Complete Remission Of Diabetic Nephropathy In A Type 1 Diabetic Patient With Near-nephrotic Range Proteinuria And Reduced Renal Function

Abstract

There is scant knowledge on the changes in renal histological findings in type 1 diabetic patients those initially had nephrotic proteinuria and decreased renal function and later had complete remission of diabetic nephropathy by multifactorial treatment (MFT). A 44-year-old Japanese type 1 diabetic woman (duration of diabetes: 17 years) with massive proteinuria (2.9 g/day) and decreased renal function (creatinine clearance rate (Ccr): 86 mL/min) was admitted. Aggressive MFT was started with intensive insulin treatment, a low protein and low salt diet, angiotensin converting enzyme inhibitor and a diuretic. Her levels of HbA1c decreased to less than 7% within 4 months, and her high blood pressure gradually decreased and remained around mean 116/68 mmHg. Her Ccr level gradually improved and reached 108 mL/min after 78 months. Her first renal biopsy performed before MFT demonstrated diffuse and/or global accumulation of periodic acid-Schiff staining-positive mesangial matrix with increased mesangial matrix/glomerulus ratio and tubulo-interstitial fibrosis. Her second renal biopsy performed 5 years after MFT demonstrated decreased mesangial matrix/glomerulus ratio (42.0+/-4.0% to 29.2+/-1.9% [mean+/-S.D.], p<0.001) and increased her number of glomerular capillaries lumen per glomerulus (47+/-11 to 77+/-12, p<0.006). The number of vascular endothelial growth factor (VEGF)-expressing cells in the glomerular capillary significantly increased. Increased tubulo-interstitial fibrosis and the thickness of glomerular basement membrane (GBM) seen in the first biopsy specimen had decreased in the specimen taken at the second biopsy. Our case provides evidence that glomerular morphological improvements including decreased mesangial deposit and VEGF-related vasculogenesis in response to MFT goes along with functional normalization of diabetic nephropathy, which could not be attained in type 1 diabetic patients that underwent pancreas transplantation.