Effect of oral purine load and allopurinol on the crystallization of calcium salts in urine of patients with hyperuricosuric calcium urolithiasis

Abstract

The pathogenetic importance of hyperuricosuria in the formation of calcium-containing renal stones was sought in 11 patients with hyperuricosuric calcium urolithiasis. The renal excretion of uric acid was altered over a wide range, from low normal values with a low purine diet and/or allopurinol therapy, to high values with an oral purine load. These fluctuations in urinary uric acid were compared with measures of urinary “crystallization” determined concurrently. As the renal excretion of urlc acid increased, urine specimens became more supersaturated with respect to monosodium urate. These changes were associated with a decline in the formation product ratio of calcium oxalate, a finding indicating that the spontaneous nucleation of calcium oxalate was facilitated. In separate experiments, “colloidal” or bound urate fraction, obtained by ultrafiltration, was found to be significantly increased in samples which were supersaturated with respect to monosodium urate than in undersaturated samples. Although unproved, monosodium urate so formed may facilitate nucleation of calcium oxalate, directly via heterogeneous nucleation or indirectly by removal of inhibitors of calcium oxalate nucleation. The results supported the following scheme: hyperuricosuria → supersaturation with respect to monosodium urate → formation of monosodium urate → nucleation of calcium oxalate. Conversely, treatment with allopurinol was shown to lower the urinary saturation with respect to monosodhim urate, commensurate with a decline in the renal excretion of uric acid. These changes were accompanied by a retardation of nucleation and of crystal growth of calcium oxalate. These studies provide the rationale, albeit partial, for the use of allopurinol in hyperuricosuric calcium urolithiasis.