Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes

Abstract

Background - Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease worldwide. Despite significant advances in kidney care, there is a need to improve non-invasive techniques to better predict the progression of kidney disease for patients with diabetes. Following injury, podocytes are shed in urine and may be used as a biological tool. We previously reported that SHP-1 is upregulated in the kidney of diabetic mice leading to podocyte dysfunction and loss. Our objective was to evaluate the expression levels of SHP-1 in urinary podocytes and kidney tissues of diabetic patients. Methods - In this prospective study, patients with and without diabetes were recruited for the quantification of SHP-1 in kidney tissues, urinary podocytes and peripheral blood monocytes. Immunochemistry and mass spectrometry techniques were applied for kidney tissues. Urinary podocytes were counted, and expression of SHP-1 and podocyte markers were measured by quantitative PCR. Results - A total of 66 participants (diabetic n=48, nondiabetic n=18) were included in the analyses. Diabetes was associated with increased SHP-1 expression in kidney tissues (P = 0.0286). Nephrin and podocin mRNA were not significantly increased in urinary podocytes from patients with diabetes compared to those without diabetes, whereas levels of SHP-1 mRNA expression significantly correlated with HbA1c and estimated glomerular filtration rate (eGFR). Additionally, follow-up (up to 2 years post recruitment) evaluation indicated that SHP-1 mRNA expression continued to increase with eGFR decline. Conclusions - Levels of SHP-1 in urinary podocytes may serve as an additional marker of glomerular disease progression in this population.

Research progress of natural active compounds on improving podocyte function to reduce proteinuria in diabetic kidney disease

“…Studies have shown that podocyteuria often precedes proteinuria in several renal diseases including DKD [ 19 ]. Therefore, detection of urine containing exfoliated podocytes plays a role in the early diagnosis of DKD [ 20 ]. Current research on podocyteuria includes the detection of functional proteins in podocytes in urine and the determination of microvesicles secreted by podocytes.…”