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The kidney and homocysteine metabolism
Allon N Friedman1,2, Andrew G Bostom1,3, Jacob Selhub1
1Vitamin Metabolism and Aging, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
Insights
Elevated homocysteine (Hcy) is linked to vascular disease. In renal disease, reduced kidney function impairs Hcy clearance, leading to hyperhomocysteinemia and increased cardiovascular risk.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Metabolic Biochemistry
Background:
- Homocysteine (Hcy) is a methionine metabolism intermediate.
- Elevated Hcy is an independent risk factor for vascular disease and atherothrombosis.
- Patients with renal disease often have hyperhomocysteinemia, especially with declining kidney function.
Purpose of the Study:
- Investigate the kidney's role in homocysteine handling.
- Understand the causes of hyperhomocysteinemia in renal disease.
- Explore the link between renal function and Hcy levels.
Main Methods:
- Review of existing literature on Hcy metabolism and renal function.
- Analysis of the relationship between GFR and Hcy levels.
- Consideration of renal Hcy uptake and metabolism pathways.
Main Results:
- The kidney plays a significant role in plasma amino acid clearance and metabolism, including Hcy.
- Reduced renal clearance and/or metabolism of Hcy is implicated in hyperhomocysteinemia in renal disease.
- Dietary protein intake may influence renal Hcy handling.
Conclusions:
- Declining renal function likely leads to reduced Hcy clearance, causing hyperhomocysteinemia in renal disease patients.
- Further research is needed to confirm the exact mechanisms and develop Hcy-lowering therapies.
- Understanding renal Hcy handling is crucial for managing cardiovascular risk in kidney disease.
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.