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Plasma homocysteine in renal failure
B Hultberg1, A Andersson, G Sterner
1Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Insights
Plasma homocysteine levels are elevated in patients with chronic renal failure, regardless of dialysis type. This suggests impaired homocysteine metabolism, potentially due to reduced kidney function affecting its clearance and tubular uptake.
Area of Science:
- Nephrology
- Clinical Chemistry
- Metabolic Disorders
Background:
- Elevated plasma homocysteine is a risk factor for cardiovascular disease.
- Chronic renal failure (CRF) is associated with various metabolic disturbances.
- The relationship between homocysteine levels and renal function requires further elucidation.
Purpose of the Study:
- To investigate plasma homocysteine levels in patients with varying degrees of chronic renal failure.
- To assess the impact of different dialysis modalities on homocysteine levels.
- To explore the mechanisms underlying homocysteine accumulation in CRF.
Main Methods:
- Plasma homocysteine levels were measured in control subjects and patients with CRF (without dialysis, CAPD, hemodialysis).
- Renal function was assessed by serum creatinine and glomerular filtration rate (GFR).
- Homocysteine and creatinine clearance were compared; methionine loading was performed in some patients.
Main Results:
- Plasma homocysteine was significantly increased in all CRF groups compared to controls.
- Patients with mildly reduced renal function (normal creatinine, reduced GFR) did not show elevated homocysteine.
- Homocysteine clearance as a percentage of creatinine clearance was increased in CRF patients, suggesting impaired tubular uptake.
- No significant diurnal variation in homocysteine was observed, but methionine loading caused a slight increase in severe CRF patients.
Conclusions:
- Chronic renal failure leads to elevated plasma homocysteine, independent of dialysis type.
- Impaired homocysteine clearance in CRF may involve reduced glomerular filtration and depressed tubular uptake.
- Disturbed homocysteine metabolism in CRF, possibly via the transsulphuration pathway, warrants further investigation.
Abstract:
Plasma homocysteine in three different groups of patients with chronic renal failure (one group without dialysis, one with CAPD and one with hemodialysis) was increased compared to controls. Another group of patients with slightly reduced renal dysfunction (normal serum creatinine but reduced glomerular filtration rate) did not, however, show increase of plasma homocysteine. The clearance of homocysteine as a percentage of creatinine clearance in the three different groups of patients with chronic renal failure was also significantly increased compared to controls. Thus the clearance of homocysteine was not affected to the same extent as that of creatinine in renal failure. This may be attributed to the fact that, besides the reduced glomerular filtration rate, a depressed tubular uptake of homocysteine may occur in chronic renal failure. We were also able to show that neither in patients with varying renal function nor in controls were there any significant diurnal variation of plasma homocysteine, despite the intake of a protein-rich meal. However, after methionine loading in eight patients with severe chronic renal failure, a slight but significant increase of plasma homocysteine was noted. This indicates a disturbed metabolism with high amounts of homocysteine, which might be mainly attributed to an impaired transulphuration pathway.