Collapsing Glomerulopathy (CG) in 13 Patients with Systemic Lupus Erythematosus (SLE): Cause or Coincidence?
SP Salvatore, L Barisoni, SV Seshan. Weill Cornell Medical College, New York; NYU Medical Center, New York
Background: CG is a primary podocytopathy characterized by segmental or global collapse of capillary walls with wrinkling of the glomerular basement membrane and overlying dedifferentiated podocyte proliferation. Idiopathic CG is a distinct clinicopathologic entity with poor response to immunosuppresive therapy and rapid progression to renal failure. CG has been associated with many etiologies including viral infections, autoimmune disease, and certain drugs. Although described in anecdotal case reports, we present the largest group of CG, thus far, in patients with SLE or SLE-like disease.
Design: Renal biopsies were studied from 13 patients with SLE (10) or SLE-like (3) disease diagnosed with CG. A retrospective analysis of clinicopathologic features and follow-up was done. Immunohistochemistry (IHC) for parvovirus and Ki67 were performed.
Results: The patients ranged from 16-63 years, M:F-2:11, and were predominantly of African descent (92%). At presentation, all patients had nephrotic syndrome with mean proteinuria (7g/24hr +/- 2.9), creatinine (Cr) 3 +/- 2.7 and BUN 44 +/- 37, except in one patient whose Cr/BUN was 26.5/155. The complement levels were normal (mean C3 105, C4 26). ANA was positive in 89%, anti-dsDNA 75%, and anti-Smith 25%. HIV, HCV, and Parvovirus serologies were negative in all patients tested. On morphology, globally collapsed glomeruli ranged from 1-52% (mean 20.7%), segmentally collapsed (0-20%), and globally sclerosed glomeruli (0-37%). Mild to severe tubular atrophy and interstitial fibrosis was seen in 35% with focal microcystic changes. Minimal glomerular mesangial deposits were seen by IF and EM in 57%, and extensive foot process effacement in 76%. Ki-67 positive epithelial nuclei were seen per affected glomeruli (mean 2.1). Parvovirus IHC in CG podocytes was positive in 4/11 patients. Initial treatment was pulse/oral steroids and dialysis (8). Follow-up from 9 patients showed 5 with end-stage renal disease, 0-21 months after biopsy;1 patient returned to normal cr and 3, 1.2-3.0mg/dl.
Conclusions: Immunologic (antibody or cytokine) mediated injury may lead to glomerular podocytopathy in SLE (minimal change disease, FSGS). However, other known causes of CG, having an impact on prognosis and therapy, should be considered in this setting. The high predominance of patients of African descent in our study suggests that podocytic injury and collapsing features could result from immunologic and/or environmental factors on a genetic predisposition to epithelial injury.
Category: Kidney (does not include tumors)
Monday, March 22, 2010 1:30 PM
Platform Session: Section H, Monday Afternoon