INSUDATIVE LESIONS - THEIR PATHOGENESIS AND ASSOCIATION WITH GLOMERULAR OBSOLESCENCE IN DIABETES - A DYNAMIC HYPOTHESIS BASED ON SINGLE VIEWS OF ADVANCING HUMAN DIABETIC NEPHROPATHY

Kidneys from 74 consecutive, primarily non-insulin-dependent diabetics at autopsy and 59 age-, sex-, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine the prevale nce and severity of insudative lesions (ILs) and obsolescent glomeruli with (OG (c) over bar FC) and without (OG (s) over bar FC) insudative (fibrin cap) lesions. A subset of 25 cases with advanced diabetic cha nges was examined using serial sections, immunohistochemical stains, a nd electron microscopy to determine the pathogenesis of ILs and OG (c) over bar FCs. Insudative lesions consisted of intramural accumulation s (hereafter called deposits) of presumably imbibed plasma proteins an d lipids within renal arterioles, glomerular capillaries, Bowman's cap sule, and proximal convoluted tubules. Insudative lesions in Bowman's capsule are called capsular drop lesions (CDs), in glomerular capillar ies they are oiled fibrin cap lesions (FC), and in afferent and effere nt arterioles they are called hyalinized afferent (HA) and hyalinized efferent (HE) arterioles, respectively. All ILs were much more numerou s and/or larger in diabetics than in controls. Contrary to previous op inion CDs and HE arterioles were not specific for diabetes, being pres ent in small numbers in nine (15%) controls. Controls with CD/HE arter ioles had far more HA arterioles and focal mesangiolyses (FMs) than th ose without. Insudative lesions consisted of the well known homogenous eosinophilic deposits (homogenous eosinophilic ILs) and the less fami liar foamy, reticulated and vacuolar deposits (heterogenous lucent Ifs ). Homogenous eosinophilic ILs were predominant in afferent arterioles and more so in efferent arterioles, and were segregated into globules of varying density with the denser deposits located peripherally. Two types of CDs, which differed sharply in location and composition, wer e found. The first was mostly homogenous eosinophilic, usually without capsular adhesions and located near the vascular pole close to preglo merular arterioles. The second was mostly heterogenous lucent, located away from the vascular pole, and consistently connected by adhesions to the capillary tuft usually near FMs and/or Kimneistiel-Wilson (KW) nodules. The latter ILs sometimes extended in continuity along the int ernal surface of the basement membrane from Bowman's capsule into the proximal convoluted tubule. It was hypothesized that ILs traveled cent rifugally through the walls of preglomerular arterioles to form the fi rst type of CD and longitudinally within the walls of afferent arterio les and glomerular capillaries and through adhesions to form the secon d. Contrary to previous opinion, FCs were consistently intramural. Whe n numerous, FCs were associated with a form of glomerular obsolescence called OG (c) over bar FC. Obsolescent glomeruli with fibrin cap lesi ons had patent circulations (a significant percentage of patent-enteri ng arterioles and red blood cell [RBC]-containing capillaries), slight ly more than 50% of FCs by volume, relatively mild tuft collapse, and considerably decreased nuclei without glomerular necrosis. It was hypo thesized that OG (c) over bar FCs were caused by capillary luminal com pression by migrating intramural FCs, Obsolescent glomeruli with fibri n cap lesions were increased in all diabetic cases (2.38% v 0.26% in c ontrols; P =.0029) but were most numerous in those diabetics with prot einuria (7.1%), mild to moderate renal insufficiency (17%), and end-st age renal disease (28.3%). Obsolescent glomeruli with fibrin cap lesio ns appeared to develop relatively rapidly, possibly under the influenc e of hemodynamic factors. Therein lies their potential importance, ie, common lesions capable of producing glomerular destruction that may r espond to manipulation of hemodynamic or other factors. (C) 1994 by W. B. Saunders Company