Leiden University Scholarly Publications

Siezenga, M.A.; Geest, R.N. van der; Mallat, M.J.K.; Rabelink, T.J.; Daha, M.R.; Berger, S.P. (2010)

Urinary properdin excretion is associated with intrarenal complement activation and poor renal function

Article / Letter to editor

Background. Proteinuria predicts progressive renal failure. Next to being a progression marker, non-selective proteinuria itself is thought to be toxic to the tubulointerstitium. In proteinuric states, activation of filtered or locally produced complement is toxic for renal tubular cells and likely contributes to the progression of renal failure. Recent experimental evidence suggests an important role for properdin in promoting intrarenal complement activation. We measured properdin in proteinuric urine and assessed its relation with urinary SC5b-9 levels, the soluble form of the effector phase of complement activation. Methods. Seventy patients with renal disease of different origin but all with a protein excretion of at least 1 g/day were studied. Urinary properdin and SC5b-9 levels were measured using an ELISA technique. Results. Properdin was detectable in the urine of 37 patients (53%). These subjects had higher urinary SC5b-9 levels {median 0.50 U/ml [interquartile range (IQR)...Show moreBackground. Proteinuria predicts progressive renal failure. Next to being a progression marker, non-selective proteinuria itself is thought to be toxic to the tubulointerstitium. In proteinuric states, activation of filtered or locally produced complement is toxic for renal tubular cells and likely contributes to the progression of renal failure. Recent experimental evidence suggests an important role for properdin in promoting intrarenal complement activation. We measured properdin in proteinuric urine and assessed its relation with urinary SC5b-9 levels, the soluble form of the effector phase of complement activation. Methods. Seventy patients with renal disease of different origin but all with a protein excretion of at least 1 g/day were studied. Urinary properdin and SC5b-9 levels were measured using an ELISA technique. Results. Properdin was detectable in the urine of 37 patients (53%). These subjects had higher urinary SC5b-9 levels {median 0.50 U/ml [interquartile range (IQR) 0.13-1.81] versus 0.049 U/ml (IQR 0.024-0.089), P < 0.001}. When adjusted for proteinuria and renal function, properdin excretion was strongly associated with increased urinary SC5b-9 levels (odds ratio 16.2, 95% confidence interval 3.6-74.4). Properdin excretion was associated with worse renal function. Conclusion. Our results suggest that urinary properdin excretion enhances intrarenal complement activation and thus may contribute to the progression of renal damage in proteinuric states.Show less

complement activation properdin proteinuria renal failure tubular epithelial-cells experimental nephrotic syndrome membrane attack complex alternative pathway tubulointerstitial injury progressive nephropathies interstitial disease positive regulator proximal tubules brush-border

All authors

Siezenga, M.A.; Geest, R.N. van der; Mallat, M.J.K.; Rabelink, T.J.; Daha, M.R.; Berger, S.P.

Date

2010-04-30

Journal

Nephrology Dialysis Transplantation

Volume

25

Issue

4

Pages

1157 - 1161

DOI

doi:10.1093/ndt/gfp630