TY - JOUR
T1 - Phenotypic expression of primary hyperoxaluria
T2 - Comparative features of types I and II
AU - Milliner, D. S.
AU - Wilson, D. M.
AU - Smith, L. H.
N1 - Funding Information:
This research was supported in part by a General Clinical Research Center grant from the National Institutes of Health (M01-RR00585) awarded to Mayo Clinic Rochester and by National Institutes of Health Grant AM20605.
PY - 2001
Y1 - 2001
N2 - 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/l.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.
AB - 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/l.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.
KW - Autosomal recessive disorder
KW - Calcium oxalate
KW - Crystalluria
KW - D-glycerate dehydrogenase/glyoxylate reductase
KW - Hepatic alanine:glyoxylate aminotransferase
KW - Plasma oxalate
KW - Stone forming activity
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U2 - 10.1046/j.1523-1755.2001.00462.x
DO - 10.1046/j.1523-1755.2001.00462.x
M3 - Article
C2 - 11135054
AN - SCOPUS:0035170499
SN - 0085-2538
VL - 59
SP - 31
EP - 36
JO - Kidney international
JF - Kidney international
IS - 1
ER -