Cyclophilin A (CyPA) as a Novel Biomarker for Early Detection of Diabetic Nephropathy in an Animal Model

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Abdallah Mahmoud El-Ebidi,1 Tahia H Saleem,2 Mohamed Gamal El-din Saadi,3 Hala Abdallah Mahmoud,4 Zeinab Mohamed,5 Hoda S Sherkawy1 1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Aswan University, Aswan, Egypt; 2Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assuit University, Assuit, Egypt; 3Department of Internal Medicine and Nephrology, Kasr Al-Aini School of Medicine, Cairo University, Cairo, Egypt; 4Department of Internal Medicine and Nephrology, Aswan University, Aswan, Egypt; 5Department of Zoology, Faculty of Science, Aswan University, Aswan, EgyptCorrespondence: Hoda S Sherkawy Tel +20 1150733888Fax +20 2433767Email hoda.sultan42@aswu.edu.egBackground and Aim: Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction.Materials and Methods: Thirty-four male adult Wistar rats weighing 180– 220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN.Results: The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (p-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (p-value < 0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%).Conclusion: According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.Keywords: cyclophilin A, hyperglycemia, type 2 diabetes, diabetic nephropathy early detection, albuminuria

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