Urinary excretion of complement C3d in patients with renal diseases.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Complement degradation product C3d in urine: marker of lupus nephritis.

OBJECTIVE: To examine whether serum and urine C3d, a degradation product of C3, correlate with renal and extrarenal lupus activity. METHODS: Serum and urinary C3d levels were measured by ELISA in 15 healthy individuals and 24 patients with systemic lupus erythematosus (SLE) (8 with inactive disease, 7 with active but nonrenal disease, 9 with active lupus nephritis). Disease activity variables like serum C3, C4, and anti-dsDNA antibodies were also measured. RESULTS: The median serum C3d levels were significantly higher (p < 0.01) in patients with active (26 arbitrary units/ml; AU/ml) and inactive SLE (27 AU/ml) compared to healthy controls (11.25 AU/ml); levels were comparable in patients with active renal and extrarenal SLE. On the other hand, urine C3d was elevated only in patients with active SLE; its level was highest in patients with active lupus nephritis (0.87 AU/ml) compared to patients with active extrarenal diseases (0.31 AU/ml; p < 0.05), to patients with inactive lupus nephritis (0.06 AU/ml; p < 0.001), or to levels in healthy individuals (0.06; p < 0.001). Urine C3d showed stronger correlation with disease activity score (SLE Disease Activity Index) than serum C3, C4, anti-dsDNA antibodies, and serum C3d. CONCLUSION: Urine C3d is a good index of active lupus, particularly lupus nephritis.