Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial

BACKGROUND: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis. OBJECTIVE: To determine the effect of treatment with 1) vitamin B6 or 2) folic acid plus vitamin B12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients. DESIGN: Block-randomized, placebo-controlled, 2 x 2 factorial study. SETTING: University-affiliated transplantation program. PATIENTS: 29 clinically stable renal transplant recipients. INTERVENTION: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B6, 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7); or vitamin B6, 50 mg/d, folic acid, 5 mg/d, and vitamin B12, 0.4 mg/d (n = 7). MEASUREMENTS: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels. RESULTS: Vitamin B6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine. CONCLUSIONS: Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.     

Anticardiolipin antibodies in hemodialysis patients and in renal transplant recipients: prevalence and significance

Increased anticardiolipin antibodies (aCL) serum levels have been recently described in haemodialysis patients and in renal transplant recipients, with a prevalence ranging from 4.8 to 46.4%. The causes and the clinical significance of aCL positivity in these patients are uncertain. We measured IgG- and IgM-aCL serum levels in 61 haemodialysis patients, in 14 renal transplant recipients and in 38 healthy controls. Increased levels of IgG-aCL were found in 4 haemodialysis patients (6.55%), in 2 transplant patients (14%) and in 2 of the healthy controls (5.26%). IgM-aCL serum levels were normal in all the patients. After one year of follow-up, no vascular events have been observed in aCL positive patients. It is probable that the presence of aCL in the serum of patients with end-stage renal disease is only an epiphenomenon and does not play a pathogenetic role.     

Carotid atherosclerosis in renal transplant recipients

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.     

Kaposi's sarcoma in renal transplant recipients

One hundred and seventeen of 270 (43%) recipients of organs obtained from donors with malignancies had evidence of transmitted cancers. In 9 instances these were removed from renal allografts immediately prior to transplantation. Including these cases there were 45 recipients of organs in which a neoplasm involved the allograft, 6 others in whom adjacent structures were invaded, and another 66 patients who had distant metastases. Precautions to prevent cancer transmission include meticulous preoperative screening of donors, careful examination of all organs at the time of harvesting, biopsy of any suspicious lesions, and routine donor autopsy, if possible.     

High prevalence and usual persistence of serum monoclonal immunoglobulins evidenced by sensitive methods in renal transplant recipients

BACKGROUND: The occurrence of serum monoclonal immunoglobulins in kidney transplant recipients is well known but their significance and predictive value for the occurrence of lymphoma are a matter of debate. We therefore conducted a study of monoclonal immunoglobulins by a sensitive method during the long-term follow up of grafted patients. METHODS: Monoclonal immunoglobulins were characterized by high-resolution electrophoresis, conventional immunoelectrophoretic analysis, and a sensitive Western blotting procedure in the serum from 84 renal transplant recipients prior to grafting and subsequently, with a 1-8-year follow-up and excluding the patients who developed posttransplant lymphoma. RESULTS: Low abundance monoclonal immunoglobulins were detectable prior to transplantation in 56 cases (66.6%) and after graft in 72 cases (85.5%) (and in 1 case (1.2%) and 18 cases (21.4%) of cases respectively, by immunoelectrophoresis). These abnormalities were often multiple in individual sera. Monoclonal components detected by immunoblotting were transient in 23.8% of patients only (whereas those evidenced by immunoelectrophoresis usually became undetectable by this method) and their pattern was remarkably stable in the majority of cases. The frequency of post-transplant monoclonal immunoglobulins was higher in patients of more than 50 years of age than in younger patients. The appearance of monoclonal components after grafting and their transient character correlated with CMV infections. No correlation was found with various other parameters. The isotypic distribution of monoclonal immunoglobulins with an IgM, IgG3, and IgG1 predominance and an abnormally low kappa/lambda ratio was the same as that observed in various immunodeficiency states. The monoclonal immunoglobulin pattern in three further patients who developed post-transplant lymphoma was unremarkable. CONCLUSION: Monoclonal immunoglobulins hence are not discriminant for lymphoma and their characterization does not appear to be necessary in the evaluation of followed up grafted patients, at least for a prediction of post-transplant lymphoma.     

Compliance with cyclosporine in adolescent renal transplant recipients

The percentage of non-tasters for phenylthiocarbamide in 915 Japanese students was 9.4%. The thresholds of the edge and back of the tongue to quinine hydrochloride were significantly smaller in the non-tasters than in the tasters. The thresholds of any tongue portions to NaCl, acetic acid or sucrose did not differ between the tasters and the non-tasters.