AKI is defined as at least ONE of the following (KDIGO 2012) ^[1][3][4]:

• ↑ serum creatinine (sCr) by ≥ 26.5 μmol/L (0.3 mg/dL) within 48 hours
• ↑ serum creatinine to ≥ 1.5× baseline, known or presumed to have occurred within 7 days
• Urine output < 0.5 mL/kg/h for 6 hours

Why these specific numbers?

• The 26.5 μmol/L absolute rise catches early, small increments even in patients with low baseline creatinine (e.g., a frail elderly woman with baseline Cr 50 → 77 is already AKI Stage 1).
• The 1.5× baseline catches relative changes in patients with higher baselines.
• Urine output is included because it can detect AKI before creatinine rises (creatinine is a lagging indicator — by the time it rises, GFR has already dropped ~50%) ^[4][5].

Staging allows grading of severity and guides clinical decisions ^[1][3][4]:

The objectives of AKI definition and classification are: (1) consistent meaning, (2) early identification, (3) grading according to severity, (4) expediting management and guiding clinical decisions, and (5) prognosis ^[1].

• RIFLE (Risk, Injury, Failure, Loss, ESKD) — originally developed for ICU patients; uses GFR decline and urine output ^[4][5]
• AKIN (Acute Kidney Injury Network) — refined RIFLE; essentially absorbed into KDIGO
• pRIFLE — paediatric version using estimated creatinine clearance (eCCl) ^[4]:
  • Risk: ↓eCCl by 25%
  • Injury: ↓eCCl by 50%
  • Failure: ↓eCCl by 75% or oliguria < 0.3 mL/kg/h for 24h or anuria for 12h
  • Loss: persistent failure > 4 weeks
  • End-stage: persistent failure > 3 months

• AKI is extremely common in hospitalized patients:
  • Affects approximately 10–15% of all hospital admissions
  • Up to 50–60% of ICU patients develop some degree of AKI
  • Community-acquired AKI is less common but increasingly recognized (especially in elderly patients on nephrotoxic drugs)

• In Hong Kong, pre-renal causes (especially dehydration and sepsis) remain the most common cause of AKI ^[3]
• Drug-related AKI is very important locally:
  • NSAIDs — widely available over-the-counter
  • Chinese herbal medicines — aristolochic acid nephropathy (unique to the region); causes acute-on-chronic tubulointerstitial nephritis
  • Contrast nephropathy — significant given the volume of CT scans and percutaneous coronary interventions performed
  • Aminoglycosides — still used for serious infections (e.g., gentamicin)
• The ageing population in Hong Kong means more patients have pre-existing CKD, diabetes, and heart failure — all major risk factors for AKI ^[3]

• AKI is a poor prognostic marker — even mild AKI (Stage 1) is independently associated with increased mortality
• ICU patients with AKI requiring dialysis: mortality 40–60%
• Even mild, reversible AKI can have important long-term consequences such as transition to CKD ^[3]

The nephron is the functional unit of the kidney. Each kidney contains approximately 1 million nephrons ^[7]. Each nephron consists of:

1. Glomerulus — the filtration unit

   • Receives blood from the afferent arteriole
   • Filters plasma across the glomerular basement membrane (GBM) to produce an ultrafiltrate (~180 L/day)
   • Filtrate exits via the efferent arteriole
   • Normal GBM excludes cells and large proteins (> ~70 kDa) → normally no RBCs or significant protein in urine

2. Proximal Convoluted Tubule (PCT) — the workhorse

   • Reabsorbs ~65–70% of filtered Na⁺, water, glucose, amino acids, bicarbonate, phosphate
   • Highly metabolically active → most vulnerable to ischaemic and toxic injury (this is why ATN preferentially affects the PCT and thick ascending limb)

3. Loop of Henle — concentrating mechanism

   • Descending limb: permeable to water
   • Thick ascending limb (TAL): impermeable to water, actively pumps NaCl → creates the medullary concentration gradient
   • TAL is also metabolically demanding → susceptible to ischaemic ATN

4. Distal Convoluted Tubule (DCT) and Collecting Duct

   • Fine-tuning of Na⁺, K⁺, H⁺, water reabsorption
   • Aldosterone acts here (Na⁺ reabsorption, K⁺ secretion)
   • ADH acts on collecting duct (aquaporin-2 insertion → water reabsorption)

5. Renal interstitium — the scaffolding between tubules

   • Participates in fluid/electrolyte exchange and endocrine functions (e.g., erythropoietin production by peritubular interstitial fibroblasts) ^[7]

Renal blood flow autoregulation:

• The kidney autoregulates blood flow across a MAP range of ~80–180 mmHg
• Below this range → GFR drops → AKI
• ACEI/ARBs dilate the efferent arteriole → reduce intraglomerular pressure → this is normally nephroprotective in CKD, but in acute hypovolaemia it can precipitate AKI (removes the kidney's compensatory mechanism to maintain GFR)
• NSAIDs inhibit prostaglandin synthesis → constrict the afferent arteriole → reduce renal blood flow → AKI. The "triple whammy" (ACEI/ARB + diuretic + NSAID) is a classic precipitant.

Tubuloglomerular feedback (TGF):

• The macula densa in the DCT senses NaCl delivery
• Low NaCl delivery → signals afferent arteriole dilation and renin release → maintains GFR
• This mechanism is disrupted by drugs and ischaemia

Definition: Reduced renal perfusion without structural kidney damage. The kidney itself is healthy but underperfused.

Pathophysiology: Reduced renal blood flow → reduced hydrostatic pressure in the glomerulus → reduced GFR → reduced urine output → retention of creatinine and urea. The tubules are intact and avidly reabsorb sodium and water (a normal physiological response to perceived hypovolaemia).

Key feature: Rapidly reversible if perfusion is restored. If hypoperfusion persists, it progresses to ischaemic acute tubular necrosis (ATN) — an intrinsic renal cause ^[6].

Why does pre-renal AKI have a low fractional excretion of sodium (FENa)?

• The tubules are intact and functioning normally
• In response to perceived hypovolaemia, the RAAS is activated:
  • Angiotensin II → proximal tubule Na⁺ reabsorption
  • Aldosterone → distal tubule Na⁺ reabsorption
• Therefore, the kidney holds onto sodium avidly → FENa < 1%, urine Na < 20 mmol/L
• Urine osmolality is high (> 500 mOsm/kg) because ADH is maximally active → concentrated urine

Definition: Obstruction of urinary outflow. Must be bilateral (or unilateral in a single functioning kidney) to cause significant AKI ^[6].

Pathophysiology: Obstruction → increased intratubular pressure → opposes glomerular filtration → GFR drops. Prolonged obstruction → tubulointerstitial fibrosis (irreversible intrinsic renal disease) ^[6].

Post-renal causes are important to recognize because they are often rapidly reversible ^[6] — relieving obstruction (e.g., urinary catheter for BPH, nephrostomy for ureteric obstruction) can restore kidney function.

AKI in the context of liver disease is a poor prognostic marker — the patient may be dead in the coming future ^[8].

• Occurs in advanced cirrhosis with portal hypertension
• Pathophysiology: Splanchnic vasodilation → reduced effective circulating volume → intense renal vasoconstriction → AKI despite structurally normal kidneys
• Hepatorenal syndrome is NOT the most common cause of AKI in liver disease — pre-renal (dehydration, over-diuresis, GI bleeding) and intrinsic renal (ATN from sepsis) are more common ^[8]
• Diagnosed by exclusion (no improvement with volume resuscitation, no shock, no nephrotoxins, no proteinuria, no structural renal disease)

sCr ↑ ≥ 25% from baseline OR ↑ 44 μmol/L within 48–72 hours after contrast exposure ^[11].

• Risk factors: renal impairment, diabetes, dehydration ^[12]
• GFR < 30: contraindicated for contrast; GFR 30–60: adequate hydration (IV NS), N-acetylcysteine PO 600 mg BD 1 day before and after procedure, avoid ACEI/ARB, diuretics, NSAIDs ^[11]
• May result in metformin retention → fatal lactic acidosis → MUST STOP METFORMIN BEFORE CONTRAST CT ^[12]
• Usually self-limiting (peaks at day 3–5, resolves by 1–2 weeks)

Dark brown urine, urine microscopy: myoglobin and pigmented granular casts (no RBCs), ↑↑ CK, ↑ K⁺, ↓ Ca²⁺, ↑ PO₄, ↑ urate, DIC, AKI ^[11].

• Causes: trauma (crush injury), seizures, statins, hypothyroidism/hyperthyroidism ^[11]
• Pathophysiology: myoglobin released from damaged muscle → precipitates in tubules (especially in acidic pH) → direct tubular toxicity + tubular obstruction → ATN
• Management: aggressive IV NS (1.5 L/h until stable), target UO 300 mL/h, alkalinize urine (NaHCO₃ to keep urine pH > 6.5), mannitol (keep plasma osmolar gap < 55), allopurinol if uric acid > 476, haemodialysis if refractory ^[11]

• Sepsis is the most common cause of AKI in ICU ^[13]
• Pathophysiology: multifactorial — systemic vasodilation (↓ renal perfusion), microvascular dysfunction (endothelial injury, microthrombi), direct tubular injury from inflammatory mediators (TNF-α, IL-1, IL-6), mitochondrial dysfunction
• Presents as part of multiple organ dysfunction syndrome (MODS) ^[13]
• Renal manifestation of sepsis: acute tubular necrosis / acute kidney injury ^[13]

• Occurs after chemotherapy for high-tumour-burden malignancies (e.g., acute leukaemia, Burkitt lymphoma)
• Pathophysiology: rapid cell death → release of intracellular contents → ↑ K⁺, ↑ PO₄, ↑ urate, ↓ Ca²⁺, ↑ LDH ^[14]
• Uric acid + calcium phosphate crystals precipitate in tubules → AKI
• Prevention: allopurinol/febuxostat (xanthine oxidase inhibitors), rasburicase (recombinant urate oxidase — contraindicated in G6PD deficiency), aggressive hydration ^[14]

AKI is associated with progressive kidney damage, declining GFR, increased risk of complications, and mortality. Many ICU patients require nephrology consult because critical illness involves the kidney ^[3].

The clinical features of AKI are a direct consequence of the loss of kidney functions:

1. Excretory function (waste clearance) → uraemia
2. Regulatory function (fluid, electrolytes, acid-base) → fluid overload, electrolyte disturbances, metabolic acidosis
3. Endocrine function (EPO, vitamin D, RAAS) → anaemia (if prolonged), hypertension

Acute kidney injury in liver disease is a poor prognostic marker ^[8].

• Diagnosis: KDIGO criteria — ↑ ≥ 50% Cr in 7 days OR ≥ 26.5 μmol/L Cr in 48 hours ^[8]
• Must separate causes: pre-renal, renal, and post-renal — every possible cause of AKI can occur in liver disease ^[8]
• Hepatorenal syndrome sounds like the obvious diagnosis but is actually not the most common cause ^[8]. Pre-renal causes (over-diuresis, GI bleeding, sepsis) are more frequent.

ATN is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. Common causes of ATN include low blood pressure and use of nephrotoxic drugs ^[7].

The presence of "muddy brown casts" of epithelial cells found in the urine during urinalysis is pathognomonic for ATN ^[7].

Diagnosis is made by a FENa > 3% and presence of muddy casts in urinalysis ^[7].

Light chain cast nephropathy (myeloma kidney): A specific and often-missed diagnosis. Light chain cast nephropathy occurs in 30–50% of patients with multiple myeloma. 90% of cases occur in patients > 50 years old (median age 70). Presentations include acute renal failure and proteinuria ^[17]. On renal biopsy: bright red tubular casts rimmed by macrophages on H&E; PAS-stain shows casts are only palely positive (not Tamm-Horsfall protein); immunohistochemistry demonstrates light chain restriction (kappa or lambda) ^[17].

Atypical back pain — consider (1) multiple myeloma and (2) bony metastasis of cancer. Also enquire about the medications the patient took recently — consider drug-induced AKI ^[18].

Drug sensitivity reaction: (1) fever, (2) rash, and (3) eosinophilia ^[7].

TB drug-induced acute tubulointerstitial nephritis: 74-year-old lady started on anti-TB medications 10 days ago → fever, generalized rash, hepatosplenomegaly, lymphadenopathy, WBC 17800 with eosinophilia, serum creatinine 560 μmol/L, urinalysis shows WBC casts, renal US shows large echogenic kidneys ^[17].

Key point about NSAIDs and AIN: NSAIDs can cause a unique dual pathology — NSAID-induced nephrotic syndrome combines minimal change glomerulonephropathy with acute tubulointerstitial nephritis. Features: nephrotic syndrome, no RBCs in urine, AKI, eosinophilia (~40%). Higher risk in elderly ^[19]. This is a favourite exam question.

The glomerulus is the filtration barrier. When it is inflamed, you get the nephritic syndrome: haematuria, proteinuria, hypertension, oedema, oliguria ^[10].

Differential diagnosis of haematuria (from the GC lecture) ^[20]:

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

The most feared glomerular cause of AKI is rapidly progressive glomerulonephritis (RPGN) — defined as a rapid decline in GFR over days to weeks with crescent formation on biopsy. This is a nephrological emergency.

When creatinine rises suddenly — e.g., from 126 to 355 μmol/L in 1 day (182% increase) — think RPGN ^[10].

The interactive tutorial case ^[10] — a 34-year-old Chinese lady with malaise, bilateral small joint pain, lower limb swelling, BP 152/92, urine RBC 3+ and protein 3+:

• This is a nephritic syndrome presentation
• Joint involvement + young female → think lupus nephritis (→ ask about hair loss, oral ulcers, photosensitive rash, Raynaud's)
• SLE can also cause distal RTA ^[10]
• Always ask about drug history (NSAIDs — possible given MSK complaints) ^[10]
• If rapid deterioration → RPGN — renal biopsy indicated ^[10]

AKI in liver disease is a poor prognostic marker — patient may be dead in the coming future ^[8].

• Must separate causes: pre-renal, renal, and post-renal — every possible cause of AKI can occur in liver disease ^[8].
• Hepatorenal syndrome sounds like the obvious diagnosis but is NOT the most common cause ^[8].

The differential in a cirrhotic patient with AKI:

1. Pre-renal (most common): over-diuresis (too much spironolactone/furosemide for ascites), GI bleeding (variceal), diarrhoea (lactulose overdose), sepsis (SBP)
2. Intrinsic: ATN from prolonged hypoperfusion or sepsis, drug-related (contrast, aminoglycosides)
3. Hepatorenal syndrome: diagnosis of exclusion — no improvement after 48h albumin challenge (1 g/kg/day, max 100g), no shock, no nephrotoxins, no proteinuria > 500 mg/day, no structural renal disease on US
4. Post-renal: rare but always exclude

Post-operative (e.g., post-CABG) is a risk factor for AKI ^[3][6].

Differential in a post-op patient with rising creatinine:

1. Pre-renal: hypovolaemia (intra-operative blood loss, inadequate fluid replacement, third-space losses), reduced cardiac output (post-cardiac surgery), sepsis
2. Post-renal: blocked catheter ^[6] — always check this first!
3. Intrinsic: ATN from prolonged intra-operative hypotension, contrast (if intra-operative angiography), nephrotoxic drugs (aminoglycosides for prophylaxis)

Differential for AKI + dark/cola-coloured urine:

1. Rhabdomyolysis: ↑↑↑ CK, pigmented granular casts, urine dipstick positive for blood but microscopy negative for RBCs ^[11]
2. Haemolysis: intravascular haemolysis → haemoglobinuria, ↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, schistocytes if TMA
3. Glomerulonephritis: "smoky" or "coca-cola" urine from macroscopic haematuria, RBC casts on microscopy

Young subjects are NOT expected to have AKI ^[3]. When they do, consider:

1. Glomerulonephritis — especially IgA nephropathy (most common GN worldwide), lupus nephritis (young females), post-streptococcal GN (children/young adults)
2. Drug/toxin exposure — recreational drugs, herbal medicines (aristolochic acid nephropathy — important in Hong Kong/Southern China)
3. Rhabdomyolysis — intense exercise, seizures, stimulant drugs
4. Light chain cast nephropathy — though classically in the elderly, the RTD case demonstrates a 35-year-old woman with AKI from light chain cast nephropathy due to multiple myeloma ^[17] — don't dismiss myeloma in younger patients if there is unexplained AKI and anaemia

A critical differential to recognise:

1. Anti-GBM disease (Goodpasture syndrome) — medical emergency ^[7]
2. ANCA-associated vasculitis (GPA, MPA)
3. SLE (Class IV lupus nephritis + diffuse alveolar haemorrhage)

Autoimmune and Specific Screens — ordered when intrinsic renal disease (especially GN) is suspected:

The urine is your window into the kidney. Think of it as a "liquid biopsy."

Diagnosis of renal diseases for specific treatment: basic laboratory investigations include blood for RFT (urea and creatinine), urine for microscopy (red cells and white cells), and urine for quantification of protein (e.g., 24-hour urine for protein) ^[7].

Urine Microscopy — The Most Important Non-Invasive Test:

Key Urine Biochemistry Table — Pre-Renal vs. ATN:

Hepatorenal Syndrome — Specific Urine Finding:

Spot urine sodium < 10 mmol/L is suggestive of HRS ^[8] — related to the excessive activation of the RAAS in splanchnic vasodilation. This is lower than typical pre-renal AKI (< 20) because the vasoconstriction is even more intense.

Renal biopsy is still essential for definitive diagnosis of a number of renal diseases ^[7]:

• Glomerulonephritis (MCD, FSGS, IgAN, membranous GN, MPGN)
• Tubulointerstitial diseases (acute tubular injury, tubulointerstitial nephritis)
• Vascular diseases (thrombotic microangiopathy, ANCA-associated vasculitis)
• Diseases in graft kidneys (rejection, infection, PTLD)

When to biopsy:

• Renal biopsy indicated if creatinine is markedly elevated or worsened over a course of days — provides definitive tissue diagnosis and allows therapeutic intervention to prevent ESRD ^[23]
• Consider if pre-renal cause or ATN unlikely, or persistent oliguria > 6 weeks ^[11]
• Suspected RPGN (crescent formation on biopsy is diagnostic)
• AIN not responding to drug withdrawal (to decide on steroids) — renal biopsy is usually required to confirm the diagnosis of AIN ^[7]
• Unexplained AKI with normal-sized kidneys ^[21]
• Suspected light chain cast nephropathy / myeloma kidney ^[17]
• Atypical features of diabetic nephropathy (RBC casts, rapid decline, no retinopathy) ^[22]

Procedure:

• Patient prone, radiologist uses US to find position, lower pole of kidney targeted, a few extractions (cores) taken for sufficient tissue ^[5]
• Tissue sent for: light microscopy, immunofluorescence (IF), and electron microscopy (EM) — the "triple stain" approach

Contraindications:

• Contracted/small kidneys — hard to target, may only get fibrous tissue ^[5]
• Large cysts — cannot control bleeding ^[5]
• Solitary kidney — no backup if complications occur ^[5]
• Uncontrolled hypertension (↑ bleeding risk)
• Bleeding diathesis (↑ INR, ↓ platelets)

Histopathological Findings in Specific Conditions:

Essential in all AKI patients because of the risk of hyperkalaemia:

ECG changes of hyperkalaemia ^[26]:

• K 6–7 mmol/L: Tall, peaked ("tented") T waves
• K 7–8 mmol/L: Flattened P waves, prolonged PR interval
• K 8–10 mmol/L: Widened QRS complexes
• K > 10 mmol/L: Sine wave pattern → ventricular fibrillation → cardiac arrest

Always perform an ECG before the lab K result comes back if you clinically suspect hyperkalaemia — the ECG changes may be present before the blood result is available.

• Pulmonary oedema — bilateral perihilar opacification ("bat-wing" pattern), Kerley B lines, pleural effusions → confirms fluid overload
• Cardiomegaly — if heart failure is the cause of pre-renal AKI
• Bilateral pulmonary infiltrates/haemorrhage → pulmonary-renal syndrome (anti-GBM, ANCA vasculitis)

Consider and reverse post-renal disease: S/S — palpable enlarged bladder with ↑ residual volume, blocked catheter. Mx: directed to the underlying cause ^[6].

• Blocked catheter → flush or replace (this is the simplest and most commonly missed cause on the ward)
• BPH / prostate cancer → urethral catheterisation or suprapubic catheter
• Ureteric obstruction (stones, pelvic tumour) → percutaneous nephrostomy or retrograde ureteric stent (JJ stent)
• Obstruction should be relieved if present ^[29]

Watch for post-obstructive diuresis after relief — patients can become profoundly hypovolaemic from massive polyuria (the tubules temporarily cannot concentrate urine). Monitor UO closely and replace losses.

Fluid challenge: crystalloid solution (e.g., 500–1000 mL NS) given over 1–2 hours for hypovolaemia ^[23][29].

• For hypovolaemia: Fluid challenge with normal saline (NS) or balanced crystalloid solution (Plasma-Lyte), 500–1000 mL over 1–2 hours ^[29]
• Optimise pre-load ^[29] — reassess after the challenge. If creatinine starts to fall and UO improves, you've confirmed and treated pre-renal AKI.
• If no improvement after adequate fluid resuscitation → the problem has likely progressed to intrinsic renal disease (ATN)
• Low-dose dopamine is NOT recommended ^[29] — the concept of "renal-dose dopamine" has been debunked. It does not improve outcomes and may cause arrhythmias.

Consider and reverse use of any nephrotoxic drugs: NSAIDs, aminoglycosides, ACEI/ARB ^[6].

This is one of the most impactful interventions you can make. Go through the drug chart systematically:

Drug prescribing in patients with impaired kidney function — 3 important principles: (1) avoid further nephrotoxic insult, (2) attention to correct dose, (3) beware of side-effects in patients with impaired kidney function ^[19].

Symptoms (arrhythmia, weakness) usually only when K > 6 ^[6].

Emergency management of hyperkalaemia (in order of importance) ^[29][31]:

Non-emergency (subacute) hyperkalaemia management ^[31]:

• Cation-exchange resins — Na/Ca polystyrene sulphonate (oral or enema) — bind K⁺ in the gut for faecal excretion. Newer agents: Lokelma (sodium zirconium cyclosilicate), Patiromer ^[31]
• Loop diuretic if not oliguric — increases renal K⁺ excretion
• Remove underlying cause — stop offending drugs (ACEI/ARB, K⁺-sparing diuretics, trimethoprim), volume expansion if depleted
• Correct metabolic acidosis
• Low K⁺ diet ( < 20 mmol/day) ^[23][29]

Metabolic acidosis: Kussmaul's breathing. Mx: IV bicarbonate, dialysis ^[6].

• Determine the cause and treat the underlying cause ^[31]
• IV NaHCO₃ — consider if pH < 7.2 or HCO₃⁻ < 10 mmol/L. This is a temporising measure, not definitive treatment
• Risks of NaHCO₃ therapy ^[31]:
  • Hypernatraemia (1 mmol HCO₃⁻ carries 1 mmol Na⁺ — 200 mmol NaHCO₃ = more Na⁺ than 1 litre of NS)
  • Induce hypoK (shifts K⁺ intracellularly — dangerous in patients with existing hypoK or DKA)
  • Decrease ionised calcium (problematic if already hypocalcaemic from CKD/AKI)
  • Volume expansion from Na⁺ load
  • Paradoxical cerebral acidosis — HCO₃⁻ breaks down to CO₂, which crosses the BBB and is converted to acid by carbonic anhydrase
• Dialysis if refractory (pH < 7.1 despite bicarbonate)

Fluid overload: peripheral oedema, hypertension, pulmonary oedema. Mx: IV loop diuretics (e.g., furosemide), dialysis ^[6].

• For fluid overload: Add furosemide up to 80 mg IV bolus or 10 mg/h IV infusion ^[29]
• Consider to add metolazone 5–10 mg daily PO if refractory ^[29] — a thiazide-like diuretic that acts synergistically with loop diuretics ("sequential nephron blockade": metolazone blocks Na reabsorption in the DCT, so the distal tubule can't compensate for the loop diuretic's effect)
• Sit patient upright, give O₂
• If refractory → urgent dialysis/ultrafiltration

• Uraemic pericarditis — pericardial friction rub; indication for emergency dialysis (risk of haemorrhagic pericardial tamponade)
• Uraemic encephalopathy — confusion, asterixis, seizures; indication for dialysis
• Uraemic bleeding — platelet dysfunction from uraemic toxins; desmopressin (DDAVP) can temporarily improve platelet function; dialysis is definitive

Urgent indications for dialysis in AKI ^{[6][23][29][32]}:

Access for acute haemodialysis:

• Temporary vascular catheter — large-bore double-lumen catheter inserted into internal jugular vein (preferred), subclavian vein (avoid if possible — risk of central vein stenosis that precludes future AV fistula on that side), or femoral vein
• Not an AV fistula — fistulas take weeks to mature and are for chronic dialysis

Contraindications to PD ^[32]:

• Previous extensive abdominal surgery (scarring)
• Frequent PD-related peritonitis
• Residence that does not permit PD or lacks sanitary conditions

Why it happens: Potassium is the major intracellular cation (~98% of total body K⁺ is intracellular, [K⁺]ᵢ ~140 mmol/L vs. [K⁺]ₑ ~3.5–5.0 mmol/L). The kidney — specifically the distal nephron — is the primary route for K⁺ excretion. In AKI, the failing kidney cannot excrete the daily potassium load (~50–100 mmol/day from diet). Additionally:

• Metabolic acidosis (see below) drives H⁺ into cells, and K⁺ is displaced out of cells to maintain electroneutrality → transcellular shift worsening hyperkalaemia
• Tissue catabolism, rhabdomyolysis, tumour lysis → release of intracellular K⁺ into ECF
• Drugs that impair K⁺ excretion: ACEI/ARBs (↓ aldosterone), K⁺-sparing diuretics, calcineurin inhibitors

Clinical consequences:

Hyperkalaemia: symptoms (arrhythmia, weakness) usually only when K > 6 ^[6].

• Cardiac — the most dangerous effect. Hyperkalaemia reduces the resting membrane potential (makes it less negative) → altered conduction and repolarisation. ECG progression:
  • K 6–7 mmol/L: tall, peaked T waves
  • K 7–8 mmol/L: flattened P waves, prolonged PR
  • K 8–10 mmol/L: widened QRS, aberrant complexes
  • K > 10 mmol/L: sine wave → ventricular fibrillation → cardiac arrest
• Neuromuscular — muscle weakness (ascending, can mimic GBS), paraesthesiae, flaccid paralysis
• Metabolic — can worsen metabolic acidosis (hyperkalaemia impairs renal ammoniagenesis)

Management (covered in prior section): IV calcium gluconate → NaHCO₃ → insulin/dextrose → dialysis. Non-urgent: cation-exchange resins, loop diuretics, low K⁺ diet ^[6][31].

Why it happens: The kidney normally maintains acid-base balance through two mechanisms:

1. Reabsorbing filtered bicarbonate (~4,300 mmol/day is filtered; virtually all is normally reabsorbed in the PCT)
2. Regenerating new bicarbonate by excreting H⁺ (as titratable acid and ammonium, NH₄⁺, in the distal nephron)

In AKI, both mechanisms fail → net accumulation of H⁺ → metabolic acidosis. Additionally, reduced renal clearance of organic acids (lactate, sulphate, phosphate, urate) contributes to a high anion gap metabolic acidosis (HAGMA).

Clinical consequences:

• Kussmaul's breathing — deep, laboured respirations as respiratory compensation (hyperventilation to blow off CO₂ and partially compensate for the acidosis) ^[6]
• Negative inotropic effect on the heart → reduced cardiac contractility
• Shifts K⁺ out of cells → worsens hyperkalaemia (for every 0.1 unit fall in pH, K⁺ rises by ~0.3–0.6 mmol/L)
• Resistance to catecholamines → hypotension harder to treat
• Protein catabolism → worsens uraemia

Management: Treat the underlying cause. NaHCO₃ infusion if pH < 7.2 or HCO₃⁻ < 10 mmol/L. Dialysis if refractory (pH < 7.1 despite NaHCO₃) ^[6].

Why it happens: The kidney normally excretes ~1.5–2 L of urine per day. In oliguric or anuric AKI, ongoing IV fluid administration and oral intake exceed output → positive fluid balance → extracellular fluid expansion. The excess fluid distributes into the interstitial space (peripheral oedema) and, critically, the lungs (pulmonary oedema).

Clinical consequences:

Fluid overload: peripheral oedema, hypertension, pulmonary oedema ^[6].

• Peripheral oedema — gravitational distribution (ankles when upright, sacrum when supine)
• Hypertension — volume-dependent hypertension from Na⁺ and water retention; also RAAS activation
• Pulmonary oedema — the most dangerous manifestation. Presents with acute dyspnoea, orthopnoea, pink frothy sputum, bilateral crepitations, hypoxaemia. CXR shows bilateral alveolar shadowing ("bat-wing" pattern), Kerley B lines, pleural effusions
• Pleural effusions — transudative effusions from fluid overload

Management: IV loop diuretics (furosemide up to 80 mg IV bolus or 10 mg/h infusion). Add metolazone 5–10 mg daily PO if refractory ^[29]. Fluid restriction. Sit upright, O₂. Dialysis/ultrafiltration if refractory to diuretics ^[6].

Why it happens: "Uraemia" literally means "urine in the blood" (Greek: "ouron" = urine, "haima" = blood). The kidney normally clears nitrogenous waste products: urea, creatinine, and a host of poorly characterised "uraemic toxins" (indoxyl sulphate, p-cresyl sulphate, asymmetric dimethylarginine, β₂-microglobulin, etc.). In AKI, these toxins accumulate to pathological levels.

Uraemic complications are indications for emergency dialysis:

Signs of uraemia on examination: confusion, asterixis, scratch marks, tachypnoea, pericardial rub ^[34].

Why it happens: In AKI with oliguria, ongoing water intake (oral or IV) exceeds excretory capacity → dilutional hyponatraemia. Also, uraemia can cause "sick cell syndrome" (impaired Na⁺/K⁺-ATPase → Na⁺ enters cells, K⁺ leaks out).

Clinical consequences:

• Asymptomatic if mild (Na > 125 mmol/L)
• Nausea, headache, confusion at Na 120–125
• Seizures, coma, cerebral oedema, brainstem herniation at Na < 115–120

Too rapid correction of chronic hyponatraemia may result in central pontine myelinolysis → patients become tetraplegic ^[35]. The rate of correction should be slow: < 0.5 mmol/L/h, or < 12 mmol/L/day ^[35].

Why it happens:

• Hyperphosphataemia: The kidney normally excretes phosphate. In AKI, phosphate accumulates (especially marked in rhabdomyolysis and tumour lysis syndrome where intracellular phosphate is massively released)
• Hypocalcaemia: High phosphate → calcium-phosphate precipitation in tissues (metastatic calcification) → ↓ ionised calcium. Additionally, injured kidneys cannot convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) → ↓ intestinal calcium absorption

Clinical consequences:

• Tetany, perioral tingling, muscle cramps, Chvostek's sign, Trousseau's sign (from hypocalcaemia)
• QT prolongation → risk of torsades de pointes
• Nephrocalcinosis (calcium-phosphate deposition in renal tubules → can worsen AKI)

Why it happens: The kidney excretes ~70% of daily uric acid. In AKI, uric acid accumulates. Massively elevated in tumour lysis syndrome (rapid nucleic acid catabolism). Uric acid crystals can precipitate in the renal tubules → uric acid nephropathy → can worsen or even cause AKI in a vicious cycle.

Why it happens: AKI itself is an immunocompromised state. Uraemic toxins impair neutrophil chemotaxis, phagocytosis, and lymphocyte function. Invasive procedures (urinary catheters, central venous catheters for dialysis, nasogastric tubes) provide portals of entry for pathogens. Critically ill AKI patients in ICU are at high risk for nosocomial infections.

Common infections: Catheter-related UTI, catheter-related bloodstream infection (CRBSI), hospital-acquired pneumonia, Clostridioides difficile colitis.

Why it happens in the AKI context: AKI can be both a cause and consequence of DIC:

• Sepsis-driven AKI → sepsis-induced DIC → microthrombi in renal vasculature → ATN → worsening AKI (vicious cycle)
• ABO-incompatible transfusion → complement activation → free haemoglobin release → platelet activation + coagulation system activation → DIC → thrombus formed in renal vasculature → AKI ^[36]

Why it happens: After relief of bilateral urinary obstruction (post-renal AKI), accumulated urea and sodium in the medullary interstitium act as osmotic diuretics. Additionally, the tubules are transiently unable to concentrate urine (acquired nephrogenic diabetes insipidus from chronic medullary washout). This produces massive polyuria (up to 5–10 L/day).

Clinical consequences:

• Hypovolaemia, hypotension, dehydration if losses are not replaced
• Hyponatraemia, hypokalaemia from excessive electrolyte losses

Management: Close monitoring of UO and electrolytes. Replace ~50–75% of hourly urine output with IV NS or half-NS to prevent haemodynamic collapse while allowing the physiological diuresis to resolve retained solutes. Full replacement of every mL risks perpetuating the diuresis.

Diuretic phase of ATN: gradual normalisation of GFR, markedly increased urine output — up to 3 L/day. Urine output gradually returns to normal ^[7].

Why it happens: As tubular cells regenerate, GFR begins to improve, but the regenerating tubular epithelium is initially "leaky" — unable to reabsorb sodium and water normally. Accumulated urea also acts as an osmotic diuretic.

Clinical significance:

• The diuretic phase looks encouraging (creatinine starts to fall), but patients can become dehydrated if fluid intake does not match the increased output
• Electrolyte losses (Na⁺, K⁺, Mg²⁺, PO₄³⁻) must be monitored and replaced
• Does NOT mean the kidney has fully recovered — the nephrons are regenerating but not yet fully functional

Why it happens: AKI triggers a hypercatabolic state — metabolic acidosis promotes protein catabolism, uraemic toxins suppress appetite, and the underlying illness (sepsis, surgery, trauma) increases metabolic demands. Dietary restriction (low protein, low K⁺, low PO₄³⁻) further limits caloric and nitrogen intake.

Clinical consequences: Muscle wasting, poor wound healing, immunosuppression, delayed recovery. Mortality is significantly higher in malnourished AKI patients.

Management: Early nutritional support. Protein intake should be 0.8–1.0 g/kg/day in non-dialysis AKI, increased to 1.0–1.5 g/kg/day if on CRRT (amino acid losses across the filter). Adequate caloric intake (25–30 kcal/kg/day).

Even mild, reversible AKI can have important clinical consequences, e.g., CKD transition ^[3][25].

Why it happens: Even when creatinine returns to "baseline," subclinical injury may persist:

1. Maladaptive repair — some tubular cells undergo G2/M cell cycle arrest → produce profibrotic cytokines (TGF-β, CTGF) → tubulointerstitial fibrosis
2. Nephron loss — dead nephrons are replaced by scar tissue, not new nephrons. The remaining nephrons hypertrophy to compensate (compensatory hyperfiltration), but this eventually leads to glomerulosclerosis (like CKD from any cause)
3. Microvascular rarefaction — peritubular capillary loss after AKI → chronic tubular ischaemia → further fibrosis

Risk factors for AKI-to-CKD transition:

• Severity and duration of AKI (Stage 3, prolonged oliguria, need for dialysis → higher CKD risk)
• Pre-existing CKD (reduced nephron reserve → less capacity for compensatory recovery)
• Recurrent AKI episodes
• Older age, diabetes, hypertension

Clinical implications:

• AKI is associated with increased risk of developing complications and mortality ^[3]
• Patients who survive AKI have increased long-term risk of CKD, ESRD, cardiovascular events, and death compared to matched controls even if creatinine returns to baseline
• All AKI survivors should have renal function monitored at 3 months and annually thereafter

If AKI does not fully recover and the patient develops CKD, all the complications of CKD apply:

Systemic complications of CKD ^[9][34]:

If AKI is severe enough to require dialysis, the dialysis itself carries complications:

General complications of RRT ^[34]:

Haemodialysis-specific:

• Hypotension during dialysis — rapid fluid removal (ultrafiltration) → haemodynamic instability, especially in elderly or cardiac patients
• Catheter-related complications — infection (CRBSI), thrombosis, central vein stenosis
• AV fistula/graft complications (if present for chronic access) — thrombosis, stenosis, steal syndrome, aneurysm, infection
• Dialysis disequilibrium syndrome — rapid removal of urea during dialysis creates an osmotic gradient between blood and brain → cerebral oedema → headache, confusion, seizures, coma. More common in first sessions. Prevented by slower, shorter initial dialysis runs.

Peritoneal dialysis-specific:

• PD-related peritonitis — infection of the peritoneal space, typically from skin commensals (S. epidermidis, S. aureus). Presents with cloudy PD effluent, abdominal pain, fever. Treated with intraperitoneal antibiotics.
• Catheter exit site infection
• Protein losses across the peritoneal membrane → hypoalbuminaemia
• Mechanical complications — hernia, hydrothorax (peritoneal fluid leaks through diaphragmatic defects)

AKI is an independent risk factor for cardiovascular events — not just through the CKD transition but through direct mechanisms:

• Systemic inflammation during AKI → endothelial dysfunction, accelerated atherosclerosis
• Electrolyte disturbances (hyperkalaemia) → arrhythmias, sudden cardiac death
• Volume overload → acute heart failure
• Uraemic toxins → direct myocardial toxicity, pericarditis

This is why even "mild" AKI (Stage 1) is independently associated with increased long-term mortality, cardiovascular events, and hospital readmission.