Cystinuria and other noncalcareous calculi.
Urinary stone disease is the only clinical presentation in patients with cystinuria. Two genes have been associated with type I (SLC3A1) and non-type I (SLC7A9) cystinuria and multiple mutations of these genes have been identified. The type I form is completely recessive while the non-type I form is incompletely recessive. Clinically, heterozygotes with type I mutations are silent while heterozygotes with non-type I (types II and III) present with a wide range of urinary cystine levels and some even have symptomatic urolithiasis. Although the exact molecular basis for these differences needs additional investigations, the future of medical management of cystinuria is based on molecular and gene therapy. Minimally invasive surgery using percutaneous and ureteroscopic techniques is the cornerstone of surgical management. Both cystine and struvite calculi can form staghorn configuration with propensity for rapid growth and frequent recurrences after surgical treatment. While urinary alkalinization for cystine calculi is an integral part of medical management, the effect of oral alkalinizing agents is limited because of the high pKa (8.3) of cystine. Chelating agents, therefore, are frequently used to decrease cystine solubility and stone recurrences. Similarly, urinary acidification for struvite calculi may dissolve existing stones and prevent recurrences. However, no effective oral agent is available today. A future challenge will be to introduce reliable oral agents for urinary acidification.
Shekarriz
Bijan
B
Department of Urology, SUNY, Upstate Medical University, Syracuse, NY 13210, USA.
Stoller
Marshall L
ML
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003555:Cystinuria / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008096:Lithotripsy; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018666:Ureteroscopy
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C499489:SLC7A9 protein, human