Maarten Coemans1,2,3, Elisabet Van Loon1,2, Evelyne Lerut4,5, Pieter Gillard6,7, Ben Sprangers1,2, Aleksandar Senev1,8, Marie-Paule Emonds8, Jan Van Keer1, Jasper Callemeyn1,2, Liesbeth Daniëls6, Jeroen Sichien3, Geert Verbeke3, Dirk Kuypers1,2, Chantal Mathieu6,7, Maarten Naesens9,2. 1. Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. 2. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 3. Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. 4. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 5. Department of Pathology, University Hospitals Leuven, Leuven, Belgium. 6. Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium. 7. Department of Diabetes and Endocrinology, University Hospitals Leuven, Leuven, Belgium. 8. Histocompatibility and Immunogenetic Laboratory, Red Cross Flanders, Mechelen, Belgium. 9. Laboratory of Nephrology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium maarten.naesens@uzleuven.be.
Abstract
OBJECTIVE: The kinetics and risk factors of diabetic nephropathy after kidney transplantation remain unclear. This study investigated the posttransplant occurrence of diabetic nephropathy and the contribution of posttransplant glycemic control. RESEARCH DESIGN AND METHODS: We performed a single-center prospective cohort study of 953 renal allograft recipients and 3,458 protocol-specified renal allograft biopsy specimens up to 5 years after transplantation. The effects of pretransplant diabetes and glycemic control (glycated hemoglobin levels) on the posttransplant histology were studied. RESULTS: Before transplantation, diabetes was present in 164 (17.2%) renal allograft recipients, primarily type 2 (n = 146 [89.0%]). Despite intensive glycemic control (glycated hemoglobin 7.00 ± 1.34% [53 ± 14.6 mmol/mol], 6.90 ± 1.22% [52 ± 13.3 mmol/mol], and 7.10 ± 1.13% [54 ± 12.4 mmol/mol], at 1, 2, and 5 years after transplantation), mesangial matrix expansion reached a cumulative incidence of 47.7% by 5 years in the pretransplant diabetes group versus 27.1% in patients without diabetes, corresponding to a hazard ratio of 1.55 (95% CI 1.07-2.26; P = 0.005). Mesangial matrix expansion was not specific for diabetic nephropathy and associated independently with increasing age. Pretransplant diabetes was associated with posttransplant proteinuria but not with estimated glomerular filtration rate, graft failure, or any other structural changes of the glomerular, vascular, or tubulointerstitial renal compartments. The occurrence of diabetic nephropathy was independent of posttransplant glycated hemoglobin levels. CONCLUSIONS: Mesangial matrix expansion, an early indicator of diabetic nephropathy, can occur rapidly in patients with diabetes before transplantation, despite intensive glycemic control. Prevention of diabetic nephropathy requires more than pursuing low levels of glycated hemoglobin.
OBJECTIVE: The kinetics and risk factors of diabetic nephropathy after kidney transplantation remain unclear. This study investigated the posttransplant occurrence of diabetic nephropathy and the contribution of posttransplant glycemic control. RESEARCH DESIGN AND METHODS: We performed a single-center prospective cohort study of 953 renal allograft recipients and 3,458 protocol-specified renal allograft biopsy specimens up to 5 years after transplantation. The effects of pretransplant diabetes and glycemic control (glycated hemoglobin levels) on the posttransplant histology were studied. RESULTS: Before transplantation, diabetes was present in 164 (17.2%) renal allograft recipients, primarily type 2 (n = 146 [89.0%]). Despite intensive glycemic control (glycated hemoglobin 7.00 ± 1.34% [53 ± 14.6 mmol/mol], 6.90 ± 1.22% [52 ± 13.3 mmol/mol], and 7.10 ± 1.13% [54 ± 12.4 mmol/mol], at 1, 2, and 5 years after transplantation), mesangial matrix expansion reached a cumulative incidence of 47.7% by 5 years in the pretransplant diabetes group versus 27.1% in patients without diabetes, corresponding to a hazard ratio of 1.55 (95% CI 1.07-2.26; P = 0.005). Mesangial matrix expansion was not specific for diabetic nephropathy and associated independently with increasing age. Pretransplant diabetes was associated with posttransplant proteinuria but not with estimated glomerular filtration rate, graft failure, or any other structural changes of the glomerular, vascular, or tubulointerstitial renal compartments. The occurrence of diabetic nephropathy was independent of posttransplant glycated hemoglobin levels. CONCLUSIONS: Mesangial matrix expansion, an early indicator of diabetic nephropathy, can occur rapidly in patients with diabetes before transplantation, despite intensive glycemic control. Prevention of diabetic nephropathy requires more than pursuing low levels of glycated hemoglobin.
Authors: Aleksandra Kukla; Pedro Ventura-Aguiar; Matthew Cooper; Eelco J P de Koning; David J Goodman; Paul R Johnson; Duck J Han; Didier A Mandelbrot; Martha Pavlakis; Frantisek Saudek; Marie-Christine Vantyghem; Titus Augustine; Michael R Rickels Journal: Am J Kidney Dis Date: 2021-05-14 Impact factor: 11.072
Authors: Aleksandra Kukla; Jennifer Hill; Massini Merzkani; Andrew Bentall; Elizabeth C Lorenz; Walter D Park; Matthew D'Costa; Yogish C Kudva; Mark D Stegall; Pankaj Shah Journal: Transplant Direct Date: 2020-01-13