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Homocysteine, its metabolites, and B-group vitamins in renal transplant patients
1Department of Internal Medicine IV, Institute of Pharmacology, Friedrich-Schiller-University of Jena, Jena, Germany. guenter.stein@polkim.med.uni-jena.de
Insights
Elevated homocysteine (tHcy) and its metabolites are common in renal transplant recipients (RTRs) and correlate with kidney function. Further research is needed to determine if B vitamin treatment can reduce cardiovascular risk in these patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Elevated plasma total homocysteine (tHcy) is an independent cardiovascular risk factor in patients with normal and impaired renal function.
- Limited data exists on plasma concentrations of homocysteine metabolites like cystathionine (Cys), methylmalonic acid (MMA), and 2-methylcitric acid (MC) in renal transplant recipients (RTRs).
Purpose of the Study:
- To investigate serum concentrations of homocysteine metabolites in RTRs.
- To examine the relationship between these metabolites, renal function, cardiovascular disease, immunosuppressive treatment, and vitamin levels (cobalamin, folate).
Main Methods:
- Studied 50 RTRs and 35 healthy controls (NP).
- Measured total homocysteine and its metabolites using gas chromatography-mass spectrometry (GC-MS).
Main Results:
- RTRs showed significantly elevated levels of total homocysteine, MMA, Cys, and MC compared to controls.
- Elevated metabolites, except Cys, correlated with serum creatinine. Folate levels inversely correlated with tHcy and Cys; cobalamin correlated with MMA and MCI/MCII ratio.
- No correlation was found between homocysteine metabolite levels and immunosuppressive drugs, cardiovascular history, or blood pressure.
Conclusions:
- Prospective studies are required to assess if normalizing homocysteine and metabolite levels with B vitamins can reduce cardiovascular risk.
- Further investigation is needed to determine the impact of such treatment on long-term outcomes for allografts and patients.
Background:
Increased plasma total homocysteine (tHcy) levels are an independent risk factor for cardiovascular morbidity in patients with normal and impaired renal function, including stable renal transplant recipients (RTRs). Plasma concentrations of the metabolites of Hcy, such as cystathionine (Cys), methylmalonic acid (MMA), 2-methylcitric acid (MC), and its diastereomers MCI and MCII have been reported in only a few articles. We therefore looked for the serum concentration of these metabolites and their relationship to renal function, cardiovascular diseases, the immunosuppressive treatment, and serum concentrations of cobalamin and folate.
Methods:
Fifty RTRs (mean age 50.4 +/- 11.8 years, 35.9 +/- 44.4 months after kidney transplantation) and 35 controls (NP; mean age 43.5 +/- 14.4 years) were studied. Total Hcy and its metabolites were measured by gas chromatography-mass spectrometry (GC-MS).
Results:
Total Hcy, MMA, Cys, and MC were elevated twofold to sixfold as compared with NP, with a significant interrelationship between these compounds. With the exception of Cys, they were significantly correlated with serum creatinine. Serum folate levels were inversely correlated with tHcy, Cys and cobalamin with MMA and the ratio of MCI/MCII. There was no correlation between tHcy concentration and its metabolites with immunosuppressive treatment (CsA vs. FK506), clinical history, or current findings of cardiovascular complications and blood pressure profile.
Conclusion:
Prospective studies are needed to find out whether the lowering or normalization of serum concentrations of tHcy and its metabolites due to treatment with B vitamins should be achieved to reduce the cardiovascular risk and improve the long-term outcome of allografts and of patients.
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