Acute Kidney Injury

Acute kidney injury (AKI) is an abrupt (hours to days) decline in glomerular filtration that causes retention of nitrogenous wastes and dysregulation of fluid, electrolyte and acid–base balance. It is a syndrome, not a single disease, and is one of the highest-yield Nephrology topics for NEET PG — expect questions on KDIGO staging, FENa, urine microscopy, hyperkalaemia management and dialysis indications.

Definition & KDIGO criteria

The older terms "acute renal failure" and the RIFLE/AKIN classifications have been superseded by KDIGO 2012 criteria. AKI is defined by any one of:

• Rise in serum creatinine by ≥0.3 mg/dL within 48 hours, OR
• Rise in serum creatinine to ≥1.5 times baseline (known or presumed within prior 7 days), OR
• Urine output <0.5 mL/kg/h for ≥6 hours.

High-yield: The most sensitive single criterion is the 0.3 mg/dL absolute rise in 48 hours. Creatinine is a late marker — GFR may already have fallen 50% before creatinine doubles.

KDIGO staging

Stage	Serum creatinine	Urine output
1	1.5–1.9 × baseline, OR ≥0.3 mg/dL rise	<0.5 mL/kg/h for 6–12 h
2	2.0–2.9 × baseline	<0.5 mL/kg/h for ≥12 h
3	≥3.0 × baseline, OR creatinine ≥4.0 mg/dL, OR initiation of RRT, OR (in <18 yr) eGFR <35 mL/min/1.73 m²	<0.3 mL/kg/h for ≥24 h, OR anuria ≥12 h

High-yield: Starting renal replacement therapy (RRT) automatically classifies the patient as stage 3, irrespective of creatinine.

Oliguria = urine output <400 mL/day (or <0.5 mL/kg/h); anuria = <100 mL/day. Anuria classically suggests complete urinary obstruction, bilateral cortical necrosis, or a catastrophic vascular event (e.g. renal artery occlusion).

Etiological classification

AKI is divided by anatomical site into pre-renal (≈55–60%), intrinsic renal (≈35–40%) and post-renal (≈5%).

Pre-renal (hypoperfusion)

Kidney is structurally normal; the problem is reduced perfusion. Promptly reversible if perfusion is restored. Causes:

• True volume depletion — haemorrhage, vomiting, diarrhoea, burns, diuretics.
• Decreased effective circulating volume — heart failure, cirrhosis, nephrotic syndrome, sepsis (distributive).
• Renal autoregulation failure — NSAIDs (block the afferent vasodilatory prostaglandins) and ACE inhibitors/ARBs (block efferent vasoconstriction). This combination is dangerous in renal artery stenosis.

Intrinsic renal

Subdivided by the compartment affected:

• Tubular — Acute Tubular Necrosis (ATN) is the commonest intrinsic cause. Two mechanisms: ischaemic (prolonged pre-renal state) and nephrotoxic (aminoglycosides, amphotericin B, contrast, cisplatin, myoglobin in rhabdomyolysis, haemoglobin, light chains in myeloma, tumour lysis with uric acid/phosphate).
• Glomerular — acute glomerulonephritis, rapidly progressive GN (RPGN).
• Interstitial — Acute Interstitial Nephritis (AIN): drugs (penicillins, cephalosporins, rifampicin, PPIs, NSAIDs, allopurinol), infections, autoimmune. Classic triad of fever, rash, eosinophilia is present in <10%.
• Vascular — vasculitis, thrombotic microangiopathy (HUS/TTP), malignant hypertension, atheroembolic disease (after angiography — look for blue toes, livedo reticularis, eosinophilia, hypocomplementaemia).

Post-renal (obstructive)

Obstruction must be bilateral (or unilateral in a single functioning kidney) to raise creatinine. Causes: BPH, prostate/cervical/bladder malignancy, bilateral stones, retroperitoneal fibrosis, neurogenic bladder, blocked catheter.

High-yield: Always rule out post-renal AKI early with bladder catheterisation and renal ultrasound — it is the most readily reversible category and missing it causes permanent damage.

Pathophysiology of ATN

In ischaemic/nephrotoxic ATN the proximal tubule (S3 segment) and the medullary thick ascending limb are most vulnerable because the outer medulla is relatively hypoxic. Sequence: tubular cell injury → loss of brush border, cell detachment → intraluminal cast formation and obstruction → back-leak of filtrate → afferent vasoconstriction (tubuloglomerular feedback) → fall in GFR.

Clinical course of ATN has three classic phases: Initiation → Maintenance (oliguric, days–weeks; greatest risk of hyperkalaemia/fluid overload) → Recovery (polyuric phase — risk of hypokalaemia and dehydration).

Distinguishing pre-renal from intrinsic (ATN)

This is the single most tested investigative concept. In pre-renal AKI the tubules are intact and avidly reabsorb sodium and water; in ATN they cannot.

Parameter	Pre-renal	ATN (intrinsic)
Urine osmolality (mOsm/kg)	>500 (concentrated)	<350 (isosthenuric ~300)
Urine sodium (mEq/L)	<20	>40
FENa	<1%	>2%
FEUrea	<35%	>50%
BUN : creatinine ratio	>20:1	10–15:1
Urine : plasma creatinine	>40	<20
Urine sediment	Hyaline casts / bland	Muddy brown granular casts, epithelial cells
Response to fluid	Rapid improvement	No improvement

FENa — the formula

$$ FE_{Na} (%) = \frac{U_{Na} \times P_{Cr}}{P_{Na} \times U_{Cr}} \times 100 $$

High-yield: FENa <1% = pre-renal; >2% = ATN. Important exception — FENa can be <1% in some intrinsic causes: acute glomerulonephritis, contrast nephropathy, rhabdomyolysis, and early sepsis, because of intense vasoconstriction with intact tubules.

High-yield: If the patient is on diuretics, FENa is unreliable (loop diuretics force sodium loss). Use FEUrea instead — <35% suggests pre-renal.

Urine microscopy — the visual clincher

Finding	Diagnosis
Muddy brown / pigmented granular casts	ATN
RBC casts + dysmorphic RBCs	Glomerulonephritis / RPGN
WBC casts + eosinophiluria	Acute interstitial nephritis, pyelonephritis
Broad waxy casts	Chronic kidney disease
Crystals (uric acid, oxalate, drug)	Tumour lysis, ethylene glycol, indinavir/acyclovir
Bland sediment / hyaline casts	Pre-renal or post-renal

High-yield: Muddy brown granular casts = ATN is a single-line favourite of examiners. Eosinophiluria (Hansel stain) suggests AIN or atheroembolic disease.

Clinical features

Often asymptomatic and detected on bloods. Manifestations relate to retained solutes and volume:

• Volume overload — oedema, pulmonary congestion, hypertension (or hypovolaemia if pre-renal).
• Uraemia — nausea, anorexia, confusion, asterixis, pericarditis, platelet dysfunction (bleeding).
• Electrolyte/acid–base — hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyponatraemia, high anion gap metabolic acidosis.

Investigation approach

Step 1 — Confirm AKI and stage (creatinine trend, urine output) → Step 2 — Exclude post-renal: catheterise + renal ultrasound (looks for hydronephrosis) → Step 3 — Volume assessment + urinalysis with microscopy → Step 4 — FENa / FEUrea to separate pre-renal from ATN → Step 5 — If intrinsic & unexplained: serology (ANA, ANCA, anti-GBM, complements, ASO) ± renal biopsy.

Renal ultrasound is the initial imaging of choice — distinguishes obstruction (hydronephrosis), assesses kidney size (small kidneys = CKD) and echogenicity. Renal biopsy is reserved for unexplained intrinsic AKI, suspected RPGN/vasculitis, or AKI not recovering as expected.

High-yield: Newer biomarkers detect injury earlier than creatinine — NGAL, KIM-1, cystatin C, IL-18. NGAL (neutrophil gelatinase-associated lipocalin) is the most discussed in exams.

Management

General principles

1. Treat the cause — restore perfusion (fluids/inotropes) in pre-renal; relieve obstruction in post-renal; stop the offending nephrotoxin in ATN/AIN.
2. Optimise volume — judicious fluids if hypovolaemic; diuretics/fluid restriction if overloaded (diuretics do not improve survival or renal recovery — only used to manage volume).
3. Stop nephrotoxins — NSAIDs, ACEi/ARB, aminoglycosides, contrast.
4. Dose-adjust drugs to renal function.
5. Avoid hyperkalaemia, treat acidosis, correct hyperphosphataemia.

High-yield: Low-dose ("renal-dose") dopamine, mannitol, loop diuretics and fenoldopam do NOT prevent AKI or improve outcomes — a frequently tested negative fact.

Management of hyperkalaemia (life-threatening)

ECG progression with rising K⁺: tall tented T waves → flattened/absent P waves → wide QRS → sine wave → ventricular fibrillation/asystole.

Stepwise approach — "Stabilise → Shift → Remove":

1. Stabilise the myocardium — IV calcium gluconate (10 mL of 10%) or calcium chloride. Onset 1–3 min; does NOT lower K⁺, only protects the heart. First drug given when ECG changes present.
2. Shift K⁺ into cells:
   • Insulin + dextrose (e.g. 10 units regular insulin with 25 g glucose) — most reliable shift, onset 15–30 min.
   • Salbutamol (nebulised β₂-agonist) — adjunct, onset ~30 min.
   • Sodium bicarbonate — only if significant metabolic acidosis.
3. Remove K⁺ from body:
   • Loop diuretics (if making urine).
   • Potassium binders — sodium/calcium polystyrene sulphonate (slow); newer patiromer, sodium zirconium cyclosilicate.
   • Dialysis — definitive, for refractory/severe hyperkalaemia.

High-yield: Calcium gluconate is cardioprotective but does not reduce serum potassium. Insulin–dextrose is the most effective rapid shifting agent. Memorise the first ECG change = peaked T waves.

Indications for emergency dialysis — mnemonic AEIOU

• A — Acidosis (severe metabolic, pH <7.1, refractory)
• E — Electrolytes (refractory hyperkalaemia >6.5 mEq/L or with ECG changes)
• I — Intoxication (dialysable: SLIME — Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol)
• O — Overload (fluid/pulmonary oedema refractory to diuretics)
• U — Uraemia (symptomatic — pericarditis, encephalopathy, bleeding; or urea very high)

High-yield: Uraemic pericarditis is an absolute indication for urgent dialysis. Absolute creatinine/urea numbers alone are not an indication — it is the complications that matter.

Contrast-induced nephropathy (CIN)

Defined as a rise in creatinine ≥0.5 mg/dL or ≥25% from baseline within 48–72 hours of iodinated contrast, peaking at 3–5 days. Risk factors: pre-existing CKD, diabetic nephropathy (highest risk), volume depletion, high contrast volume, concurrent nephrotoxins, age, heart failure.

Prevention (the cornerstone is hydration):

• IV isotonic saline (0.9% NaCl) before and after contrast — the single most effective measure.
• Use lowest volume of iso-osmolar/low-osmolar contrast.
• Stop nephrotoxins (NSAIDs, metformin held around procedure).
• N-acetylcysteine and sodium bicarbonate are of doubtful/no proven benefit (the large PRESERVE trial showed neither helps) — increasingly a "does not work" answer.

High-yield: Hold metformin at the time of contrast not because it is nephrotoxic but because AKI causes metformin accumulation → lactic acidosis.

Complications

• Hyperkalaemia (most immediately lethal), high anion gap metabolic acidosis, hyperphosphataemia, hypocalcaemia.
• Pulmonary oedema / volume overload.
• Uraemic complications — pericarditis, encephalopathy, platelet dysfunction with bleeding.
• Infection (leading cause of death in AKI).
• Progression to CKD; AKI is an independent risk factor for later CKD and cardiovascular disease.

Key differentials & special syndromes

Syndrome	Clue
Rhabdomyolysis	Crush injury/statins; very high CK, dark urine, dipstick "blood" positive but no RBCs, hyperkalaemia + hyperphosphataemia + hypocalcaemia + raised uric acid; FENa may be <1%
Tumour lysis syndrome	Post-chemotherapy; ↑K, ↑PO₄, ↑uric acid, ↓Ca; uric acid crystals
Hepatorenal syndrome	Advanced cirrhosis; very low urine Na (<10), FENa <1%, normal sediment, no improvement with volume; treat with terlipressin + albumin
Cardiorenal syndrome	Heart failure driving renal hypoperfusion/congestion
Atheroembolic (cholesterol embolism)	After angiography; blue toes, livedo, eosinophilia, low complement
Cast nephropathy (myeloma)	Older patient, bone pain, anaemia, hypercalcaemia, Bence-Jones protein; dipstick negative for protein but urine protein high

High-yield: In rhabdomyolysis the urine dipstick is positive for blood but microscopy shows no red cells — the dipstick detects myoglobin. Management is aggressive IV fluids (target good urine output); routine urinary alkalinisation/mannitol are not clearly beneficial.

Recently asked / exam angle

• KDIGO staging numbers (1.5–1.9× = stage 1; ≥3× or creatinine ≥4 = stage 3) — direct factual MCQs.
• FENa calculation given a set of urine/plasma sodium and creatinine values, and identifying that <1% = pre-renal; plus the exceptions (contrast, GN, rhabdomyolysis) where FENa is low despite intrinsic injury.
• Muddy brown casts → ATN; RBC casts → GN; WBC casts → AIN/pyelonephritis — image/clinical vignette style.
• First-line drug in hyperkalaemia with ECG changes = IV calcium gluconate; first ECG change = peaked T waves.
• AEIOU indications for dialysis; uraemic pericarditis as an absolute indication.
• Contrast nephropathy prevention = IV saline hydration; NAC/bicarbonate "no longer recommended"; metformin and lactic acidosis link.
• Negative facts: renal-dose dopamine, mannitol and loop diuretics do not prevent AKI.
• FEUrea (<35% pre-renal) used when the patient is on diuretics.
• NGAL as the early biomarker of tubular injury.

Rapid revision

1. AKI = creatinine rise ≥0.3 mg/dL in 48 h, or ≥1.5× baseline in 7 days, or urine <0.5 mL/kg/h for 6 h (KDIGO).
2. Starting RRT = automatically KDIGO stage 3.
3. Pre-renal is the commonest overall cause; ATN is the commonest intrinsic cause.
4. FENa <1% = pre-renal; >2% = ATN; use FEUrea <35% if on diuretics.
5. FENa is paradoxically low in contrast nephropathy, glomerulonephritis and rhabdomyolysis.
6. Muddy brown granular casts = ATN; RBC casts = GN; WBC casts/eosinophiluria = AIN.
7. Renal ultrasound is the initial imaging — rules out obstruction, assesses kidney size.
8. Hyperkalaemia: first ECG change = peaked T waves; first drug with ECG changes = IV calcium gluconate (protects heart, doesn't lower K⁺); insulin–dextrose is the best shifter.
9. Dialysis indications = AEIOU; uraemic pericarditis is an absolute indication.
10. Contrast nephropathy: peaks at 3–5 days; prevent with IV isotonic saline; NAC/bicarbonate not recommended; hold metformin (lactic acidosis risk).
11. Rhabdomyolysis: dipstick blood positive, no RBCs on microscopy; treat with aggressive fluids.
12. Renal-dose dopamine, mannitol and loop diuretics do NOT prevent or treat AKI — diuretics only manage fluid overload.