Heterozygous cystinuria and calcium oxalate urolithiasis

Many variables are known to be associated with the formation of calcium oxalate urolithiasis but none is essential for the initiation or growth of stones. It is likely that the predisposition to stone formation is related to multiple factors. We herein describe still another metabolic state that seems to predispose to calcium oxalate stone disease, namely heterozygosity for cystinuria. Cystine screening tests were done on 24-hour urine specimens obtained from 126 patients in whom recurrent calcium oxalate stones form and 84 controls and quantitative amino acid determinations were done on all positive specimens. Of those studied 17 of 126 stone patients and 1 of 84 controls were heterozygous cystinurics. A test of the differences between the relative frequencies of cystinuria heterozygotes in the 2 groups with Fisher's exact test revealed them to be highly significant (p less than 0.001). Our study indicates that carrier status for 1 of the cystinuria genes predisposes to calcium oxalate stone formation but, like other factors related to urolithiasis, it is not a necessary cause of stone disease.