Primary hyeroxaluria type 2 is a rare condition characterized by the overproduction of a substance called oxalate (also called oxalic acid). In the kidneys, the excess oxalate combines with calcium to form calcium oxalate, a hard compound that is the main component of kidney stones. Deposits of calcium oxalate can lead to kidney damage, kidney failure, and injury to other organs.
Primary hyperoxaluria type 2 is caused by the shortage (deficiency) of an enzyme called glyoxylate reductase/hydroxypyruvate reductase (GRHPR) that normally prevents the buildup of oxalate. This enzyme shortage is caused by mutations in the GRHPR gene. Primary hyperoxaluria type 2 is inherited in an autosomal recessive pattern
Primary hyperoxaluria type 2 (PH2) is characterized by recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis/urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), and end-stage renal disease (ESRD). After ESRD, oxalosis (widespread tissue deposition of calcium oxalate) usually develops. Symptom onset is typically in childhood and leads to:
- elevated oxalate levels
- kidney stones
- frequent urinary tract infections
The main preventative treatment is to maintain adequate hydration of at least 2.5 L of water a day, and to enhance calcium oxalate solubility with exogenous citrate and neutral phosphates.
Diagnosis relies on detection of increased urinary excretion of oxalate and commonly L-glycerate (although cases without L-glyceric aciduria have been reported), and either assay of glyoxylate reductase (GR) enzyme activity from liver biopsy or molecular genetic testing of GRHPR, the only gene associated with PH2.
Reduction of calcium oxalate supersaturation. As with PH1, conservative therapy is applied with the aim of minimizing oxalate-related renal injury and preserving renal function. Treatment of persons with preserved renal function, reviewed by Leumann & Hoppe , essentially aims to improve oxalate solubility as follows: * Adequate fluid intake (>2.5L/m2 surface area/day) * Urinary inhibitors of calcium oxalate crystallization: - Orthophosphate treatment (20-60 mg/kg body weight/day) [Leumann & Hoppe 2001] (20-60 mg/kg body weight/day) - Potassium citrate (0.1-0.15 g/kg body weight/day) [Leumann & Hoppe 2001] - Magnesium supplements (200-300 mg/day in divided doses) [Watts 1994] Dialysis. Because the plasma oxalate concentration begins to rise when the renal clearance is less than 40 mL/min/1.73m2, early initiation of dialysis or preemptive kidney-only transplantation is preferred. For patients in ESRD, intensive (daily) dialysis is required to maximize oxalate removal. As in PH1, the longer the individual with PH2 is on dialysis the more likely systemic oxalate deposition will occur. Organ transplantation. Kidney transplantation alone has been used in PH2 with varying success. Careful management in the postoperative period, with attention to brisk urine output and use of calcium oxalate urinary inhibitors, minimizes the risk of allograft loss as a result of oxalate deposition. To date, liver-kidney transplantation has not been used in PH2; however, as there is more enzyme present in the liver than in other tissues [Cregeen et al 2003], this strategy may have some merit. Pharmacologic doses of pyridoxine are used as a treatment in PH1 because of its role as cofactor for the defective enzyme. Its role in PH2 is unproven, but doses in the range of that found in typical multivitamin tablets have been used in an attempt to boost transaminases (including alanine:glyoxylate aminotransferase) with glyoxylate metabolizing activity.