C5b-9 does not mediate tubulointerstitial injury in experimental acute glomerular disease characterized by selective proteinuria

AIM: To determine whether complement membrane attack complex(C5b-9) has a pathogenic role in tubulointerstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS: Protein-overload nephropathy(PON) was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 deficiency(C6- and C6+) by daily intraperitoneal injections of bovine serum albumin(BSA, 2 g/d), and examined on days 2, 4 and 8.RESULTS: Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6+ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells(TECs), whereas it was undetectable in C6- animals. TEC proliferation(as assessed by the number of BrdU +cells) increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU + TECs on day 4 in the C6- PON group(P = 0.10 compared to C6+) but not at any other time-point. Kidney enlargement, TEC apoptosis(TUNEL+ cells) and markers of tubular injury(tubule dilatation, loss of TEC height, protein cast formation) were not altered by C6 deficiency in PON. Interstitial monocyte(ED-1+ cell) accumulation was partially reduced in C6- animals with PON on day 4(P = 0.01) but there was no change in myofibroblast accumulation. CONCLUSION: These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.

AIM： To determine whether complement membrane attack complex （C5b-9） has a pathogenic role in tubuloin-terstitial injury in a renal disease model characterized by acute highly selective proteinuria. METHODS： Protein-overload nephropathy （PON） was induced in adult female Piebald-Viral-Glaxo rats with or without complement C6 defciency （C6- and C6＋） by daily intraperitoneal injections of bovine serum albumin （BSA, 2 g/d）, and examined on days 2, 4 and 8.RESULTS： Groups with PON developed equivalent levels of heavy proteinuria within 24 h of BSA injection. In C6＋ rats with PON, the tubulointerstitial expression of C5b-9 was increased and localized predominantly to the basolateral surface of tubular epithelial cells （TECs）, whereas it was undetectable in C6- animals. TEC proliferation （as assessed by the number of BrdU＋cells） increased by more than 50-fold in PON, peaking on day 2 and declining on days 4 to 8. There was a trend for a reduction in the number of BrdU＋ TECs on day 4 in the C6- PON group （ P = 0.10 compared to C6＋） but not at any other time-point. Kidney enlargement, TEC apoptosis （TUNEL＋ cells） and markers of tubular injury （tubule dilatation, loss of TEC height, protein cast formation） were not altered by C6 deficiency in PON. Interstitial monocyte （ED-1＋ cell） accumulation was partially reduced in C6- animals with PON on day 4 （ P = 0.01） but there was no change in myofbroblast accumulation. CONCLUSION： These data suggest that C5b-9 does not mediate tubulointerstitial injury in acute glomerular diseases characterized by selective proteinuria.