Causes — ischaemic, toxic and septic
Ischaemic Atn
- Prolonged pre-renal AKI: hypovolaemia, haemorrhage, cardiogenic shock, severe heart failure, decompensated cirrhosis
- Major surgery (cardiac, vascular, transplant)
- Renal artery cross-clamping
- Severe sepsis (microcirculatory failure)
Nephrotoxic Atn
- Aminoglycosides (gentamicin, amikacin) — cumulative dose-dependent
- Iodinated contrast (now uncommon with modern low-osmolar agents — see contrast-induced nephropathy page)
- Cisplatin, ifosfamide, methotrexate (high dose)
- Amphotericin B
- Vancomycin (especially with concurrent piperacillin-tazobactam)
- Tenofovir disoproxil fumarate (TDF)
- Calcineurin inhibitors (tacrolimus, ciclosporin) — acute toxicity
- Heavy metals (lead, mercury, arsenic) — rare in modern UK
- Recreational: cocaine, MDMA, synthetic cannabinoids (often via rhabdomyolysis)
Pigment-induced
- Rhabdomyolysis — CK often >5,000 IU/L; myoglobin-induced
- Massive intravascular haemolysis — transfusion reaction, malaria, G6PD crisis
CRYSTAL-INDUCED (overlap with crystal nephropathy):
- Tumour lysis (uric acid)
- Aciclovir IV bolus
- Methotrexate
- Indinavir, atazanavir
- Ethylene glycol
Sepsis-associated Atn
- Now recognised as a distinct mechanism — microvascular injury, mitochondrial dysfunction
- Often without overt hypotension
Diagnosis
Clinical Context
- Hospitalised, post-operative, septic, recently administered nephrotoxin
- Acute rise in creatinine fulfilling KDIGO AKI criteria
- Failure to respond to a fluid challenge in pre-renal AKI strongly suggests transition to ATN
Urine
- Microscopy: muddy-brown granular casts and renal tubular epithelial cells (hallmark)
- Urine sodium >40 mmol/L (not on diuretics)
- Fractional excretion of sodium (FENa) >2% in oliguric ATN
- Fractional excretion of urea (FEUrea) >50% — useful when on diuretics
- Urine osmolality <450 mOsm/kg
- Mild proteinuria; absent/minor haematuria
Blood
- Rising creatinine, urea
- Hyperkalaemia, metabolic acidosis, hyperphosphataemia in advanced AKI
- Elevated CK, myoglobinuria in rhabdomyolysis
- Tumour lysis labs (urate, K, phosphate, Ca, LDH) in oncology
Imaging
- Ultrasound to exclude obstruction — within 24 hours of unexplained AKI (NICE NG148)
- Normal-sized non-dilated kidneys in ATN
When To Biopsy
- Failure to recover after 2-3 weeks of optimal supportive care
- Active urine sediment (red cells, casts) suggesting GN
- Suspected AIN (eosinophils, rash, drug exposure)
- Suspected TMA (low platelets, MAHA)
- Atypical clinical picture
Differential
- Pre-renal AKI (responds to volume; FENa <1%)
- Acute interstitial nephritis (white cell casts, eosinophils, drug history)
- Glomerulonephritis (red cell casts, heavy proteinuria, autoimmune features)
- Thrombotic microangiopathy (haemolysis, thrombocytopenia)
- Obstruction (hydronephrosis)
- Vascular: renal artery / vein thrombosis, cholesterol emboli
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
Management
GENERAL — KDIGO AKI BUNDLE:
- Stop all nephrotoxins (NSAIDs, ACE/ARB, aminoglycosides, diuretics where appropriate)
- Avoid iodinated contrast unless essential — use IV hydration if unavoidable
- Treat the precipitant: source control for sepsis, restore haemodynamics, relieve obstruction
- Maintain euvolaemia — under-resuscitation perpetuates ischaemia, over-resuscitation worsens outcomes
- Avoid hyperchloraemic acidosis from large-volume 0.9% saline; balanced crystalloids (Hartmann's, Plasma-Lyte) preferred in most settings
- Treat hyperkalaemia (calcium gluconate, insulin-dextrose, salbutamol, potassium binders)
- Treat acidosis (bicarbonate if severe; renal replacement therapy if refractory)
- Adjust drug doses for AKI (vancomycin, gentamicin, DOACs, opioids, gabapentinoids, metformin)
Nutrition
- Adequate calorie and protein intake — do not under-feed
- Avoid high-potassium and high-phosphate foods during oliguria
- Restrict fluids in fluid overload, allow free water in polyuric phase
RENAL REPLACEMENT THERAPY (RRT) — initiate when:
- Refractory hyperkalaemia
- Refractory metabolic acidosis
- Fluid overload not controlled medically
- Uraemic encephalopathy or pericarditis
- Some toxin removal (lithium, ethylene glycol, severe salicylate)
- Modality choice (intermittent HD vs CVVHDF) depends on haemodynamic stability — STARRT-AKI and IDEAL-ICU trials show no benefit of routine early RRT in critically ill AKI
Specific Scenarios
- Rhabdomyolysis: aggressive IV crystalloid (200-300 ml/h) to maintain urine output 200-300 ml/h; urinary alkalinisation controversial
- Tumour lysis: hydration, allopurinol (prophylaxis) or rasburicase (treatment/high risk)
- Sepsis: timely antibiotics, source control, balanced fluids, vasopressors (noradrenaline first-line)
- Cardiorenal: sequential nephron blockade for decongestion (see cardiorenal page)
Recovery, polyuric phase and long-term outlook
Recovery Phases
- Oliguric phase (days-weeks): low urine output, rising creatinine
- Polyuric phase: urine output can exceed 3-6 L/day as tubular function recovers ahead of concentrating ability
- Recovery phase: creatinine slowly falls, eGFR stabilises
POLYURIC PHASE — KEY POINTS:
- Replace 50-75% of urine losses with IV fluid containing sodium
- Monitor U&E every 6-12 hours initially
- Watch for hypokalaemia, hypomagnesaemia, hypophosphataemia
- Wean IV fluids as oral intake resumes
- Do not over-replace — perpetuates the diuresis
Long-term
- ~30-40% return to baseline kidney function
- Many have residual CKD; risk highest with prior CKD, age >65, sepsis, prolonged AKI
- AKI doubles long-term cardiovascular and mortality risk
- Follow-up: U&E, ACR, BP at 6 weeks and 3 months minimum
- Re-introduce ACE/ARB cautiously once eGFR stable; restart SGLT2 inhibitor in proteinuric residual CKD
- Refer to nephrology if persistent eGFR <60 or ACR ≥3 mg/mmol
- Patient education on nephrotoxin avoidance and sick-day rules
KEY MESSAGE: ATN is the everyday face of hospital AKI. Prevention (nephrotoxin stewardship, sepsis bundles, careful prescribing) and structured post-AKI follow-up matter more than any specific treatment in the acute phase.
