title: C1q nephropathy: a variant of focal segmental glomerulosclerosis.
abstract: BACKGROUND
  C1q nephropathy is a poorly understood and controversial entity with distinctive immunopathologic features. In order to better define the clinical-pathologic spectrum, we report the largest single-center series.
  
  
  METHODS
  Nineteen biopsies with C1q nephropathy were identified from among 8909 native kidney biopsies received from 1994 to 2002 (0.21%). Defining criteria included (1). dominant or co-dominant immunofluorescence staining for C1q, (2). mesangial electron dense deposits, and (3). no clinical or serologic evidence of systemic lupus erythematosus (SLE).
  
  
  RESULTS
  The 19 patients were predominantly African American (73.7%), female (73.7%), young adults and children (range, 3 to 42 years; mean, 24.2 years). Presentation included nephrotic range proteinuria (78.9%), nephrotic syndrome (50%), renal insufficiency (27.8%), and hematuria (22.2%). No patient had hypocomplementemia or evidence of underlying autoimmune or infectious disease. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 17 (including six collapsing and two cellular) and minimal-change disease (MCD) in two. All biopsies displayed co-deposits of immunoglobulin G (IgG), with more variable IgM (84.2%), IgA (31.6%), and C3 (52.6%). Foot process effacement varied from 20% to 100% (mean, 51%). Twelve of 16 patients with available follow-up received immunosuppressive therapy. One patient had complete remission of proteinuria and six had partial remission. Four patients with FSGS pattern had progressive renal insufficiency, including two who reached end-stage renal disease (ESRD). Median time from biopsy to ESRD was 81 months. On multivariate analysis, the best correlate of renal insufficiency at biopsy and at follow-up was the degree of tubular atrophy and interstitial fibrosis (P = 0.0495 and 0.0341, respectively).
  
  
  CONCLUSIONS
  C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a non-specific marker of increased mesangial trafficking in the setting of glomerular proteinuria.
authors.affiliation: Department of Pathology, Columbia University,College of Physicians & Surgeons, New York, New York 10032, USA.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Markowitz
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Schwimmer
authors.forename: M Barry
authors.initials: MB
authors.lastname: Stokes
authors.forename: Samih
authors.initials: S
authors.lastname: Nasr
authors.forename: Robert L
authors.initials: RL
authors.lastname: Seigle
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Valeri
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015922:Complement C1q / Q000378:metabolism*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006417:Hematuria / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D015999:Multivariate Analysis; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000209:etiology; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology; D051437:Renal Insufficiency / Q000209:etiology; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D015922:Complement C1q