Oxalate Nephropathy

Oxalate nephropathy is kidney injury from deposition of calcium oxalate crystals in the tubules and interstitium, producing acute or chronic kidney disease.

• Causes: enteric hyperoxaluria (jejuno-ileal bypass, Roux-en-Y gastric bypass, short bowel syndrome, Crohn disease, pancreatic insufficiency, chronic diarrhoea, orlistat), primary hyperoxaluria (types 1 to 3), ethylene glycol poisoning, excessive oxalate intake (star fruit, rhubarb, spinach, tea, peanuts, vitamin C above 2 g daily or high dose IV), Aspergillus niger infection, vitamin C and low calcium intake.
• Fat malabsorption binds calcium, leaving soluble oxalate free for absorption in the colon.
• Risk factors: chronic kidney disease, volume depletion, antibiotics (loss of oxalate degrading gut bacteria).

Acute or subacute kidney injury with little proteinuria, or progressive chronic kidney disease; flank pain; recurrent kidney stones; anaemia.

• Ethylene glycol poisoning: intoxication, vomiting, seizures, coma, high anion gap metabolic acidosis within hours, then renal failure at 24 to 72 hours.
• Primary hyperoxaluria: recurrent stones from childhood, nephrocalcinosis, systemic oxalosis (bone pain, fractures, arrhythmia, retinopathy, neuropathy, heart block, skin ulcers).
• Differential diagnosis: acute tubular necrosis, acute interstitial nephritis, uric acid nephropathy, phosphate nephropathy, hypercalcaemic nephropathy, cystinosis, nephrocalcinosis, other stone diseases.
• Complications: kidney failure, systemic oxalosis, bone disease, cardiac conduction defects, recurrent stones, death.

Creatinine, eGFR, bicarbonate and anion gap, serum calcium, urinalysis (envelope or dumbbell shaped calcium oxalate crystals), urine oxalate on a 24-hour sample (above 0.5 mmol/day or 45 mg/day), urine citrate, and plasma oxalate (in kidney failure).

• Ethylene glycol: osmolar gap, anion gap acidosis, ethylene glycol level, urine calcium oxalate crystals, hypocalcaemia.
• Renal ultrasound or CT (echogenic cortex, nephrocalcinosis); kidney biopsy shows birefringent calcium oxalate crystals under polarised light with tubular injury.
• Stool fat (steatorrhoea), faecal elastase, small bowel imaging; genetic testing (AGXT, GRHPR, HOGA1) for primary hyperoxaluria.

Supportive: stop offending diet, vitamin C and orlistat; hydration to urine volume above 2.5 L daily; low oxalate and low fat diet; avoid high dose ascorbic acid.

Pharmacological

• Enteric hyperoxaluria: calcium carbonate or citrate 1 to 1.5 g with each meal (binds oxalate in the gut), low fat diet (40 g or less daily), cholestyramine 4 g with meals, potassium citrate 30 to 60 mmol daily, pancreatic enzymes (pancrelipase 25,000 to 40,000 lipase units with meals), treat the underlying bowel disease.
• Primary hyperoxaluria type 1: pyridoxine 5 to 20 mg/kg/day (responsive in about 30 percent), lumasiran 3 mg/kg SC monthly for 3 doses then every 3 months (body weight bands), fluid intake 3 L/m2 daily, potassium citrate 0.1 to 0.15 g/kg/day.
• Ethylene glycol poisoning: fomepizole 15 mg/kg IV loading dose then 10 mg/kg every 12 hours for 4 doses then 15 mg/kg every 12 hours until ethylene glycol level is below 0.3 g/L (or ethanol 10 percent IV 0.6 g/kg loading then 66 mg/kg/h as alternative), sodium bicarbonate for acidosis, pyridoxine 100 mg and thiamine 100 mg IV daily, calcium for symptomatic hypocalcaemia.
• Hyperkalaemia: calcium gluconate 10 percent 10 mL IV over 10 minutes for ECG changes, insulin 10 units with 25 g glucose IV, and salbutamol 10 to 20 mg nebulised; acidosis: sodium bicarbonate for pH below 7.1; dialysis if refractory.

Procedures

• Haemodialysis, intensive and frequent (daily) when oxalate burden is high; haemodialysis for ethylene glycol poisoning with acidosis, renal failure or level above 0.5 g/L.
• Liver transplant or combined liver-kidney transplant for primary hyperoxaluria type 1; kidney transplantation for other causes after correction of enteric disease.
• Surgical reversal of bariatric bypass in selected cases.

Special groups: children (primary hyperoxaluria), patients with bariatric surgery (calcium with meals, avoid high oxalate food), patients on chronic high dose vitamin C (stop).

Red flags: anion gap acidosis, oliguria, systemic oxalosis, creatinine doubling, ethylene glycol ingestion.

Follow-up: creatinine, urine oxalate and eGFR every 3 months; stone imaging yearly; nephrology review.