C1q nephropathy: a variant of focal segmental glomerulosclerosis

Kidney Int. 2003 Oct;64(4):1232-40. doi: 10.1046/j.1523-1755.2003.00218.x.


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).

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • Cohort Studies
  • Complement C1q / metabolism*
  • Female
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Hematuria / etiology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology
  • Male
  • Multivariate Analysis
  • Nephrosis, Lipoid / metabolism
  • Nephrosis, Lipoid / pathology
  • Nephrotic Syndrome / etiology
  • Prognosis
  • Proteinuria / etiology
  • Renal Insufficiency / etiology
  • Retrospective Studies


  • Immunosuppressive Agents
  • Complement C1q