Studies on some possible biochemical treatments of primary hyperoxaluria.
The effects of some putative inhibitors of oxalate production or urinary oxalate excretion have been investigated in the Cynamolgus monkey and in patients with Type I primary hyperoxaluria (hyperoxaluria with glycollic aciduria). Sodium-1-hydroxybutan-sulphonate, D,L-phenyllactate, succinimide and isocarboxazide did not reduce the urinary oxalate excretion in the monkeys. Pyridoxine reduced the excretion of oxalate and glycollate in some patients, and its therapeutic use has been documented over a five-year period. Succinimide, which has been used by other workers for the treatment of non-hyperoxaluric stone formers, did not decrease the excretion of either oxalate or glycollate in three patients in whom it was tried. It did not change the inhibitory activity of the urine with respect to the growth and aggregation of calcium oxalate crystals in any of the three patients, and it did not have any consistent effect on the excretion of calcium oxalate crystals in the one patient who had detectable crystaluria before treatment. We have identified several metabolites of succinimide in the urine of patients taking the drug. These include 2,3-dehydrosuccinamic, 2-hydroxysuccinamic and 3-hydroxysuccinamic acids. Isocarboxazide, cholestyramine and thiamine did not affect the urinary oxalate excretion in the patients. The significance of these observations from the viewpoint of the treatment of primary hyperoxaluria is discussed.
D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002792:Cholestyramine Resin / Q000627:therapeutic use; D005260:Female; D000882:Haplorhini; D006801:Humans; D007520:Isocarboxazid / Q000627:therapeutic use; D008252:Macaca fascicularis; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000652:urine; D010070:Oxalates / Q000037:antagonists & inhibitors / Q000652:urine*; D011736:Pyridoxine / Q000627:therapeutic use; D013388:Succinimides / Q000627:therapeutic use; D013831:Thiamine / Q000627:therapeutic use
D010070:Oxalates; D013388:Succinimides; D002792:Cholestyramine Resin; D007520:Isocarboxazid; D011736:Pyridoxine; D013831:Thiamine