sodium-bicarbonate and Nephrolithiasis

Cystinuria is a relatively uncommon cause of pediatric stone disease, but has significant morbidity if not properly controlled because of its significant stone recurrence rate. Cystinuria is caused by the inability of the renal tubules to reabsorb filtered cystine, which is poorly soluble at a typical urine pH <7. Although many advances have been made in the understanding of the genetic and physiological basis of cystinuria, the cornerstones of treatment still involve stone prevention with dietary measures and pharmacological therapy, coupled with surgical interventions for stone removal. Pharmacological treatments can carry significant side effects that must be monitored and can limit therapy as well as impede compliance. Most patients will require surgical intervention for stone removal, although compliance with prevention strategies reduces the need for intervention.

Topics: Absorption; Animals; Cystine; Cystinuria; Diet, Protein-Restricted; Diet, Sodium-Restricted; Genetic Predisposition to Disease; Humans; Hydrogen-Ion Concentration; Kidney Tubules; Nephrolithiasis; Patient Compliance; Phenotype; Potassium Citrate; Sodium Bicarbonate; Solubility; Sulfhydryl Compounds; Treatment Outcome; Urologic Surgical Procedures

Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3-13.6) and 2.6 (range, 0.7-16.7) years, respectively. The median followed up was 7.7 (range, 3.4-14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.

Topics: Adolescent; Amino Acid Transport Systems, Basic; Amino Acid Transport Systems, Neutral; Asian People; Child; Child, Preschool; Cystinuria; DNA; DNA Mutational Analysis; Female; Genetic Association Studies; Genotype; Heterozygote; Humans; Infant; Male; Nephrolithiasis; Polymorphism, Genetic; Republic of Korea; Retrospective Studies; Sodium Bicarbonate; Tiopronin