On glomerular structural alterations in type-1 diabetes. Companions of early diabetic glomerulopathy.
Glomerular structural modifications were measured in kidney biopsies from two follow-up studies in type-1 diabetic patients with microalbuminuria and in kidney donors. Stereologic methods were used to obtain data on glomerular composition and absolute quantities per glomerulus to supplement data on diabetic glomerulopathy previously published. Diabetic patients at baseline (n=37) showed significant changes compared with controls (n=11). The volume fraction of tuft/glomerulus was increased, the proportion of capillary surface facing peripheral basement membrane was decreased (0.72+/-0.04 vs 0.77+/-0.03, P=0.0008), the ratio of mesangial surfaces, urinary/capillary, was decreased (0.67+/-0.17 vs 1.11+/-0.28, P<10(-4)), and the average capillary diameter was increased (8.9+/-0.9 microm vs 7.5+/-1.0 microm, P=0.0002). The total volume of mesangial extracellular material per glomerulus was increased (P=0.01), whereas glomerular volume was not significantly different from controls. Follow-up biopsies after antihypertensive treatment with ACE-inhibitor (n=7) or beta-blocker (n=6; 36-48 months) and after intensive insulin treatment (n=7; 24-33 months) showed no change. In a conventionally treated group (n=9), the glomerular volume, the volume of extracellular material/glomerulus, and the capillary length increased. The mean capillary diameter did not correlate with the glomerular volume. In conclusion, the development of diabetic glomerulopathy entails structural modifications of the glomerular tuft. Antihypertensive and intensified insulin treatment seem to slow the progression of ultrastructural changes.
Electron Microscopy Laboratory, University Institute of Pathology, Aarhus Kommunehospital, Denmark. ro@em.au.dk
R
R
Osterby
H J
HJ
Bangstad
G
G
Nyberg
S
S
Rudberg
D000328:Adult; D000419:Albuminuria; D002196:Capillaries / Q000000981:diagnostic imaging / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology*; D004656:Enalapril / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D008854:Microscopy, Electron; D016896:Treatment Outcome; D014463:Ultrasonography
D007328:Insulin; D004656:Enalapril; D008790:Metoprolol