Acute Kidney Disease

Acute kidney disease is abnormal kidney function or structure lasting 7 to 90 days after an initiating insult. It occupies the interval between acute kidney injury (the first 7 days) and chronic kidney disease (more than 90 days), and it is a time window diagnosis: function has not recovered by day 7, but chronicity cannot yet be declared.

Operational criteria, any one of which is sufficient:

• Acute kidney injury criteria persisting beyond 7 days
• GFR below 60 mL/min/1.73 m2 for less than 3 months
• Fall in GFR of 35% or more, or rise in serum creatinine of more than 50% from baseline, within 3 months
• Markers of kidney damage (albuminuria, glomerular haematuria, structural abnormality) for less than 3 months

Common substrates are unresolved ischaemic or septic acute tubular injury, acute interstitial nephritis, glomerulonephritis, thrombotic microangiopathy, persisting obstruction, renal vascular disease and cardiorenal haemodynamic injury.

The window matters because it is when the cause can still be reversed: stopping a nephrotoxin, relieving obstruction, starting immunosuppression for a biopsy proven lesion. A substantial minority of patients who survive acute kidney injury have persistent dysfunction at 90 days, and the risk of progression to chronic kidney disease, end stage kidney disease, cardiovascular events and death rises with each additional week of non-recovery and with each episode of injury.

Many patients are asymptomatic and are identified only through persistently raised creatinine. Presentation is otherwise that of the underlying cause.

• Recovering tubular injury: polyuria with urine output above 3 L daily, risking volume depletion, hypokalaemia, hypomagnesaemia and hypophosphataemia
• Persisting oliguria (below 0.5 mL/kg/h) or anuria in obstruction, cortical necrosis or severe tubular injury
• Oedema, hypertension and frothy urine suggest glomerular disease
• Rash, fever, arthralgia and eosinophilia suggest interstitial nephritis or vasculitis
• Weight loss, bone pain and anaemia suggest myeloma

Red flags: potassium above 6.0 mmol/L, bicarbonate below 15 mmol/L, haemoptysis, palpable purpura, red cell casts, schistocytes with thrombocytopenia, oliguria below 0.3 mL/kg/h for 24 hours or more, and no improvement in creatinine after 14 days without an explanation.

Measure creatinine, urea, electrolytes and bicarbonate at least twice weekly during the first 2 weeks, then weekly until stable.

First line tests:

• Urinalysis with microscopy: muddy brown granular casts in tubular injury, white cell casts in interstitial nephritis, red cell casts and dysmorphic red cells in glomerulonephritis
• Urine albumin:creatinine and protein:creatinine ratios
• Full blood count and film (schistocytes), reticulocytes, LDH, haptoglobin, creatine kinase
• Renal ultrasound: hydronephrosis, kidney length (below 9 cm favours chronicity), cortical echogenicity, asymmetry above 1.5 cm

Second line tests when the cause is unclear: complement C3 and C4, ANCA, anti-GBM antibody, antinuclear antibody, serum protein electrophoresis with free light chains, hepatitis B, hepatitis C and HIV serology, urine eosinophils (low sensitivity).

Kidney biopsy is indicated when there is no recovery by day 7 to 14 without a clear tubular cause, an active urinary sediment, nephrotic range proteinuria, or suspected interstitial nephritis, paraprotein disease or vasculitis.

Differentials:

• Acute-on-chronic kidney disease: prior creatinine, small echogenic kidneys, anaemia, raised PTH, vascular calcification
• Prerenal azotaemia: urine sodium below 20 mmol/L, fractional excretion of sodium below 1%, recovery within 48 to 72 hours of volume restoration
• Obstruction: hydronephrosis, residual bladder volume above 200 mL after voiding

First line

• Relieve any obstruction: urethral or suprapubic catheter for bladder outlet obstruction, nephrostomy or ureteric stent for upper tract obstruction.
• Restore euvolaemia. If hypovolaemic, give a balanced crystalloid in 250 to 500 mL aliquots over 15 to 30 minutes and reassess after each. If overloaded, give furosemide 40 to 80 mg intravenously, doubling the dose after 2 hours if urine output is less than 100 mL/h.
• Withdraw nephrotoxins: NSAIDs, aminoglycosides, contrast, proton pump inhibitors, vancomycin. Hold ACE inhibitors, angiotensin receptor blockers, SGLT2 inhibitors, metformin and diuretics until creatinine is stable on two consecutive measurements.
• Adjust renally cleared drugs to the current eGFR.
• Metabolic acidosis with bicarbonate below 22 mmol/L: sodium bicarbonate 500 mg to 1 g orally two to three times daily, titrated to bicarbonate 22 to 26 mmol/L.
• Mean arterial pressure at least 65 mmHg in the acutely unwell; in the stable patient with albuminuria, target below 130/80 mmHg once recovered.

Hyperkalaemia (potassium above 6.0 mmol/L)

• Calcium gluconate 10%, 10 mL intravenously over 10 minutes if there are ECG changes; repeat after 10 minutes if changes persist.
• Insulin soluble 10 units with glucose 25 g intravenously; monitor glucose hourly for 6 hours.
• Salbutamol 10 to 20 mg nebulised.
• Sodium zirconium cyclosilicate 10 g orally three times daily for up to 48 hours, then 10 g daily.

Specialist

• Biopsy directed treatment: methylprednisolone 500 mg to 1 g intravenously daily for 3 days for crescentic glomerulonephritis or biopsy proven interstitial nephritis, then prednisolone 0.5 to 1 mg/kg daily (maximum 60 mg) tapered over 6 to 8 weeks.
• Revascularisation or thrombolysis for renal artery occlusion within hours of onset.

Emergency: renal replacement therapy when potassium is above 6.5 mmol/L refractory to medical treatment, pH is below 7.15, there is fluid overload unresponsive to diuretics, uraemic pericarditis or encephalopathy, or a dialysable toxin is present.

Follow up

• Repeat creatinine, eGFR and albumin:creatinine ratio at 90 days. If abnormal, the diagnosis becomes chronic kidney disease and staging begins.
• Restart ACE inhibitor or angiotensin receptor blocker once creatinine is stable and potassium is below 5.0 mmol/L, rechecking creatinine and potassium at 1 to 2 weeks.
• Refer to nephrology when creatinine has not returned to within 20% of baseline by day 14, or at any time if potassium is above 6.0 mmol/L, oliguria persists or an active urinary sediment is present.