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Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients
M Arnadottir1, B Hultberg, V Vladov
1Department of Nephrology, University Hospital, Lund, Sweden.
Insights
Elevated homocysteine levels are common in kidney transplant recipients, linked to poorer kidney function and potentially exacerbated by cyclosporine. This suggests cyclosporine may interfere with homocysteine metabolism, increasing cardiovascular risk.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Clinical Chemistry
Background:
- Moderate hyperhomocysteinemia is an established cardiovascular risk factor.
- Previous reports indicate elevated homocysteine levels in renal transplant recipients.
Purpose of the Study:
- To investigate plasma homocysteine concentrations in renal transplant recipients.
- To compare homocysteine levels between transplant recipients, non-transplanted renal patients, and healthy controls.
- To explore the influence of cyclosporine and renal function on homocysteine levels.
Main Methods:
- Plasma total homocysteine concentrations were measured.
- Glomerular filtration rates (GFR) were assessed.
- Comparisons were made between renal transplant recipients (n=120), healthy controls (n=60), and non-transplanted renal patients (n=53).
- Subgroup analyses included recipients with and without cyclosporine treatment.
Main Results:
- Renal transplant recipients exhibited significantly higher homocysteine levels than healthy controls (19.0 vs. 11.6 mumol/L).
- Elevated homocysteine was also observed in transplant recipients compared to non-transplanted renal patients (19.0 vs. 16.0 mumol/L).
- A significant inverse correlation was found between GFR and plasma homocysteine (r = -0.52).
- Recipients on cyclosporine showed higher homocysteine levels than those not on cyclosporine (19.5 vs. 16.2 mumol/L).
- Homocysteine levels were higher in recipients with a history of atherosclerotic complications (20.8 vs. 18.5 mumol/L).
Conclusions:
- Renal insufficiency is a primary driver of hyperhomocysteinemia in non-cyclosporine-treated recipients and non-transplanted renal patients.
- Cyclosporine appears to contribute to hyperhomocysteinemia through an additional mechanism, possibly interfering with folate metabolism.
- Elevated homocysteine in transplant recipients may be associated with increased atherosclerotic risk.
Abstract:
Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).