Nephropathology
   
Case 82
Diagnosis
 
     
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Diagnosis: C3 Glomerulonephritis

Whereas early classifications of glomerulonephritis (GN) were based on morphologic features, the modern approach is directed at immunofluorescence findings. Glomerular deposits of C3 alone, without immunoglobulin, are the hallmark of alternative complement pathway dysregulation through inherited or acquired defects. These immunoglobulin-negative forms are referred to as C3 glomerulopathy, which encompasses both dense deposit disease and C3 glomerulonephritis. Distinguishing C3 glomerulopathy from immunoglobulin-mediated GN is opening the way to better diagnostic, prognostic, and treatment algorithms (D'Agati VD, Bomback AS. C3 glomerulopathy: what's in a name? Kidney Int. 2012;82(4):379-81. [PubMed link])

C3 GN equally affect all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remain stable in the majority of patients with native kidney disease. Alternative pathway of complement abnormalities are heterogeneous, both acquired and genetic. The most common acquired abnormality appears to be the presence of C3 nephritic factors, while the most common genetic finding appears to be the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities include Factor H autoantibodies and mutations in CFH, CFI, and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN show accumulation of alternative pathway and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury (Sethi S, et al. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82(4):465-73. [PubMed link])

So, in patients with C3GN it is required a strict clinical follow-up with continuous measurement of serum complement, which helps to confirm the diagnosis and to differentiate of post-infectious and other GN.

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References

  • Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, Nasr SH, Smith RJ. Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int. 2012 Dec 12. [Epub ahead of print] [PubMed link]
  • Bomback AS, Appel GB. Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol. 2012;8(11):634-42. [PubMed link]
  • D'Agati VD, Bomback AS. C3 glomerulopathy: what's in a name? Kidney Int. 2012;82(4):379-81. [PubMed link]
  • Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, Theis JD, Dogan A, Smith RJ. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82(4):465-73. [PubMed link]
  • Beck LH Jr. Monoclonal antibodies for the treatment of the C3 glomerulopathies. Clin J Am Soc Nephrol. 2012;7(5):704-6. [PubMed link]
  • Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82(4):454-64. [PubMed link]
  • Sethi S, Nester CM, Smith RJ. Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int. 2012;81(5):434-41. [PubMed link]
  • Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol. 2011;31(4):341-8. [PubMed link]
  • Sethi S, Fervenza FC, Zhang Y, Nasr SH, Leung N, Vrana J, Cramer C, Nester CM, Smith RJ. Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol. 2011;6(5):1009-17. [PubMed link]

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