Document Detail


Metabolism of complement factor D in renal failure.
MedLine Citation:
PMID:  3199673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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)
Authors:
M Pascual; G Steiger; J Estreicher; K Macon; J E Volanakis; J A Schifferli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Kidney international     Volume:  34     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  1988 Oct 
Date Detail:
Created Date:  1989-01-25     Completed Date:  1989-01-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  529-36     Citation Subset:  IM    
Affiliation:
Département de Médecine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Complement Activating Enzymes / metabolism*
Complement C3 / metabolism
Complement Factor D / metabolism*
Complement Pathway, Alternative
Creatinine / metabolism
Humans
Kidney Diseases / metabolism*
Grant Support
ID/Acronym/Agency:
AI-21067/AI/NIAID NIH HHS; AR-03555/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Complement C3; 60-27-5/Creatinine; EC 3.-/Complement Activating Enzymes; EC 3.4.21.46/Complement Factor D; EC 3.4.21.46/complement factor D, human

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