The Early Natural History of Nephropathy in Type 1 Diabetes

Abstract

Renal structural abnormalities are known to precede the development of proteinuria, hypertension, and reduced renal function in patients with type 1 diabetes. The determinants of these early structural abnormalities are, however, largely unknown. The International Diabetic Nephropathy Study (IDNS) has recruited 243 children and adults (aged 10 -40 years) in Montreal, Minneapolis, and Paris to identify and quantify these determinants. All study subjects were normotensive and had normal-to-high glomerular filtration rates (GFRs) and urinary albumin excretion rates (AERs) <100 g/ min at study entry. Only 8

Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients

“…Moreover, these patients were relatively young and had a relatively short duration of diabetes. Nonetheless, consistent with our previous reports [13,20], glomerular structure was abnormal in both groups, although Vv(Mes/glom) did not exceed normal in the JGA T-cell positive group. However, there was no difference in GBM width or Vv(Mes/glom) between the two Type 1 diabetic groups.…”

“…The present study was done to determine whether these prior observations [17] could be confirmed and whether demographic, clinical or renal morphometric differences exist between Type 1 diabetic patients with and without JGA T-cell infiltration. This study was possible because of the large number of renal biopsies available from the NHDN study, ranging from young patients with a relatively brief duration of diabetes to older patients with diabetes for as long as 20 years [19,20]. The study included two highly polarized groups, one clearly positive and the other clearly negative for JGA T-cell infiltration in renal biopsy tissues containing at least seven glomeruli or four JGA's.…”

“…The cohort for this study came from the International Diabetic Nephropathy Study Group, an international study of the natural history of diabetic nephropathy (NHDN) in young Type 1 diabetic patients [19,20]. The baseline clinical characteristics, renal function and renal structure data have been detailed elsewhere [19,20]. Centers participating in this study included McGill University, Montreal, University of Minnesota, Minneapolis and Hôpital Robert Debré, Hôpital St. Louis, and Hôpital Necker Enfants Malades, Unité Inserm U423, Paris.…”

“…Renal biopsy studies: Immunoperoxidase (IP) studies. Renal tissues were obtained by percutaneous biopsy and processed for light microscopy in Zenker's or Brazil solution and embedded in paraffin and electron microscopy fixed in 2.5% glutaraldehyde in Millonig's buffer as described [20].…”

“…Mean glomerular volume (GV) was measured using a projecting microscope at a magnification of 150× using the Cava- lieri method which is independent of glomerular size or shape [20,22]. Serial sections obtained at 20 µm intervals were examined and glomerular profiles were mapped and numbered.…”