Metabolism of complement factor D in renal failure.
Factor D is an essential enzyme of the alternative pathway of complement. Its plasma concentration increases approximately tenfold in end-stage renal failure (ESRF). To analyze its metabolism in humans, we injected purified radiolabelled factor D into 5 healthy individuals and 12 patients with various renal diseases or renal failure. Fractional metabolic rates (FMR) and extravascular/intravascular distributions (EV/IV) were calculated using a compartmental model. The FMR was very rapid in normal individuals (mean 59.6%/hr; range 74.1 to 50.5), significantly diminished in the five patients with ESRF (5.7%/hr; 7.0 to 2.8; P less than 0.004), and correlated well with the creatinine clearance (r = 0.89; P less than 0.001). The extrarenal catabolic rate was not modified in renal failure. Despite a significant inverse correlation between plasma levels of factor D and creatinine clearance [r = 0.68; P less than 0.002], factor D levels were not a sensitive indicator of renal function because the synthesis rate (SR) varied widely from one individual to another (mean SR: 62.9 micrograms/kg/hr; 14.9 to 136.5). Factor D synthesis was not significantly altered by renal function, and did not correlate with C-reactive protein, suggesting that factor D is not an acute phase protein. The proportion of intact factor D elimination in the urine was increased in patients with tubular dysfunction (up to 15% compared to less than 0.2% in normal individuals) confirming that under normal circumstances factor D is filtered through the glomerulus and catabolized by tubular cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Pascual
M
M
Département de Médecine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Steiger
G
G
Estreicher
J
J
Macon
K
K
Volanakis
J E
JE
Schifferli
J A
JA
D003166:Complement Activating Enzymes / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D011416:Complement Factor D / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003404:Creatinine / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*
D003176:Complement C3; D003404:Creatinine; D003166:Complement Activating Enzymes; C493488:CFD protein, human; D011416:Complement Factor D