Complement Activation and Progression of Chronic Kidney Disease

Proteinuria is a strong predictor of progression in chronic kidney disease. Complement proteins are a major constituent of the urine of proteinuric patients. Complement is activated in the tubular lumen through the alternative pathway, and complement activation products are deposited on the apical surface of tubular epithelial cells. Recent animal studies have suggested that complement activation in the tubular compartment plays an important role in proteinuria-associated tubulointerstitial injury. Complement deficiency, depletion or inhibition all reduce the tubular cell damage and interstitial fibrosis that develops in proteinuric animals. In particular, inhibition of anaphylatoxin receptors protects the kidneys from proteinuria-associated damage. In this review, we discuss the evidence for a role of complement activation in the progression of chronic kidney disease.