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