Cystinuria is a hereditary aminoaciduria causing recurrent cystine nephrolithiasis, impaired quality of life and potential renal function decline. Despite established treatment guidelines, real-world data reveal a persistent gap between recommended targets and clinical outcomes. Preliminary data from the EUROCYS 2024 prospective European registry (269 patients, 29 centers, 8 countries) showed that only 16.3% of patients achieved the target urinary pH range, 55.2% remained above the conventional urinary cystine threshold of 250 mg/L, and approximately 39% experienced a new stone event within the preceding 12 months, despite follow-up in specialist centers. Discontinuation rates for available thiol drugs have been reported to reach 30-50%. This narrative review, based on a structured non-systematic search of major databases and guideline repositories (2009-2026), synthesizes current evidence on cystinuria diagnosis and management and appraises emerging adjunctive interventions. Next-generation sequencing-based genetic testing and the cystine capacity assay represent key recent advances in monitoring. Thulium fiber laser lithotripsy and miniaturized percutaneous approaches offer less traumatic surgical options in this high-burden population. Oral N-acetylcysteine has mechanistic plausibility and a favorable, well-characterized safety profile in other clinical settings, making it a rational candidate for formal prospective evaluation; however, robust clinical trial evidence in cystinuria using contemporary monitoring parameters is lacking. Current standard treatment remains insufficient for a substantial proportion of patients, underscoring the need to evaluate accessible adjunctive therapies with defined mechanisms and measurable outcomes.
Cystinuria is a rare inherited condition in which the kidneys cannot properly reabsorb certain amino acids, leading to the formation of kidney stones made of cystine. These stones recur frequently, often require surgery, and can cause long-term kidney damage over time. Diagnosis relies on urine and blood tests, genetic testing, and a newer urine test called the cystine capacity assay, which more accurately reflects how close a patient is to forming stones. Treatment begins with drinking large amounts of fluid, alkalinizing the urine with potassium citrate, and reducing salt and protein in the diet. When these measures are insufficient, a drug called tiopronin is added to help prevent stone formation. Despite specialist care, real-world data show that most patients still do not meet recommended treatment targets and continue to form stones. For stone removal, ureteroscopy with laser lithotripsy and percutaneous nephrolithotomy are the main surgical options; newer thulium fiber lasers show promising results for this stone type. Oral N-acetylcysteine has a plausible mechanism and known safety from other conditions, but clinical evidence in cystinuria is lacking and it cannot yet be considered a standard treatment. This review highlights a persistent gap between treatment targets and real-world outcomes, underscoring the urgent need for accessible adjunctive therapies supported by well-designed clinical trials.
Research and reports in urology. 2026 Jul 27*** epublish ***
Alberto Zambudio Munuera, Patricia Rodriguez Parras, Juan Antonio Galan Llopis, Feliciano Grases Freixedas, Maria Del Carmen Cano Garcia, Miguel Arrabal-Martin, Miguel Angel Arrabal Polo
Urology Department, San Cecilio University Hospital, Granada, Spain., Department of Urology, General University Hospital Dr Balmis, ISABIAL, Alicante, Spain., Instituto Universitario de Investigaciones de Ciencias de la Salud (IUNICS), Universitat de les Illes Balears, Illes Balears, Spain.