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Lifelong Prevention of Mesangial Enlargement by Whole Pancreas Transplantation in Rats With Diabetes Mellitus
Lisa A. Orloff, MD;
Mark S. Orloff, MD;
Susan L. Orloff, MD;
Marshall J. Orloff, MD
Arch Surg. 1999;134:889-897.
Background Mesangial enlargement (ME) is one of the hallmark lesions of diabetic nephropathy and plays a major role in diabetic renal failure. Conventional treatment of type 1 diabetes mellitus with insulin injections, diet, and medications has often failed to prevent development and progression of ME, presumably because of difficulty in achieving tight metabolic control. Although many pancreas transplantations have been done in patients with type 1 diabetes mellitus, there is insufficient information about their influence on ME or other diabetic lesions that are responsible for its morbidity and mortality.
Hypothesis Whole pancreas transplantation will prevent diabetic ME throughout the life of the rat with alloxan-induced diabetes mellitus.
Design Mesangial enlargement was studied for 28 months by a highly reproducible quantitative morphologic method in 55 nondiabetic control rats, 57 control rats with alloxan-induced diabetes mellitus, 97 diabetic rats that received a pancreaticoduodenal isograft shortly after the induction of diabetes mellitus, and 126 diabetic rats that received a duct-ligated pancreas isograft shortly after the induction of diabetes mellitus. Mesangial enlargement was determined by measuring the area occupied by camera lucida tracings of the mesangium using an electronic planimeter connected to a computer.
Results Monthly metabolic studies showed that whole pancreas transplantation maintained very tight metabolic control of diabetes mellitus. Alloxan-induced diabetes mellitus produced progressive accumulation of mesangial matrix and progressive enlargement of all elements of the mesangium during the study. The 2 types of whole pancreas transplants provided lifelong protection against abnormal ME (P=.006).
Conclusions These results, combined with our previous finding of lifelong prevention of abnormal glomerular capillary basement membrane thickening, demonstrate that whole pancreas transplantation performed early in the course of alloxan-induced diabetes mellitus is capable of preventing diabetic kidney lesions. Moreover, these results suggest that whole pancreas transplants might be useful preventive therapy in patients with diabetes mellitus who undergo kidney transplantation for renal failure, in whom recurrence of nephropathy often develops in the transplanted kidney.
From the Department of Surgery, University of California, San Diego, Medical Center, San Diego (Drs L. A. Orloff and M. J. Orloff); Department of Surgery, University of Rochester Medical Center, Rochester, NY (Dr M. S. Orloff); and the Department of Surgery, Oregon Health Sciences University, Portland (Dr S. L. Orloff).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Initial Characterization of a Rat Model of Diabetic Nephropathy
Nobrega et al.
Diabetes 2004;53:735-742.
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