Enhanced SHP-1 expression in podocyturia is associated with kidney dysfunction in patients with diabetes

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.