#2278 EUROCYS, a European cystinuria registry
Authors: Servais Aude , Capolongo Giovanna , Tostivint Isabelle , Lemoine Sandrine , Ferraro Pietro Manuel , Decramer Stephane , Ruggenent Piero , Capelli Irene , Engberink Rik Olde , Schaefer Franz , Knebelmann Bertrand , Courbebaisse Marie 
Published: May 2024

Abstract

Background and Aims
Cystinuria (OMIM 220100) is a rare autosomal recessive disorder in which high urinary cystine excretion leads to formation of cystine stones due to its low solubility at normal urinary pH. Retrospective series have been published but precise data to guide long term optimal management of these patients are lacking. Our goal was to collect consistent and comparative prospective clinical, biological, genetic and radiological data from patients (children and adults) with cystinuria followed in European centers.

Method
We developed EUROCYS, a multidisciplinary, European, multicenter registry of patients with cystinuria in which demographic, clinical, surgical, biological, genetic, radiological and therapeutic data are collected longitudinally. These data are recorded via the European Rare Kidney Disease Registry (ERKReg) platform.

Results
Enrolment started in July 2021. To date, 269 patients have been included at 29 different centers in 8 European countries. Mean age at diagnosis was 18.7 years (SD 17.3) and mean age at inclusion was 35.4 years (20.2). 86.9% of patients had less than 9 calculi extractions reported, 11.0% had between 10 to 19, and 2.0% had more than 20. 61.4% (418/680) were treated by ureteroscopy, 16.2% (110/680) by shock wave lithotripsy and 16.0% (109/680) by percutaneous nephrolithotomy. 39% of patients had a new stone expulsion or surgery during the last 12 months.
At the inclusion visit, mean urinary pH was below the recommended level at 6, 8 (0.8). Only 16.3% of patients had a urinary pH between 7.5 and 8: 77.2% of patients had a urinary pH below 7.5 and 6.3% above 8. In adults, mean 24-hour urinary volume was 2653 mL (1077). 34.9% had a target urine volume above 3000 ml. Under treatment, spot urine cystine concentration was 345.5 mg/l (255.2) and 44.8% of patients had a concentration below target concentration (250 mg/l). Mean sodium urinary excretion was 147 mmol/24 h (67). Only 29% of patients had a sodium urinary excretion below 100 mmol/24 h.
As alkalinizing agent, 87.2% of patients received potassium citrate, 16.3% sodium bicarbonate and 9.1% potassium bicarbonate. As cystine binding drug, 71 patients (26.7%) were treated with Tiopronin and 3 experienced serious adverse events (hematological, cutaneous, proteinuria). 15 (5.6%) were treated with D-Penicillamine and 2 had adverse events (proteinuria and gastrointestinal).
In adults, mean eGFR at inclusion was 82.1 ml/min/1.73 m² (26.3): 40.9% of patients were at chronic kidney disease (CKD) stage 1, 40.1% at CKD2, 16.7% at CKD3, 0.7% at CKD 4 and 1.5% at CKD5.

Conclusion
The EUROCYS registry shows real life data on cystinuria patients followed in European centers. Despite alkalinizing treatment, most patients do not reach the recommended urinary pH level and only one third have an adequate urinary volume. This registry will allow analyzing the impact of adhesion to recommendations on disease activity.