title: Correlation of membranous glomerular ultrastructural changes with disease severity and outcome in lupus patients initiating cyclophosphamide therapy.
abstract: The aim of this study was to assess the utility applying an electron microscopy (EM) scoring system used in idiopathic membranous nephritis based on the location of subepithelial and/or intramembranous electron dense deposits in interpretation of renal biopsies from patients with lupus nephritis. We selected patients with electron dense deposits traditionally associated with membranous changes on EM from 84 patients treated with bolus cyclophosphamide, with five years follow-up. An EM scoring system designed for idiopathic membranous nephritis was applied (stages I or II, mild changes; stages III or IV, advanced changes). Twenty-seven out of 84 had membranous changes by light microscopy, of whom 22 had satisfactory tissue for EM membranous analysis. Eleven out of 22 had mild EM changes (EM stage I or II); 11 had advanced disease (EM stage III). Advanced EM stage was associated with a higher serum creatinine at entry when tests were adjusted for WHO class (2.62 +/- 0.6 versus 1.31 +/- 0.28 mg/dL, P < 0.022 by ANOVA), and EM stage was independent of NIH activity or chronicity indexes or disease duration. After five years, adverse outcomes (death or dialysis) were seen in one of the 11 patients with EM stages I-II versus five of the 11 EM stage III patients (P < 0.07). Advanced membranous type electron dense deposition in lupus as assessed by EM was associated with worse renal function in patients with comparable WHO classification and NIH activity and chronicity indexes. In this group of lupus patients initiating cyclophosphamide for severe nephritis, EM stage provided important additional information regarding the extent of renal injury.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, 1500 E. Medical Center Dr., Taubman 3918, Ann Arbor, MI 48109, USA. jmccune@umich.edu
authors.forename: W J
authors.initials: WJ
authors.lastname: McCune
authors.forename: M
authors.initials: M
authors.lastname: Saluja
authors.forename: S
authors.initials: S
authors.lastname: Bhat
authors.forename: L A
authors.initials: LA
authors.lastname: Lange
authors.forename: L
authors.initials: L
authors.lastname: Holzman
authors.forename: K
authors.initials: K
authors.lastname: Johnson
mesh_terms: D001485:Basement Membrane / Q000648:ultrastructure; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000648:ultrastructure*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D011379:Prognosis
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide