Immunization of AGE-modified albumin inhibits diabetic nephropathy progression in diabetic mice

Musthika Wida Mashitah,1 Nurona Azizah,1 Nur Samsu,2 Muhammad Rasjad Indra,1 Muhammad Bilal,3 Meti Verdian Yunisa,4 Amildya Dwi Arisanti41Department of Biomedicine, Faculty of Medicine, Brawijaya University, Malang, 2Department of Internal Medicine, Division of Nephrology and Hypertension, Saiful Anwar General Hospital, Malang, 3Department of Medicine, Faculty of Medicine, Brawijaya University, Malang, 4Department of Nursing, Faculty of Medicine, Brawijaya University, Malang, IndonesiaBackground: Diabetic nephropathy (DN) is a serious vascular complication of diabetes and an important cause of end-stage renal disease. One mechanism by which hyperglycemia causes nephropathy is through the formation of advanced glycation end products (AGE). Development of vaccination would be a promising therapy for the future, while to date, anti-AGE therapy is based on medicines that are needed to be consumed lifelong. This study aimed to find out the effect of immunization of AGE-modified albumin against DN pathogenesis in streptozotocin-induced diabetic in mice.Methods: We used 24 BALB/c male mice as experimental animals, which were divided into six groups, two nondiabetic groups (negative control and AGE-modified bovine serum albumin [BSA] preimmunized groups) and four streptozotocin-induced diabetic groups (diabetic control group and diabetic preimmunized groups for AGE-BSA, Keyhole limpet hemocyanin (KLH), and AGE-BSA-KLH, respectively).Results: Diabetic preimmunized groups for AGE-BSA, KLH, and AGE-BSA-KLH showed amelioration in renal function and histopathology compared with the diabetic control group. Preimmunization also maintained nephrin intensity and decreased serum AGE level, kidney AGE deposition, and kidney cells apoptosis.Conclusion: AGE-BSA and AGE-BSA-KLH immunizations inhibit the progression of DN. Our results strengthen the evidence that the anti-AGE antibodies have a protective role against diabetic vascular complication, especially DN. This study provides a basis for the development of DN-based immunotherapy with AGE immunization as a potential candidate.Keywords: immunization, advanced glycation end products (AGE), AGE-modified albumin, anti-AGE antibody, diabetic nephropath