Unraveling the natural history of presymptomatic cystinuria

Abstract

Purpose of review Servais et al. recently published clinical practice recommendations for the care of cystinuria patients. However, these guidelines were largely based on retrospective data from adults and children presenting with stones. Significant questions remain about the natural history of cystinuria in presymptomatic children. Recent findings We review the natural history of cystinuria in presymptomatic children followed from birth. In total, 130 pediatric patients were assigned putative genotypes based on parental urinary phenotype: type A/A (N = 23), B/B (N = 6), and B/N (N = 101). Stones were identified in 12/130 (4% of A/A, 17% of B/B, and 1% of B/N patients). Type B/B patients had lower cystine excretion than type A/A patients. Although urine cystine/creatinine fell with age, urine cystine/l rose progressively in parallel with the risk of nephrolithiasis. Each new stone was preceded by 6–12 months of urine specific gravity of more than 1.020. However, average urine specific gravity and pH were not different in stone formers vs. nonstone formers, suggesting that intrinsic stone inhibitors or other unknown factors may be the strongest determinants of individual risk. Summary The current study reviews the clinical evolution of cystinuria in a cohort of children identified by newborn screening, who were categorized by urinary phenotype and followed from birth.