Chronic interstitial damage in proteinuria. Does complement mediate tubulointerstitial injury?

Tubulointerstitial injury is seen in some patients with glomerular proteinuria and when present is a poor prognostic indicator. However, the mechanism by which proteinuria results in tubular and interstitial damage is unknown. Activation of the complement system has been implicated in many forms of tissue injury, including immune-mediated renal disease. Immunohistochemical studies suggest that complement is deposited on the tubular epithelium in proteinuric states raising the possibility that complement activation may contribute to tubular injury. In this review, we discuss how complement proteins reach the tubular epithelium and why the complement system is activated at this site. We also discuss the effects this may have on tubular cells and how this could result in progressive interstitial disease. The possibility that complement inhibition may reduce progression of tubulointerstitial injury is also considered.