What are the treatment options for hyperoxaluria?

Treatment of Hyperoxaluria

All patients with hyperoxaluria require aggressive hyperhydration (3.5-4 L/day in adults, 2-3 L/m² body surface area in children) and potassium citrate (0.1-0.15 g/kg/day), with additional type-specific therapy determined by whether the hyperoxaluria is primary or secondary. 1, 2

Initial Conservative Management for All Types

Fluid Management

• Target fluid intake of 3.5-4 liters daily for adults and 2-3 liters/m² body surface area for children, distributed throughout the entire 24-hour period to achieve urine output of at least 2.5 liters per 24 hours. 1, 2
• Morning spot urine analysis helps monitor the efficacy of fluid management. 1
• In infants with primary hyperoxaluria, a gastrostomy tube may be necessary to achieve adequate fluid intake. 1

Dietary Modifications

• Limit foods with extremely high oxalate content (spinach, rhubarb) rather than implementing a strict low-oxalate diet. 1
• Maintain normal dietary calcium intake of 1,000-1,200 mg/day rather than restricting it, as calcium restriction paradoxically increases oxalate absorption and urinary excretion. 1
• Avoid high-dose vitamin C supplements as they metabolize to oxalate. 1

Potassium Citrate Therapy

• Administer potassium citrate at 0.1-0.15 g/kg/day for adults and 4 mEq/kg/day for children, divided into 3-4 daily doses. 1, 2, 3
• This therapy increases urinary citrate from subnormal to normal values (400-700 mg/day) and raises urinary pH from 5.6-6.0 to approximately 6.5, significantly reducing stone formation rates. 3, 4

Type-Specific Treatment for Primary Hyperoxaluria

Pyridoxine (Vitamin B6) for PH1

• Test pyridoxine responsiveness immediately upon diagnosis in all patients with PH1, using a maximum dose of 5 mg/kg/day. 1, 2
• Pyridoxine responsiveness is defined as >30% decrease in urinary oxalate excretion after at least 3 months of treatment. 1
• Approximately 30% of PH1 patients respond to pyridoxine therapy. 5
• Urinary oxalate measurements should be repeated on at least two occasions after at least 2 weeks of pyridoxine administration to evaluate responsiveness. 1

RNA Interference (RNAi) Therapy for PH1

• RNAi therapy is indicated for patients with PH1 who have pyridoxine non-responsive mutations or inadequate response to pyridoxine. 2

Management of Advanced Kidney Disease in Primary Hyperoxaluria

• Initiate intensified hemodialysis when plasma oxalate exceeds 30 μmol/L, even if GFR would not typically warrant dialysis, using a high-flux hemodialyzer with maximal blood flow. 2
• Increase weekly session frequency rather than prolonging individual sessions, targeting pre-dialysis plasma oxalate levels around 50-70 μmol/L. 2

Transplantation Decisions

• Combined liver-kidney transplantation is recommended for patients with PH1 who do not respond to pyridoxine and have no access to RNAi therapy, as the native liver must be completely removed. 2, 5
• Isolated kidney transplantation should be considered for patients with PH1 who are homozygous for pyridoxine-responsive mutations and demonstrate adequate response. 2
• Isolated kidney transplantation is the preferred method for PH2. 5

Treatment for Secondary Hyperoxaluria

Addressing Underlying Causes

• Identify and manage intestinal diseases causing increased oxalate absorption, including short bowel syndrome, chronic inflammatory bowel disease, cystic fibrosis, and other malabsorption syndromes. 6, 7
• Enteric hyperoxaluria may require higher calcium intake specifically timed with meals. 1

Additional Therapeutic Options

• Consider intestinal recolonization with Oxalobacter formigenes or treatment with other oxalate-degrading bacteria in patients lacking this intestinal bacterium. 6
• Specific therapeutic measures depend on the underlying pathology causing malabsorption. 6

Monitoring Protocol

For Patients with Preserved Renal Function

• Monitor urinary levels of oxalate, glycolate, citrate, calcium, and creatinine every 3-6 months during the first year of therapy, then every 6 months for 5 years. 1, 2
• Assessment of crystalluria can be useful to monitor treatment efficacy. 1

For Patients with Advanced Kidney Disease

• Monitor plasma oxalate levels every 3 months in patients with CKD Stage 4 or higher. 1, 2
• Plasma oxalate levels should only be used for diagnosis in patients with kidney failure, as urine results become misleading when oxalate excretion has declined. 8

Specialized Monitoring for Primary Hyperoxaluria

• Perform fundus examination at least yearly in infantile forms of PH1 before transplantation and in patients with PH1 and eGFR <30 ml/min/1.73m² or on dialysis. 8
• Perform cardiac ultrasound (preferably by speckle tracking) at least yearly in patients with PH1 with eGFR <30 ml/min/1.73m² or on dialysis. 8
• Monitor growth parameters, bone metabolism markers (iPTH, calcium, phosphorus, alkaline phosphatase, bicarbonate), and endocrine functions regularly. 8

Critical Pitfalls to Avoid

• Do not restrict dietary calcium, as this paradoxically worsens hyperoxaluria by increasing intestinal oxalate absorption. 1
• Do not delay diagnosis or treatment, as early intervention can prevent or delay progression to end-stage renal disease, which occurs in >30% of untreated PH1 patients. 5
• Do not use urinary oxalate measurements for diagnosis in patients with kidney failure; plasma oxalate is the appropriate test. 8
• Minimize time on dialysis to avoid overt systemic oxalosis. 5