Effect of urine alkalization on urinary inflammatory markers in cystinuric patients

Background Cystinuria is associated with a high prevalence of chronic kidney disease (CKD). We previously described a urinary inflammatory-protein signature (UIS), including 38 upregulated proteins, in cystinuric patients (Cys-patients), compared with healthy controls (HC). This UIS was higher in Cys-patients with CKD. In the present observational study, we aimed to investigate the UIS in Cys-patients without CKD and patients with calcium nephrolithiasis (Lith-patients), versus HC and the effect of urine alkalization on the UIS of Cys-patients. Methods UIS was evaluated by nano-liquid chromatography coupled to high-resolution mass spectrometry in adult HC, Lith-patients and non-treated Cys-patients with an estimated glomerular filtration rate >60 mL/min/1.73 m(2), and after a 3-month conventional alkalizing treatment in Cys-patients. Results Twenty-one Cys-patients [12 men, median age (interquartile range) 30.0 (25.0-44.0) years], 12 Lith-patients [8 men, 46.2 (39.5-54.2) years] and 7 HC [2 men, 43.1 (31.0-53.9) years] were included. Among the 38 proteins upregulated in our previous work, 11 proteins were also upregulated in Cys-patients compared with HC in this study (5 circulating inflammatory proteins and 6 neutrophil-derived proteins). This UIS was also found in some Lith-patients. Using this UIS, we identified two subclusters of Cys-patients (5 with a very high/high UIS and 16 with a moderate/low UIS). In the Cys-patients with very high/high UIS, urine alkalization induced a significant decrease in urinary neutrophil-derived proteins. Conclusion A high UIS is present in some Cys-patients without CKD and decreases under alkalizing treatment. This UIS could be a prognostic marker to predict the evolution towards CKD in cystinuria.