C3 metabolism in acute glomerulonephritis: Implications for sites of complement activation

Immunochemical and metabolic studies of complement were performed in 11 patients with acute poststreptococcal glomerulonephritis (AGN) to determine the mechanism(s) of hypocomplementia. Four patients with profound reduction in serum C3 showed metabolic changes comparable to those seen in hypocomplementemic mesangiocapillary GN (MCGN), that is, nonlinear plasma disappearance of 125I.C3 and a gross (that is, 30-fold) reduction in C3 synthesis (0.01 to 0.02 mg/kg/hr; fractional catabolic rate (FCR) and extravascular/intravascular distribution (EV/IV) ratio were also increased (3.02 to 6.99% hr; 1.14 to 2.96, respectively). The remaining seven patients had less (or no) reduction in C3 and showed normal or elevated values for all three metabolic parameters; six had linear plasma disappearance curves. Metabolic data in five simultaneously studied control subjects were FCR: 1.56 to 2.12%/hr; EV/IV ratio: 0.12 to 0.41 and synthesis rate: 0.30 to 0.52 mg/kg/hr. C3 nephritic factor (NeF) could not be detected in any sera and a significant reduction in serum C5 accompanied the changes in C3 (r = 0.89; P < 0.001). Previous studies of C3 NeF-associated MCGN show that the fluid phase alternative pathway convertase seen in this condition has little or no C5 cleaving ability. We propose, therefore, that complement activation in AGN occurs via a surface-bound convertase which is capable of cleaving both C3 and C5. The glomerular capillary could provide such a side for activation.