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

Autor: Lizotte F; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Robillard S; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Lavoie N; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Rousseau M; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Denhez B; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Moreau J; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada., Higgins S; Department of Medicine, Division of Nephrology, Université de Sherbrooke, Québec, Canada., Sabbagh R; Department of Surgery, Université de Sherbrooke, Québec, Canada., Côté AM; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada.; Department of Medicine, Division of Nephrology, Université de Sherbrooke, Québec, Canada., Geraldes P; Research Center, Centre Hospitalier, Université de Sherbrooke, Québec, Canada.; Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Québec, Canada.
Jazyk: angličtina
Zdroj: Kidney360 [Kidney360] 2022 Aug 31; Vol. 3 (10), pp. 1710-1719. Date of Electronic Publication: 2022 Aug 31 (Print Publication: 2022).
DOI: 10.34067/KID.0002152022
Abstrakt: 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.
Competing Interests: P. Geraldes reports research funding from the Canadian Institutes of Health Research. All remaining authors have nothing to disclose.
(Copyright © 2022 by the American Society of Nephrology.)
Databáze: MEDLINE