Correlation of Asymmetric Dimethylarginine With Podocytopathy Markers in Diabetic Kidney Disease Patients

Pringgodigdo Nugroho,1 Riahdo Juliarman Saragih,2 Aida Lydia,1 Muhadi Muhadi,3 Harry Isbagio,4,5 Hamzah Shatri,6 Carissa Cornelia Chundiawan,1 Fidel Hermanto1 1Division of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Cardiovascular Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 4Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 5Geriatric Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 6Psychosomatic Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital, Jakarta, IndonesiaCorrespondence: Pringgodigdo Nugroho, HDivision of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia—Dr. Cipto Mangunkusumo Hospital Jl, Diponegoro no. 71, Jakarta, 10430, Indonesia, Email [email protected]: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and podocytopathy is an early manifestation of DKD characterized by the urinary excretion of podocyte-specific proteins, such as nephrin and podocin. Asymmetric dimethylarginine (ADMA)—a biomarker of endothelial dysfunction—is associated with progressive kidney dysfunction. However, the mechanism of endothelial dysfunction in DKD progression is unclear. The aim of this study was to investigate the correlations of ADMA levels with nephrin, podocin, and the podocin:nephrin ratio (PNR) in DKD patients.Methods: A cross-sectional study of 41 DKD outpatients was performed in two hospitals in Jakarta from April–June 2023. The collected data included the subjects’ characteristics, histories of disease and medication, and relevant laboratory data. Serum ADMA was measured using liquid chromatography, while urinary podocin and nephrin were measured using the enzyme-linked immunosorbent assay (ELISA) method. A correlation analysis was performed to evaluate the correlation of ADMA with nephrin, podocin, and PNR. Regression analysis was performed to determine confounding factors.Results: The mean value of ADMA was 70.2 (SD 17.2) ng/mL, the median for nephrin was 65 (20– 283 ng/mL), and the median of podocin was 0.505 (0.433– 0.622) ng/mL. ADMA correlated significantly with nephrin (r = 0.353, p = 0.024) and PNR (r = − 0.360, p = 0.021), but no correlation was found between ADMA and podocin (r = 0.133, p = 0.409). The multivariate analysis showed that body mass index was a confounding factor.Conclusion: This study revealed weak positive correlations between ADMA and urinary nephrin and between ADMA and PNR. No correlation was found between ADMA and urinary podocin.Keywords: diabetic kidney disease, ADMA, nephrin, podocin, podocin:nephrin ratio