Chronic Kidney Disease
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.
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):
- 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
- 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
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
| 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] |
| 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) |
| 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 |
- 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].
| 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:
- 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 Interstitial Nephritis
Chronic interstitial nephritis is a progressive tubulointerstitial kidney disease characterized by chronic inflammation and fibrosis of the renal interstitium, leading to tubular atrophy and gradual decline in renal function.
Acute Kidney Injury
Acute kidney injury is a rapid decline in renal function occurring over hours to days, marked by rising serum creatinine and/or decreased urine output, leading to impaired waste excretion and fluid-electrolyte imbalance.