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The Kidney and Homocysteine Metabolism

ALLON N. FRIEDMAN, ANDREW G. BOSTOM, JACOB SELHUB, ANDREW S. LEVEY and IRWIN H. ROSENBERG
JASN October 2001, 12 (10) 2181-2189; DOI: https://doi.org/10.1681/ASN.V12102181
ALLON N. FRIEDMAN
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ANDREW G. BOSTOM
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JACOB SELHUB
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ANDREW S. LEVEY
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IRWIN H. ROSENBERG
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Abstract

Abstract. Homocysteine (Hcy) is an intermediate of methionine metabolism that, at elevated levels, is an independent risk factor for vascular disease and atherothrombosis. Patients with renal disease, who exhibit unusually high rates of cardiovascular morbidity and death, tend to be hyperhomocysteinemic, particularly as renal function declines. This observation and the inverse relationship between Hcy levels and GFR implicate the kidney as an important participant in Hcy handling. The normal kidney plays a major role in plasma amino acid clearance and metabolism. The existence in the kidney of specific Hcy uptake mechanisms and Hcy-metabolizing enzymes suggests that this role extends to Hcy. Dietary protein intake may affect renal Hcy handling and should be considered when measuring Hcy plasma flux and renal clearance. The underlying cause of hyperhomocysteinemia in renal disease is not entirely understood but seems to involve reduced clearance of plasma Hcy. This reduction may be attributable to defective renal clearance and/or extrarenal clearance and metabolism, the latter possibly resulting from retained uremic inhibitory substances. Although the currently available evidence is not conclusive, it seems more likely that a reduction in renal Hcy clearance and metabolism is the cause of the hyperhomocysteinemic state. Efforts to resolve this important issue will advance the search for effective Hcy-lowering therapies in patients with renal disease.

  • © 2001 American Society of Nephrology
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Journal of the American Society of Nephrology: 12 (10)
Journal of the American Society of Nephrology
Vol. 12, Issue 10
1 Oct 2001
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The Kidney and Homocysteine Metabolism
ALLON N. FRIEDMAN, ANDREW G. BOSTOM, JACOB SELHUB, ANDREW S. LEVEY, IRWIN H. ROSENBERG
JASN Oct 2001, 12 (10) 2181-2189; DOI: 10.1681/ASN.V12102181

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The Kidney and Homocysteine Metabolism
ALLON N. FRIEDMAN, ANDREW G. BOSTOM, JACOB SELHUB, ANDREW S. LEVEY, IRWIN H. ROSENBERG
JASN Oct 2001, 12 (10) 2181-2189; DOI: 10.1681/ASN.V12102181
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  • Article
    • Abstract
    • Plasma Hcy Levels, Protein Binding, and Flux
    • General Metabolism
    • Normal Kidneys and Hcy Handling
    • Diseased Kidneys and Hcy Handling
    • Conclusion
    • Acknowledgments
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More in this TOC Section

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  • Emerging Insights into Glomerular Vascular Pole and Microcirculation
  • High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity
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  • Fasting Plasma Total Homocysteine Levels and Mortality and Allograft Loss in Kidney Transplant Recipients: A Prospective Study
  • Age and Gender Affect the Relation between Methylenetetrahydrofolate Reductase C677T Genotype and Fasting Plasma Homocysteine Concentrations in the Framingham Offspring Study Cohort
  • B vitamin status and concentrations of homocysteine and methylmalonic acid in elderly German women
  • Proteinuria as a Predictor of Total Plasma Homocysteine Levels in Type 2 Diabetic Nephropathy
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