acute kidney injury
Classify by mechanism: prerenal (decreased perfusion), intrinsic (parenchymal damage), or postrenal (obstruction). Urine indices and sediment narrow the differential rapidly. Most hospital AKI is prerenal or ATN — the clinical question is which one, because the management diverges completely.
- focused history, volume/perfusion exam, and full medication reconciliation (including OTC NSAIDs, herbals, recent contrast)
- retrieve baseline creatinine (lowest stable value in prior 3 months) → distinguish new AKI from AKI-on-CKD
- bladder scan or point-of-care US → rule out obstruction first; if relieved, monitor for post-obstructive diuresis (>200 mL/h — replace ~half hourly output with half-normal saline)
- urine dip + microscopy (casts, cells) and urine lytes (Na, Cr, urea) → FeNa or FeUrea (use FeUrea if on diuretics)
- formal renal US if obstruction suspected, cause unclear, or to assess kidney size/echogenicity
- ECG if K⁺ >5.5 mmol/L → calcium gluconate for membrane stabilisation if ECG changes; treat hyperkalaemia before investigating
- hold nephrotoxins: NSAIDs, ACEi/ARB (hold in significant AKI; may cautiously continue in mild AKI/CRS), aminoglycosides, iodinated contrast
- renally dose-adjust all medications
- volume assessment → isotonic crystalloid if prerenal; diuresis if overloaded
- if active sediment (RBC casts, dysmorphic RBCs) → urgent nephrology consult + send ANA, ANCA, anti-GBM, C3/C4, SPEP/UPEP
- if suspected rhabdomyolysis → CK, aggressive IV crystalloid targeting UO 1–3 mL/kg/h (up to 300 mL/h)
- monitor urine output (Foley or strict I/O) and trend creatinine q12–24h
- consider RRT if refractory hyperkalaemia, acidosis, pulmonary oedema, or uraemic symptoms (AEIOU)
- hyperkalaemia — ECG immediately if K⁺ >5.5 mmol/L; treat before investigating
- pulmonary oedema with oliguria → urgent dialysis if not responding to diuretics
- urinary obstruction — bladder scan or point-of-care US; relief is the treatment
- rapidly progressive glomerulonephritis — active sediment + rapidly rising creatinine → nephrology same day; delay costs nephrons
- bilateral renal artery occlusion or renal vein thrombosis — consider in flank pain with anuria
KDIGO staging
| stage | creatinine criteria | urine output |
|---|---|---|
| 1 | rise ≥26.5 µmol/L in 48 h OR 1.5–1.9× baseline in 7 d | <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× baseline OR creatinine ≥353.6 µmol/L OR initiation of RRT | <0.3 mL/kg/h for ≥24 h OR anuria ≥12 h |
Baseline = lowest stable creatinine in preceding 3 months. If unavailable, use the admission value or back-calculate from eGFR 75 mL/min/1.73 m².
A “normal” creatinine does not exclude significant AKI. Urine output is often the earlier signal. In low-muscle-mass patients (elderly, cirrhotic, cachectic), creatinine underestimates the severity.
classification
prerenal (~60% of hospital AKI)
Reduced renal perfusion with intact tubules. Reversible if perfusion restored promptly; prolonged prerenal AKI becomes ATN.
Causes: hypovolaemia (haemorrhage, GI losses, burns), heart failure (cardiorenal), cirrhosis (hepatorenal syndrome), drugs reducing effective perfusion (ACEi/ARBs, NSAIDs, calcineurin inhibitors).
intrinsic
| compartment | examples |
|---|---|
| tubular (ATN, ~85% of intrinsic) | ischaemia (prolonged prerenal), nephrotoxins (aminoglycosides, contrast, myoglobin, tumour lysis syndrome) |
| interstitial (AIN) | drugs (PPIs, antibiotics, NSAIDs), infection, autoimmune — see AIN section below |
| glomerular | RPGN (anti-GBM, ANCA vasculitis, lupus nephritis, IgA) |
| vascular | TMA (TTP/HUS, malignant HTN), renal artery thrombosis/dissection, cholesterol emboli |
postrenal (~5–10%)
Obstruction at any level. Bilateral ureteral obstruction (or unilateral in a single kidney) → anuria. Causes: BPH (most common in older men), malignancy (pelvic, retroperitoneal), stones, neurogenic bladder, catheter obstruction.
Bladder scan or US is mandatory in any unexplained AKI — obstruction is the most treatable cause.
workup
urine studies — the first branch point
| test | prerenal | ATN |
|---|---|---|
| urine Na | <20 mmol/L | >40 mmol/L |
| FeNa | <1% | >2% |
| urine osmolality | >500 mOsm/kg | <350 mOsm/kg |
| sediment | bland or hyaline casts | muddy brown granular casts |
FeNa = (urine Na × plasma Cr) / (plasma Na × urine Cr) × 100.
On diuretics → use FeUrea instead (<35% = prerenal physiology). FeNa is also unreliable in CKD (chronically impaired Na reabsorption raises baseline FeNa), contrast exposure, myoglobinuria, and early obstruction. A “prerenal” FeNa does not exclude intrinsic disease — it reflects tubular sodium handling at that moment, not aetiology.
sediment — free diagnostic information
- Muddy brown granular casts → ATN
- WBC casts → AIN or pyelonephritis
- RBC casts → glomerulonephritis (urgent nephrology referral)
- Bland → prerenal, obstruction, or HRS
imaging
- Renal US — hydronephrosis (obstruction), kidney size (small = CKD, large = infiltration/amyloid/diabetes), echogenicity
- Bladder scan — post-void residual >200 mL suggests obstruction
further investigations by clinical context
- Suspected glomerulonephritis → ANA, ANCA, anti-GBM, C3/C4, SPEP/UPEP, hepatitis serologies
- Suspected TMA → blood film (schistocytes), LDH, haptoglobin, ADAMTS13
- Suspected rhabdomyolysis → CK, urine myoglobin
- Drug-induced AIN → stop offender; biopsy if no recovery by 5–7 days
management principles
prerenal
Volume resuscitation — balanced crystalloids (Ringer’s lactate preferred over normal saline). Target euvolaemia, not hypervolaemia. In cardiorenal syndrome → diuresis, not volume. In HRS → vasoconstrictors (see hepatorenal syndrome).
intrinsic
- ATN — supportive. Remove the cause, maintain euvolaemia, avoid further nephrotoxins. No pharmacological therapy accelerates recovery.
- AIN — see below.
- RPGN — immunosuppression urgently (pulse methylprednisolone ± cyclophosphamide or rituximab depending on cause). Plasma exchange for anti-GBM with pulmonary haemorrhage.
Across all stages: reconcile medications — renally dose-adjust, hold nephrotoxins (aminoglycosides, NSAIDs, ACEi/ARBs in the acute setting), and review contrast timing.
postrenal
Relieve the obstruction. Foley catheter for bladder outlet obstruction. Nephrostomy or ureteral stent for ureteral obstruction. Monitor for post-obstructive diuresis (>200 mL/h) — can lose litres of fluid; replace approximately half the hourly output with half-normal saline and reassess frequently.
specific aetiologies
acute interstitial nephritis
Drug-induced in >70% of cases. Onset typically 7–14 days after exposure but can be weeks to months (especially PPIs).
Common culprits: PPIs (most frequent cause by biopsy series), penicillins, cephalosporins, sulphonamides, fluoroquinolones, NSAIDs, allopurinol, phenytoin
Non-drug causes: sarcoidosis, Sjögren syndrome, IgG4-related disease, SLE (tubulointerstitial lupus), infections (Legionella, CMV, EBV, leptospirosis)
Clues: sterile pyuria, WBC casts, non-nephrotic proteinuria, eosinophilia (present in <50%), skin rash and fever (classic triad but uncommon). Urine eosinophils have poor sensitivity and specificity — do not rely on them.
Management: stop the offending drug — most recover within weeks. If no improvement by 5–7 days, consider prednisone 1 mg/kg (max 60 mg) tapered over 4–6 weeks. Biopsy if diagnostic uncertainty or to guide steroid decision. NSAIDs and PPI-induced AIN may have a more indolent course with incomplete recovery.
pigment nephropathy (rhabdomyolysis)
Myoglobin precipitates in tubules → direct toxicity and obstruction, compounded by renal vasoconstriction.
Clues: markedly elevated CK (typically >5000 U/L), dipstick positive for blood with zero RBCs on microscopy (dipstick detects haem in myoglobin), dark urine, hyperkalaemia, hyperphosphataemia, hyperuricaemia, severe hypocalcaemia (early)
Management:
- Aggressive IV crystalloid (target UO 200–300 mL/h) — the single most important intervention
- Do not replete asymptomatic hypocalcaemia — calcium deposits in damaged muscle and may cause rebound hypercalcaemia during recovery
- Monitor for compartment syndrome (the cause may also be the consequence)
- Dialysis if refractory hyperkalaemia or volume overload
contrast-associated AKI and cholesterol atheroemboli
Two post-procedural AKI syndromes separated by timeline. Contrast-associated AKI peaks 24–72 h post-contrast, is typically non-oliguric, and recovers over 7–14 days; prevention is isotonic hydration (1–3 mL/kg/h pre/post) and holding nephrotoxins — NAC has no benefit. Cholesterol atheroemboli presents days to weeks after vascular instrumentation with a subacute, often irreversible decline; look for livedo reticularis, blue toes, eosinophilia, and hypocomplementaemia. No specific treatment exists beyond supportive care and statin therapy.
In critically ill patients, creatinine fluctuations coinciding with contrast are often from haemodynamic instability, not contrast itself. Do not withhold necessary imaging — volume-optimise and proceed. This message bears repeating: the risk of delaying a necessary CT is almost always greater than the risk of contrast.
hepatorenal syndrome
Functional renal failure driven by splanchnic vasodilation in advanced cirrhosis with portal hypertension — no longer conceived as pure exclusion (see hepatorenal syndrome for full detail).
Diagnostic criteria: cirrhosis with ascites, AKI by KDIGO, no response to diuretic withdrawal + albumin volume challenge (1 g/kg, max 100 g — duration of 24 vs 48 h is contested), bland sediment, UNa <10 mmol/L, FeNa <0.2%, no shock or nephrotoxins, no parenchymal disease on US.
Management (Canadian practice):
- Albumin (20–40 g/d, titrate to euvolaemia — do not continue into overload) + norepinephrine (0.5–3 mg/h IV, titrated to MAP rise ≥10 mmHg) — first-line, requires monitored/ICU setting
- Midodrine + octreotide — substantially inferior; only when ICU-level care is unavailable
- Terlipressin — international standard but not marketed in Canada
- Bridge to liver transplant — the only definitive treatment
- Avoid lactulose-induced volume depletion (common precipitant)
renal replacement therapy
Indications (mnemonic AEIOU): Acidosis (refractory), Electrolytes (refractory hyperkalaemia), Ingestion (dialysable toxin), Overload (refractory pulmonary oedema), Uraemia (encephalopathy, pericarditis).
STARRT-AKI (NEJM 2020) — accelerated RRT initiation (within 12 h of KDIGO 3) vs standard strategy (wait for conventional indications): no mortality benefit from early initiation, and accelerated initiation had higher 90-day RRT dependence (10.4% vs 6.0%) and more adverse events. Start RRT for clinical indications, not for a creatinine number.
traps
- Creatinine alone misses early AKI — a patient can lose 50% of GFR before creatinine exceeds the upper limit of normal. Trend matters more than absolute value.
- Assuming AKI in CKD is “just progression” — always check for a reversible superimposed cause (obstruction, drugs, volume depletion).
- NSAIDs in a patient on ACEi + diuretic — the “triple whammy” that causes predictable prerenal AKI. NSAIDs block the afferent arteriole prostaglandin rescue; ACEi blocks the efferent compensation; diuretics reduce volume. Any two are risky; all three nearly guarantee trouble.
- Failing to check post-void residual — especially in older men and patients on anticholinergics. Obstruction is the most fixable cause and the most embarrassing to miss.
related: nephrotic syndrome · hepatorenal syndrome · diuretic therapy · tumour lysis syndrome · spontaneous bacterial peritonitis