Insudative lesions-Their pathogenesis and association with glomerular obsolescence in diabetes: A dynamic hypothesis based on single views of advancing human diabetic nephropathy

L. Clarke Stout, Shimareet Kumar, Elbert B. Whorton

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Abstract

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 prevalence and severity of insudative lesions (ILs) and obsolescent glomeruli with (OGcFC) and without (OGsFC) insudative (fibrin cap) lesions. A subset of 25 cases with advanced diabetic changes was examined using serial sections, immunohistochemical stains, and electron microscopy to determine the pathogenesis of ILs and OGcFCs. Insudative lesions consisted of intramural accumulations (hereafter called deposits) of presumably imbibed plasma proteins and lipids within renal arterioles, glomerular capillaries, Bowman's capsule, and proximal convoluted tubules. Insudative lesions in Bowman's capsule are called capsular drop lesions (CDs), in glomerular capillaries they are called fibrin cap lesions (FC), and in afferent and efferent arterioles they are called hyalinized afferent (HA) and hyalinized efferent (HE) arterioles, respectively. All ILs were much more numerous and/or larger in diabetics than in controls. Contrary to previous opinion, CDs and HE arteioles were not specific for diabetes, being present in small numbers in nine (15%) controls. Controls with CD HE arterioles had far more HA arterioles and focal mesangiolyses (FMs) than those without. Insudative lesions consisted of the well known homogenous eosinophilic deposits (homogenous eosinophilic ILs) and the less familiar foamy, reticulated, and vacuolar deposits (heterogenous lucent ILs). 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, were found. The first was mostly homogenous eosinophilic, usually without capsular adhesions and located near the vascular pole close to preglomerular 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 Kimmelstiel-Wilson (KW) nodules. The latter ILs sometimes extended in continuity along the internal surface of the basement membrane from Bowman's capsule into the proximal convoluted tubule. It was hypothesized that ILs traveled centrifugally through the walls of preglomerular arterioles to form the first type of CD and longitudinally within the walls of afferent arterioles and glomerular capillaries and through adhesions to form the second. Contrary to previous opinion, FCs were consistently intramural. When numerous, FCs were associated with a form of glomerular obsolescence called OGcfc. Obsolescent glomeruli with fibrin cap lesions had patent circulations (a significant percentage of patententering arterioles and red blood cell [RBC]-containing capillaries), slightly more than 50% of FCs by volume, relatively mild tuft collapse, and considerably decreased nuclei without glomerular necrosis. It was hypothesized that OGcFCs were caused by capillary luminal compression by migrating intramural FCs. Obsolescent glomeruli with fibrin cap lesions were increased in all diabetic cases (2.38% ν 0.26% in controls; P = .0029) but were most numerous in those diabetics with proteinuria (7.1%), mild to moderate renal insufficiency (17%), and end-stage renal disease (28.3%). Obsolescent glomeruli with fibrin cap lesions appreared to develop relatively rapidly, possibly under the influence of hemodynamic factors. Therein lies their potential importance, ie, common lesions capable of producing glomerular destruction that may respond to manipulation of hemodynamic or other factors.

Original languageEnglish (US)
Pages (from-to)1213-1227
Number of pages15
JournalHuman Pathology
Volume25
Issue number11
DOIs
StatePublished - Nov 1994

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Keywords

  • capsular drop lesions
  • diabetic nephropathy
  • fibrin cap lesions
  • glomerular obsolescence
  • hyalinized arterioles
  • insudative lesions

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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