Long-Term Study of Normal Kidneys Transplanted Into Patients With Type I Diabetes

Abstract

We examined the rate of development of the lesions of diabetic nephropathy in transplanted kidneys residing for 6-14 yr in type I (insulin-dependent) diabetic kidney-allograft recipients. Although each recipient had end-stage diabetic nephropathy with his/her own kidneys, there was marked variability in the rate of development of mesangial expansion observed in the transplanted kidneys. The progression of glomerular pathology, including widening of the glomerular basement membrane and expansion of the mesangium, did not correlate significantly with several potential risk factors (e.g., donor source--cadaver or living related, histocompatibility match, age of the recipient or donor, age at onset of diabetes, duration of diabetes before renal failure, immunosuppressive drug dose, blood pressure, and severity of lesions of chronic rejection). However, there was a direct albeit imprecise relationship between the index of mesangial expansion at the final biopsy and the index of glycemic control (r = .61, P less than .01). These observations suggest that currently unknown factor(s) may modulate the progression of diabetic renal disease, even in a population that had uniformly demonstrated nephropathy risk. Our data support the hypothesis that in addition to glycemic control per se, there are risk factors intrinsic to the kidney itself.

Kidney transplantation in Type 1 (insulin-dependent) diabetic patients

“…Although we could not identify such sensibility on the basis of HLA-tissue type, this remains a possibility. Mauer et al [9] have suggested that intrinsic factors in the transplanted kidney may play a major role.…”

“…Previous transplant biopsy studies [7][8][9][10] have indicated that within the first 10 years after transplantation the structural changes are modest and unlikely to have any immediate clinical significance. However, histopathological changes develop during the clinically silent phase and analysis of the relationship between structural changes and clinical variables in this early stage may elucidate factors that significantly influence the process.…”

Frederick C. Goetz, MD: A Profile of the Intersection Among Science, the Fine Arts, and Education

“…Under Fred's leadership, the University of Minnesota program regularly reported on both lessons learned in the field of pancreas transplantation and contributed to the sustained success of many pancreas transplant procedures (12,14-17). Other major scientific contributions supported, mentored, and guided by Fred, Sutherland, and Robertson during the 1980s and 1990s included important studies of the effects of hemipancreas graft donation on glucose tolerance, assessment of the impact of persistent diabetes on renal transplant grafts, early evidence of the familial clustering of renal disease risk in diabetes that predated years of analysis of genetic linkage in diabetic nephropathy, and evidence of no adverse effects/possible benefits of pancreas transplantation on diabetic retinopathy (11)(12)(13)(18)(19)(20)(21).…”

“…His mentoring of young scientists was characterized by support and collaboration as well as modeling his humble, but unwavering, support of other areas of interest including the prevention of renal disease in diabetes (18,19), studies of the natural history of b-cell function in type 2 diabetes (22), studies of nutrient and glucocorticoid effects on b-cell response (23)(24)(25)(26)(27)(28)(29), and unending interests in seemingly simple (30) but clinically important areas of research. Many who worked with Fred over the years were touched both by his thoughtful scientific curiosity and his warm, compassionate, and perpetual focus on the individual affected by diabetes.…”

Pancreas Transplantation for Patients With Diabetes Mellitus

“…However, another study in 18 patients 6-to 14-yr posttransplant demonstrated that not all diabetic patients with kidney-only transplants develop the histological lesions of diabetic kidney disease. Thus, the long-term incidence of diabetic nephropathy in transplanted kidneys is unknown, and undefined factors intrinsic to the kidney itself may operate to modulate diabetic renal disease (26). A study of 12 subjects who received pancreas transplants after having undergone renal transplantation found that they had significantly less severe histological changes in the glomerulus than a control group of diabetic renal transplant patients treated with conventional insulin therapy (27).…”