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


CONCLUSIONS
Our results suggest that urinary properdin excretion enhances intrarenal complement activation and thus may contribute to the progression of renal damage in proteinuric states.
Siezenga
Machiel A
MA
Leiden University Medical Center, Department of Nephrology, Leiden, The Netherlands. m.a.siezenga@lumc.nl
van der Geest
Reinier N
RN
Mallat
Marko J K
MJ
Rabelink
Ton J
TJ
Daha
Mohamed R
MR
Berger
Stefan P
SP
D015415:Biomarkers / Q000652:urine*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology / Q000652:urine*; D007677:Kidney Function Tests; D008875:Middle Aged; D011379:Prognosis; D011414:Properdin / Q000652:urine*; D011507:Proteinuria / Q000652:urine*
D015415:Biomarkers; D015938:Complement Membrane Attack Complex; C047610:SC5b-9 protein complex; D011414:Properdin