Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.

Abstract

BACKGROUND:

The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available.

METHODS:

Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation.

RESULTS:

PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03).

CONCLUSION:

The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

• Authors: D S Milliner, D M Wilson, L H Smith
• Journal: Kidney international (Kidney Int) Vol. 59 Issue 1 Pg. 31-6 (Jan 2001) ISSN: 0085-2538 [Print] United States
• PMID: 11135054 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Oxalates
• Calcium Oxalate
• Citric Acid
• Magnesium
• Calcium

Topics

• Adolescent
• Adult
• Calcium (urine)
• Calcium Oxalate (antagonists & inhibitors)
• Child
• Child, Preschool
• Citric Acid (urine)
• Crystallization
• Female
• Humans
• Hyperoxaluria (classification, complications, genetics, urine)
• Kidney Failure, Chronic (etiology)
• Magnesium (urine)
• Male
• Osmolar Concentration
• Oxalates (urine)
• Phenotype
• Urinary Calculi (etiology)
• Urine (physiology)