Medicine chapters
Acute kidney injury: prerenal, intrinsic and postrenal (incl. hepatorenal syndrome)
How to define and stage acute kidney injury, sort it into prerenal, intrinsic and postrenal causes with urine tests and ultrasound, and manage it, including hepatorenal syndrome and obstruction.
- AKI is an abrupt fall in kidney function over hours to days, staged by creatinine rise and urine output (KDIGO stages 1–3).
- Causes are prerenal (poor perfusion; kidney tries to save salt and water: urine Na below 10–20, FENa below 1%), intrinsic (mostly ATN) or postrenal (obstruction, excluded by ultrasound).
- Hepatorenal syndrome is functional prerenal failure in cirrhosis with ascites: kidneys are normal, treat with albumin plus terlipressin; liver transplant cures it.
On this page
Overview
Acute kidney injury (AKI) is a sudden drop in kidney function, usually over hours or days, that is often reversible over days to weeks. It replaced the older term "acute renal failure".
It is recognised by a rising serum urea and creatinine, a falling urine output, or both. AKI is common in hospital (especially with sepsis, surgery and nephrotoxic drugs) and can kill through hyperkalaemia, pulmonary oedema and acidosis.
Think of causes in three boxes:
Think of the kidney as a water tap: no water reaching the tap (prerenal), a broken tap (intrinsic), or a blocked hose (postrenal).
- Prerenal: the kidney is normal but under-perfused.
- Intrinsic (renal): damage to tubules, interstitium, glomeruli or small vessels.
- Postrenal: the urine cannot get out (obstruction).
Definition and staging (KDIGO)
The KDIGO system grew out of the older RIFLE (Risk, Injury, Failure, Loss, End-stage) and AKIN criteria. It uses the worst of creatinine or urine output.
| Stage | Serum creatinine | Urine output |
|---|---|---|
| 1 | 1.5–1.9 × baseline, or a rise of 0.3 mg/dL (26.5 µmol/L) or more within 48 h | Under 0.5 mL/kg/h over 6–12 h |
| 2 | 2.0–2.9 × baseline | Under 0.5 mL/kg/h over 12 h or more |
| 3 | 3 × baseline, or creatinine ≥354 µmol/L (about 4 mg/dL), or starting dialysis (in under-18s, eGFR <35) | <0.3 mL/kg/h for 24 h, or anuria for 12 h or more |
Baseline creatinine 80 µmol/L; today 250 µmol/L
Ratio = 250 ÷ 80 = 3.1 × baseline
3 × baseline or more → KDIGO stage 3
Creatinine takes 48–72 hours to rise after an injury, so a "normal" creatinine on day one does not exclude AKI. Urine output falls earlier.
Non-renal changes: urea rises with GI bleeding and steroids and falls with liver failure or low protein intake; creatinine is low with small muscle mass, and trimethoprim or cimetidine raise it by blocking its tubular secretion.
Prerenal AKI (prerenal azotaemia)
Aetiology
The kidney is structurally normal, but blood flow to it falls and GFR drops.
| Mechanism | Examples |
|---|---|
| True hypovolaemia | Vomiting, diarrhoea, poor intake, burns, sweating, haemorrhage, diuretics, osmotic diuresis (hyperglycaemia), third-space loss (pancreatitis, peritonitis, bowel obstruction) |
| Low blood pressure without volume loss | Septic shock, cirrhosis (systemic vasodilatation) |
| Low cardiac output | Heart failure, myocardial infarction, cardiogenic shock, tamponade, arrhythmia |
| Drugs that impair autoregulation | NSAIDs (block afferent dilating prostaglandins), ACE inhibitors/ARBs (block efferent constriction), calcineurin inhibitors, amphotericin |
| Renal artery disease | Bilateral renal artery stenosis plus ACE inhibitor |
Normally the kidney keeps GFR steady over a wide range of blood pressure (autoregulation): prostaglandins and nitric oxide widen the afferent arteriole, and angiotensin II tightens the efferent arteriole. When these fail, or are blocked by drugs, GFR falls.
The classic "triple whammy" is an NSAID + ACE inhibitor (or ARB) + diuretic in a dehydrated patient. Each removes a defence of GFR.
Clinical presentation
- History of fluid loss, poor intake, sepsis or heart failure.
- Thirst, dizziness on standing, postural hypotension, tachycardia, low JVP, dry mucous membranes, cool peripheries (in hypovolaemia); warm peripheries in septic vasodilatation; raised JVP and oedema in cardiac failure.
- Oliguria with concentrated urine.
Laboratory investigations
In prerenal AKI the tubules work well, so they grab sodium and water to restore volume. In ATN the tubules are damaged and cannot.
| Test | Prerenal | Intrinsic (ATN) |
|---|---|---|
| Sodium in urine, mmol/L | <10 (often quoted <20) | >20 |
| Specific gravity | >1.020 | <1.010 (fixed) |
| Osmolality, mOsm/kg | >500 | <350 |
| FENa | <1% | >1% (often >2%) |
| BUN : creatinine ratio | High (>15) | Lower (<15) |
| Urine sediment | Bland, hyaline casts | Muddy brown granular casts, tubular cells |
FENa = (urine Na × plasma creatinine) ÷ (plasma Na × urine creatinine) × 100
Urine Na 10 mmol/L, plasma Na 140 mmol/L
Urine creatinine 10 mmol/L, plasma creatinine 0.2 mmol/L (200 µmol/L)
FENa = (10 × 0.2) ÷ (140 × 10) × 100 = 0.14% → below 1% → prerenal
Diuretics raise urine sodium and FENa, so a prerenal patient on furosemide can look like ATN. Use clinical volume assessment; no single urine test is reliable on its own.
Two other conditions give a low FENa despite not being simple dehydration: hepatorenal syndrome and early acute glomerulonephritis (tubules still work). Contrast nephropathy and rhabdomyolysis can also give a low FENa early.
Management of prerenal AKI
- Treat the cause. Most AKI has some hypovolaemia, so give prompt crystalloid. A 250 mL fluid challenge shows whether the blood pressure is fluid-responsive.
- Balanced crystalloids (Ringer's lactate, Plasma-Lyte) are preferred; large volumes of 0.9% saline can cause hyperchloraemic acidosis.
- Avoid hydroxyethyl starch: it worsens AKI.
- Stop nephrotoxins and drugs that lower GFR (NSAIDs, ACE inhibitors, ARBs, diuretics, metformin).
- Monitor pulse, BP, urine output (catheter), daily weight.
Corrected early, prerenal AKI recovers fully. Left uncorrected, it turns into ischaemic ATN.
Hepatorenal syndrome (HRS)
What it is
Kidney failure in a patient with advanced cirrhosis, portal hypertension and ascites (often jaundiced), in the absence of another cause. The kidneys are histologically normal: the failure is functional. Kidneys from such patients work when transplanted, and the patient's own kidneys recover after a liver transplant.
Mechanism
- Portal hypertension causes splanchnic and systemic vasodilatation, so effective arterial volume and BP fall.
- Renin, aldosterone, noradrenaline and ADH rise sharply and cause intense renal (pre-glomerular) vasoconstriction. GFR falls.
- Prostaglandins normally protect renal flow, which is why NSAIDs readily trigger HRS.
Precipitants
- Over-vigorous diuretics.
- Large-volume paracentesis without albumin.
- Spontaneous bacterial peritonitis and other infections.
- GI bleeding, diarrhoea (including lactulose excess).
- NSAIDs, nephrotoxins.
Features and diagnosis
- Low urine output with very low urine sodium (often <10 mmol/L), concentrated urine, bland sediment, no significant proteinuria or haematuria.
- No response to stopping diuretics and expanding volume with albumin.
- No shock, no nephrotoxins, normal kidneys on ultrasound.
- It is a diagnosis of exclusion; patients are not truly hypovolaemic.
Two clinical patterns are described: a rapidly progressive form (type 1, now called HRS-AKI), often after SBP, with very poor short-term survival, and a slower form (type 2) associated with diuretic-resistant ascites.
Management
- Stop diuretics and nephrotoxins; treat infection (SBP).
- Expand volume with IV albumin.
- Vasoconstrictor + albumin: terlipressin (or noradrenaline) with albumin improves kidney function in about half.
- Liver transplantation is the definitive treatment.
- Haemodialysis may bridge to transplant but is often difficult; survival depends on the liver.
Prevention: albumin with large-volume paracentesis and with antibiotics for SBP; antibiotic prophylaxis in selected patients.
HRS = prerenal physiology (low urine sodium, intact tubules) with normal kidney histology in a patient with cirrhosis and ascites. It does not respond to fluid alone.
Intrinsic (intrarenal) AKI: overview
| Site | Main causes |
|---|---|
| Tubules | Acute tubular necrosis (80–90% of intrinsic AKI): prolonged ischaemia, toxins (aminoglycosides, contrast, myoglobin, haemoglobin) |
| Interstitium | Acute interstitial nephritis (drugs: penicillins, NSAIDs, PPIs), pyelonephritis, crystal nephropathy (tumour lysis) |
| Glomeruli | Rapidly progressive glomerulonephritis, post-infectious GN, lupus |
| Vessels | Vasculitis, malignant hypertension, cholesterol emboli, HUS/TTP, pre-eclampsia, cortical necrosis |
ATN and interstitial nephritis are covered in their own chapter; glomerular causes in the glomerulonephritis chapters.
Postrenal AKI (obstruction)
Aetiology
Obstruction must affect both kidneys, or a single functioning kidney, to cause AKI.
| Level | Causes |
|---|---|
| Urethra / bladder neck (commonest) | Benign prostatic hyperplasia, prostate cancer, urethral stricture, blocked catheter, clots, posterior urethral valves (boys), anticholinergic drugs causing retention |
| Bladder | Bladder cancer, neurogenic bladder (spinal cord disease, diabetes) |
| Both ureters | Stones (in a single kidney), pelvic tumours (cervix, bladder, prostate, rectum), retroperitoneal fibrosis, lymphoma, accidental surgical ligation, schistosomiasis |
| Within the kidney | Crystals (uric acid in tumour lysis), papillary necrosis |
Presentation
- Complete anuria strongly suggests obstruction (or a vascular catastrophe).
- Fluctuating urine output, or polyuria alternating with oliguria (partial obstruction).
- Lower urinary tract symptoms, suprapubic pain, a palpable, dull bladder; loin pain with ureteric causes.
- Pelvic mass on rectal or vaginal examination.
Lab findings
- Raised urea and creatinine, hyperkalaemia, acidosis.
- Early: urine indices may look prerenal (FENa <1%). Later, when the tubules are damaged by back-pressure: FENa rises and the urine cannot be concentrated.
- Urinalysis may show blood (stones, tumour) or infection.
- Raised PSA with prostate disease.
Diagnosis
- Bladder scan or catheterisation: a large residual volume confirms outflow obstruction.
- Renal ultrasound is the key test: hydronephrosis (dilated pelvicalyceal systems). Absence of upper tract dilatation almost always excludes obstruction.
- CT shows stones, masses, lymph nodes and the level of the block.
- Antegrade or retrograde pyelography defines the site and allows drainage.
Ultrasound can be falsely negative very early, or when the collecting system is encased by tumour or retroperitoneal fibrosis.
Management
- Relieve the obstruction:
- Bladder outflow: urethral catheter; suprapubic catheter if this fails.
- Ureteric: percutaneous nephrostomy (ultrasound guided) or retrograde ureteric stent.
- An obstructed, infected kidney is an emergency: drain urgently and give IV antibiotics.
- Treat the cause later (prostate surgery, stone removal, tumour treatment).
- Dialysis may be needed in a very sick patient before definitive surgery.
Post-obstructive diuresis: after relief of bilateral obstruction, a large diuresis can follow (excreting retained salt, water and urea, with temporarily poor tubular reabsorption). It is usually self-limiting, but some patients lose a lot of sodium, water and potassium and need IV replacement. Monitor hourly urine output, electrolytes and weight.
Ultrasound for every unexplained AKI. Relieving an acute obstruction usually returns renal function to baseline.
Assessing a patient with AKI
Ask four questions: what is the volume status; is this acute or acute-on-chronic; is it prerenal, renal or postrenal; and is there an urgent complication (potassium, acidosis, pulmonary oedema, uraemic pericarditis or encephalopathy)?
Acute vs chronic
| Favours chronic kidney disease | Favours AKI |
|---|---|
| Small kidneys with thin, bright (echogenic) cortex on ultrasound | Normal or large kidneys |
| Long history of nocturia, itching, tiredness | Recent illness, drugs, surgery |
| Normocytic anaemia, raised PTH, renal bone disease | Previous creatinine normal |
| Old results showing raised creatinine | Rapid rise over days |
Kidneys stay normal or large in some chronic diseases: diabetic nephropathy, amyloidosis, polycystic kidneys, myeloma and HIV nephropathy. Normal size does not prove AKI.
Key tests
Urea, creatinine, electrolytes, venous gas, calcium, phosphate, CK, FBC, clotting and cultures; urine dipstick (blood and protein point to glomerular disease, and red cell casts mean glomerulonephritis); ECG and chest X-ray. If GN is possible: ANCA, anti-GBM, ANA, complement, ASO titre, then renal biopsy.
General management of AKI
- Early senior or renal review; high-dependency care if unwell.
- Fluid balance chart, daily weight; once euvolaemic, daily intake = urine output + other losses + about 500 mL insensible loss (more if febrile).
- Stop or adjust nephrotoxic and renally cleared drugs; take care with anticoagulants.
- Treat sepsis promptly with non-nephrotoxic antibiotics.
- Restrict salt and potassium; maintain nutrition (oral or nasogastric preferred).
- Diuretics help fluid overload but do not prevent AKI or improve survival. Low-dose ("renal") dopamine, mannitol and furosemide do not protect the kidney.
Hyperkalaemia
| Step | Treatment |
|---|---|
| 1. Protect the heart | 10 mL of 10% calcium gluconate IV over 5 min (repeat if ECG changes persist). It does not lower potassium. |
| 2. Shift K+ into cells | 50 mL of 50% glucose with 10 units of soluble insulin IV; check glucose. Salbutamol nebuliser may help. Sodium bicarbonate if severe acidosis (avoid in fluid overload). |
| 3. Remove K+ | Potassium binders (patiromer, sodium zirconium cyclosilicate, polystyrene resins), treat cause, dialysis if refractory. |
ECG progression: tall tented T waves → flat P waves and wide QRS → sine-wave pattern → VF or asystole.
Indications for urgent dialysis (AEIOU)
- Acidosis (severe, refractory metabolic acidosis).
- Electrolytes: refractory hyperkalaemia.
- Intoxication with dialysable drugs (lithium, salicylate, methanol, ethylene glycol).
- Overload: pulmonary oedema not responding to diuretics.
- Uraemia: pericarditis, encephalopathy, bleeding.
In unstable ITU patients, continuous venovenous haemofiltration (CVVHF) is usually preferred because it gives smoother fluid removal.
Recovery phase
Function usually improves after 1–3 weeks. GFR recovers before the tubules regain full reabsorptive power, so a polyuric (diuretic) phase follows, with risk of hypokalaemia, hyponatraemia and dehydration. Replace losses carefully.
Expect: the urine indices that separate prerenal from intrinsic AKI (urine sodium, osmolality, specific gravity, FENa) and why diuretics confuse them; the first investigation in unexplained AKI (ultrasound to exclude obstruction); renal size to tell AKI from CKD and the exceptions (diabetes, amyloid, polycystic kidney, myeloma); KDIGO creatinine and urine output cut-offs; ACE inhibitor in bilateral renal artery stenosis; hepatorenal syndrome features, precipitants and treatment with albumin and terlipressin; post-obstructive diuresis; first drug in hyperkalaemia with ECG changes; and the AEIOU indications for dialysis.
Quick revision
- AKI = rise in creatinine ≥26.5 µmol/L in 48 h or ≥1.5 × baseline in 7 days, or urine <0.5 mL/kg/h for 6 h.
- Prerenal: urine Na <20, FENa <1%, osmolality >500; ATN: urine Na >20, FENa >1%, osmolality <350, brown granular casts.
- Diuretics falsely raise urine Na and FENa.
- NSAID + ACE inhibitor + diuretic = triple whammy.
- Hepatorenal: cirrhosis + ascites, normal kidneys, low urine Na, no fluid response; albumin + terlipressin; liver transplant.
- Obstruction: ultrasound for hydronephrosis; catheter or nephrostomy; watch post-obstructive diuresis.
- Small kidneys = CKD (except diabetes, amyloid, PKD, myeloma).
- Hyperkalaemia with ECG change: calcium gluconate first, then insulin–glucose.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Fundamentals of Pathology).
FAQ
What is the single most useful test in unexplained acute kidney injury?
A renal tract ultrasound, because it shows obstruction (which is quickly reversible) and gives kidney size, which helps separate acute from chronic disease.
Why is the urine sodium low in prerenal AKI?
The tubules are healthy and respond to low perfusion by reabsorbing as much sodium and water as possible, so little sodium appears in the urine.
Is hepatorenal syndrome a kidney disease?
No. The kidneys are structurally normal; the failure comes from intense renal vasoconstriction caused by advanced liver disease, and it reverses after liver transplantation.
Does furosemide help AKI?
It can relieve fluid overload, but it does not prevent AKI, speed recovery or reduce mortality, and it can make urine sodium tests misleading.