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Unraveling the natural history of presymptomatic cystinuria
Fatima Tokhmafshan1, Paul R Goodyer2
1Research Institute of McGill University Health Centre.
Insights
This study tracks cystinuria in children from birth, finding that while stone risk varies by genetic type, factors beyond urine concentration significantly influence nephrolithiasis in presymptomatic pediatric patients.
Area of Science:
- Nephrology
- Pediatric Urology
- Genetics
Background:
- Clinical practice guidelines for cystinuria often lack data on presymptomatic children.
- Understanding the natural history of cystinuria in infants is crucial for early intervention.
Approach:
- Reviewed the clinical evolution of 130 pediatric cystinuria patients identified by newborn screening.
- Categorized patients by urinary phenotype (A/A, B/B, B/N) and followed them from birth.
- Analyzed stone formation, cystine excretion, and urine parameters in relation to genotype.
Key Points:
- Nephrolithiasis occurred in 12% of patients (4% A/A, 17% B/B, 1% B/N).
- Type B/B patients showed lower cystine excretion but higher stone risk than type A/A.
- Rising urine cystine/creatinine correlated with nephrolithiasis risk, but specific gravity and pH did not reliably predict stone formation.
Conclusions:
- The natural history of cystinuria in presymptomatic children varies significantly by genotype.
- Factors other than urine concentration, potentially intrinsic stone inhibitors, are key determinants of individual nephrolithiasis risk.
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.
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