PREMATURE CELL AGING AND EVOLUTION OF DIABETIC NEPHROPATHY

The rate of development and progression of renal disease varies greatl y in insulin-dependent diabetic (IDDM) patients. The cellular and mole cular reasons for this difference are largely unknown but could be rel ated to early cell differentiation, a phenomenon recently reported in IDDM patients with nephropathy. In this study we compared cell differe ntiation and cell volume between IDDM patients with and without nephro pathy and investigated the cell ageing characteristics in relation to the rate of evolution of renal disease in the IDDM patients with diabe tic nephropathy. Cell volume was larger and the percentage of post-mit otic fibrocytes was higher in skin fibroblasts derived from IDDM patie nts with diabetic nephropathy compared to those from IDDM patients wit hout kidney disease (mean +/- SD in arbitrary units 817.3 +/- 25.7 vs 760 +/- 32.8; p = 0.005; and mean +/-SD % 33.6 +/- 11.8 vs 20.8 +/- 10 ; p = 0.02 respectively). Analysis of the interaction of the time to p roteinuria (TTP) and the rate of change of glomerular filtration rate (GFR) with glycaemic control, arterial blood pressure and cell volume and the state of cell differentiation showed that glycated haemoglobin and the percentage of post-mitotic fibrocytes were negatively correla ted to TTP (r = -0.68; p = 0.008; p = -0.52; p = 0.05 respectively) an d positively associated with the rate of change of GFR (r = 0.76; p = 0.03; r = 0.56; p = 0.037 respectively). Cell volume was negatively co rrelated to ?TP (r = -0.53; p = 0.05). Diastolic blood pressure was al so related to the rate of GFR change (r = 0.56; p = 0.039). In a multi ple linear regression analysis glycated haemoglobin maintained its sig nificant independent relationship with TTP at the 1% level, while the strength of the association between the percentage of post-mitotic cel ls and cell volume was reduced to the 11 and 9% level, respectively. C ultured skin fibroblasts from IDDM patients with nephropathy show sign s of early differentiation. Glycaemic control is a key factor in the r ate of onset of proteinuria and different rates of cell ageing appear to contribute to the rate of development and progression of diabetic n ephropathy. Their interaction may be responsible for the severity of r enal involvement in susceptible IDDM patients.