Hyperhomocysteinemia and transplant coronary artery disease

BACKGROUND: Transplant coronary artery disease (TCAD) is a major cause of morbidity and mortality among heart transplant recipients. A variety of immunologic and nonimmunologic mechanisms are involved in the pathogenesis of the disease. Hyperhomocysteinemia has been recognized as an important risk factor for atherosclerotic vascular disease. The purpose of this article is to evaluate the prevalence of hyperhomocysteinemia in heart transplant recipients but more specifically to assess the published literature regarding the association between hyperhomocysteinemia and TCAD. METHODS: A MEDLINE search using the key words hyperhomocysteinemia, transplant coronary artery disease, and heart transplant was performed. RESULTS: Hyperhomocysteinemia has been commonly found among heart transplant recipients (average prevalence 51% to 76%). Worsening renal function and impaired vitamin metabolism seem to be the major causes of hyperhomocysteinemia in this particular population. TCAD has been found to be more prevalent and severe among patients with higher serum homocysteine levels. Vitamin supplementation is safe and effective in reducing serum homocysteine among heart transplant recipients. CONCLUSION: A large, long-term, double-blind, placebo-controlled prospective trial aimed at assessing the clinical significance of homocysteine-lowering therapy on the natural history of TCAD seems warranted.     

Mild hyperhomocysteinemia is not associated with cardiac allograft coronary disease

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease. METHODS: Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months. RESULTS: For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001). CONCLUSIONS: Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.     

Trapidil decreases the aggregation of platelets from heart transplant recipients ex vivo

Heart transplant recipients show platelet hyperaggregability, which may be related to the incidence of graft vasculopathy. We investigated whether trapidil can inhibit the aggregation of platelets from these patients. Platelet count, mean platelet volume (MPV), and adenosine diphosphate (ADP)-induced platelet aggregation were determined in 18 heart transplant recipients and 12 healthy subjects. Additionally, platelet-rich plasma from the patients was incubated with trapidil or with saline, prior to measuring ADP-induced aggregation. The MPV was significantly greater in patients compared to controls (9.4+/-1.1 vs 8.5+/-0.7 fL; P=.01), and ADP-induced platelet aggregation was significantly increased in patients compared to controls (81.2%+/-13.1% vs 69.6%+/-16.2%; P=.04, respectively). The trapidil-treated samples showed significantly decreased platelet aggregation compared to the control samples (24.2%+/-12.6% vs 66.7%+/-11.7%; P<.001). Platelets from heart transplant recipients showed an increased MPV and increased ADP-induced aggregation. Trapidil effectively reduced the ADP-induced aggregation ex vivo.     

Hyperhomocysteinemia in organ transplantation

An elevated total homocysteine plasma concentration is associated with an increased morbidity and mortality due to cardiovascular disease in the general population, in patients with renal failure and in recipients of kidney or heart transplants. The fasting or post-methionine loading plasma concentration of total homocysteine is elevated in 50-60% of renal transplant recipients with stable graft function and in the majority of heart transplant recipients. Fasting and post-methionine loading hyperhomocysteinemia can be normalized in virtually all renal transplant patients by a combination of folic acid (5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (0.4 mg/d). In individuals without renal failure much lower doses of folate and vitamin B12 are able to correct hyperhomocysteinemia. Currently, prospective studies are under way to clarify whether folate and vitamin therapy improves cardiovascular disease morbidity and mortality in the general population and in organ transplant recipients. While population wide screening for and treatment of hyperhomocysteinemia is generally not recommended, treatment of high risk patients, including renal failure patients and kidney and heart transplant recipients, can be considered but still represents an experimental therapy.     

Smoking After Cardiac Transplantation

Although smoking cessation is a prerequisite prior to listing for cardiac transplantation, some patients return to smoking after recovery. We have covertly assessed the smoking habits of our cardiac transplant recipients (with ethical approval) since 1993 by measuring urinary cotinine: a level of >500 ng/mL signifying continued tobacco use. We retrospectively analyzed survival, causes of death and the development of graft coronary artery disease (GCAD) with respect to the number of positive and negative cotinine levels. One hundred four of 380 (27.4%) patients tested positive for active smoking at some point posttransplant, and 57 (15.0%) tested positive repeatedly. Smokers suffered significantly more deaths due to GCAD (21.2% vs. 12.3%, p < 0.05), and due to malignancy (16.3% vs. 5.8%, p < 0.001). In univariate analysis, smoking after heart transplantation shortened median survival from 16.28 years to 11.89 years. After correcting for the effects of pretransplant smoking in time-dependent multivariate analysis, posttransplant smoking remained the most significant determinant of overall mortality (p < 0.00001). We conclude that tobacco smoking after cardiac transplantation significantly impacts survival by accelerating the development of graft vasculopathy and malignancy. We hope that this information will deter cardiac transplant recipients from relapsing, and intensify efforts in improving cessation rates.     

Interplay between methylenetetrahydrofolate reductase gene polymorphism 677C→T and serum folate levels in determining hyperhomocysteinemia in heart transplant recipients

BACKGROUND: Homocysteine metabolism is often impaired in heart transplant recipients, and increased total homocysteine plasma levels may constitute a risk factor for the development of heart allograft vascular disease. Although 677C-->T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population, it is unclear whether MTHFR polymorphism influences homocysteine metabolism after heart transplant. METHODS: Homocysteine, serum folate, renal function, concentrations of cyclosporine and its metabolites, and MTHFR genotype were determined in 57 heart transplant recipients (age, 55 +/- 11 yr; 21% women; time from transplant, 48 +/- 42 months). RESULTS: Forty nine percent of the study population presented with hyperhomocysteinemia. Homocysteine was 17.1 +/- 5.9 micromol/liter, 19.4 +/- 4.9 micromol/liter, and 26.3 +/- 14.2 micromol/liter for genotypes CC, CT, and TT, respectively (p = 0.028, Kruskal-Wallis test). At multivariate analysis, MTHFR genotype was independently associated with homocysteine (p = 0.005). When the study population was divided into 2 groups accordingly to serum folate levels (above/below the median value of 6.1 ng/ml), MTHFR genotype remained a significant predictor of homocysteine only in patients with low serum folate (p = 0.048). CONCLUSIONS: This study demonstrates that hyperhomocysteinemia is frequent in heart transplant recipients and that the 677C-->T transition in the MTHFR gene independently and unfavorably influences homocysteine metabolism in this group of patients. Adequate folate intake may overcome genetic predisposition to hyperhomocysteinemia.     

Tobacco and alcohol use in lung transplant candidates and recipients

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.     

Ethical analysis and consideration of health behaviors in organ allocation: focus on tobacco use

Health behaviors are significantly understudied in transplant patients, contributing to significant ethical debate among transplant professionals. Some of these health behaviors (tobacco use and overweight/obesity) are the leading preventable causes of mortality in the US general population and likely have a higher prevalence and impact among transplant populations. For example, tobacco use has been linked to worse graft survival, patient survival, complications, and comorbidities, whereas tobacco cessation has been associated with improved patient and graft survival. Over time, transplant professionals increasingly believe that tobacco use should be a relative contraindication to organ allocation. That belief seems to be strengthened after provider education on pertinent evidence linking tobacco use to medical consequences in both the general and the transplant populations. A core framework for ethical analysis of health behaviors in the context of organ allocation is described, using concepts of utility, justice, and respect for all persons. This framework is designed to help transplant professionals discuss and formulate policy on consideration of health behaviors in the context of organ allocation. More research is needed to advance our knowledge of the impact of health behaviors on transplant patient outcomes.     

Determinants of fasting plasma total homocysteine levels among chronic stable renal transplant recipients.

BACKGROUND: Although several studies have demonstrated an unadjusted association between folate status and fasting plasma total homocysteine (tHcy) levels among renal transplant recipients, no data confirming the strength or independence of this association have been reported. METHODS: We determined fasting plasma folate, B12, and pyridoxal 5'-phosphate (active vitamin B6) levels, along with other potential determinants of plasma tHcy levels (i.e., age, sex, creatinine levels, and Cockcroft-Gault estimated creatinine clearance, current immunosuppressive regimen, and history of clinical cardiovascular disease), among 86 renal transplant recipients. The recipients were > or =6 months after transplantation, lived in the Providence, Rhode Island metropolitan area, and were examined between February and June 1998. RESULTS: Stepwise general linear modeling with analysis of covariance revealed that only creatinine level, age, and vitamin status were independent regressors (i.e., P<0.100) of tHcy levels. Moreover, creatinine level alone determined most of the variability in tHcy levels (i.e., R2) accounted for by these independent variables (R2=0.416 for creatinine level alone; total R2=0.575). In contrast, the R2 for folate alone was only 0.046, and even for all three B vitamins combined, the R2 was just 0.088. CONCLUSIONS: We conclude that renal function is the overriding independent determinant of fasting tHcy levels among stable renal transplant recipients. In comparison to renal function, vitamin status has a relatively marginal influence on tHcy levels and cyclosporine use has essentially none at all.     

Treatment of hyperhomocysteinemia in pediatric heart transplant recipients.

BACKGROUND: Graft coronary artery vasculopathy is the main cause of late morbidity and mortality in pediatric cardiac allograft recipients. Growing evidence suggests that elevated plasma homocysteine levels are associated with cardiac allograft vasculopathy following heart transplantation. The purpose of this study was to evaluate the effect of vitamin supplementation as a potential strategy for reducing homocysteine levels in pediatric heart transplant recipients and examine creatinine levels as potential determinants of plasma homocysteine concentration after transplantation. METHODS: We studied 27 pediatric heart transplant patients with homocysteine levels higher than normal. All children received vitamin supplementation (vitamin B(12), vitamin E, vitamin A and folic acid). During treatment, levels of homocysteine, vitamins and creatinine were evaluated after 3, 6, 9 and 12 months. RESULTS: We observed a significant homocysteine concentration decrease after treatment at every determination, whereas no significant change occurred for creatinine. Vitamin B(12) serum level increased markedly, whereas folic acid, vitamin E and vitamin A serum levels showed only minor increases. CONCLUSIONS: We observed a significant increase of mean levels of vitamin B(12) and a moderate increase in the other 3 vitamins. We also observed a significant reduction in homocysteine levels, which returned to normal levels for age. In our patients, there was a correlation, before and after treatment, between homocysteine and creatinine levels, but there was no a direct correlation between creatinine serum levels and homocysteine reduction. We conclude that vitamin supplementation reduces and may normalize homocysteine serum level after pediatric heart transplantation.     

Treating tobacco use and dependence in kidney transplant recipients: development and implementation of a program

Tobacco use adversely affects transplant outcomes such as graft survival, patient survival, and other conditions that alter transplant patient longevity. Especially concerning is tobacco's relationship to cardiovascular disease, the number 1 cause of death in kidney transplant recipients. Many authors conclude that tobacco interventions ought to be provided to patients and sometimes lament that there are no tobacco dependence interventions designed for kidney transplant recipients. European Best Practice Guidelines for Renal Transplantation also support tobacco dependence interventions. The purpose of this article is to describe one institution's experience in implementing the clinical practice guideline for treating tobacco use and dependence within a kidney and pancreas transplant program.     

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74 %, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups. Received: 14 April 1998 Received after revision: 24 September 1998 Accepted: 18 December 1998     

Invasive Pneumococcal Infections in Adult Lung Transplant Recipients

An increased risk of invasive pneumococcal infection (IPI) has been described among kidney or heart transplant recipients, but the epidemiology of IPI among lung transplant recipients has not been previously reported. We undertook a single center, retrospective cohort study to define the incidence, timing, clinical, and microbiologic features of IPI in lung transplant patients. Fourteen out of 220 recipients (6.4%) developed IPI at a median of 1.3 years after transplantation (incidence rate: 22.7 cases per 1000 person-years). All patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis, and 10 (71%) had TMP-SMX-resistant isolates. All isolates were from the 23 valent polysaccharide vaccine-associated serogroups. The high incidence of IPI in lung transplant recipients is similar to that reported in kidney and heart recipients. Alternative prevention strategies, including use of the conjugated pneumococcal vaccine, should be explored in future studies.     

Metaanalysis of statins and survival in de novo cardiac transplantation

BACKGROUND: The use of HMG CoA reductase inhibitors (statins) after cardiac transplantation has been suggested to decrease the incidence of severe rejection and improve survival. Individual investigations that have led to this suggestion are randomized (but not placebo-controlled) studies, including small patient numbers that have (and thus underpowered) and enrolling heterogeneous subjects (including retransplant recipients). The purpose of this pooled analysis was to quantify the benefit of statins on survival in de novo cardiac transplant recipients. METHODS: Medline (1966 to 2003) was queried using the keywords statin, HMG CoA reductase inhibitors, cardiac transplantation, transplant, cholesterol, atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. In addition, we searched the cited literature and previously published systematic reviews. Of 36 articles retrieved, 3 randomized controlled studies met our population inclusion criteria; namely age >18 years, de novo heart transplant recipients, statin therapy within 3 months, and > or = 1-year follow-up. Pooled data were metaanalyzed by Mantel-Haenszel tests using a random effects model that included tests for heterogeneity. RESULTS: The three pooled studies included 246 patients (statin, n = 129; no statin, n = 117) and 27 events (11%). The pooled analysis demonstrated a significant reduction in mortality with statin use (RR 0.31; 95% CI 0.13 to 0.7; P = .006) without significant heterogeneity (P = .7) among the studies. Two of the three studies reported allograft rejection with hemodynamic compromise. The pooled analysis demonstrated a significant benefit on this endpoint (RR 0.22, 95% CI 0.08 to 0.63; P = .004). CONCLUSION: This meta-analysis demonstrates that statin therapy decreases rejection episodes with hemodynamic consequences and improves 1-year heart transplant survival.     

Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea

BACKGROUND: Diarrhea is the most frequently reported adverse event in mycophenolate mofetil (MMF)-treated transplant patients. The aim of this study was to explore the gastrointestinal tract in MMF-treated renal transplant recipients with persistent afebrile diarrhea to characterize its nature and etiology. METHODS: Renal transplant recipients with persistent afebrile diarrhea (daily fecal output >200 g) were prospectively investigated for infections, morphologic, and functional (gastrointestinal motility and intestinal absorptive capacity) integrity of the gastrointestinal tract; 26 patients met the inclusion criteria. RESULTS: All but one patient had an erosive enterocolitis. Seventy percent of the patients had malabsorption of nutrients, contributing to the diarrhea. In +/-60%, an infectious origin was demonstrated and successfully treated with antimicrobial agents without changes in immunosuppressive regimen. In +/-40%, no infection occurred, but a Crohn's disease-like pattern of inflammation was noted. These patients also had a less pronounced bile-acid malabsorption but a significant faster colonic transit time, correlating with the trough level of mycophenolic acid (MPA). Cessation of MMF, however, was associated with allograft rejection in one third of these patients. CONCLUSIONS: Persistent afebrile diarrhea in renal transplant recipients is characterized by erosive enterocolitis, which is of infectious origin in +/-60%. In +/-40%, a Crohn's disease-like (entero-)colitis was present. Because reduction or cessation of MMF was the only effective therapy, MPA or one of its metabolites may be suggested as a possible cause. However, reduction or cessation of MMF was associated with an increased risk for rejection.     

Human Herpesvirus-8 Serology in Pediatric Organ Transplantation

Human herpesvirus (HHV)-8 has been demonstrated to be involved in the pathogenesis of Kaposi's sarcoma, body cavity lymphomas, multicentric Castleman disease, and, more recently, acute bone marrow failure. In order to study the correlation between HHV-8 and immunosuppression, we performed a serological study in a group of 28 pediatric heart and heart-lung transplant recipients; of mean age 11.5 ± 2.5 years. We analyzed blood samples prior to, at 3 to 6 months, and at least 12 months after transplantation. All patients were negative pretransplantation. We observed 10 seroconversions: one patient at 6 months; two patients at 12 months; and seven within the third year after transplantation. Our preliminary data demonstrated that HHV-8 seroconversion is frequent among pediatric transplant recipients. It was probably related to the length of immunosuppression rather than the organ transplantation; Serological assays of all donor specimens of seroconverted patients were negative.     

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.     

Findings of Doppler sonography do not correlate with serum lipoprotein and total homocysteine concentrations in renal transplant recipients

Atherosclerosis may be evaluated by structural or functional changes of the main arteries. We sought to investigate the probable associations of static and dynamic arterial changes with lipoprotein (a) and homocysteine levels, the two risk factors for atherosclerosis. Intima-media thickening and vasodilatory responses to nitroglycerine of the common carotid artery and the renal transplant artery were studied by color Doppler sonography in 75 renal transplant recipients and 30 controls. At 3, 5, and 10 minutes after 0.4 mg of sublingual nitroglycerine are measured resistive index and peak systolic velocity of the common carotid artery and renal transplant artery. Intima-media thickening in renal transplant recipients and controls were 0.86 +/- 0.34 mm and 0.74 +/- 0.14 mm (P = .05), respectively. Although intima-media thickness did not correlate with the duration of renal transplantation, it was significantly higher in older renal transplant recipients. Peak systolic velocity of common carotid artery was significantly decreased by nitroglycerine in the controls (81.8 +/- 16.7 m/s to 73.2 +/- 12.8 m/s, P = .03). This decrement was more obvious in renal transplant recipients, especially at 10 minutes (69.6 +/- 18.5 m/s vs 59.3 +/- 2 m/s, P = .01). These reductions did not correlate with intima-media thickening, latter of which also did not correlate with homocysteine concentrations, which were higher among renal transplant patients with creatinine more than 1.8 mg/dL. Basal resistive indices of the common carotid artery and renal transplant artery were higher among graft recipients with dysfunction than recipients with good function, (0.7 vs 0.59, P = .003). In conclusion, neither homocysteine nor lipoprotein(a) concentrations predict static and dynamic vascular properties.     

Hyperhomocysteinemia in Liver Transplant Recipients: Prevalence and Multivariate Analysis of Predisposing Factors

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 μmol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 μmol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, γ-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P = .006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P = .01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels. (Liver Transpl 2000;6:614-618.)     

Severe vitamin D deficiency among heart and liver transplant recipients

Abstract: Introduction: Although patients with end‐stage organ failure are at high risk for vitamin D deficiency because of limited sunlight exposure and hepatic dysfunction, few studies have measured 25‐hydroxy vitamin D (25OHD) at the time of transplantation. Methods: We measured serum 25OHD immediately after transplantation in 69 heart and liver transplant recipients. Results: Forty‐six heart and 23 liver transplant recipients were evaluated (mean age 53 yr). Mean 25OHD was well below the lower limit of the normal range (43.2 ± 21.2 nmol/L). Ninety‐one percent had levels below 75 nmol/L, the threshold commonly used to denote sufficiency, and 71% had levels below 50 nmol/L. Severe deficiency (25OHD <25 nmol/L) was found in 16%. Vitamin D levels did not differ by race, age, gender, or season. Mean 25OHD was lower among liver than heart transplant recipients (34.4 ± 17.5 vs. 47.7 ± 20.7 nmol/L; p < 0.03). Among liver transplant recipients, 22% had undetectable levels (<17 nmol/L). Conclusions: Vitamin D deficiency is highly prevalent among heart and liver transplant recipients; those with liver failure are at greatest risk. As vitamin D deficiency has many serious skeletal and extra‐skeletal sequelae, physicians who treat transplant patients should maintain a high degree of vigilance for this problem.