Comparison of whole pancreas and pancreatic islet transplantation in controlling nephropathy and metabolic disorders of diabetes

Abstract

To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders and preventing the kidney lesions of alloxan diabetes, metabolic and morphologic studies were performed in four groups of rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants not long after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500 and usually 2000 syngeneic pancreatic islets soon after induction of diabetes with alloxan. Each month for 24 months after diabetes was well established, body weight and plasma concentrations of glucose and insulin were measured, and five lesions were scored by light microscopy in 50 glomeruli and related tubules in each kidney by a "blind" protocol: glomerular basement membrane thickening, mesangial enlargement, Bowman's capsule thickening, Armanni-Ebstein lesions of the tubules, and tubular protein casts. There were progressive and highly significant increases in the incidence and severity of all five kidney lesions in the diabetic control rats compared with the nondiabetic control rats. No significant differences were found between the kidneys of Group PDT and those of Group NC, demonstrating that whole pancreas transplantation prevented all of the diabetic kidney lesions throughout the 2-year study period. In contrast, within 3-9 months after pancreatic islet transplantation and thereafter, the incidence and severity of the five diabetic kidney lesions were similar in Group IT and Group DC. Whole pancreas transplantation produced precise metabolic control of diabetes throughout the 24 months of study, whereas pancreatic islet transplantation did not accomplish complete metabolic control, particularly beyond the first several months after transplantation. The difference in the completeness of metabolic control achieved by the two types of transplants is the most likely explanation for their sharp difference in effectiveness in preventing diabetic nephropathy.