Intrinsic Acute Kidney Injury

Intrinsic acute kidney injury is acute loss of kidney function caused by damage to the renal parenchyma: tubules, interstitium, glomeruli or vessels.

• Acute tubular necrosis (about 45 percent of hospital cases): ischaemic (prolonged hypoperfusion, sepsis, surgery) or toxic (aminoglycosides, vancomycin, amphotericin, cisplatin, radiocontrast, rhabdomyolysis, haemolysis, myeloma light chains, tenofovir, snake venom, herbal remedies).
• Acute interstitial nephritis: beta-lactams, NSAIDs, proton pump inhibitors, rifampicin, sulfonamides, quinolones, allopurinol, infections, sarcoidosis, autoimmune disease.
• Glomerular and vascular: acute glomerulonephritis, vasculitis, anti-glomerular basement membrane disease, thrombotic microangiopathy (haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura), malignant hypertension, cholesterol emboli, scleroderma crisis, renal vein thrombosis.
• Intratubular crystals: tumour lysis, acute uric acid nephropathy, methotrexate, acyclovir, myeloma cast nephropathy.

Oliguria (below 400 mL daily) or non-oliguria, oedema, hypertension, nausea, drowsiness, uraemic symptoms.

• Rhabdomyolysis: muscle pain, tea-coloured urine.
• Acute interstitial nephritis: fever, rash, eosinophilia, arthralgia, flank pain after a new drug.
• Glomerulonephritis: haematuria, red cell casts, hypertension, oedema.
• Differential diagnosis: prerenal and postrenal acute kidney injury, acute-on-chronic kidney disease, hepatorenal syndrome.
• Complications: hyperkalaemia, metabolic acidosis, hypocalcaemia followed by hypercalcaemia (rhabdomyolysis), fluid overload, uraemic encephalopathy, bleeding, infection, chronic kidney disease, end stage kidney disease (in 10 to 30 percent), and death.

Creatinine, urea, electrolytes, bicarbonate, calcium, phosphate, urate, creatine kinase, lactate dehydrogenase, full blood count, film (schistocytes), liver profile, glucose, drug levels (vancomycin, gentamicin).

• Urine microscopy: muddy brown granular casts (acute tubular necrosis), white cell casts and eosinophils (interstitial nephritis), red cell casts and dysmorphic red cells (glomerulonephritis); urine protein-to-creatinine ratio, myoglobin.
• Fractional excretion of sodium above 2 percent, urine sodium above 40 mmol/L, urine osmolality below 350 mOsm/kg, urine-to-plasma creatinine ratio below 20.
• Serology: ANCA, anti-glomerular basement membrane antibody, antinuclear antibody, complement C3 and C4, hepatitis B and C, HIV, antistreptolysin O, cryoglobulins, serum free light chains and protein electrophoresis.
• Ultrasound (normal or enlarged kidneys); renal biopsy for unexplained disease, suspected glomerulonephritis, interstitial nephritis or thrombotic microangiopathy, or failure to recover in 2 to 3 weeks.

Supportive: remove the cause, stop nephrotoxins, adjust drug doses, optimise volume and blood pressure, nutrition (protein 0.8 to 1.2 g/kg/day, 20 to 30 kcal/kg/day, potassium and phosphate restriction), avoid contrast, glucose control.

Pharmacological

• Hyperkalaemia: calcium gluconate 10 percent 10 mL IV, insulin 10 units with 25 g glucose, salbutamol 10 to 20 mg nebulised, binders; acidosis: sodium bicarbonate 1.26 percent IV.
• Volume overload: furosemide 40 to 120 mg IV (infusion 5 to 20 mg/h) in non-oliguric patients; do not use to prevent or treat acute tubular necrosis.
• Rhabdomyolysis: isotonic saline 1 to 1.5 L/h for the first hours then 200 to 300 mL/h to maintain urine output 200 to 300 mL/h until creatine kinase is below 5000 IU/L; treat hyperkalaemia early; avoid calcium unless symptomatic.
• Acute interstitial nephritis: stop the drug; prednisolone 1 mg/kg daily (maximum 60 mg) for 2 to 4 weeks then taper over 4 to 6 weeks if no improvement in 5 to 7 days.
• Rapidly progressive glomerulonephritis and vasculitis: methylprednisolone 500 to 1000 mg IV daily for 3 days then prednisolone 1 mg/kg daily, plus cyclophosphamide 15 mg/kg IV every 2 to 3 weeks (3 doses then every 3 weeks) or rituximab 375 mg/m2 weekly for 4 doses; plasma exchange (4 L daily for 14 days) for anti-glomerular basement membrane disease or severe ANCA vasculitis with dialysis dependence.
• Thrombotic thrombocytopenic purpura: daily plasma exchange plus prednisolone 1 mg/kg and caplacizumab or rituximab; haemolytic uraemic syndrome: supportive care and eculizumab for atypical disease.
• Tumour lysis and uric acid: rasburicase 0.2 mg/kg IV daily for up to 5 days, hydration.
• Myeloma cast nephropathy: dexamethasone 40 mg daily, bortezomib-based chemotherapy, hydration.
• Toxin removal: dialysis for lithium, methanol and ethylene glycol poisoning (fomepizole 15 mg/kg IV load then 10 mg/kg every 12 hours).
• Sepsis: appropriate antibiotics, avoiding aminoglycosides and vancomycin in high doses.

Procedures: renal replacement therapy (intermittent haemodialysis, continuous therapy, or peritoneal dialysis) for hyperkalaemia above 6.5 mmol/L, pH below 7.15, pulmonary oedema, uraemic pericarditis, encephalopathy or bleeding, intoxication, and urea above 40 mmol/L (about 240 mg/dL).

Special groups: children (peritoneal dialysis, dosing by weight), pregnancy (obstetric and renal care), HIV and tenofovir toxicity (replace the drug), snakebite (antivenom and dialysis).

Red flags: oliguria for more than 24 hours, potassium above 6.5 mmol/L, pulmonary oedema, uraemic encephalopathy, rapidly progressive glomerulonephritis.

Follow-up: daily creatinine and electrolytes; creatinine and urinalysis at 3 months; blood pressure control; avoid nephrotoxins; renal review annually if recovery is incomplete.