Podocyte Density and Albuminuria in Aging Diabetic Ins2± Mice with or Without Adenosine A1 Receptor Signaling

Robert Faulhaber-Walter, 1–3 Lanping Jiang, 4 Diane Mizel, 2 Patricia M Zerfas, 2 Jeffrey B Kopp, 2 Jurgen B Schnermann, 2 Limeng Chen, 2, 4 Mario Schiffer 3, 5 1Facharztzentrum Aarberg, Waldshut-Tiengen, Germany; 2NIDDK, National Institutes of Health, Bethesda, MD, USA; 3Department of Nephrology, Medical School Hannover, Hannover, Germany; 4Peking Union Medical College Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, University of Erlangen, Erlangen, GermanyCorrespondence: Robert Faulhaber-WalterFacharztzentrum Aarberg, Tannenstrasse 4, Waldshut-Tiengen 79761, GermanyTel +49-151-27164882Fax +49-321-21036268Email rofaulhaber@web.deAim of Study: To investigate podocyte density in aging diabetic Ins2± and Ins2±, A1AR-/- mouse models in C57Bl/6 background.Methods: Ins2± mice and especially Ins2±, adenosine A1 receptor knockout mice (Ins2±, A1AR-/-) are mouse models with a phenotype of diabetic nephropathy. Aged mice (at ∼ 40 weeks) were assessed for glomerular filtration barrier function by measuring albuminuria, glomerular filtration, glomerular damage by electron microscopy, and podocyte numbers by Wilms Tumor protein (WT-1) staining.Results: Compared to healthy wild-type mice, both diabetic mouse models developed diabetic nephropathy, including hyperfiltration (p< 0.01) and albuminuria (p< 0.05). Typical diabetic structural glomerular and podocyte damage was visualized by electron microscopy. Podocyte count per glomerular area (podocyte density) was significantly decreased in both diabetic mouse models (p< 0.01). In contrast, no significant correlation was detected between albuminuria and absolute podocyte count per glomerulus.Conclusion: The amount of albuminuria as marker of diabetic nephropathy does not correlate with the podocytes density; however, a relative podocyte deficiency became evident with an increase in glomerular area in the diabetic animals, suggesting a relative podocytopenia.Keywords: diabetes nephropathy podocyte mouse Akita WT-1