Nephrology
Acute Kidney Injury
Pre-renal, intrinsic, and post-renal — three places a kidney can fail
AKI is a sudden drop in glomerular filtration — diagnosed when serum creatinine rises by 0.3 mg/dL in 48 hours, by 50% in 7 days, or urine output falls below 0.5 mL/kg/hr for 6 hours. It splits cleanly into pre-renal (poor perfusion), intrinsic (tubular or glomerular damage), and post-renal (obstruction), and that anatomy decides the work-up.
- KDIGO Stage 1Cr ×1.5–1.9 or UOP <0.5 mL/kg/hr × 6h
- Pre-renal share~60% of community AKI
- Hospital AKI~20% of admissions
- ICU AKI mortality~50%
- FENa cutoff<1% pre-renal, >2% ATN
- Long-term CKD risk~2× even after full Cr recovery
Interactive visualization
A nephron under each of the three failure modes — see how perfusion, tubular damage, and obstruction each shut down filtration.
Watch the 60-second explainer
A condensed visual walkthrough — narrated, captioned, under a minute.
The three anatomies of AKI
Glomerular filtration depends on three things in series: arrive (blood reaches the glomerulus under enough pressure), filter (the glomerulus and tubules are intact), and leave (urine drains down the ureter without obstruction). Pre-renal AKI breaks the first; intrinsic AKI breaks the second; post-renal AKI breaks the third. The clinical work-up rebuilds that picture in reverse — ultrasound first to rule out post-renal, urinalysis next to read tubular and glomerular injury, then perfusion assessment.
Pre-renal AKI — perfusion failure
~60% of community-acquired AKI. Causes: volume depletion (vomiting, diarrhea, hemorrhage, diuretics, burns), hypotension (sepsis, cardiogenic, distributive shock), local glomerular hemodynamics (NSAID-induced afferent constriction, ACE inhibitor-induced efferent dilation, bilateral renal artery stenosis, hepatorenal syndrome). The tubules are structurally intact — they just lack filtrate. They respond by aggressively reabsorbing water, sodium, and urea, which explains the diagnostic signature: BUN:Cr >20:1, FENa <1%, urine osmolality >500 mOsm/kg, bland sediment. Volume challenge that promptly drops creatinine confirms pre-renal physiology.
Worked clinical example — the post-op patient
A 72-year-old man, baseline creatinine 1.0 mg/dL (eGFR ~75), has a hip replacement. Pre-op he takes lisinopril 20 mg and meloxicam 15 mg. On post-op day 2 his creatinine is 1.7 mg/dL, urine output 280 mL over 12 hours (about 0.3 mL/kg/hr for an 80 kg man). KDIGO Stage 1 by both criteria. Urine Na is 12 mEq/L, FENa 0.5%, BUN 38, BUN:Cr ratio 22. The story: surgical blood loss + NSAID afferent constriction + ACE-inhibitor efferent dilation collapsed glomerular pressure. Held the lisinopril and meloxicam, 1 liter Lactated Ringer's bolus over 2 hours, then maintenance. By morning UOP was 1.4 mL/kg/hr; creatinine 1.1 by post-op day 4. Pure pre-renal, fully reversible — but a delayed call would have tipped into ischemic ATN.
Intrinsic AKI — the kidney itself
- Acute tubular necrosis (ATN). Most common intrinsic cause. Two pathways: ischemic (continuation of pre-renal — once perfusion is low enough, long enough, tubular cells die) and nephrotoxic (aminoglycosides accumulating in proximal tubule, IV contrast, cisplatin, myoglobin, hemoglobin). Hallmark sediment: muddy brown granular casts and renal tubular epithelial cells.
- Acute interstitial nephritis (AIN). Drug allergy — PPIs, NSAIDs, β-lactams, allopurinol. Eosinophiluria (50% sensitive), pyuria, white cell casts, rash, fever in classic but uncommon triad. Stop the drug; consider steroids.
- Glomerulonephritis. See the glomerulonephritis explainer — RBC casts and proteinuria distinguish it.
- Vascular. Renal artery thrombosis or embolism, cholesterol embolism (post-arteriography, livedo reticularis, eosinophilia), thrombotic microangiopathy (HUS, TTP).
Post-renal AKI — obstruction
~5–10% of AKI. Single-kidney patients can obstruct unilaterally; otherwise it requires bilateral obstruction or obstruction of a solitary functioning kidney. Causes: BPH (the commonest in older men), pelvic malignancy (cervix, bladder, prostate), retroperitoneal fibrosis or lymphoma, bilateral ureteral stones (rare), papillary necrosis. Pressure backs up: ureter → renal pelvis → tubules → glomerulus → drop in GFR. Bedside renal ultrasound shows hydronephrosis 85–95% of the time; false-negatives in early or encased (retroperitoneal mass) obstruction. Relief — Foley for bladder outlet, percutaneous nephrostomy or stent for ureter — restores filtration, often with a brisk post-obstructive diuresis (watch K, Mg, hypovolemia).
Pre-renal vs ATN vs post-renal
| Feature | Pre-renal | ATN (intrinsic) | Post-renal |
|---|---|---|---|
| Share of AKI | ~60% | ~30% | ~5–10% |
| Trigger | Volume loss, sepsis, NSAID, ACEi | Ischemia, nephrotoxins, rhabdo | BPH, stones, malignancy |
| BUN:Cr ratio | >20:1 | 10–15:1 | Variable |
| FENa | <1% | >2% | Variable (>1% if chronic) |
| Urine osmolality | >500 mOsm/kg | ~300 (isosthenuric) | ~300 |
| Urine sediment | Bland, hyaline casts | Muddy brown granular, RTE | Bland or crystals/blood |
| Imaging | Normal | Normal or echogenic | Hydronephrosis |
| Reversal | Hours with fluids | 1–3 weeks; ~25% don't recover | Immediate with drainage |
When AKI needs dialysis — AEIOU
- A — Acidosis. pH <7.1 not responsive to bicarbonate.
- E — Electrolytes. K >6.5 with ECG changes or unresponsive to medical therapy.
- I — Ingestion. Dialyzable toxins: methanol, ethylene glycol, lithium, salicylates, valproate, metformin.
- O — Overload. Pulmonary edema or anasarca unresponsive to diuretics.
- U — Uremia. Pericarditis, encephalopathy, platelet dysfunction with bleeding.
STARRT-AKI (2020) put a stake in "earlier is better" — accelerated RRT in critically ill AKI didn't improve 90-day mortality and led to more long-term dialysis dependence. Wait for an indication.
Common misconceptions
- "Normal creatinine = normal kidneys." Creatinine lags GFR by 24–48h. A patient with Cr 1.4 from baseline 0.6 has lost >50% of function — that's Stage 2 AKI.
- "Give furosemide to convert oliguric to non-oliguric AKI." Diuretics improve urine output without improving kidney function or survival — they only help if volume overloaded.
- "NSAIDs are safe occasionally." A single dose can tip CKD or volume-depleted patients into AKI within hours.
- "All contrast causes nephropathy." Modern low-osmolar contrast in well-hydrated patients with eGFR >30 is low risk; the contrast-induced nephropathy literature is increasingly skeptical of risk except in very advanced CKD.
- "AKI is reversible — back to baseline." Even Stage 1 AKI doubles long-term CKD and mortality risk. The episode leaves a permanent scar on tubular reserve.
Frequently asked questions
How is AKI diagnosed by KDIGO criteria?
KDIGO 2012 defines AKI by any of: rise in serum creatinine ≥0.3 mg/dL within 48 hours, rise to ≥1.5× baseline within 7 days, or urine output <0.5 mL/kg/hr for ≥6 hours. Staging: Stage 1 — Cr 1.5–1.9× baseline OR ≥0.3 mg/dL rise OR UOP <0.5 mL/kg/hr × 6–12h. Stage 2 — Cr 2.0–2.9× OR UOP <0.5 mL/kg/hr × ≥12h. Stage 3 — Cr ≥3× baseline, Cr ≥4.0 mg/dL, anuria ≥12h, or initiation of renal replacement therapy.
How do you tell pre-renal from intrinsic AKI?
Both raise BUN and creatinine. The classic separators: BUN:Cr ratio (>20:1 favors pre-renal, where tubules avidly reabsorb urea), fractional excretion of sodium (FENa <1% in pre-renal versus >2% in ATN — tubules can't conserve Na when injured), urine osmolality (>500 mOsm in pre-renal, ~300 in ATN), urine sediment (bland in pre-renal, muddy brown granular casts in ATN). Diuretic use confounds FENa — switch to fractional excretion of urea (<35% pre-renal). Volume challenge that promptly improves creatinine confirms pre-renal.
What drugs cause AKI?
NSAIDs constrict the afferent arteriole — disastrous in CKD or volume depletion. ACE inhibitors / ARBs dilate the efferent arteriole, dropping glomerular pressure. Iodinated contrast causes contrast-induced nephropathy 24–72h after exposure. Aminoglycosides accumulate in proximal tubule cells — non-oliguric ATN at 5–10 days. Vancomycin at troughs >20. Cisplatin, cyclosporine/tacrolimus, amphotericin B. Drug-induced interstitial nephritis — PPIs, β-lactams, allopurinol — presents with eosinophilia and rash.
What is acute tubular necrosis (ATN)?
ATN is the most common intrinsic AKI. The proximal tubule and thick ascending limb are most vulnerable — high ATP demand, blood supply downstream of the glomerulus. Triggers: prolonged ischemia (>30 min of hypotension), nephrotoxins, pigment nephropathy. Urinalysis shows muddy brown granular casts. Recovery passes through oliguric (1–3 weeks) and polyuric (days, watch for hypokalemia) phases; ~50% recover full function, ~25% partial, ~25% don't recover and progress to CKD or ESRD.
When does AKI need urgent dialysis?
The mnemonic AEIOU — Acidosis (pH <7.1 refractory), Electrolytes (K >6.5 with ECG changes or refractory), Ingestion (dialyzable toxins — methanol, ethylene glycol, salicylate, lithium), Overload (pulmonary edema unresponsive to diuretics), Uremia (pericarditis, encephalopathy, bleeding). STARRT-AKI (2020, NEJM) showed accelerated RRT didn't improve 90-day mortality versus standard timing.
Does AKI fully reverse?
Often partially. Mortality in hospitalized AKI ~20%; ICU AKI ~50%. Among survivors, ~20–30% develop or progress to CKD at one year; risk doubles even after complete creatinine recovery. Follow-up creatinine, eGFR, and urine albumin-creatinine ratio at 3 and 12 months are recommended after KDIGO Stage 2 or 3 AKI.
What does oliguria mean and when is it dangerous?
Oliguria = urine output <0.5 mL/kg/hr in adults (about <400 mL/day for a 70 kg adult). Anuria = <100 mL/day, often signaling complete obstruction, cortical necrosis, or vascular catastrophe. Bedside steps: Foley catheter to rule out retention, bladder scan, renal ultrasound for hydronephrosis (sensitivity 85–95% for obstruction). Pure pre-renal physiology usually responds to a 500–1000 mL crystalloid bolus within 1–2 hours.