Molecular mechanisms of complications development of nephrolithiasis associated with diabetes type 2

Abstract

BACKGROUND. Until recently there is no understanding of the clinical features and the reasons for the progression of complications of diabetes-associated nephrolithiasis (NLT) which limits the development of effective treatment for patients with this kidney pathology.THE AIM was to investigate the molecular mechanisms of hematuria and leukocyturia in the comorbidity of nephrolithiasis with type 2 diabetes. PATIENTS AND METHODS. The study analyzed the clinical, instrumental, and laboratory data of 196 patients with NLT; the study included 48 (24.5 %) patients with comorbidity of NLT with type 2 diabetes. All patients at the stage of hospitalization underwent a comprehensive clinical and laboratory examination according to the traditional scheme adopted for the diagnosis of NLT. ATP, PAF, and collagen (Sigma) agonists at EC50 concentrations causing aggregation at the 50 % level in healthy individuals were used to analyze the functional activity of platelet (PLT) receptors. PLT aggregation was assessed by the turbidimetric method using a ChronoLog analyzer (USA). RESULTS. Microhematuria occurred in 27 (56.2 %) patients and gross hematuria in 21 (43.8 %) patients out of 48 patients with type 2 diabetes-associated NLT. Microscopy of urine in patients with comorbidity of NLT revealed a greater number of erythrocytes (P = 0.014); gross hematuria (P = 0.034) and leukocyturia (р=0,003) were more common in this cohort of patients. NLT complications occurred against the background of increased reactivity of P2X receptors, PAF receptor, and GPVI receptor (p <0.001) of PLT compared with that in patients with NLT without DM. The progression of leukocyturia was accompanied by increased severity of hematuria and was manifested by increased activity of GPVI receptors (p <0.001). CONCLUSION. The influence of diabetes on the pathogenesis of NLT complications is associated with increased ischemia of kidney tissue, systemic inflammatory response, and vascular wall remodeling. The activity of P2X, PAF, and GPVI platelet receptors could be considered as a system of potential biomarkers and prognostic factors of complications in the comorbidity of NLT with type 2 diabetes.