Acute Uric Acid Nephropathy

Acute uric acid nephropathy is acute kidney injury caused by precipitation of uric acid crystals in the renal tubules and collecting ducts, obstructing flow.

• The most common cause is tumour lysis syndrome after chemotherapy for leukaemia and lymphoma (including Burkitt lymphoma, which is frequent in Kenyan children), but it may occur spontaneously in bulky tumours.
• Other causes: rhabdomyolysis, severe exercise, heat stroke, status epilepticus, haemolysis, severe volume depletion, and treatment with uricosuric drugs.
• Acidic urine (pH below 5.5), low urine volume and very high urinary uric acid favour crystallisation.

Oliguria or anuria, flank pain, nausea, vomiting, lethargy, haematuria, crystalluria.

• Tumour lysis syndrome features: hyperkalaemia (arrhythmia), hyperphosphataemia, hypocalcaemia (tetany, seizures), hyperuricaemia, lactic acidosis.
• Differential diagnosis: other causes of acute kidney injury with malignancy (acute tubular necrosis, sepsis, nephrotoxic drugs, myeloma cast nephropathy, leukaemic infiltration, obstruction), calcium phosphate nephropathy, rhabdomyolysis.
• Complications: acute kidney injury, life threatening hyperkalaemia, cardiac arrhythmia, seizures, fluid overload, need for dialysis, and death.

Serum uric acid very high (usually above 0.7 mmol/L or 12 mg/dL), creatinine, potassium, phosphate, calcium, lactate dehydrogenase, bicarbonate, full blood count.

• Urine uric acid-to-creatinine ratio above 1 mg/mg (above 0.75 mmol/mmol) in a spot sample supports uric acid nephropathy over other causes; urine microscopy shows rhomboid or rosette uric acid crystals at acidic pH.
• Renal ultrasound (enlarged echogenic kidneys); ECG for hyperkalaemia.
• Samples for uric acid measurement on rasburicase must be placed on ice and analysed promptly.

Supportive

• Prevention in patients at risk: vigorous hydration with isotonic saline (2.5 to 3 L/m2/day or 3 L daily in adults) beginning 24 to 48 hours before chemotherapy to keep urine output at 100 mL/m2/h or higher (above 2 L daily).
• Monitor potassium, calcium, phosphate, uric acid and creatinine every 4 to 6 hours in high risk patients, with cardiac monitoring.
• Urinary alkalinisation is not advised since it promotes calcium phosphate precipitation.

Pharmacological

• Rasburicase 0.2 mg/kg IV over 30 minutes daily for 1 to 7 days (often a single dose of 3 to 6 mg suffices); contraindicated in glucose-6-phosphate dehydrogenase deficiency (haemolysis, methaemoglobinaemia); check for G6PD status first.
• Allopurinol 300 to 600 mg daily orally (100 mg/m2 three times daily in children; maximum 800 mg daily) beginning 2 to 3 days before chemotherapy, with dose reduction in renal impairment (100 mg daily if eGFR below 20); continue until risk has passed.
• Febuxostat 40 to 80 mg daily for patients intolerant of allopurinol.
• Furosemide 40 to 80 mg IV if volume overloaded and the urine output is falling.
• Hyperkalaemia: calcium gluconate 10 percent 10 mL IV, insulin 10 units with 25 g glucose, salbutamol 10 to 20 mg nebulised, sodium zirconium cyclosilicate 10 g three times daily.
• Hyperphosphataemia: avoid phosphate; phosphate binder (calcium carbonate 500 mg to 1 g with meals or sevelamer 800 mg three times daily).
• Hypocalcaemia is treated only if symptomatic (calcium gluconate 10 percent 10 mL IV over 10 minutes).

Procedures: haemodialysis or continuous venovenous haemofiltration for refractory hyperkalaemia, phosphate above 3 mmol/L, symptomatic hypocalcaemia, oliguria and fluid overload, or creatinine rising; dialysis removes uric acid efficiently.

Special groups: children with Burkitt lymphoma or leukaemia (high risk; rasburicase and hydration), G6PD deficiency (allopurinol and hydration only), pregnancy (specialist care).

Red flags: potassium above 6.0 mmol/L, ECG changes, anuria, seizures, uric acid above 0.7 mmol/L.

Follow-up: daily creatinine, electrolytes and uric acid until stable; kidney function at 3 months; prophylaxis before each chemotherapy cycle.