Pancreas transplantation in patients with type 1 diabetes can reverse diabetic nephropathy lesions, but this process requires more than five years of normoglycemia. The study followed eight patients with type 1 diabetes and mild to advanced diabetic nephropathy who had not received a kidney transplant. Before and after pancreas transplantation, they underwent renal biopsies and had their kidney function monitored. All patients maintained normal glycosylated hemoglobin levels after transplantation. The median urinary albumin excretion rate decreased from 103 mg/day at baseline to 30 mg/day at 5 years and 20 mg/day at 10 years. Creatinine clearance declined over time, but the thickness of the glomerular and tubular basement membranes decreased significantly by 10 years. The mesangial fractional volume increased initially but decreased by 10 years, mostly due to a reduction in mesangial matrix. These findings suggest that pancreas transplantation can reverse diabetic nephropathy lesions, but the process takes more than five years of normoglycemia. The study also highlights the importance of long-term normoglycemia in preventing and reversing diabetic nephropathy. The results indicate that the beneficial effects of pancreas transplantation are due to prolonged normoglycemia, not immunosuppressive therapy. The study also discusses the mechanisms by which diabetic nephropathy lesions can be reversed, including the reduction of extracellular matrix accumulation and the potential for glycosylated matrix molecules to be degraded over time. The study concludes that pancreas transplantation can reverse diabetic nephropathy lesions in patients with type 1 diabetes, but the process requires long-term normoglycemia. The study also emphasizes the importance of monitoring patients with type 1 diabetes for early signs of diabetic nephropathy and the potential for pancreas transplantation to reverse these lesions. The study also discusses the risks and benefits of pancreas transplantation, including the nephrotoxic effects of some immunosuppressive agents and the risks of surgery. The study concludes that pancreas transplantation can reverse diabetic nephropathy lesions in patients with type 1 diabetes, but the process requires long-term normoglycemia. The study also highlights the importance of long-term follow-up in patients with type 1 diabetes to monitor for the development of diabetic nephropathy and to assess the effectiveness of pancreas transplantation in reversing these lesions. The study also discusses the potential for other methods, such as improved immunomodulation or islet transplantation, to achieve similar results with less risk. The study is supported by grants from the National Institutes of Health and the Juvenile Diabetes Foundation International. The authors thank the patients who participated in the study and the technical and secretarial staff who assisted in the research.Pancreas transplantation in patients with type 1 diabetes can reverse diabetic nephropathy lesions, but this process requires more than five years of normoglycemia. The study followed eight patients with type 1 diabetes and mild to advanced diabetic nephropathy who had not received a kidney transplant. Before and after pancreas transplantation, they underwent renal biopsies and had their kidney function monitored. All patients maintained normal glycosylated hemoglobin levels after transplantation. The median urinary albumin excretion rate decreased from 103 mg/day at baseline to 30 mg/day at 5 years and 20 mg/day at 10 years. Creatinine clearance declined over time, but the thickness of the glomerular and tubular basement membranes decreased significantly by 10 years. The mesangial fractional volume increased initially but decreased by 10 years, mostly due to a reduction in mesangial matrix. These findings suggest that pancreas transplantation can reverse diabetic nephropathy lesions, but the process takes more than five years of normoglycemia. The study also highlights the importance of long-term normoglycemia in preventing and reversing diabetic nephropathy. The results indicate that the beneficial effects of pancreas transplantation are due to prolonged normoglycemia, not immunosuppressive therapy. The study also discusses the mechanisms by which diabetic nephropathy lesions can be reversed, including the reduction of extracellular matrix accumulation and the potential for glycosylated matrix molecules to be degraded over time. The study concludes that pancreas transplantation can reverse diabetic nephropathy lesions in patients with type 1 diabetes, but the process requires long-term normoglycemia. The study also emphasizes the importance of monitoring patients with type 1 diabetes for early signs of diabetic nephropathy and the potential for pancreas transplantation to reverse these lesions. The study also discusses the risks and benefits of pancreas transplantation, including the nephrotoxic effects of some immunosuppressive agents and the risks of surgery. The study concludes that pancreas transplantation can reverse diabetic nephropathy lesions in patients with type 1 diabetes, but the process requires long-term normoglycemia. The study also highlights the importance of long-term follow-up in patients with type 1 diabetes to monitor for the development of diabetic nephropathy and to assess the effectiveness of pancreas transplantation in reversing these lesions. The study also discusses the potential for other methods, such as improved immunomodulation or islet transplantation, to achieve similar results with less risk. The study is supported by grants from the National Institutes of Health and the Juvenile Diabetes Foundation International. The authors thank the patients who participated in the study and the technical and secretarial staff who assisted in the research.