Serum total homocysteine concentration before and after renal transplantation

Abstract

BACKGROUND: Hyperhomocysteinemia is by now an established risk factor for the development of atherosclerosis. Total homocysteine concentration (tHcy) correlates inversely with glomerular filtration rate, and it is roughly three times as high in hemodialysis patients as in healthy individuals. Therefore, tHcy would be expected to fall markedly after successful renal transplantation. The aim of the present study was to assess the changes in tHcy associated with renal transplantation. METHODS: tHcy was analyzed in samples collected before renal transplantation and at six months after transplantation in 55 stable patients, all of whom were treated with cyclosporine (CS). tHcy was also analyzed in samples from 55 controls characterized by markers of renal function that matched those of the post-transplant state. RESULTS: At six months after transplantation, tHcy was significantly decreased as compared with pretransplant tHcy (27.7 +/- 14.8 vs. 36.9 +/- 21.3 micromol/liter, P < 0.001). Post-transplant tHcy was markedly higher than the tHcy of the control group (27.7 +/- 14.8 vs. 16.0 +/- 5.3 micromol/liter, P < 0.0001). The post-transplant change in tHcy ranged widely, the average change being a reduction of 14%. Sixteen patients (29%) actually manifested an increase in post-transplant tHcy. The post-transplant changes in tHcy correlated inversely with pretransplant tHcy (r = -0.66, P < 0.0001) and directly with the changes in serum albumin concentrations (r = 0.35, P < 0.05) and CS trough concentrations (r = 0.29, P < 0.05). A multivariate analysis, including the post-transplant changes in serum concentrations of folate and albumin as well as creatinine clearances explained 21% of the change in tHcy (P < 0.05). After inclusion of the CS concentration, an independent predictor, the model accounted for 28% of the post-transplant change in tHcy (P < 0.01). CONCLUSION: The post-transplant reduction in tHcy was far smaller than expected with respect to renal function, and the post-transplant changes in the major biochemical determinants of tHcy contributed relatively little to explain the change in tHcy. Thus, the results suggest the post-transplant introduction of one or more factors that induce an increase in tHcy. Treatment with CS appears to be such a factor.