Abstract
Cystinuria is an autosomal recessive disorder that results in altered reabsorption of a group of amino acids (cystine, ornithine, lysine, and arginine) in the renal proximal tubule. Cystine is poorly soluble in urine resulting in crystal formation and the generation of stones. Patients may also develop intranephronal obstruction. Thus, renal obstruction at the level of the collecting system or the nephron may be significant drivers for the high prevalence of chronic kidney disease in this cohort, a small number also progressing to end stage renal disease (ESRD). Cystinuria is caused by mutations of either the SLC3A1 (coding for a neutral and dibasic amino acid transporter, rBAT) or SLC7A9 (coding for bo,+, AT). These proteins join together to form a sodium-independent transport complex.
The authors have provided a nice overview of management of this patient cohort. Unfortunately, the evidence that we base recommendations for stone prevention in this cohort is weak; there are no substantive, randomized, and controlled studies to date. Therapy is based on relatively generic dietary modifications, urinary pH manipulation, and selective utilization of agents that result in a disulfide exchange reaction creating a more soluble compound. One agent that is under investigation is alpha lipoic acid that reduces stone formation in the knockout mouse model and is currently being evaluated in a clinical trial. This agent supposedly works by increasing the solubility of cystine. Although such approaches may prove to be safe and effective, I believe that treatment of patients in the future will be with somatic cell gene editing!