / Nitrites	UTI	Infection screen

This is arguably the most important investigation for determining the compartment of kidney disease:

Finding	Indicates	Mechanism
Dysmorphic RBCs	Glomerular haematuria	RBCs squeezed through damaged GBM → distorted morphology (acanthocytes) ^[13]^[17]
RBC casts	Glomerulonephritis (diagnostic of intrarenal origin)	RBCs entrapped in Tamm-Horsfall protein matrix within tubular lumen ^[13]
WBC casts	Tubulointerstitial nephritis, pyelonephritis	WBCs aggregate in inflamed tubular lumen
Granular / epithelial cell casts	ATN	Necrotic tubular epithelial cells shed → form casts; "muddy brown casts" are pathognomonic for ATN ^[9]
Broad waxy casts	Chronic kidney disease (end-stage)	Formed in dilated, atrophic tubules with very slow flow — indicates chronicity
Hyaline casts	Non-specific; can be normal	Tamm-Horsfall protein alone; seen in concentrated urine, exercise, dehydration

Casts have an organic matrix composed primarily of Tamm-Horsfall mucoprotein, which forms different types of casts when other elements (RBC/WBC/epithelial cells) are embedded in the cast matrix. Their significance = diagnostic of an intrarenal origin ^[13].

Method	Description	Clinical Use	Limitations
24-hour urine protein	Gold standard for quantification ^[4]	Research; accurate total protein measurement	Very cumbersome; patient may add water or miss collections ^[4]
Spot urine protein-to-creatinine ratio (uPCR)	Done on first morning void; correlates with 24h protein	Used clinically in QMH/HK ^[4]	Affected by urine concentration
Spot urine albumin-to-creatinine ratio (uACR)	Especially for diabetic patients and CKD staging (KDIGO) ^[4]	Screening, staging, monitoring	In QMH, uPCR is used more commonly; formulas exist to interconvert uPCR ↔ uACR ^[4]

Measured: CrCl = (U × V) / P ^[13] using blood and 24-hour urine sample
Provides a measured GFR rather than an estimated one
Useful when estimating equations are less accurate: extremes of body habitus, extremes of age ^[5]
At ESRD (GFR < 15): take average of eGFR and 24h CrCl ^[3]

Test	Indication
Urine culture	Suspected UTI or chronic pyelonephritis
Urine protein electrophoresis	Suspected myeloma — detects Bence Jones proteins ^[21]
Urine Na⁺ and osmolality	Differentiate pre-renal from intrinsic AKI (not primary CKD use, but relevant in acute-on-chronic)
FENa	< 1% = pre-renal; > 2% = ATN ^[3] — mainly for AKI workup

3.3 Imaging

Best, most non-invasive way to assess and visualise kidneys ^[1]. This is the first-line imaging modality in all patients with suspected CKD.

What to Assess	Normal	CKD Findings	Significance
Size	10–12 cm, symmetrical ^[1]	Small (< 9 cm)	Chronic scarring and atrophy → CKD ^[1]
Echogenicity	Normal cortical echogenicity	↑ Renal parenchymal echogenicity ^[13]	Indicates chronic parenchymal change (fibrosis)
Corticomedullary differentiation	Clear distinction between cortex and medulla	↓ or lost corticomedullary differentiation ^[3]^[5]	Chronic change; key differentiator from AKI
Obstruction	No hydronephrosis	Hydronephrosis	Post-renal cause
Cysts	Few simple cysts (age-related)	Multiple bilateral cysts	PKD
Symmetry	Symmetrical	Asymmetric	Unilateral RAS, reflux nephropathy

Differential diagnosis by kidney size on USS ^[1]:

Size	Differential
Small	CKD: dysplastic kidney, scarred or shrunken kidney
Normal + high Cr	AKI — worry about glomerulonephritis, etc. → will require kidney biopsy
Large	PKD; infiltration (amyloidosis — rarer); obstruction (post-renal)

Ultrasound doppler to visualise perfusion ^[4] — used to assess renal artery stenosis
Renal duplex ultrasound: first-line screening for RAS (peak systolic velocity, resistive index) ^[5]

Modality	Indication	Notes
KUB X-ray	Renal calcification, nephrocalcinosis, stones	Simple, cheap, limited information
Non-contrast CT	Renal stones, structural abnormalities	Non-contrast preferred over contrast in CKD ^[4] — avoids contrast nephropathy
CT angiography / MR angiography	Renal artery stenosis (confirmatory after duplex USS)	Contrast risk must be weighed; gadolinium in MRI risks nephrogenic systemic fibrosis (NSF) in severe CKD ^[13]
DTPA scan	Renal perfusion and drainage (split function)	Nuclear medicine; assesses differential function
DMSA scan	Renal scarring	Used particularly in reflux nephropathy (paediatrics)

Contrast and CKD — Critical Safety Points

MRI with gadolinium should be avoided since administration of gadolinium is associated with the potentially severe syndrome of nephrogenic systemic fibrosis (NSF) ^[13] — especially at GFR < 30.

Iodinated CT contrast: GFR < 30 = generally contraindicated. GFR 30–60 = adequate hydration with IV NS, consider N-acetylcysteine, withhold ACEI/ARB/diuretics/NSAIDs periprocedurally ^[3].

3.4 Renal Biopsy

Renal biopsy provides the definitive tissue diagnosis ^[9]^[13]. However, it is NOT always needed in CKD and has specific indications and contraindications.

Situation	Rationale
Cause of CKD unclear and would change management	Need histological diagnosis to guide immunosuppressive or specific therapy
Normal-sized kidneys + high creatinine	Worried about AKI or potentially treatable GN ^[1] — biopsy needed to guide specific treatment
Atypical features in a diabetic patient	Haematuria/active sediment; absence of retinopathy; acute/early-onset proteinuria; features of systemic disease; significant ↓GFR > 30% after starting ACEI/ARB ^[5]^[10]
Suspected RPGN (rapidly rising creatinine)	Medical emergency — need urgent tissue diagnosis to start immunosuppression
Unexplained nephrotic syndrome	To differentiate MCD/FSGS/MN and guide treatment

Contraindication	Reason
Contracted/small kidneys	Hard to locate; you might just get fibrous tissue; pathologist cannot determine original cause ^[4]^[8]
Large cysts	Cannot stop the bleeding ^[4]
Solitary kidney	No backup if complication occurs ^[4]
Uncontrolled bleeding diathesis	Risk of haemorrhage
Uncontrolled severe hypertension	Risk of haemorrhage
Active renal or perirenal infection	Risk of abscess dissemination

For chronic GN with shrunken atrophic kidneys — kidney biopsy is usually unnecessary ^[8]. Even after obtaining tissue, it is difficult to interpret because the pathologist cannot determine the original cause given the fibrotic, sclerotic, and progressive damage. The result has no implications on management (which is supportive at this stage). It is possible that chronic GN patients are diagnosed without histological proof ^[8].

Patient is prone; radiologist uses USS to locate the kidney; biopsy targets the lower pole; multiple extractions to get sufficient tissue for light microscopy, immunofluorescence, and electron microscopy ^[4].

Many glomerulonephritides are immune-mediated, so autoimmune markers are essential ^[4]:

Test	Disease	Pattern
ANA + anti-dsDNA	SLE / lupus nephritis	Positive ANA (sensitive), anti-dsDNA (specific)
C3, C4	Immune complex GN (SLE, post-infectious, MPGN, cryoglobulinaemia)	Low complement (consumed by immune complexes)
c-ANCA / anti-PR3	Granulomatosis with polyangiitis (GPA)	Cytoplasmic ANCA pattern
p-ANCA / anti-MPO	Microscopic polyangiitis (MPA)	Perinuclear ANCA pattern
Anti-GBM	Goodpasture syndrome	Linear IgG on IF; cross-reacts with pulmonary alveolar basement membrane
ASOT / anti-DNase B	Post-streptococcal GN	Elevated; often delayed 1–3 weeks after pharyngitis
Anti-PLA2R	Primary membranous nephropathy	Present in ~70% of primary MN; useful to avoid biopsy in some cases
Serum Ig levels	Immunoparesis in myeloma	IgG/IgA/IgM; reduced in myeloma (except the monoclonal component)
HBsAg, anti-HCV	Hepatitis-associated GN	HBV → membranous; HCV → cryoglobulinaemic MPGN

Feature	Modality	Interpretation
Small kidneys	USS	CKD — chronic scarring/atrophy ^[1]^[13]
↑ Parenchymal echogenicity	USS	Chronic parenchymal fibrosis ^[13]
↓ Corticomedullary differentiation	USS	Loss of normal architecture; chronicity marker ^[3]^[5]
Bilateral hydronephrosis	USS	Obstructive uropathy (post-renal)
Multiple bilateral cysts	USS	ADPKD
Subperiosteal bone resorption	X-ray (hands)	Renal osteodystrophy — secondary hyperparathyroidism ^[13]
Loss of bone density at distal 1/3 of clavicles	X-ray	Renal osteodystrophy ^[13]
Vascular calcification	X-ray / CT	CKD-MBD ^[1]
Rugger jersey spine	Lateral spine X-ray	Alternating sclerotic and lucent bands — pathognomonic for renal osteodystrophy

Investigation	Normal	CKD Pattern	What It Tells You
Serum Cr	65–100 μmol/L (varies)	Elevated	↓ GFR; insensitive early marker
eGFR	90–120 mL/min/1.73m²	< 60 for > 3 months	Diagnostic and staging of CKD
Hb	M: 130–170, F: 120–160 g/L	Low (NcNc)	EPO deficiency; chronicity marker
Ca²⁺	2.15–2.55 mmol/L	Low	↓ 1α-hydroxylase → ↓ active vitamin D
PO₄	0.8–1.5 mmol/L	High	↓ Renal excretion
ALP	40–120 IU/L	High	Secondary hyperparathyroidism → ↑ bone turnover
PTH	1.6–6.9 pmol/L	High	Secondary (or tertiary) hyperparathyroidism
K⁺	3.5–5.0 mmol/L	High	↓ Distal tubular secretion
HCO₃⁻	22–28 mmol/L	Low	Metabolic acidosis (↓ H⁺ excretion)
uACR	< 3 mg/mmol	Elevated	Albuminuria — marker of glomerular damage
USS kidneys	10–12 cm	Small (< 9 cm), ↑ echogenicity, ↓ CMD	Chronicity; extent of scarring

High Yield Summary — Diagnosis and Investigations of CKD

CKD = GFR < 60 OR markers of kidney damage, persisting > 3 months — need two readings at least 3 months apart
KDIGO staging uses both GFR (G1–G5) and albuminuria (A1–A3) — report as "GxAy"
Three-step approach: establish chronicity → determine cause → evaluate complications
Features confirming CKD (not AKI): ↓Ca, ↑PO₄, ↑ALP, NcNc anaemia, small kidneys with ↓ CMD on USS
eGFR is insensitive early on — Cr doesn't rise until GFR has already dropped ~50%
MDRD is used in HA labs (underestimates when > 60); Cockcroft-Gault for drug dosing; CKD-EPI is recommended
Urine microscopy tells you which compartment is affected: RBC casts = glomerular; WBC casts = TIN; muddy brown casts = ATN; bland = vascular/obstructive
Bence Jones proteins not detected by dipstick — need UPEP and free light chains for myeloma
Renal biopsy when cause unclear + normal-sized kidneys; contraindicated in small/cystic/solitary kidneys
Always check HBsAg urgently if haemodialysis is anticipated

Active Recall — CKD Diagnostic Criteria, Algorithm and Investigations

References

^[1] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf ^[2] Lecture slides: GC 034. Chronic Kidney Disease and its Complications [update 2025].pdf ^[3] Senior notes: Maksim Medicine Notes.pdf (Sections 10.4–10.5) ^[4] Senior notes: Block A - Introduction to Renal Investigations (RFT, urine tests and US kidneys).pdf ^[5] Senior notes: Ryan Ho Urogenital.pdf (Section 5.2) ^[8] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf ^[9] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf ^[10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf ^[12] Senior notes: Block A – Nephrology Data Interpretation.pdf ^[13] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (CKD section) ^[16] Senior notes: Ryan Ho Critical Care.pdf (AKI workup) ^[17] Senior notes: Ryan Ho Fundamentals.pdf (Isolated Glomerular Haematuria) ^[21] Senior notes: Block A - An old man with bone pain and anaemia_ multiple myeloma; monoclonal gammopathy.pdf

Management of Chronic Kidney Disease

The management of CKD is not a single intervention — it is a longitudinal strategy that evolves as the patient moves from early-stage disease toward ESRD. Think of it as a journey with distinct milestones: slowing progression, treating complications, preparing for RRT, and ultimately delivering RRT or conservative care.

The therapeutic objectives for a patient with CKD ^[1]:

Delay kidney failure
Control hypertension
Reduce albuminuria
Treat anaemia and MBD disorder
Treat any acidosis, high K
Control lipid and CV risk

These map directly onto the pathophysiology we discussed: each failing kidney function generates a complication, and each complication has a specific treatment target.

This is obvious but often forgotten: CKD has a cause, and if that cause is still active, treating it can slow or even halt progression.

Cause	Treatment
Diabetic nephropathy	Glycaemic control (HbA1c < 7–8%) ^[22]; prefer SGLT2i and GLP-1RA ^[10]^[22]
Glomerulonephritis	Immunosuppression based on biopsy diagnosis (steroids, MMF, cyclophosphamide, rituximab depending on type) ^[8]
Obstructive uropathy	Relieve obstruction (catheterisation, stenting, surgery)
Drug-induced	Stop the offending agent (NSAIDs, lithium, PPIs, TCM, calcineurin inhibitors) ^[1]
Renovascular disease	Angioplasty ± stenting; antihypertensives (avoid ACEI if bilateral RAS)
SLE / vasculitis	Immunosuppression (steroids + cyclophosphamide/rituximab/MMF)
Chronic GN (end-stage, shrunken kidneys)	Supportive therapy only; minimise metabolic disturbance; prepare for RRT ^[8]

Chronic GN — Biopsy Not Always Needed

For chronic GN with shrunken, atrophic kidneys — biopsy is usually unnecessary. Even if tissue is obtained, the pathologist cannot determine the original cause given the fibrotic damage. Management is supportive regardless ^[8].

4. Step 2 — Slow Progression (Renoprotection)

This is the core of CKD management. Six principles of renoprotection ^[23]:

Prevent additional injury/insult to the kidneys
Optimal blood pressure control
Proteinuria reduction (RAAS inhibition/blockade)
SGLT2 inhibition
No smoking
Vascular risk factor management

Why? Hypertension accelerates glomerulosclerosis through increased intraglomerular pressure. Lowering BP reduces shear stress on remaining nephrons.

Target: < 130/80 mmHg ^[24]

Drug choice for CKD ^[15]:

Scenario	First-Line	Rationale
CKD (any cause)	ACEI or ARB	Renoprotective — dilates efferent arteriole → ↓ intraglomerular pressure → ↓ proteinuria → slows progression ^[1]^[10]^[15]
CKD + DM	ACEI or ARB	Same as above; compelling indication ^[15]
If ACEI/ARB insufficient	Add long-acting CCB or thiazide diuretic	Second-line agents; loop diuretics preferred if GFR < 30 (thiazides become ineffective)
Refractory HTN	Add beta-blocker or MRA (spironolactone/finerenone)	Monitor K⁺ closely with MRA

Combination ACEI + ARB is NOT recommended — trials (ONTARGET) showed no benefit but increased hyperkalaemia and AKI risk.

ACEI/ARB — Expected Creatinine Rise

When you start ACEI/ARB, expect a small rise in creatinine (up to 25–30% is acceptable) because you are reducing intraglomerular pressure. This is a sign the drug is working. But if creatinine rises > 30%, think about renal artery stenosis — ACEI/ARB removes the efferent arteriolar tone that is maintaining GFR in a critically stenosed kidney ^[10]^[5].

Must monitor renal function for ACEI/ARB ^[1]. Check RFT and K⁺ 1–2 weeks after starting or dose change.

Proteinuria is not just a marker — it is a mediator of progressive kidney damage ^[5]. Filtered proteins are reabsorbed by proximal tubular cells, causing lysosomal overload, inflammatory cytokine release, and tubulointerstitial fibrosis.

ACEI/ARB are the cornerstone — reduce proteinuria by 30–50%
Target: reduce proteinuria to < 0.5–1 g/day or reduce by > 50% from baseline
RAAS blockade is very effective in preventing renal failure ^[10]

SGLT2i (sodium-glucose cotransporter 2 inhibitor) — "SGLT2" = the cotransporter in the Sodium-Glucose Linked Transporter family, type 2, located in the proximal tubule S1 segment.

SGLT2i → massive reduction in risk of renal failure ^[10]

Mechanism of renoprotection:

Blocks glucose and Na⁺ reabsorption in proximal tubule → more Na⁺ delivered to macula densa → tubuloglomerular feedback activated → afferent arteriole constriction → ↓ intraglomerular pressure
This is complementary to ACEI/ARB (which dilates efferent arteriole)
Additional benefits: weight loss, ↓ BP, ↓ HbA1c, cardioprotective (↓ HF hospitalisations)

Key trials: DAPA-CKD, EMPA-KIDNEY, CREDENCE — all showed significant reduction in CKD progression, cardiovascular events, and mortality in both diabetic and non-diabetic CKD.

Indications (current guidelines):

DKD patients — well-established benefit
UK Renal Association 2023 update: SGLT2i also recommended in CKD patients WITHOUT diabetes, provided they have albuminuria > 0.5 g ^[1]
Once initiated, SGLT2i can be continued unless it is not tolerated or RRT has been commenced ^[24]

Key examples: dapagliflozin, empagliflozin, canagliflozin

Side effects to monitor: UTI, genital mycotic infections, euglycaemic DKA (rare), initial eGFR dip (expected and acceptable, similar to ACEI/ARB)

GC Lecture High Yield — SGLT2i in CKD

Consider SGLT2i in CKD patients according to latest guideline indications. Once initiated, SGLT2i can be continued unless it is not tolerated or renal replacement therapy has been commenced ^[24]. This point is directly from the HA Handbook and GC lecture material.

Finerenone ("fine" = selective; "-renone" = mineralocorticoid receptor antagonist) — a new-generation non-steroidal MRA ^[10].

Why is it different from spironolactone/eplerenone?

Reduces kidney fibrosis — direct anti-fibrotic and anti-inflammatory effects on the kidney
Molecular structure permits finerenone to be much more targeted → hyperkalaemia side effect is much lower than conventional MRAs ^[10]
Can be combined with ACEI/ARB (unlike traditional MRAs which carry high hyperK risk when combined) ^[10]

Key trials: FIDELIO-DKD, FIGARO-DKD — showed reduction in CKD progression and cardiovascular events in diabetic kidney disease.

Indication: Type 2 DM with CKD (albuminuria) already on maximum tolerated ACEI/ARB

GLP-1RA (e.g. semaglutide / Ozempic) ^[10] — originally a diabetes drug, now shown to have renal and cardiovascular benefits:

Reduces albuminuria
Slows GFR decline
Weight reduction → helps obesity-related CKD
Cardiovascular risk reduction

Key trial: FLOW (semaglutide) — showed significant reduction in kidney outcomes in DKD.

Measure	Target	Why
Smoking cessation	Complete cessation	Smoking accelerates atherosclerosis and CKD progression ^[23]
Weight management	BMI < 30; weight loss if obese	Obesity → hyperfiltration → secondary FSGS ^[1]
Dietary protein restriction	0.8 g/kg/day (non-dialysis CKD); avoid high-protein diets	Reduces hyperfiltration and uraemic toxin generation
Salt restriction	< 100 mmol/day (< 6 g NaCl/day) ^[24]	Reduces BP and oedema; enhances ACEI/ARB efficacy
Potassium restriction	< 20 mmol/day if hyperK ^[24]	Prevents life-threatening arrhythmias
Phosphate restriction	< 800 mg/day ^[24]	Reduces hyperphosphataemia and CKD-MBD
Exercise	Regular moderate exercise	Cardiovascular fitness, weight control

For CKD patients requiring enteral nutrition: use low-nitrogen, renal-specific formulas (e.g. Novasource Renal or Nepro) ^[25].

Must monitor kidney function for many drugs → metformin, ACEI/ARB ^[1].

Drug	Risk	Action
NSAIDs	Vasoconstriction, AKI, nephrotic syndrome, papillary necrosis; nephrologists seldom use this ^[1]	Avoid if possible; if essential, closely monitor RFT
Aminoglycosides	AKI (tubular toxicity)	Therapeutic drug monitoring; avoid prolonged courses
Contrast agents	Contrast nephropathy	Hydration; avoid if GFR < 30
Metformin	Lactic acidosis risk in severe CKD	Stop if eGFR < 30 (some guidelines < 20 with caution)
PPIs	Acute and chronic TIN	Use lowest effective dose; review regularly
Calcineurin inhibitors	Vascular calcification, AKI, CKD	Monitor levels; dose adjust
TCM / herbal medicines	Aristolochic acid nephropathy	Counsel patients (important in HK!)

Drug dosing in CKD: use Cockcroft-Gault equation for dose adjustment ^[3]. Many drugs require dose reduction or interval prolongation in CKD.

GC Lecture — DPP-4 Inhibitor in CKD

Which DPP-4 inhibitor is most convenient in a DM patient with renal impairment? Linagliptin (Tradjenta) — 5 mg/day, hepatobiliary elimination, no need to change according to renal function ^[23].

5. Step 3 — Treat Complications

Prevalence: 1% at eGFR 60, 9% at 30, 33–67% at 15 ^[5].

Evaluation:

Screening: CBC at least annually for CKD stage 3; every 6 months for stage 4–5; every 1–3 months for stage 5 on dialysis ^[5]
Diagnosis: Hb < 13 g/dL (M) or < 12 g/dL (F); typically NcNc at ~8 g/dL ^[5]
Investigations: reticulocyte count, ferritin, transferrin saturation, serum B12/folate — to exclude non-renal causes ^[5]

Treatment:

Modality	Details	Target
Erythropoiesis-stimulating agents (ESAs) e.g. darbepoetin, Mircera (methoxy polyethylene glycol-epoetin beta)	Mechanism: activates EPO receptor → erythropoiesis ^[5]. Start when Hb < 10 g/dL provided other causes excluded	Hb target: 10–11.5 g/dL ^[5]
Iron supplementation	IV iron preferred in dialysis patients (oral poorly absorbed); replete if Tf saturation < 30% or ferritin < 500 ng/mL ^[5]	Tf sat > 30%, ferritin > 500
Blood transfusion	When symptomatic and acute correction needed; HD patients: transfuse during dialysis; PD patients: transfuse with extra PD fluid cover (e.g. 4.25% over 2 hours) ^[24]	Symptom relief

Functional Iron Deficiency

Many CKD patients have adequate iron stores but insufficient iron availability for erythropoiesis — this is "functional iron deficiency" ^[5]. It occurs because:

Anaemia of chronic disease → ↑ hepcidin → traps iron in macrophage stores → ↓ release
ESA administration drives erythropoiesis faster than iron can be released from stores
Result: anaemia refractory to ESA with ↓ MCV → treat with IV iron

ESA over-treatment (Hb > 13) increases cardiovascular risk (thrombotic events, hypertension worsening). Don't push Hb above 11.5 g/dL.

Treatment	Mechanism	Notes
Low phosphate diet (< 800 mg/day)	Reduces phosphate intake	First-line; dietary counselling ^[24]
Phosphate binders with meals	Bind dietary phosphate in gut → ↓ absorption	Calcium-based (calcium carbonate/acetate) — cheap but risk of vascular calcification if Ca-PO₄ product is high; Non-calcium-based (sevelamer, lanthanum) — preferred in vascular calcification
Activated vitamin D analogues (calcitriol / alfacalcidol 0.25–2 μg/day; or paricalcitol)	Replaces the 1,25(OH)₂D₃ that the kidney can no longer produce → ↑ intestinal Ca²⁺ absorption, ↓ PTH secretion	For secondary hyperparathyroidism ^[24]; monitor Ca²⁺ (risk of hypercalcaemia)
Calcimimetics (e.g. cinacalcet)	Allosteric activator of the calcium-sensing receptor (CaSR) on parathyroid gland → makes the gland "think" Ca²⁺ is higher than it is → ↓ PTH secretion	Consider according to guideline indications ^[24]; used when PTH remains elevated despite phosphate binders and vitamin D
Parathyroidectomy	Surgical removal of hyperplastic parathyroid tissue	For tertiary hyperparathyroidism (autonomous PTH secretion unresponsive to medical therapy); look for collar scar on exam

Treatment: NaHCO₃ or citrate supplement to keep serum HCO₃⁻ within normal range (23–29 mEq/L) ^[5]^[24]
Efficacy: ↓ CKD progression, ↓ bone buffering, ↑ nutritional status and lean body mass ^[5]
Risk: fluid overload (each mmol NaHCO₃ carries 1 mmol Na⁺) → monitor carefully ^[5]^[14]
Additional risks of NaHCO₃: may induce hypokalaemia (shifts K⁺ into cells), decrease ionised calcium, too rapid correction may cause paradoxical cerebral acidosis ^[14]

Treatment	Mechanism	Setting
Dietary K restriction (< 20 mmol/day)	↓ K⁺ intake	All CKD with hyperK tendency ^[24]
K⁺ binders (e.g. calcium resonium / sodium polystyrene sulfonate; sodium zirconium cyclosilicate / Lokelma; patiromer)	Bind K⁺ in gut → ↓ absorption / ↑ faecal excretion	Chronic management ^[24]
Review ACEI/ARB/MRA dose	These drugs ↓ K⁺ excretion	Dose-reduce or hold if severe hyperK
Loop diuretics	↑ renal K⁺ excretion	If residual urine output
Emergency management (K⁺ > 6.5 or ECG changes)	IV calcium gluconate (membrane stabiliser), insulin-dextrose, salbutamol nebuliser, NaHCO₃, dialysis	Acute setting

Salt restriction (< 100 mmol/day) ^[24]
Fluid restriction — strict I/O chart, daily body weight (< 1 kg increase per day) ^[24]
Diuretics: loop diuretics (furosemide) — up to high doses; consider adding metolazone 5–10 mg daily PO if refractory ^[24]
Dialysis if refractory to above

Statins for dyslipidaemia (CKD patients have accelerated atherosclerosis; statin benefit well-established for CKD G3–5 not on dialysis)
Antiplatelet therapy where indicated (secondary prevention of CVD)
BP control as above

The leading cause of death in CKD patients is vascular disease and infection ^[23].

6. Step 4 — Preparation for Renal Replacement Therapy

Indications for referral ^[5]:

AKI or abrupt, sustained ↓ GFR
GFR < 30 mL/min/1.73m² (G4–5)
Consistent significant albuminuria (UACR ≥ 300 mg/g)
Progressive CKD: drop in GFR category with > 25% ↓ GFR from baseline
Sustained unexplained haematuria
Significant CKD complications: HTN refractory to ≥ 4 agents, persistent K⁺ abnormalities
Hereditary kidney disease, recurrent nephrolithiasis

Begin discussions on RRT at eGFR ~20–30 mL/min → allow preparation for dialysis access ^[5]
Consider living donor pre-emptive renal transplantation if eGFR < 20 with progressive irreversible CKD over 6–12 months ^[5]
Create AV fistula at least 6 months before anticipated dialysis start (fistula needs time to "mature")
Insert PD (Tenckhoff) catheter at least 2 weeks before PD initiation

7. Step 5 — Renal Replacement Therapy (RRT)

Mnemonic for urgent indications (mainly AKI): "AEIOU" ^[3]^[16]^[26]:

Letter	Indication	Details
A	Acidosis	Refractory metabolic acidosis with HCO₃⁻ < 10 mmol/L or pH < 7.1 refractory to bicarbonate ^[26]
E	Electrolyte disturbance	Uncontrolled hyperkalaemia > 6 mmol/L (or rapidly rising, refractory to medical therapy) ^[26]
I	Intoxication	Dialysable toxins: alcohol, NSAIDs, metformin, lithium, salicylates ^[26]
O	Oedema	Refractory pulmonary oedema / fluid overload unresponsive to diuretics ^[26]
U	Uraemia	Uraemic pericarditis, uraemic encephalopathy, intractable uraemic symptoms ^[26]

For CKD specifically ^[3]^[5]^[26]:

eGFR < 5 mL/min/1.73m² (regardless of symptoms)
eGFR 5–15 mL/min + uraemic complications (pericarditis, pleuritis, encephalopathy)
Other: poor nutrition refractory to dietary intervention, refractory volume overload/acidosis/hyperK/hyperPO₄

eGFR should NOT be used alone to guide initiation of RRT — it is guided by clinical need (symptoms, complications) ^[5].

HK follows a "PD-first policy" ^[3] — peritoneal dialysis is the default first choice, moving to haemodialysis if PD fails, and renal transplant is the treatment of choice when available.

Mechanism:

Uses the peritoneal membrane as a semipermeable dialysis membrane
Advantages: thin and semi-permeable, large surface area, highly vascularised ^[3]
Dialysis fluid instilled into peritoneal cavity via Tenckhoff catheter → solutes move by diffusion (urea, creatinine, K⁺ from blood → dialysate) and water by osmosis (dextrose in dialysate creates osmotic gradient → ultrafiltration)

Types of PD ^[26]:

Type	Description	Advantage
CAPD (Continuous Ambulatory PD)	Manual exchanges: multiple exchanges during the day (usually 3) + overnight dwell	Simple, no machine needed
APD (Automated PD)	Overnight cycler device; shorter dwells, more rapid exchange	Frees up waking hours — preferred for most patients ^[26]
CCPD	APD + daytime dwell (abdomen full during day)	Maximum clearance
NIPD	Night-only APD (abdomen empty during day)	Better for patients with peritoneal membrane issues

Contraindications to PD ^[22]:

Peritoneal membrane failure:
- History of major abdominal surgery with extensive peritoneal scarring → membrane can no longer act as semipermeable membrane
- Damage/thickening of peritoneal membrane from long-term dextrose-containing PD fluids or repeated peritonitis
Inadequate home environment (requires clean space for exchanges)
Large hernias, pleuroperitoneal communication, severe respiratory compromise

Complications of PD:

PD-related peritonitis (most important) — presents with cloudy dialysate, abdominal pain, fever; culture dialysate effluent
Catheter exit-site infection
Peritoneal membrane failure (over years)
Encapsulating peritoneal sclerosis (rare, devastating)
Protein loss in dialysate → malnutrition
Metabolic: hyperglycaemia from dextrose absorption, weight gain

For PD patients: monitor exit site condition and perform exit site care daily ^[24].

Mechanism:

Blood is pumped through an extracorporeal circuit containing a semi-permeable membrane (dialyser/artificial kidney)
Solutes move by diffusion against dialysate flowing in the opposite direction (countercurrent)
Fluid removal by ultrafiltration (transmembrane pressure)

Vascular access (in order of preference):

Access	Description	Notes
AV fistula (arteriovenous fistula)	Surgically created connection between artery and vein (usually radiocephalic or brachiocephalic in non-dominant arm)	Preferred long-term access; needs 6–12 weeks to mature; avoid blood taking or BP measurement from AV fistula arm ^[24]; monitor function daily (check thrill and bruit)
AV graft	Synthetic tube connecting artery to vein	Used when native fistula not possible; higher infection and thrombosis risk
Tunnelled CVC (central venous catheter)	Cuffed catheter in internal jugular vein	Temporary access; highest infection risk; used while fistula matures or in emergencies

Contraindications to HD ^[22]:

Poor cardiac function — patient unable to tolerate the haemodynamic changes (rapid fluid shifts, hypotension)
Lack of suitable vascular access

Complications during HD:

Hypotension (most common — rapid fluid removal)
Muscle cramps
Arrhythmias (electrolyte shifts)
Dialysis disequilibrium syndrome (rapid urea clearance → osmotic gradient → cerebral oedema — seen mainly in first few sessions)
Vascular access complications (thrombosis, stenosis, infection)

Renal transplantation is the treatment of choice for ESRD — offers the best quality of life, lowest long-term mortality, and freedom from dialysis.

HK statistics: 60 deceased donor and 16 living donor transplants in 2018; 2,237 still on waiting list ^[5].

Pre-requisites ^[5]^[26]:

Requirement	Details
ABO matching	Generally required
HLA matching	Degree of matching predicts long-term graft survival
Cross-match	Negative cross-match required (no pre-formed anti-donor antibodies)
Screening	TB + HBV + HCV + HIV; G6PD deficiency (cotrimoxazole for PCP prophylaxis is contraindicated in G6PD deficiency → substitute pentamidine) ^[26]

Contraindications ^[5]:

Absolute	Relative
Active malignancy (need ≥ 2 years of complete remission)	Extremes of age (< 1y, > 75y)
Active infection	High risk of recurrence in transplant kidney
Active vasculitis or recent anti-GBM disease	Lower urinary tract disease
Severe heart disease or occlusive aortoiliac vascular disease	Significant comorbidity

Post-transplant management:

Immunosuppression — lifelong; typical triple regimen:
- Calcineurin inhibitor (tacrolimus > cyclosporin)
- Antimetabolite (mycophenolate mofetil > azathioprine)
- Corticosteroids (tapered over months)
- ± Induction agent (basiliximab / anti-thymocyte globulin)
Monitor allograft function: urine output, serial Cr/GFR, proteinuria, transplant kidney biopsy if dysfunction ^[5]
Complications of immunosuppression: infection (PCP, CMV, BK virus), malignancy (PTLD, skin cancer), diabetes, hypertension, nephrotoxicity of calcineurin inhibitors

Always ask if any siblings are available for kidney donation ^[26]. Living donor transplantation has the best outcomes.

Option of conservative treatment should be open to people who refuse RRT ^[5]:

Indication: usually elderly patients with multiple comorbidities
Involves: limiting ESRD symptoms and treatment of complications without commencing RRT
Palliative care with full medical, psychological and social support ^[5]

Drug	CKD Consideration
Metformin	Stop if eGFR < 30 (risk of lactic acidosis); reduce dose at eGFR 30–45
SGLT2 inhibitors	Can be initiated down to eGFR 20 (latest guidelines); continue even below 20 if already started ^[24]
Linagliptin	Hepatobiliary elimination — no dose adjustment needed in renal impairment ^[23]
NSAIDs	Avoid — multiple mechanisms of kidney damage ^[1]
Gabapentin/pregabalin	Renally excreted — dose reduction required
Opioids	Avoid morphine (active metabolite M6G accumulates); use fentanyl or buprenorphine
Antibiotics	Many require dose adjustment (aminoglycosides, vancomycin — monitor levels)
Contrast agents	Avoid iodinated contrast if GFR < 30; avoid gadolinium (NSF risk)

CKD Stage	Monitoring Frequency	Key Parameters
G1–G2 (if markers present)	Annually	RFT, uACR, BP
G3a	Every 6–12 months	RFT, eGFR, uACR, bone profile, CBC
G3b	Every 3–6 months	As above + electrolytes, HCO₃⁻
G4	Every 1–3 months	Full panel + PTH, iron studies; discuss RRT
G5 / on dialysis	Monthly or more	Full panel + dialysis adequacy (Kt/V); transplant assessment

High Yield Summary — Management of CKD

Therapeutic objectives: delay kidney failure, control HTN, reduce albuminuria, treat anaemia and MBD, correct acidosis and hyperK, control CV risk
Six principles of renoprotection: prevent additional injury, optimal BP control, proteinuria reduction (RAAS blockade), SGLT2 inhibition, no smoking, vascular risk factor management
ACEI/ARB is first-line for CKD and DKD (dilates efferent arteriole → ↓ intraglomerular pressure); accept ≤ 30% Cr rise
SGLT2i is a game-changer — activates tubuloglomerular feedback → ↓ intraglomerular pressure; indicated in DKD AND non-diabetic CKD with albuminuria > 0.5 g
Finerenone — non-steroidal MRA for DKD; lower hyperK risk than spironolactone; reduces kidney fibrosis
Anaemia: ESA (start Hb < 10, target 10–11.5); IV iron if Tf sat < 30%/ferritin < 500; treat functional iron deficiency
CKD-MBD: phosphate binders + activated vitamin D + calcimimetics (cinacalcet); parathyroidectomy for refractory tertiary hyperPTH
RRT indications (AEIOU): Acidosis, Electrolyte (hyperK), Intoxication, Oedema (refractory), Uraemia; for CKD: eGFR < 5 regardless or eGFR 5–15 with uraemic complications
HK PD-first policy: PD → HD if PD fails → renal transplant (treatment of choice)
PD contraindications: peritoneal membrane failure (surgery, scarring, repeated peritonitis); HD contraindications: poor cardiac function, no vascular access
Avoid nephrotoxins: NSAIDs, aminoglycosides, contrast; adjust drug doses using Cockcroft-Gault
Conservative care is an option for those who decline RRT — palliative approach with full support

Active Recall — Management of CKD

References

^[1] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf ^[3] Senior notes: Maksim Medicine Notes.pdf (Sections 10.5–10.6) ^[5] Senior notes: Ryan Ho Urogenital.pdf (Sections 5.2–5.3) ^[8] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf ^[10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (Case P2) ^[14] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf ^[15] Senior notes: Block A - High blood pressure_ hypertension.pdf ^[16] Senior notes: Ryan Ho Critical Care.pdf (AKI management) ^[22] Senior notes: Block A - Renal Replacement Therapies.pdf ^[23] Senior notes: Block A - Drugs and the Kidney.pdf ^[24] Lecture slides: Handbook of Internal Medicine 2024.pdf (K23–K24) ^[25] Senior notes: Ryan Ho Fluids and Nutrition.pdf ^[26] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (RRT and Transplantation)

Complications of Chronic Kidney Disease

CKD complications are not random — each one flows logically from a specific kidney function that has been lost or impaired. The GC 034 lecture ^[2] explicitly lists the complications of CKD as a key learning objective, and the lecture summary slide confirms the examinable complications: hypertension, anaemia, hyperkalaemia, MBD ^[2].

Six systemic complications of CKD ^[1]:

Fluid retention
Metabolic acidosis
High blood pressure
Normochromic normocytic anaemia
Secondary hyperparathyroidism
Bone disease

But the full picture is broader — let us go through each systematically.

1. Cardiovascular Complications

The leading cause of death in CKD patients is vascular disease (~50%) ^[3]^[23]. Most CKD patients die from cardiovascular events before they ever reach dialysis.

Prevalence: > 80% of CKD patients
Mechanisms:
- Na⁺ and H₂O retention → volume expansion (the kidney can no longer excrete the daily salt load)
- RAAS activation (↓ renal perfusion sensed by JGA → renin release → angiotensin II → vasoconstriction + aldosterone → further Na⁺/H₂O retention)
- Sympathetic nervous system overactivity
- ↓ Renal vasodilator production (PGE₂, nitric oxide)
- Endothelial dysfunction from uraemic toxins
Consequences: Hypertension causes LVH, congestive cardiac failure (systolic HF, HFrEF) ^[1]. HTN can be both a cause and a complication of renal disease — a bidirectional relationship.

Given how insidious CKD can be, good practice for a patient presenting with HT is to get a urine dipstick ^[1] — this may be the first clue to underlying CKD.

When having DM and HT at the same time, you double the risk of stroke, sextuple the risk of CKD, triple the risk of heart diseases ^[15].

Pathophysiology: Chronic pressure overload (from HTN) + volume overload (from fluid retention and anaemia) → concentric and eccentric LV remodelling → diastolic and then systolic dysfunction → congestive cardiac failure (HFrEF) ^[1]
Anaemia contributes to a high-output state → further cardiac demand
Uraemic cardiomyopathy: direct myocardial toxicity from uraemic toxins, myocardial fibrosis

CKD patients have dramatically accelerated atherosclerosis due to:
- Traditional risk factors: HTN, DM, dyslipidaemia
- CKD-specific factors: vascular calcification (calcium-phosphate deposition in vessel walls — part of CKD-MBD) ^[1], chronic inflammation, oxidative stress, endothelial dysfunction, uraemic toxins
Results in: coronary artery disease, cerebrovascular disease, peripheral arterial disease
Causes of death: vascular (50%), infection (30%), termination of dialysis (7%) ^[3]

Occurs in severe uraemia (typically BUN > 60 mg/dL) ^[11]
Mechanism: Uraemic toxins cause fibrinous inflammation of pericardial surfaces → serosal irritation
Presentation: chest pain (pleuritic, positional), pericardial friction rub, fever
This is an indication for urgent dialysis ^[3]^[16]
If untreated → pericardial effusion → tamponade

GC Lecture High Yield — Cardiovascular Complications

CKD complications listed on GC 034 lecture summary: hypertension, anaemia, hyperkalaemia, MBD ^[2]. Together with accelerated atherosclerosis, these drive the 50% cardiovascular mortality rate in CKD. The GC diabetic complications lecture ^[27] also emphasises nephropathy → raised serum creatinine → end-stage renal failure as a microvascular complication contributing to overall CVD burden.

Normochromic normocytic anaemia is one of the hallmark complications of CKD ^[1]^[3].

Prevalence: 1% at eGFR 60; 9% at eGFR 30; 33–67% at eGFR 15 ^[5]
Primary mechanism: ↓ EPO production — the kidney's peritubular interstitial fibroblasts produce ~90% of erythropoietin; as functioning renal mass is lost, EPO production falls → ↓ erythropoiesis → NcNc anaemia
Contributing mechanisms:
- Uraemic toxins directly suppress bone marrow erythropoiesis
- Shortened RBC lifespan in the uraemic milieu
- Functional iron deficiency — adequate iron stores but insufficient iron availability for erythropoiesis due to ↑ hepcidin (an acute-phase reactant elevated in chronic inflammation → traps iron in macrophages → ↓ release to transferrin) ^[5]
- Chronic blood loss (from dialysis circuits, GI bleeding — uraemia impairs platelet function)
- B12/folate deficiency (dietary, dialysis losses)
Consequences:
- Fatigue, exercise intolerance, reduced quality of life
- Contributes to café au lait complexion (pallor from anaemia + yellow-brown urochrome pigment retention) [27b]
- High-output cardiac state → worsens LVH → heart failure
Diagnosis: Hb < 13 g/dL (male), < 12 g/dL (female); typically NcNc; investigate with reticulocyte count, ferritin/Tf saturation, serum B12/folate to exclude non-renal causes ^[5]
Treatment: ESA (target Hb 10–11.5); IV iron if iron-deficient; blood transfusion if symptomatic (covered in Management section)

3. CKD-Mineral and Bone Disorder (CKD-MBD)

This is one of the most complex and frequently examined complications. It encompasses biochemical abnormalities, bone disease, and vascular calcification — all interconnected.

Let's trace this step by step from first principles:

↓ GFR → ↓ phosphate excretion → hyperphosphataemia ^[1]^[12]
- Why? Phosphate is excreted primarily by the kidneys. As GFR falls, the remaining nephrons cannot clear enough PO₄.
- Initially, ↑ FGF-23 (from osteocytes) and ↑ PTH increase per-nephron PO₄ excretion to compensate. But eventually this fails.
↓ Functioning renal mass → ↓ 1α-hydroxylase activity → ↓ active vitamin D [1,25(OH)₂D₃] ^[1]
- 1α-hydroxylase is located in proximal tubular cells and converts 25(OH)D₃ → 1,25(OH)₂D₃ (calcitriol), the active form
- Less renal mass = less enzyme = less active vitamin D
↓ Active vitamin D → ↓ intestinal Ca²⁺ absorption → hypocalcaemia ^[12]
Hyperphosphataemia directly suppresses 1α-hydroxylase (vicious cycle worsening vitamin D deficiency) and binds ionised Ca²⁺ in serum (further lowering free Ca²⁺)
Hypocalcaemia + ↓ vitamin D + hyperphosphataemia → stimulates PTH secretion → secondary hyperparathyroidism ^[1]^[12]
PTH attempts to restore calcium by:
- ↑ Bone resorption → releases Ca²⁺ and PO₄ from bone
- ↑ Renal PO₄ excretion (but this mechanism is already maxed out in CKD)
- ↑ 1α-hydroxylase stimulation (but substrate is limited)
Chronic PTH elevation → parathyroid gland hyperplasia → eventually autonomous (tertiary) hyperparathyroidism where PTH is secreted independently of Ca²⁺

In secondary hyperparathyroidism, there is hypercalcaemia with high ALP ^[12] — this is because the relentless bone resorption eventually pushes calcium above normal. Calcium level should not change AT ALL in acute renal failure ^[12] — changes in calcium are a feature of chronicity.

Renal osteodystrophy ("osteo" = bone, "dys" = abnormal, "trophy" = growth) is the umbrella term for bone disease in CKD. It comprises several histological patterns:

Type	Mechanism	Features
Osteitis fibrosa cystica (high-turnover)	Secondary hyperparathyroidism → excessive osteoclastic bone resorption	Subperiosteal bone resorption (especially radial side of middle phalanges); brown tumours; bone pain; pathological fractures; loss of bone density at distal 1/3 of clavicles; "salt-and-pepper" skull; rugger jersey spine ^[13]
Adynamic bone disease (low-turnover)	Over-suppression of PTH (from excessive calcium/vitamin D supplementation or calcimimetics)	Low bone formation; ↑ fracture risk; ↓ ALP
Osteomalacia (low-turnover)	↓ Active vitamin D → defective mineralisation	Bone pain, proximal myopathy, Looser's zones
Mixed uremic osteodystrophy	Combination of high and low turnover features	Variable

Radiological features of renal osteodystrophy ^[13]:

Subperiosteal bone resorption (pathognomonic — best seen on hand X-ray, radial aspect of middle phalanges)
Loss of bone density at distal 1/3 of clavicles
Rugger jersey spine (alternating sclerotic and lucent horizontal bands on lateral spine X-ray)
Pathological fractures
On physical exam: collar scar from parathyroidectomy ^[3]

CKD-MBD is characterised by vascular calcification ^[1].

Mechanism: ↑ calcium × phosphate product → deposition of calcium-phosphate crystals in arterial walls (medial calcification, Mönckeberg-type) and cardiac valves
This is distinct from atherosclerotic intimal calcification (though both occur in CKD)
Consequences: arterial stiffness → systolic hypertension → ↑ pulse pressure → LVH; coronary artery calcification → IHD
This is a major contributor to the disproportionate cardiovascular mortality in CKD

Rare but devastating complication of advanced CKD/ESRD
Medial calcification of small dermal/subcutaneous arterioles → thrombosis → ischaemic skin necrosis
Presents as extremely painful, violaceous skin lesions → necrotic eschars
High mortality (60–80%) due to sepsis from superinfected wounds
Risk factors: obesity, warfarin use, high Ca×PO₄ product, hyperPTH

4. Fluid and Electrolyte Complications

Mechanism: ↓ nephron number → inability to excrete daily Na⁺ and H₂O load → progressive volume expansion
Consequences: peripheral oedema (bilateral pitting ankle oedema), pulmonary oedema (dyspnoea, orthopnoea, crepitations), raised JVP, hypertension
Refractory pulmonary oedema is an indication for urgent dialysis ^[3]^[16]

Mechanism: ↓ distal tubular K⁺ secretion as nephron number falls; worsened by ACEI/ARB/MRA, metabolic acidosis (drives K⁺ out of cells), dietary excess
Clinical significance: the most immediately life-threatening electrolyte complication of CKD
Symptoms: often asymptomatic until dangerous levels; muscle weakness (LL > UL); cardiac arrhythmias
ECG changes (progressive): peaked T waves → widening of QRS → loss of P waves → sine wave → asystole ^[14]
K⁺ > 6.0: start worrying; K⁺ > 6.5: consider emergency treatment ^[14]
Rate of rise matters — chronic hyperkalaemia is more tolerable than acute (cells adapt their membrane potentials) ^[14]
Refractory hyperkalaemia is an indication for urgent dialysis ^[3]^[16]

Usually dilutional (excess free water relative to sodium due to impaired renal diluting capacity)
Less common than hyperkalaemia in CKD

Mechanism: ↓ nephron mass → ↓ NH₄⁺ and titratable acid excretion → HAGMA ^[5]; ± tubular damage → ↓ HCO₃⁻ reabsorption or ↓ H⁺ secretion → NAGMA (RTA pattern) ^[5]
Consequences (covered in GC lecture):
- ↑ Bone resorption (chronic acidosis is buffered by bone mineral — releases Ca²⁺/PO₄ → worsens osteoporosis)
- ↑ Protein catabolism → muscle wasting, malnutrition
- ↑ Secondary hyperPTH (acidosis stimulates PTH secretion independently)
- Kussmaul's breathing (deep, regular — respiratory compensation)
- ↓ Myocardial contractility (acidosis impairs Na⁺/K⁺-ATPase → cardiac depression)
- ↑ CKD progression and ↑ mortality ^[5]
Treatment: NaHCO₃ or citrate supplement to keep serum HCO₃⁻ within 23–29 mEq/L — this ↓ CKD progression, ↓ bone buffering, ↑ lean body mass ^[5]

Risk of NaHCO₃ therapy: hypernatraemia, inducing hypokalaemia (shifts K⁺ into cells), decreasing ionised calcium, volume expansion from Na⁺ load, and paradoxical cerebral acidosis if corrected too rapidly ^[14].

Uraemia is the clinical syndrome from accumulation of nitrogenous waste products, typically manifest at GFR < 15 mL/min (Stage 5) ^[5]^[11]. It affects virtually every organ system.

System	Complications	Mechanism
General	Anorexia, nausea (most specific symptom), malaise, weight loss ^[3]	Uraemic toxins → gastroparesis, CTZ stimulation, protein-energy wasting
Skin	Pruritus, scratch marks, café au lait complexion, uremic frost [27b]	Pruritus: multifactorial (Ca²⁺-PO₄ deposition, uraemic toxins, dry skin, neuropathy, ↑ PTH). Uremic frost: urea crystallised on skin from sweat [27b]. Complexion: impaired excretion of urochromes + anaemia [27b]
Neurological	Uraemic encephalopathy (↓ concentration, confusion, seizures, coma); peripheral neuropathy (glove-and-stocking sensory loss); myoclonic jerks; asterixis	Direct neurotoxicity of uraemic toxins; neuromuscular irritability from electrolyte disturbances (hypocalcaemia); hiccupping is an ominous sign of advanced uraemia [27b]; seizures can be precipitated by overvigorous correction of acidosis [27b]
Haematological	Uraemia-induced platelet dysfunction → bleeding tendency (bruising, epistaxis, GI bleeding); anaemia	Uraemic toxins interfere with platelet adhesion/aggregation; ↓ prothrombin consumption, defect in platelet factor III, abnormal platelet aggregation [27b]
Cardiovascular	Uraemic pericarditis; accelerated atherosclerosis; cardiomyopathy	Serosal inflammation; vascular calcification; direct myocardial toxicity
GI	Metallic taste; fetor uremicus (ammoniacal fish breath); anorexia; nausea/vomiting	Urea breakdown by oral flora → ammonia [27b]
Endocrine	Sexual dysfunction; amenorrhoea; infertility; growth retardation (paediatric)	Disrupted HPG axis from uraemic toxins; hyperprolactinaemia
Immunological	↑ Risk of infection (2nd leading cause of death, ~30%) ^[3]	Uraemic toxins impair leukocyte function (chemotaxis, phagocytosis); immunocompromised state; vaccination recommended: influenza, pneumococcus, HBV ^[3]
Respiratory	Kussmaul's breathing; uraemic pleuritis; pulmonary oedema	Metabolic acidosis; serosal inflammation; fluid overload

Café au Lait Complexion — What Causes It?

This distinctive "dirty brown" skin tinge results from two processes [27b]:

Impaired excretion of urochromes (pigmented metabolites normally cleared by the kidney) → yellow-brown discolouration
Anaemia (↓ EPO) → pallor

The combination of pallor and urochrome retention produces the characteristic café au lait appearance. An additional finding in dialysis patients is slate grey to bronze discolouration from iron deposition (from repeated blood transfusions) — though this is less common now with use of exogenous erythropoietin [27b].

7. Complications of Dialysis

General complications of RRT ^[3]:

Malnutrition (protein losses in dialysate, anorexia, catabolic state)
Accelerated atherosclerosis (ongoing CVD risk factors)
Dialysis-related amyloidosis (β₂-microglobulin accumulation → deposition in joints, carpal tunnel syndrome, bone cysts — takes years)
Acquired cystic disease ± malignant transformation (cysts develop in native kidneys of dialysis patients → small risk of renal cell carcinoma)
Dialysis-related dementia (cerebral aluminium toxicity — from aluminium-containing phosphate binders; now rare with non-aluminium binders) ^[3]

PD-related peritonitis — most common serious complication; presents with cloudy dialysate, abdominal pain ± fever; diagnosed by cell count (> 100 WBC/μL with > 50% PMN) and culture; treat with intraperitoneal antibiotics
Catheter exit-site/tunnel infection
Peritoneal membrane failure (progressive loss of ultrafiltration capacity from repeated inflammation)
Encapsulating peritoneal sclerosis (EPS) — rare but devastating; thick fibrous cocoon encases bowel → intestinal obstruction; occurs after years of PD
Metabolic: hyperglycaemia from dextrose absorption, weight gain, dyslipidaemia

Intradialytic hypotension (most common acute complication — from rapid fluid removal)
Muscle cramps
Arrhythmias (rapid electrolyte shifts, especially K⁺)
Dialysis disequilibrium syndrome (rapid urea clearance → osmotic gradient → cerebral oedema; mainly in first sessions)
Vascular access complications: thrombosis, stenosis, infection (bacteraemia from infected lines/fistulae), steal syndrome (distal ischaemia), aneurysm formation
Air embolism (rare with modern machines)

8. Complications of Renal Transplantation

Long-term complications following kidney transplant (GC 080 lecture slide) ^[28]:

Infections
Malignancy
Cardiovascular disease
Drug-related side effects
Chronic allograft injury
Recurrence of primary disease

Type	Onset	Mechanism	Management
Hyperacute	Minutes	Preformed IgG against donor antigens	No effective treatment; prevention by cross-match ^[3]
Acute	Days to weeks	T cell–mediated rejection (TCMR): anti-foreign HLA T cells; Antibody-mediated rejection (ABMR)	TCMR: pulse steroid + antibodies; ABMR: plasma exchange + antibodies ^[3]
Chronic	Months to years	Immune + non-immune factors (HTN, DM, cyclosporin toxicity) → interstitial fibrosis and tubular atrophy	Untreatable once initiated; control BP, lipid, DM; change cyclosporin to MMF or sirolimus ^[3]

Chronic allograft injury is the leading cause of late graft failure ^[22].

The timeline is classic and frequently examined ^[3]:

Period	Common Infections	Why
First month	Line/wound infection; pre-existing infections (HSV, TB reactivation)	Surgical factors; high-dose immunosuppression
1–6 months	Opportunistic infections: CMV, PJP (Pneumocystis jirovecii pneumonia), BK virus	Peak immunosuppression period
After 6 months	Chronic viral infections (EBV, hepatitis); community-acquired infections	Chronic lower-level immunosuppression

Prophylaxis: cotrimoxazole (PJP) + acyclovir (CMV) for 6 months ^[3]; cotrimoxazole is contraindicated in G6PD deficiency → substitute pentamidine ^[26]

Immunosuppression increases cancer risk 3–5 fold
Post-transplant lymphoproliferative disorder (PTLD): B-cell lymphoma, EBV-related ^[22] — most important transplant-specific malignancy
Skin cancers: squamous cell carcinoma (most common post-transplant skin cancer — reversed ratio compared to general population where BCC is more common)
Kaposi sarcoma (HHV-8 related)
Management: reduce immunosuppression; switch CNI to mTOR inhibitors (e.g. sirolimus, everolimus) if new cancer after transplant ^[3]

Drug	Side Effects
Corticosteroids	↑ BP, hyperglycaemia (H'stix marks), proximal myopathy, abdominal striae, Cushingoid features, osteoporosis, cataracts, weight gain ^[3]
Calcineurin inhibitors (cyclosporin, tacrolimus)	Gum hypertrophy (cyclosporin), hirsutism, coarse tremor ^[3]; nephrotoxicity (the immunosuppressant itself damages the transplanted kidney — ironic but true); hypertension, DM, neurotoxicity
Mycophenolate (MMF)	GI side effects (diarrhoea, nausea), bone marrow suppression (leukopenia)
mTOR inhibitors (sirolimus, everolimus)	Impaired wound healing, mouth ulcers, dyslipidaemia, proteinuria, pneumonitis

Causes of early allograft dysfunction ^[22]:

Urological complications (e.g. urine leakage from anastomotic site)
Vascular complications (e.g. renal vein thrombosis, renal artery stenosis)
Infections (e.g. UTI, viral)
Drug toxicity (e.g. calcineurin inhibitor nephrotoxicity)

9. Other Complications

CKD reduces renal clearance of many drugs → accumulation → toxicity
Renal tubular cells are very metabolically active → many substances/metabolites are concentrated within the kidney → increased susceptibility to both direct and indirect injury ^[23]
CKD increases susceptibility to further kidney damage — a patient with CKD is even more vulnerable to nephrotoxic insults ^[23]
In patients with impaired kidney function, side effects of certain drugs are amplified:
- Ethambutol → optic neuritis ^[23]
- Acyclovir, imipenem, INAH, quinolones → CNS side effects (seizures) ^[23]
Three important principles in drug prescription for CKD: avoid further nephrotoxic insult; attention to correct dose; beware of side effects ^[23]

Multifactorial: anorexia from uraemia, dietary restrictions, protein losses in dialysis, metabolic acidosis (↑ protein catabolism), chronic inflammation
Associated with increased mortality, impaired immunity, poor wound healing

Infection is the 2nd leading cause of death (~30%) in CKD/ESRD patients ^[3]
Uraemic toxins impair leukocyte chemotaxis, phagocytosis, and T-cell function
Further immunosuppression in transplant recipients
Vaccination is essential: influenza, pneumococcal, HBV (HBV vaccine response is impaired in CKD → may need higher dose or additional boosters) ^[3]

Most common cause in adults is diabetic nephropathy — destruction of JGA due to vascular hyalinosis ^[10]
Results in ↓ renin → ↓ aldosterone → ↓ distal K⁺ and H⁺ secretion → hyperkalaemia + NAGMA (hyperchloraemic metabolic acidosis)
A common reason for disproportionate hyperkalaemia in diabetic CKD patients

Native kidneys of patients on long-term dialysis develop multiple cysts
Small risk (~1–2% per year) of malignant transformation to renal cell carcinoma
Screen with periodic USS in long-term dialysis patients

High Yield Summary — Complications of CKD

Six key complications: fluid retention, metabolic acidosis, hypertension, NcNc anaemia, secondary hyperPTH, bone disease ^[1]
#1 cause of death = cardiovascular disease (50%); #2 = infection (30%) ^[3]
CKD-MBD cascade: ↓PO₄ excretion + ↓vitamin D activation → hypoCa → secondary hyperPTH → renal osteodystrophy (subperiosteal resorption, rugger jersey spine) + vascular calcification
Anaemia: EPO deficiency → NcNc; functional iron deficiency (↑ hepcidin); treat with ESA + IV iron
Hyperkalaemia: the most immediately life-threatening electrolyte complication; ECG: peaked T → wide QRS → loss of P → sine wave → asystole
Uraemic syndrome (GFR < 15): nausea (most specific), pruritus, encephalopathy, platelet dysfunction, pericarditis, fetor, café au lait complexion
Dialysis complications: PD — peritonitis, membrane failure; HD — hypotension, access complications; general — amyloidosis, acquired cystic disease, dementia
Transplant long-term complications (GC 080): infections, malignancy (PTLD), CVD, drug side effects, chronic allograft injury, disease recurrence
Chronic allograft injury is the leading cause of late graft failure
Drug accumulation in CKD: adjust doses; beware ethambutol (optic neuritis), acyclovir/quinolones (CNS toxicity)
NaHCO₃ risks: hyperNa, hypoK, ↓ ionised Ca, volume overload, paradoxical cerebral acidosis

Active Recall — Complications of CKD

References

^[1] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf ^[2] Lecture slides: GC 034. Chronic Kidney Disease and its Complications [update 2025].pdf ^[3] Senior notes: Maksim Medicine Notes.pdf (Sections 10.5–10.6) ^[5] Senior notes: Ryan Ho Urogenital.pdf (Sections 5.2–5.3) ^[10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf ^[11] Senior notes: Adrian Lui Pediatrics Notes.pdf (Section 9.3.2) ^[12] Senior notes: Block A – Nephrology Data Interpretation.pdf ^[13] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (CKD section) ^[14] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf ^[15] Senior notes: Block A - High blood pressure_ hypertension.pdf ^[16] Senior notes: Ryan Ho Critical Care.pdf ^[22] Senior notes: Block A - Renal Replacement Therapies.pdf ^[23] Senior notes: Block A - Drugs and the Kidney.pdf ^[26] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (RRT and Transplantation) ^[27] Lecture slides: GC 042. Deterioration of eyesight in a diabetic patient diabetic complications [Update 2025].pdf [27b] Senior notes: Ryan Ho Fundamentals.pdf (General Examination in renal patients) ^[28] Lecture slides: GC 080. Renal Replacement Therapies.pdf

High Yield Summary

Definition: CKD = kidney structure/function abnormality > 3 months; diagnosed by GFR < 60 OR ACR > 3 mg/mmol (with confirmatory repeat at ≥ 3 months)
Commonest cause in HK adults: Diabetic nephropathy (~40–51%); in children: CAKUT (53%)
Commonest GN in HK/Asia: IgA nephropathy
Key pathophysiology: Nephron loss → compensatory hyperfiltration → glomerulosclerosis → more nephron loss (vicious cycle); ACEI/ARB breaks this cycle
Few symptoms early — nocturia is often earliest. Late symptoms: nausea (most specific), pruritus, anorexia, café au lait complexion
Anuria is NEVER seen in CKD alone — always think AKI or acute-on-chronic
Features distinguishing CKD from AKI: ↓Ca²⁺, ↑PO₄, ↑ALP, anaemia, small kidneys on USS
CKD-MBD cascade: ↓PO₄ excretion + ↓vitamin D activation → hypoCa → secondary hyperparathyroidism → renal osteodystrophy + vascular calcification
Most CKD patients die of CVD (50%), not ESRD
GFR estimation: CKD-EPI recommended; Cockcroft-Gault for drug dosing; at ESRD take average of eGFR and 24h CrCl
HK PD-first policy: HK has highest PD utilisation worldwide
Red flags for non-diabetic nephropathy in a diabetic: haematuria, rapid GFR decline, short DM duration, absence of retinopathy

High Yield Summary — Differential Diagnosis of CKD

Always first establish chronicity (AKI vs CKD vs acute-on-chronic) using previous RFT, USS kidney size, bone profile, and anaemia status
Anatomical classification: Vascular / Glomerular / Tubulointerstitial / Obstructive / Congenital-Hereditary
#1 cause in HK: Diabetic nephropathy (~51%); #2: Hypertension/vascular
IgA nephropathy is the most common primary GN in HK/Asia
USS kidney size is crucial: Small = CKD; Normal + high Cr = AKI (consider biopsy); Large = PKD, amyloid, obstruction
Urinalysis pattern guides compartment: RBC casts = glomerular; WBC casts = TIN; bland = vascular/obstructive
Always ask about TCM/herbal medicine use in HK — aristolochic acid nephropathy
Red flags in diabetic CKD for non-diabetic cause: haematuria, rapid GFR decline, short DM duration, absent retinopathy → biopsy indicated
Myeloma is a must-not-miss: CRAB features; Bence Jones protein NOT detected by dipstick
Renal biopsy when cause is unclear and kidneys are normal-sized and result would change management

High Yield Summary — Diagnosis and Investigations of CKD

CKD = GFR < 60 OR markers of kidney damage, persisting > 3 months — need two readings at least 3 months apart
KDIGO staging uses both GFR (G1–G5) and albuminuria (A1–A3) — report as "GxAy"
Three-step approach: establish chronicity → determine cause → evaluate complications
Features confirming CKD (not AKI): ↓Ca, ↑PO₄, ↑ALP, NcNc anaemia, small kidneys with ↓ CMD on USS
eGFR is insensitive early on — Cr doesn't rise until GFR has already dropped ~50%
MDRD is used in HA labs (underestimates when > 60); Cockcroft-Gault for drug dosing; CKD-EPI is recommended
Urine microscopy tells you which compartment is affected: RBC casts = glomerular; WBC casts = TIN; muddy brown casts = ATN; bland = vascular/obstructive
Bence Jones proteins not detected by dipstick — need UPEP and free light chains for myeloma
Renal biopsy when cause unclear + normal-sized kidneys; contraindicated in small/cystic/solitary kidneys
Always check HBsAg urgently if haemodialysis is anticipated

High Yield Summary — Management of CKD

Therapeutic objectives: delay kidney failure, control HTN, reduce albuminuria, treat anaemia and MBD, correct acidosis and hyperK, control CV risk
Six principles of renoprotection: prevent additional injury, optimal BP control, proteinuria reduction (RAAS blockade), SGLT2 inhibition, no smoking, vascular risk factor management
ACEI/ARB is first-line for CKD and DKD (dilates efferent arteriole → ↓ intraglomerular pressure); accept ≤ 30% Cr rise
SGLT2i is a game-changer — activates tubuloglomerular feedback → ↓ intraglomerular pressure; indicated in DKD AND non-diabetic CKD with albuminuria > 0.5 g
Finerenone — non-steroidal MRA for DKD; lower hyperK risk than spironolactone; reduces kidney fibrosis
Anaemia: ESA (start Hb < 10, target 10–11.5); IV iron if Tf sat < 30%/ferritin < 500; treat functional iron deficiency
CKD-MBD: phosphate binders + activated vitamin D + calcimimetics (cinacalcet); parathyroidectomy for refractory tertiary hyperPTH
RRT indications (AEIOU): Acidosis, Electrolyte (hyperK), Intoxication, Oedema (refractory), Uraemia; for CKD: eGFR < 5 regardless or eGFR 5–15 with uraemic complications
HK PD-first policy: PD → HD if PD fails → renal transplant (treatment of choice)
PD contraindications: peritoneal membrane failure (surgery, scarring, repeated peritonitis); HD contraindications: poor cardiac function, no vascular access
Avoid nephrotoxins: NSAIDs, aminoglycosides, contrast; adjust drug doses using Cockcroft-Gault
Conservative care is an option for those who decline RRT — palliative approach with full support

High Yield Summary — Complications of CKD

Six key complications: fluid retention, metabolic acidosis, hypertension, NcNc anaemia, secondary hyperPTH, bone disease ^[1]
#1 cause of death = cardiovascular disease (50%); #2 = infection (30%) ^[3]
CKD-MBD cascade: ↓PO₄ excretion + ↓vitamin D activation → hypoCa → secondary hyperPTH → renal osteodystrophy (subperiosteal resorption, rugger jersey spine) + vascular calcification
Anaemia: EPO deficiency → NcNc; functional iron deficiency (↑ hepcidin); treat with ESA + IV iron
Hyperkalaemia: the most immediately life-threatening electrolyte complication; ECG: peaked T → wide QRS → loss of P → sine wave → asystole
Uraemic syndrome (GFR < 15): nausea (most specific), pruritus, encephalopathy, platelet dysfunction, pericarditis, fetor, café au lait complexion
Dialysis complications: PD — peritonitis, membrane failure; HD — hypotension, access complications; general — amyloidosis, acquired cystic disease, dementia
Transplant long-term complications (GC 080): infections, malignancy (PTLD), CVD, drug side effects, chronic allograft injury, disease recurrence
Chronic allograft injury is the leading cause of late graft failure
Drug accumulation in CKD: adjust doses; beware ethambutol (optic neuritis), acyclovir/quinolones (CNS toxicity)
NaHCO₃ risks: hyperNa, hypoK, ↓ ionised Ca, volume overload, paradoxical cerebral acidosis

Chronic Kidney Disease

1. Definition

2. Epidemiology

3. Risk Factors

4. Anatomy and Function of the Kidney (Review)

4.1 Gross Anatomy

4.2 The Nephron — Functional Unit

4.3 Key Kidney Functions

5. Aetiology (with Hong Kong Focus)

5.1 Adult CKD — Causes (Hong Kong / General)

5.2 Paediatric CKD — Causes (Different from Adults!)

5.3 Classification of Aetiologies by Anatomical Site

6. Pathophysiology

6.1 The Central Concept: Nephron Loss and Hyperfiltration

6.2 The Final Common Pathway

6.3 Pathophysiology of CKD Complications (Mechanism by Mechanism)

6.3.1 Fluid and Electrolyte Disturbances

6.3.2 Hyperkalaemia

6.3.3 Metabolic Acidosis

6.3.4 Mineral and Bone Disorder (CKD-MBD)

6.3.5 Anaemia

6.3.6 Uraemia

6.3.7 Cardiovascular Disease

6.3.8 Hypertension

7. Classification / Staging

7.1 KDIGO CKD Staging

7.2 Differentiating CKD from AKI

8. Clinical Features

8.1 Symptoms

8.2 Signs

8.3 Red Flags in a Diabetic CKD Patient — When to Suspect Non-Diabetic Nephropathy

9. Proteinuria — Understanding Quantification

10. Imaging in CKD

11. Investigations Overview (Pre-DDx/Diagnosis Section)

Active Recall — Chronic Kidney Disease: Definition, Epidemiology, Pathophysiology and Clinical Features

References

1. First-Level Differential: AKI vs CKD vs Acute-on-Chronic

2. Second-Level Differential: What Is the Cause of the CKD?

2.1 Systematic Aetiological Framework

2.2 Differential by Kidney Size on USS

2.3 Differential by Urinalysis Pattern

2.4 Differential Guided by Clinical Clues

3. Differential of Haematuria in CKD

4. Special Considerations in Hong Kong

5. Approach to Working Up the Cause of CKD

6. Summary Differential Diagnosis Table

Active Recall — Differential Diagnosis of CKD

1. Diagnostic Criteria for CKD

1.1 KDIGO 2012 Diagnostic Criteria

1.2 KDIGO Staging — The "Heat Map"

1.3 Age-Related eGFR Decline — Context Matters

2. Diagnostic Algorithm

3. Investigation Modalities — Detailed Breakdown

3.1 Blood Tests

3.1.1 Renal Function Test (RFT)

3.1.2 Full Blood Count (CBC)

3.1.3 Bone Profile (Ca²⁺, PO₄, ALP, PTH)

3.1.4 Electrolytes and Acid-Base

3.1.5 Investigations for Aetiology

3.2 Urine Tests

3.2.1 Urine Dipstick

3.2.2 Urine Microscopy

3.2.3 Urine Protein Quantification

3.2.4 Creatinine Clearance (CrCl)

3.2.5 Other Urine Tests

3.3 Imaging

3.3.1 Ultrasound (USS) Kidneys

3.3.2 Doppler USS

3.3.3 Other Imaging

3.4 Renal Biopsy

3.4.1 Indications for Renal Biopsy in CKD

3.4.2 Contraindications for Renal Biopsy

3.4.3 Biopsy Technique

3.5 Special Investigation: Autoimmune and Serological Workup

3.6 Radiological Features of CKD on Imaging — Summary of Key Findings

4. Putting It All Together — The Complete Diagnostic Algorithm

5. Interpretation Summary Table — Key Bloods and Urine

Active Recall — CKD Diagnostic Criteria, Algorithm and Investigations

1. Therapeutic Objectives

2. Management Algorithm — Overview