Events In Renal Transplant Recipients Research Articles

Evidence of enhanced systemic inflammation in stable kidney transplant recipients with low Framingham risk scores

While the Framingham risk score (FRS) predicts cardiovascular risk in the general population, it underestimates cardiovascular events in renal transplant recipients (RTR). Inflammation is common in RTR, and it is also a hallmark of vascular injury contributing to cardiovascular events. To explore the relationship between inflammatory chemokines (CCL family) and FRS in a stable RTR. The modified FRS (2009) was used to calculate the 10-yr probability of CVE in 150 RTR. A cross-sectional study measured plasma levels of 14 CCLs by Luminex technique in 53% (79/150) of the cohort and 28 controls. 43.3% of RTR was classified as low, 16% moderate, and 40.7% high FRS. FRS correlated with eGFR and all CCLs with R of <0.2(p = n.s). Compared with controls, CCL 1,4,8,15, and 27 were equally increased in both the high and low FRS groups (p < 0.04 and 0.03, respectively). The percentage of patients with low FRS and CCL 8,15, and 27 values above the 95% cutoff control levels was 46.1%, 76.9%, and 53.8%, respectively. Over one half of stable RTR, including those with low FRS, have increased inflammatory chemokine levels. Inflammation is not accounted for in the FRS, and this may explain the poor performance of FRS in transplant patients.

Masked hypertension in renal transplant recipients

Purpose: Arterial hypertension is a risk factor affecting graft function in renal transplant recipients (RTRs). In pediatric RTRs, high prevalence of masked and nocturnal hypertension was reported. Most of the RTRs had a history of hypertension and some of them were normotensive at outpatient visits whereas home blood pressure (BP) levels were higher. Masked hypertension (MHT) is defined as a normal office BP but an elevated ambulatory BP. Previous reports have demonstrated the detrimental role of MHT in clinical outcomes in hypertensive patients. However, the true prevalence of MHT in RTRs is yet to be defined. Methods: A total of 113 RTRs (mean age 44 ± 16 years, 72 males, 41 females) with normal office BP (< 140/90 mmHg) were enrolled to the study from the outpatient renal transplantation clinic. Ambulatory BP monitoring (ABPM) was performed in all participants for a 24-h period. Average daytime BP values above 135 mmHg systolic and 85 mmHg diastolic were defined as MHT. Results: The prevalence of MHT in our cohort was 39% (n = 45). Fasting glucose and C-reactive protein levels were higher in patients with MHT compared with normal BP group (p = 0.02 and p = 0.04, respectively). RTRs with deceased donor type had higher prevalence of MHT than RTRs with living donor (40% vs 19%, p = 0.003). In multivariate analysis, deceased donor type could predict the MHT independent of age, gender, office systolic BP level, diabetes mellitus, serum creatinine, C-reactive protein, and glucose levels (OR = 3.62, 95% CI 1.16–11.31, p = 0.03). Conclusion: We demonstrated an increased prevalence of MHT in a typical renal transplant cohort. In addition, transplantation from a deceased donor may be a predictor of MHT. The prevalence of MHT may help to explain high rate of cardiovascular events in RTRs. Therefore, routine application of ABPM in RTRs may be plausible, particularly in RTRs with deceased donor type.

Excellent Results With High-Dose Mizoribine Combined With Cyclosporine, Corticosteroid, and Basiliximab in Renal Transplant Recipients: Multicenter Study in Japan

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 μg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve0–9). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

Abstract 16874: Predictors of Major Adverse Cardiac Events in Renal Transplant Recipients

Background: Renal transplantation has become the treatment of choice in end stage renal disease patients. Though the incidence of acute myocardial infarction is reduced after kidney transplant as compared to patients awaiting kidney transplant, major adverse cardiac events (MACE) are still common after renal transplant, especially in early post operative period. Methods: We reviewed medical records of 321 consecutive adult patients from our institution who received renal allograft transplantation between1995 and 2003. Details on cardiac risk factors, medications, stress test results, coronary angiogram and coronary intervention were collected and related to MACE. Results: The characteristics of 321 patients were as follows: age at transplant 49±13 years, 40% male, 37% diabetics, 87% with hypertension, LV ejection fraction 58±17%. MACE occurrd in 21 patients with cumulative MACE rate of 6.5% over the 3 years after renal transplant, most of them (57%) occurring within 30 days, 67% within 90 days and 84% within 180 days. MACE was not predicted by any of the clinical or pharmacological variables including age, gender, hypertension, diabetes, prior myocardial infarction, smoking, duration of dialysis, LV ejection fraction, or therapy with beta blockers, angiotensin converting enzyme inhibitors or calcium channel blockers. However, a clinical decision to perform a stress test or a coronary angiogram was predictive of a higher MACE rate. The MACE rate was 12.3% in the group with positive stress tests (n=65), 6.1 % in those with negative stress tests (n=134), and 4.1% in the those not referred for a stress test (n=122) (p=0.03). Patients who underwent pre-transplant coronary angiography (n=91), regardless of coronary anatomy, had a higher MACE rate (11 vs 4.8%, p=0.04) than those who did not undergo coronary angiography (n=230). Conclusions: (1) The MACE rate following renal transplantation decreases exponentially over time, most occurring in the first 90 days and is not predicted by any of the traditional risk factors or drug therapies. (2) However, a clinical decision leading to a stress test or coronary angiography and stress test positivity are highly predictive of a higher MACE rate.

Aortic Stiffness and Central Wave Reflections Predict Outcome in Renal Transplant Recipients

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659-0.776) for pulse wave velocity, 0.670 (95% CI 0.604-0.736) for central augmentation pressure, and 0.595 (95% CI 0.529-0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104-1.649; P=0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219-1.814; P<0.001) remained independent predictors of outcome. Aortic stiffness and increased wave reflections are independent predictors of cardiovascular events in renal transplant recipients. As single parameter of wave reflection, central augmentation pressure was better than central augmentation index. Combined measurement of pulse wave velocity and central augmentation pressure may contribute to an accurate cardiovascular risk estimation in this heterogeneous population.

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs. Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up. Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio=1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene. These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.

Slow and steady. Reducing thrombotic events in renal transplant recipients treated with IVIg for antibody‐mediated rejection

Intravenous immunoglobulin (IVIg) therapy for antibody-mediated rejection (AMR) is increasing and is associated with a small but significant incidence of thrombosis. We determined thrombosis rates in patients treated with high-dose IVIg for AMR before and after alteration of an infusion protocol. The newer protocol introduced routine administration of aspirin 300 mg, enoxaparin 1 mg/kg, intravenous hydration and a maximum infusion rate of 100 mg/kg per hour (previously 200 mg/kg per hour). Nine thromboses in 275 infusions occurred before the protocol alteration (event rate 3.3%). Two were arterial thromboses including an acute myocardial infarct and a renal transplant artery thrombosis, which resulted in infarction of 2/3 of the graft. Seven venous thromboses occurred, six in arteriovenous fistulae and one case with bilateral above knee deep venous thromboses. Significant associations with thromboses were seen with higher IVIg dose and male sex. In the 6 months since the introduction of the new infusion protocol, 74 infusions have been administered with no thrombotic events. There have been no significant bleeding or fluid overload side-effects. Infusion times, however, have been doubled. A slower rate of infusion combined with antiplatelet and anticoagulation has thus far eliminated the small but significant IVIg-related thrombosis rate previously observed in our patients treated for AMR without resulting in significant side-effects. Further study is now required to define which elements of this protocol are essential.

Incidence of cardiovascular events after kidney transplantation and cardiovascular risk scores: study protocol

BackgroundCardiovascular disease (CVD) is the major cause of death after renal transplantation. Not only conventional CVD risk factors, but also transplant-specific risk factors can influence the development of CVD in kidney transplant recipients.The main objective of this study will be to determine the incidence of post-transplant CVD after renal transplantation and related factors. A secondary objective will be to examine the ability of standard cardiovascular risk scores (Framingham, Regicor, SCORE, and DORICA) to predict post-transplantation cardiovascular events in renal transplant recipients, and to develop a new score for predicting the risk of CVD after kidney transplantation.Methods/DesignObservational prospective cohort study of all kidney transplant recipients in the A Coruña Hospital (Spain) in the period 1981-2008 (2059 transplants corresponding to 1794 patients).The variables included will be: donor and recipient characteristics, chronic kidney disease-related risk factors, pre-transplant and post-transplant cardiovascular risk factors, routine biochemistry, and immunosuppressive, antihypertensive and lipid-lowering treatment. The events studied in the follow-up will be: patient and graft survival, acute rejection episodes and cardiovascular events (myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances and peripheral vascular disease).Four cardiovascular risk scores were calculated at the time of transplantation: the Framingham score, the European Systematic Coronary Risk Evaluation (SCORE) equation, and the REGICOR (Registre Gironí del COR (Gerona Heart Registry)), and DORICA (Dyslipidemia, Obesity, and Cardiovascular Risk) functions.The cumulative incidence of cardiovascular events will be analyzed by competing risk survival methods. The clinical relevance of different variables will be calculated using the ARR (Absolute Risk Reduction), RRR (Relative Risk Reduction) and NNT (Number Needed to Treat).The ability of different cardiovascular risk scores to predict cardiovascular events will be analyzed by using the c index and the area under ROC curves. Based on the competing risks analysis, a nomogram to predict the probability of cardiovascular events after kidney transplantation will be developed.DiscussionThis study will make it possible to determine the post-transplant incidence of cardiovascular events in a large cohort of renal transplant recipients in Spain, to confirm the relationship between traditional and transplant-specific cardiovascular risk factors and CVD, and to develop a score to predict the risk of CVD in these patients.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Asymptomatic patients with normal myocardial scans (n=57) had significantly fewer cardiac events (log-rank=0.0002) and deaths (log-rank=0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n=76) and individuals with CAD (n=34) documented angiographically. CAD increased the probability of events (HR=2.27, % CI 1.007-5.11; p=0.04). The incidence of cardiac events (log-rank=0.349) and deaths (log-rank=0.588) was similar among patients treated medically (n=23) or by intervention (n=11). Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support preemptive myocardial revascularization for renal transplant candidates.

Coronary artery calcification progression and cardiovascular events in renal transplant recipients, bad inheritance from previous kidney disease: Commentary on the study of Roe et al.

Cardiovascular disease is the leading cause of death in subjects with stage 5 chronic kidney disease or end stage renal disease (ESRD) [1]. Many studies have shown that despite controversies whether coronary artery calcification (CAC) indicates coronary atherosclerosis or coronary medial layer calcification secondary to metabolic bone disease, CAC is associated with an increased risk of cardiovascular events [1–4]. Atherosclerosis is an inflammatory disease and ESRD is also associated with a pro-inflammatory state [5].

Coronary artery calcification: a strong predictor of cardiovascular events in renal transplant recipients

Coronary artery calcification (CAC) independently predicts cardiovascular events (CVE) in the general population. Whether this applies to renal transplant recipients (RTR) is unknown. This prospective study assessed the prognostic impact of CAC on CVE in RTR. We followed up a published cohort of 281 prevalent RTR. At baseline, 16-slice chest spiral computerized tomography scan was performed and classical as well as CKD-related risk factors were recorded. Major CVE (MCVE) was defined as cardiovascular death, myocardial infarction, stroke or transient ischaemic attack. All CVE (ACVE) included MCVE and revascularizations. Prognostic factors were assessed by univariate and multivariate Cox regression. During 2.3 ± 0.5 years of follow-up, 16 patients died from CV (n = 8) or non-CV causes (n = 8). Thirty-one RTR developed at least one CVE (first CVE cardiac in 15, peripheral in 12 and cerebrovascular in 4) for a total of 36 CVE. Thirty-month CV survival, MCVE-free survival and ACVE-free survival was 96.4, 93.9 and 87.9%, respectively. By multivariate analysis, the independent predictors of ACVE were CAC score (hazards ratios [HR] = 1.40 [1.12; 1.75] for a 2.72-fold increase in CAC, P < 0.003) and history of CVE (HR = 2.76 [1.21; 6.39], P < 0.02). Our study shows for the first time that CAC is a strong independent predictor of CVE in RTR.

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post–kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.

Low levels of high-density lipoprotein cholesterol: an independent risk factor for late adverse cardiovascular events in renal transplant recipients

Long-term kidney transplant graft and patient survival is often limited by cardiovascular (CV) disease. Risk factors for CV disease such as diabetes, hypertension and elevated low-density lipoprotein levels are well documented; however, the impact of low levels of high-density lipoprotein (HDL) has not been defined. We performed a retrospective chart review of 324 consecutive renal transplant recipients from 2001 to 2007 to correlate baseline HDL levels with major adverse cardiovascular events (MACEs) defined as a composite of new onset CV illness, cerebral vascular events and peripheral vascular disease. A total of 92 MACEs occurred over a total of 1913 patient years of follow-up. Low HDL cholesterol levels were noted in 58.3% of patients. Compared with those with normal HDL levels, a greater percentage of patients with low HDL levels had post-transplant MACEs (20% vs. 60% respectively) and experienced an increased rate of all cause mortality. Sixty-two percent of all MACEs occurred in patients with low HDL levels. In the low HDL group, the odds ratio for experiencing a MACE was 1.92. Therefore, HDL cholesterol may provide an important new therapeutic target to prevent vascular morbidity and mortality following renal transplantation.

Comparison of predictive ability of lipoprotein components to that of traditional risk factors of coronary events in renal transplant recipients

Objective Risk factors for major adverse coronary events (MACE) in renal transplant recipients are often different from those of non-transplanted populations. We compared the predictive power of lipoprotein components (LC) to that of more traditional risk factors such as serum creatinine, diabetes and inflammation measured by C-reactive protein (CRP) in the assessment of lescol in renal transplantation (ALERT) trial population. Methods From the 2102 randomized patients in ALERT we selected 1734 patients with a complete set of risk and adjustment factors used in the study. Cox regression analysis was used to estimate relationships between baseline values of risk factors and first occurrence of MACE. Chi square statistics, receiver operating characteristics (ROC) and net reclassification improvement (NRI) were used to compare the information value of different risk factors. Results Atherogenic LC and especially non-high density cholesterol (nHDL-C) were as predictive as creatinine and nHDL-C was about as predictive as diabetes. CRP, body mass index, hypertension and glucose had less prediction ability than nHDL-C. The rank order of prediction was the same in the two treatment groups. By regression modelling the actual MACE risk reduction from 6 weeks onwards was well predicted from the difference in LC at 6 week. Conclusion LC and especially nHDL-C predicted MACE at least as good as creatinine. Diabetes was about equally good as nHDL-C to predict MACE occurrence. Inflammation had less prediction ability than the other factors. Treated levels of atherogenic LC predicted MACE risk reduction well.

Inflammation in Renal Transplantation

Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo‐controlled study

Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5-6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7-8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3-40%), from a mean +/- SD of 4.0 +/- 0.9 mmoles/liter to 2.8 +/- 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7-27.5%), from 6.4 +/- 0.9 mmoles/liter to 5.1 +/- 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9-119.4], P = 0.064). Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

Cerebrovascular Events in Renal Transplant Recipients

The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. Risk factors for CBV events in renal transplant recipients differ according to subtype.

Incidence of Cardiovascular Events in Renal Transplant Recipients and Clinical Relevance of Modifiable Variables

Introduction The aims of this study were to quantify the incidence of cardiovascular events and identify the clinical relevance of modifiable variables. Materials and Methods The 1729 patients who underwent renal transplantation from 1981 to 2004 were evaluated in an observational, prospective follow-up study with no exclusions. A cardiovascular event was defined as the presence of ischemic cardiac disease (chest pain-myocardial infarction), cardiac insufficiency, arrhythmia (auricular fibrillation), peripheral vascular disease, or cerebrovascular accident. A survival analysis was performed using the Kaplan-Meier method. A Cox regression analysis was applied. Having identified the predictive variables of cardiovascular events, the population attributable fraction (PAF) and the etiological fraction (EF) were estimated. A risk score was calculated using Cox regression coefficients. Results The accumulated incidence of cardiovascular events was 22.2%, with an incidence rate of 468.6 × 10,000 follow-up years. From the Cox regression model, the variables with an independent effect close to statistical significance to predict cardiovascular events were as follows: recipient age (RR = 1.05), smoking at the time of the transplantation (RR = 2.1), left ventricle hypertrophy during follow-up (RR = 2.4), prior diabetes mellitus, and obesity (body mass index ≥30). At the time of transplantation, 41.7% were smokers. During follow-up, a clear difference was observed in the incidence rates of cardiovascular events between smokers and nonsmokers. Similar phenomena were observed for left ventricle hypertrophy and obesity. The resulting scores ranged between 0 and 5. The area under the ROC curve of the score for the prediction of cardiovascular events was 0.74. Conclusion The incidence of cardiovascular events was consistent with the literature. A series of modifiable variables of major clinical relevance exist to decrease the frequency of cardiovascular events following renal transplantation.

Metabolic Syndrome and Atherosclerotic Events in Renal Transplant Recipients

Metabolic syndrome (MS) is a known cardiovascular risk factor in the general population. We explored the influence of MS on the occurrence of atherosclerotic events (AEs) after renal transplantation. Three hundred thirty-seven renal transplant recipients were included in the study. Various parameters (e.g., anthropometric and biological) were measured 1 year after transplant. One year after transplant, 32% of the study population met criteria for MS. Older age, male gender, pretransplant high body mass index, and an increase in body mass index>or=5% in the first year after transplant were predictive factors for development of MS at 1 year after transplant. Forty-two patients (12.4%) experienced AEs during the 8 years of follow-up. The cumulated incidence of AEs was greater in patients with MS compared with others without MS (25% vs. 7%; P<0.001). In multivariate analysis, patients with MS at 1 year after transplant had an increased risk of AE (hazard ratio 3.40, 95% confidence interval 1.58-7.32, P=0.002). Older age, low creatinine clearance, high C-reactive protein level, and a past history of cardiovascular disease were other independent risk factors for AE. Similar to the general population, MS is an independent risk factor for AE after renal transplantation. Relevant preventive measures targeting different aspects of MS would then have a potential impact on prevalence of AE in this population.

The Association Between Cytomegalovirus Infection and Atherosclerotic Events in Renal Transplant Recipients

Cytomegalovirus (CMV) infection is a risk factor for arteriosclerosis in renal transplant recipients. We sought to investigate the effects of CMV infection on atherosclerotic events (AE) in renal transplant recipients. This retrospective analysis included 200 patients: 52 women and 148 men of overall mean age of 36.18 ± 10.23 years who were transplanted at our center between 1998 and 2001. We analyzed demographic features, dialysis duration, diabetes, blood pressure level, body mass index (BMI), medications, and lipid parameters. CMV infection was diagnosed in 23.5% of patients in the first 2 years after transplantation; these patients were followed for 4 years. All patients had been assessed for AE, including previous myocardial infarction, angina, revascularization procedures, intermittent claudication, stroke, or transient ischemic attack. AE occurred in 13% during the follow-up period. CMV infection was more frequent among these patients compared to those without AE, namely 42.3% versus 20.6%, respectively. Although the gender, dialysis duration, serum cholesterol level, presence of acute rejection, and BMI were not associated with AE, age, hypertension, and CMV infection did show a relation. A multivariate analysis by logistic regression revealed mean age and CMV infection to be independent risk factors for AE: odds ratio (OR) = 5.6, 95% confidence interval (CI) = 1.3 to 24.6 ( P = 0.02) and OR = 4, 95% CI = 1.3 to 12.3 ( P = .01). This study suggested that the presence of CMV infection may be a triggering factor for AE in renal transplant recipients.