Test ID: HYOX    
Hyperoxaluria Panel, Urine

Distinguishing between primary and secondary hyperoxaluria

Distinguishing between type 1 and type 2 primary hyperoxaluria

Distinguishing between primary and secondary hyperoxaluria.

Increased urinary oxalate frequently leads to renal stone formation and renal insufficiency. Identification to the cause of hyperoxaluria has important implications in therapy, management and prognosis.

Hyperoxalurias are classified as primary (genetically determined) and secondary. Type I (PH1), an autosomal recessive deficiency of peroxisomal alanine: glyoxylate aminotransferase due to mutations in the AGXT gene, is characterized by increased urinary oxalic, glyoxylic, and glycolic acids. PH1 manifestations include deposition of calcium oxalate in the kidneys (nephrolithiasis, nephrocalcinosis), and end-stage renal disease. Calcium oxalate deposits can be found in other tissues such as the heart and eyes, and lead to a variety of additional symptoms. Age of onset is variable with a small percentage of patients presenting in the first year of life with failure to thrive, nephrocalcinosis, and metabolic acidosis. Approximately half of affected individuals show manifestations of PH1 in late childhood or early adolescence, and the remainder present in adulthood with recurrent renal stones. Some PH1 individuals respond to supplementary pyridoxine therapy.

Hyperoxaluria type II (PH 2) is due to a defect in GRHPR gene resulting in a deficiency of the enzyme hydroxypyruvate reductase. PH2 is autosomal recessive and identified by an increase in urinary oxalic and glyceric acids. Like PH1, PH2 is characterized by deposition of calcium oxalate in the kidneys (nephrolithiasis, nephrocalcinosis), and end-stage renal disease. Most individuals have symptoms of PH2 during childhood, and it is thought that PH2 is less common than PH1.

Secondary hyperoxalurias are due to hyperabsorption of oxalate (enteric hyperoxaluria); total parenteral nutrition in premature infants; ingestion of oxalate, ascorbic acid, or ethylene glycol; or pyridoxine deficiency, and may respond to appropriate therapy.

A diagnostic workup in an individual with hyperoxaluria demonstrates increased concentration of oxalate in urinary metabolite screening. If either glycolate or glycerate is present, a primary hyperoxaluria is indicated. Additional analyses can include molecular testing for PH1 or PH2.

GLYCOLATE

0-31 days: 0-57 mg/g creatinine

1-5 months: 0-54 mg/g creatinine

6-12 months: 0-60 mg/g creatinine

1-5 years: 0-89 mg/g creatinine

> or =6 years: 0-78 mg/g creatinine

GLYCERATE

0-31 days: 0-38 mg/g creatinine

1-5 months: 0-71 mg/g creatinine

6-12 months: 0-56 mg/g creatinine

1-5 years: 0-17 mg/g creatinine

> or =6 years: 0-8 mg/g creatinine

OXALATE

0-31 days: 0-301 mg/g creatinine

1-5 months: 0-398 mg/g creatinine

6-12 months: 0-280 mg/g creatinine

1-5 years: 0-128 mg/g creatinine

6-10 years: 0-72 mg/g creatinine

> or =11 years: 0-56 mg/g creatinine

GLYOXYLATE

0-31 days: 0.0-7.9 mg/g creatinine

1-5 months: 0.0-11.4 mg/g creatinine

6-12 months: 0.0-5.5 mg/g creatinine

1-5 years: 0.0-3.9 mg/g creatinine

> or =6 years: 0.0-2.9 mg/g creatinine

Increased concentrations of oxalate and glycolate indicate type 1 hyperoxaluria.

Increased concentrations of oxalate and glycerate indicate type 2 hyperoxaluria.

Increased concentrations of oxalate with normal concentrations of glycolate and glycerate indicate secondary hyperoxaluria.

Ascorbic acid will falsely elevate oxalic acid results.

1. Monico CG, Persson M, Ford GC, et al: Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II. Kidney Int 2002;62:392-400

2. Danpure CJ: Primary hyperoxaluria. In The Metabolic Bases of Inherited Disease. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 2001, pp 3323-3367

3. Byrd DJ, Latta K: Hyperoxaluria. In Physician's Guide to the Laboratory Diagnosis of Metabolic Disease. Edited by N Blau, ED Chapman. Hall Medical, 1996, pp 377-390

4. Fraser AD: Importance of glycolic acid analysis in ethylene glycol poisoning. Clin Chem 1998;44(8):1769

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