Acute kidney injury, including acute tubular necrosis
Description
- Abrupt fall in GFR over hours to days, with retention of nitrogenous waste and dysregulation of volume and electrolytes
KDIGO staging - creatinine OR urine output, whichever is worse
| Stage | Creatinine | Urine output |
|---|---|---|
| 1 | 1.5-1.9x baseline, OR rise >=26.5 micromol/L in 48h | <0.5 mL/kg/h for 6-12 h |
| 2 | 2.0-2.9x baseline | <0.5 mL/kg/h for >12 h |
| 3 | >=3x baseline, OR rise to >=353.6 micromol/L, OR initiation of RRT | <0.3 mL/kg/h for >=24 h, or anuria >=12 h |
- Creatinine is a late and insensitive marker - GFR may have halved before it moves
- Oliguria = <0.5 mL/kg/h; anuria (<50 mL/day) means obstruction, vascular catastrophe, or severe cortical necrosis until proven otherwise
Three buckets - the framework for every case
- Pre-renal (~40-70%) - hypoperfusion, tubules intact, reversible on restoring perfusion
- Intrinsic (~10-50%) - ATN >> AIN > glomerular > vascular
- Post-renal (~5-10%) - obstruction; must be excluded in everyone, it is the one that is fully reversible
Epidemiology
- 10-20% of hospital admissions; ~50% of ICU admissions
- ATN accounts for ~45% of hospital-acquired AKI; pre-renal ~20%
- Community-acquired AKI: mostly pre-renal and obstructive
- Mortality: stage 3 AKI in ICU ~40-50%; AKI needing dialysis in ICU >50%
- Risk factors: age >65, CKD, diabetes, heart failure, cirrhosis, sepsis, major surgery, nephrotoxins
Aetiopathogenesis
Pre-renal
- True volume depletion - haemorrhage, GI losses, burns, diuretics, poor intake
- Reduced effective circulating volume - heart failure, cirrhosis (hepatorenal syndrome), nephrotic syndrome, sepsis
- Drugs altering glomerular haemodynamics - NSAIDs (afferent constriction), ACEi/ARB (efferent dilatation), calcineurin inhibitors
- Renovascular - bilateral renal artery stenosis, abdominal compartment syndrome
Intrinsic - ATN
- Ischaemic - prolonged pre-renal state, sepsis, hypotension, cardiac surgery
- Proximal tubule (S3 segment) and thick ascending limb of the outer medulla are most vulnerable - highest metabolic demand, lowest O2 tension
- Nephrotoxic
- Aminoglycosides - ATN in 10-20%; filtered, then taken up into proximal tubular cells via megalin -> lysosomal injury. Non-oliguric, day 5-10, with Mg2+ and K+ wasting
- Adefovir, cidofovir, indinavir, zoledronate, tenofovir disoproxil, cisplatin, amphotericin B - direct proximal tubular toxicity
- Radiocontrast, vancomycin (uromodulin cast formation)
- Endogenous pigment/protein
- Rhabdomyolysis - myoglobin: tubular obstruction + direct toxicity + vasoconstriction. CK >5000, urine dipstick blood-positive with no RBCs on microscopy
- Haemolysis; myeloma cast nephropathy (free light chains + uromodulin)
- Tumour lysis syndrome - urate and calcium-phosphate crystals
Intrinsic - non-ATN
- AIN - drugs (PPI, NSAID, beta-lactam, checkpoint inhibitors)
- Glomerular - RPGN (ANCA, anti-GBM, lupus, post-infectious, IgA)
- Vascular - TMA (HUS, TTP, aHUS, malignant HTN, scleroderma renal crisis, APS), cholesterol embolism (post-angiography, livedo, eosinophilia, low complement), large vessel occlusion
Post-renal
- Bladder outlet obstruction (prostate) is the commonest - always exclude first, it is quick and fully reversible
- Bilateral ureteric obstruction (stones, malignancy, retroperitoneal fibrosis, clot), or unilateral in a single functioning kidney
Why ATN takes weeks to recover
- Tubular cell death -> sloughing -> cast obstruction -> back-leak of filtrate
- Persistent afferent vasoconstriction and medullary congestion
- Repair requires tubular cell dedifferentiation, proliferation and redifferentiation - typically 1-3 weeks
Diagnosis
First three questions
- 1. Is it acute? Find an old creatinine. Small kidneys, anaemia, hyperphosphataemia, hypocalcaemia and hyperparathyroidism suggest chronicity
- 2. Is it obstructed? Bladder scan and renal ultrasound
- 3. Is it volume responsive?
Urine - the highest-yield test
| Finding | Cause |
|---|---|
| Bland urine | Pre-renal, obstruction, vascular |
| Muddy brown granular casts, renal tubular epithelial cells | ATN |
| Dysmorphic RBCs, RBC casts, proteinuria | Glomerulonephritis |
| Sterile pyuria, WCC casts | AIN, pyelonephritis |
| Crystals | Urate, oxalate (ethylene glycol), aciclovir, sulfa |
| Dipstick blood positive, no RBCs | Myoglobin or haemoglobin |
Urinary indices - pre-renal vs ATN
| Pre-renal | ATN | |
|---|---|---|
| FENa | <1% | >2% |
| FEurea (use if on diuretics) | <35% | >50% |
| Urine Na | <20 mmol/L | >40 mmol/L |
| Urine osmolality | >500 mosm/kg | <350 (isosthenuric) |
| Urine:plasma creatinine | >40 | <20 |
| Urea:creatinine ratio | inc (>100:1) | Normal |
- *FENa is unreliable with diuretics, CKD, contrast nephropathy, rhabdomyolysis, sepsis and early GN - all can give a low FENa with intrinsic disease*
Other
- UEC, K+, HCO3-, Ca, PO4, urate, CK, LDH, FBE, blood film, LFT, VBG
- UACR/UPCR on every AKI
- Immunology if intrinsic disease suspected: ANCA, anti-GBM, ANA, C3/C4, SPEP + serum free light chains, hepatitis serology
- Renal ultrasound within 24 h (immediately if obstruction or single kidney suspected)
- Biopsy if the cause is not clear after the above, or if RPGN is possible - a delayed biopsy in RPGN loses the kidney
Management
Immediate - the emergencies first
- Hyperkalaemia - ECG, IV calcium gluconate, insulin-dextrose, salbutamol, then removal (resonium/SZC, dialysis)
- Pulmonary oedema, severe acidosis, uraemic encephalopathy or pericarditis
Indications for urgent dialysis - AEIOU
- Acidosis (refractory, pH <7.1)
- Electrolytes (refractory hyperkalaemia)
- Intoxication (lithium, salicylate, methanol, ethylene glycol, metformin, theophylline - small Vd, low protein binding, water soluble)
- Overload (refractory pulmonary oedema)
- Uraemia (pericarditis, encephalopathy, bleeding)
- No creatinine or urea number mandates dialysis; and starting early does not improve outcomes (STARRT-AKI, AKIKI)
Then
- Optimise perfusion - balanced crystalloid to euvolaemia; assess volume status repeatedly, do not fluid-load reflexively
- Over-resuscitation causes venous congestion and worsens AKI
- Vasopressors (noradrenaline) once euvolaemic - restore renal perfusion pressure
- Relieve obstruction - catheter, nephrostomy, stent
- Stop nephrotoxins: NSAIDs, ACEi/ARB, diuretics, metformin, SGLT2i, aminoglycosides, contrast
- Dose-adjust every drug to the current (falling) function
- Treat sepsis; nutrition; avoid hypoglycaemia
Lesion-specific
- Rhabdomyolysis - aggressive isotonic fluid to urine output 200-300 mL/h; forced alkaline diuresis and mannitol are not proven
- RPGN - immunosuppression immediately (see anti-GBM, ANCA)
- AIN - stop the drug, corticosteroids
- TLS - rasburicase, fluids; avoid alkalinisation (promotes calcium-phosphate deposition)
- Hepatorenal syndrome - albumin + terlipressin
- TMA - plasma exchange (TTP), eculizumab/ravulizumab (aHUS)
- *Frusemide and low-dose dopamine do NOT prevent or treat AKI* - frusemide manages volume only
Recovery phase
- Post-ATN diuresis - polyuria with electrolyte wasting; replace K+, Mg2+, PO4 and match urine output
- Follow-up creatinine and UACR at 3 months - AKI is a defined CKD risk state
Associations
- Sepsis - the commonest single cause of AKI in hospital
- Cardiac surgery, major surgery, trauma, burns
- Heart failure (cardiorenal syndrome), cirrhosis (hepatorenal syndrome)
- CKD - the single strongest risk factor for AKI
- Diabetes, age >65, myeloma, malignancy, obstructive uropathy
- Nephrotoxins - NSAIDs, ACEi/ARB, aminoglycosides, vancomycin, contrast, cisplatin, calcineurin inhibitors
- Rhabdomyolysis - trauma, immobility, statins, seizure, stimulants, hyperthermia
- Intra-abdominal hypertension / abdominal compartment syndrome
Natural history & complications
- Pre-renal reverses within 24-72 h of restoring perfusion
- ATN: oliguric phase days to weeks -> polyuric recovery phase -> gradual return of concentrating ability over months
- Non-oliguric ATN has a substantially better prognosis than oliguric
- Cortical necrosis (obstetric catastrophe, severe sepsis) does not recover
Outcome
- Mortality of hospital AKI 20-30%; ICU stage 3 with dialysis >50%
- Death is usually from the precipitating illness, not the kidney
- ~15-30% do not fully recover baseline function; dialysis dependence in ~5-10% of severe AKI
AKI is not a discrete event
- Every AKI episode increases long-term risk of CKD, ESKD, cardiovascular disease and death - proportional to severity and number of episodes
- *AKI and CKD are bidirectional* - CKD predisposes to AKI, AKI accelerates CKD
- Discharge actions: medication reconciliation (which nephrotoxins to restart and when), written sick-day rules, follow-up creatinine and UACR at 3 months
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