Pedro Geraldes

Key Points Diabetes-induced elevated expression of Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP-1) in podocytes is associated with glomerular sclerosis. Increased SHP-1 mRNA levels in urinary podocytes correlated with eGFR decline in patients with diabetes. Expression of SHP-1 in urinary podocytes may serve as a marker of glomerular disease progression 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 noninvasive techniques to predict the progression of kidney disease better for patients with diabetes. After injury, podocytes are shed in urine and may be used as a biologic 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 patients with diabetes. 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 =0.03). Nephrin and podocin mRNA was not significantly increased in urinary podocytes from patients with diabetes compared with 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.