DECREASING GLOMERULAR-FILTRATION RATE - AN INDICATOR OF MORE ADVANCEDDIABETIC GLOMERULOPATHY IN THE EARLY COURSE OF MICROALBUMINURIA IN IDDM ADOLESCENTS

Background. Overt diabetic nephropathy is accompanied by a progressive decline in glomerular filtration rate (GFR). In this study we have in vestigated if a reduction of GFR already during the transition from no rmo- to microalbuminuria is associated with glomerular structural chan ges. 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 me asured again at the time for the biopsy, after in mean 1.8 years of mi croalbuminuria (15-200 mu g/min). HbAlc and albumin excretion rate wer e measured 3 or 4 times yearly and blood pressure 1-4 times yearly bet ween the GFR examinations. The associations between the yearly rate of fall in GFR and basement membrane (BM) thickness, mesangial and matri x volume fractions, matrix star volume, mean capillary diameter (CAPD) , area of filtration surface (peripheral BM) per glomerulus, total cap illary length per glomerulus, the ratio of peripheral BM to capillary surface. glomerular volume, and interstitial volume, fraction were ana lysed. Results. BM thickness and matrix star volume were increased in patients with, as compared to those without, a decline in GFR greater than or equal to 6 ml/min per year (P<0.005 respectively). Patients wi th previous glomerular hyperfiltration (greater than or equal to 135 m l/min per 1.73 m(2)) showed the steepest decline in GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering patient s, P<0.001. The rate of fall in GFR was positively correlated to BM th ickness (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 t he early stage of microalbuminuria may be due to more advanced diabeti c glomerulopathy than in IDDM patients with stable GFR.