C5b-9 does not mediate chronic tubulointerstitial disease in the absence of proteinuria

Kidney Int. 2005 Feb;67(2):492-503. doi: 10.1111/j.1523-1755.2005.67106.x.


Background: In nephrotic glomerular diseases, the intratubular assembly of the membrane attack complex (C5b-9) is one of the principal mediators of chronic tubulointerstitial damage. Here, we examined whether C5b-9 has a pathogenic role in tubulointerstitial disease in the absence of proteinuria.

Methods: Three pathophysiologically distinct models of nonproteinuric chronic tubulointerstitial disease were induced in Piebald-Viral-Glaxo (PVG) rats, with or without C6 deficiency (C6+ and C6): (1) unilateral ureteric obstruction (UUO, days 1, 3, 6, 14, and 21; N= 5-6/group); (2) cyclosporine (CsA) nephropathy (15 mg/kg SC daily with 0.05% sodium diet; day 14, 35 N= 9/group); and (3) streptozotocin (STZ)-induced diabetes (day 90, N= 8/group).

Results: The peritubular deposition of C5b-9 increased in all three models. In UUO, the number of vimentin-positive tubules, interstitial volume expansion, and monocyte accumulation were similar in both the C6+ and C6- groups at all time points. There was a trend toward an earlier peak in myofibroblast accumulation in C6- rats with UUO (d3 vs. d6; P= 0.05), but this did not prevent fibrosis at later time points. In CsA nephropathy, cortical tubulointerstitial damage was also similar in both C6+ and C6- groups on day 14, despite equivalent CsA trough levels. Finally, in STZ-induced diabetes, rats did not develop proteinuria, and tubulointerstitial disease (distal tubule glycogen nephrosis, interstitial volume expansion, and tubular dilatation) was not altered by C6 deficiency.

Conclusion: These data suggest that, in contrast to proteinuric states, C5b-9 does not have a significant impact on the progression of tubulointerstitial damage in nonproteinuric chronic renal disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chronic Disease
  • Complement Membrane Attack Complex / physiology*
  • Cyclosporine / toxicity
  • Diabetes Mellitus, Experimental / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Immunohistochemistry
  • Kidney Tubules / pathology*
  • Nephritis, Interstitial / pathology*
  • Proteinuria / pathology*
  • Rats
  • Streptozocin
  • Ureteral Obstruction / pathology


  • Complement Membrane Attack Complex
  • Extracellular Matrix Proteins
  • Streptozocin
  • Cyclosporine