Cystinuria poorly responding to treatment - the risk of chronic kidney disease

Cystinuria is the genetic condition for the increased excretion of cystine in the urine. Patients mainly suffer from afflictions related to the presence and passage of kidney stones. The currently available treatment methods include conservative treatment based on increased fluid intake, appropriate diet, medications and urological procedures. The causal treatment has not yet been invented.

A patient case was described whose first symptomatic kidney stones appeared after the second year of life. Urinary cystine excretion was significantly increased - 25,431 μmol/1g creatinine (norm: 167-333 μmol/1g creatinine), which was also shown, but lower, in both parents of the patient. Despite the early initiation of therapy including low sodium diet, abundant hydration, alkalization, captopril and compliance with stringent restrictions, the level of urinary cystine excretion was still not within the normal range. There have been many modifications to the therapy and dose increases of drugs, but without visible results. The patient underwent several urological procedures, including: ESWL (Extracorporeal shock wave lithotripsy), URSL (Ureteroscopic lithotripsy), PCNL (Percutaneous nephrolithotomy) and open surgery to remove cystine deposits that were still produced in the kidneys. In addition, for many years the disease was complicated by recurrent urinary tract infections, underweight and lesions like epithelial metaplasia in the bladder. Renal parameters were repeatedly examined. Elevated results such as: serum creatinine 0.9 mg/dl, cystatin C concentration 1.10 mg/l, albumin-creatinine index 0.197, creatinine clearance 50.7 ml/min /1.73 m2 and eGFR 73 ml/min/1.73 m2 allowed for the diagnosis of chronic kidney disease before the age of 18. After many years of conservative treatment, only the introduction of thiopronine, still little known in Poland, reduced the level of cystine excreted in the urine. The inclusion of the drug reduced the tendency to produce kidney stones, which allowed to inhibit the progression of renal failure.

Despite many years of research and modern drugs, cystinuria is still a disease with which patients are associated for the rest of their lives. The ongoing research, along with attempts to understand the genetic and epigenetic mechanisms responsible for the emergence of mutations in the main genes causing the disease and the course of the disease, gives hope for finding a method of causal treatment for cystinuria.