Decreasing glomerular filtration rate - An indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents?

Abstract

Background. Overt diabetic nephropathy is accompanied by a progressive decline in glomerular filtration rate (GFR). In this study we have investigated if a reduction of GFR already during the transition from normo- to microalbuminuria is associated with glomerular structural changes. Methods. Seventeen adolescents (11 girls/6 boys) with 10.5 (3.3) (mean, SD) years of IDDM were studied. GFR was previously measured in the normoalbuminuric stage 2 - 5 years prior to the renal biopsy, and measured again at the time for the biopsy, after in mean 1.8 years of microalbuminuria (15 - 200 μg/min). HbAlc and albumin excretion rate were measured 3 or 4 times yearly and blood pressure 1 - 4 times yearly between the GFR examinations. The associations between the yearly rate of fall in GFR and basement membrane (BM) thickness, mesangial and matrix volume fractions, matrix star volume, mean capillary diameter (CAPD), area of filtration surface (peripheral BM) per glomerulus, total capillary length per glomerulus, the ratio of peripheral BM to capillary surface, glomerular volume, and interstitial volume fraction were analysed. Results. BM thickness and matrix star volume were increased in patients with, as compared to those without, a decline in GFR ≤ 6 ml/min per year (P < 0.005 respectively). Patients with previous glomerular hyperfiltration (≤ 135 ml/min per 1.73 m2) showed the steepest decline in GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering patients, P < 0.001. The rate of fall in GFR was positively correlated to BM thickness (P < 0.001), interstitial volume fraction (P = 0.02) and CAPD (P = 0.04), mean HbAlc (P = 0.01), but not to the change in HbAlc between GFR examinations. Conclusion. A decreasing glomerular filtration rate in the early stage of microalbuminuria may be due to more advanced diabetic glomerulopathy than in IDDM patients with stable GFR.