Urinary excretion of complement C3d in patients with renal diseases

Complement-mediated tubular injury may play an important role in the progression of renal diseases. C3d is a presumed marker of complement activation. Its precursor C3dg has been detected in the urine of patients with membranous nephropathy. However, little is known of the renal handling of C3d or its excretion in other renal diseases.

We measured the urinary excretion of albumin, IgG, beta2-microglobulin (beta2m), and of complement C3d in patients with tubulo-interstitial nephritis (TIN; n= 8), in patients with membranous nephropathy (n = 35) and in patients with nonmembranous glomerular diseases (23 nonproliferative and 21 proliferative). Fractional excretions (FE) were calculated using creatinine clearance as marker of GFR.

C3d was not measurable in the urine of the healthy controls, but was detectable in seven out of eight of the TIN patients (median excretion 0.11 mU min-1, range 0.006-2.4 mU min-1). In these patients the urinary excretion of beta2m was clearly elevated (median 26.6 micro g min-1, range 1.0-103 micro g min-1). The FE of C3d correlated with the FE of beta2microglobulin (r = 0.83, P = 0.01), and their ratio amounted to 0.03 (range 0.003-0.06), a value in agreement with the expected sieving coefficient. Urine C3d was detectable in all but three of the patients with glomerular diseases (median excretion 0.36 mU min-1, range 0.004-7.9 mU min-1); C3d-excretion did not differ between the three subgroups of patients with glomerular diseases. FEC3d correlated with FEIgG (r = 0.88, P < 0.01). The ratio FEC3d/FEbeta2m was 0.78 (range 0.04-9.99). Selected patients with membranous nephropathy were re-analyzed after (partial) remission of proteinuria. Reduction of proteinuria resulted in a decrease of C3d excretion.

Urinary excretion of C3d is elevated in patients with TIN, most likely as a mere consequence of decreased tubular reabsorption. In patients with glomerular diseases urinary excretion of C3d is increased and related to proteinuria, independent of the underlying glomerular disease. In these patients there is evidence of increased local formation of C3d.