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

Abstract

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.

• Authors: Gopala K Rangan, Jeffrey W Pippin, Jason D Coombes, William G Couser
• Journal: Kidney international (Kidney Int) Vol. 67 Issue 2 Pg. 492-503 (Feb 2005) ISSN: 0085-2538 [Print] United States
• PMID: 15673297 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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)