Events In Renal Transplant Recipients Research Articles

Risk of Cardiovascular Events in Renal Transplant Recipients Undergoing PCI: A Systematic Review and Meta-Analysis

Risk of Cardiovascular Events in Renal Transplant Recipients Undergoing PCI: A Systematic Review and Meta-Analysis

MO949: Metabolic Syndrome and Longitudinal Risk of Renal and Cardiovascular Events in Renal Transplant Recipients: A Single Center Study in Japan

Abstract BACKGROUND AND AIMS Metabolic syndrome (MetS) is a condition that promotes arteriosclerosis due to various arteriosclerosis risk factors such as impaired glucose tolerance, impaired lipid metabolism and hypertension, caused by insulin resistance as a result of visceral fat obesity. There have been several epidemiological studies on MetS after renal transplantation conducted in the U.S. and Europe, indicating that MetS is an accumulation of non-immunological risks of renal transplantation, which affects the patient's prognosis as well as that of the kidney. However, the incidence of MetS in Japanese renal transplant recipients is 20 to 30% and lower compared with that of American and European recipients, and its effects on cardiovascular complications and kidney prognosis are not clear. We report on the results of our long-term longitudinal study on MetS in renal transplant recipients. METHOD A total of 104 renal transplant outpatients, over 6 months after their transplants and in stable condition, were diagnosed with MetS from January 2006 and June 2007 and followed up until December 2020. The effects of MetS on outcomes including renal and cardiovascular events were studied using four diagnostic criteria [NCEP-ATP III (Japanese, original, Asian) and IDF criteria]. We performed multivariate Cox proportional hazards regression analysis to examine the association between the presence or absence of MetS and combined vascular events in renal transplant recipients. This study protocol was conducted in accordance with the Principles of the Declaration of Helsinki and the Declaration of Istanbul, and was approved by the ethics committee of Osaka City University (No. 2020–197). All analyses were performed using R ver. 4.0.3 (https://www.r-project.org/foundation/) with the ‘rms’ and ‘RcmdrPlugin.EZR’ packages. RESULTS The incidence of MetS among our renal transplant recipients in our baseline investigation was 24.0% by the NCEP-ATP III (Japanese) criteria, and our longitudinal study showed that MetS was a significant risk factor even after adjustment of background factors using the propensity score (HR: 2.82; 95% CI: 1.26–6.34, P = 0.012). In addition, the effects of MetS diagnosed using the NCEP (original), NCEP (Asian) and IDF criteria on cardiac composite events were HR: 2.39; 95% CI: 1.07–5.38, P = 0.035, HR: 2.35; 95% CI: 1.00–5.55, P = 0.051, and HR: 1.90; 95% CI: 0.84–4.31, P = 0.12, respectively. CONCLUSION Although the incidence of MetS in Japanese renal transplant recipients was lower compared to that of American and European renal transplant recipients, our results indicated that MetS also affected cardiovascular complications and kidney prognosis in Japanese renal transplant recipients. Moreover, depending on the diagnostic criteria for MetS, the HR was shown to be around 2.0–3.0.

Intravenous immunoglobulin therapy for COVID-19 ARDS

Intravenous immunoglobulin therapy for COVID-19 ARDS

The Use of Non–Vitamin K Antagonist Oral Anticoagulants in Post-Kidney Transplantation, Single-Center Experience

Novel oral anticoagulants (NOACs) are widely used alternatives to warfarin, because they do not require routine monitoring and have better safety profile. There is limited experience for NOACs in organ transplant recipients. This study assessed NOAC safety and efficacy among renal transplant recipients in a single center. A retrospective matched cohort study was conducted among the adult renal transplant recipients concomitantly administered calcineurin inhibitors (tacrolimus or cyclosporin) and NOACs between November 2015 and December 2019. The study included 16 patients divided into 2 equal groups on NOACs and warfarin. Male patients constitute 50% and 75% of the NOAC group and warfarin group, respectively, and 75% and 87.5% of cases are post living donor transplants in the NOAC group and warfarin group, respectively. In the NOAC group, the most common indication for anticoagulation was atrial fibrillation (62.5%), followed by deep vein thrombosis (37.5%), whereas in the warfarin group, the most common indication was atrial fibrillation (50%), followed by valve replacement (25%). In the NOAC group, 6 patients (75%) received rivaroxaban, 1 patient (12.5%) received dabigatran, and 1 patient (12.5%) received apixaban; 68.75% of patients were on a tacrolimus-based regimen. There were no thromboembolic events, rejection episodes, bleeding, or admissions due to NOAC adverse events. There were 3 cases of bleeding in the warfarin group. Calcineurin inhibitor levels and estimated glomerular filtration rate did not change significantly in the NOAC group (P=.34 and .96, respectively). Compared to warfarin, NOACs are well tolerated and effective for preventing and treating thromboembolic events in renal transplant recipients. A larger randomized controlled study is required.

Coronary artery calcification progression and long-term cardiovascular outcomes in renal transplant recipients: an analysis by the joint model.

ABSTRACTBackground Compared with the general population, the risk of death is substantially higher in renal transplant recipients than in age- and sex-matched individuals in the general population. In the general population, coronary artery calcification (CAC) predicts all-cause and cardiovascular mortality. In this study we aimed to analyse these relationships in renal transplant recipients.MethodsWe examined 178 renal transplant patients in this prospective observational cohort study. We measured CAC with multidetector spiral computed tomography using the Agatston score at multiple time points. Overall, 411 scans were performed in 178 patients over an average 12.8 years follow-up. The clinical endpoint was a composite including all-cause death and non-fatal cardiovascular events. Data analysis was performed by the joint model.ResultsDuring a follow-up of 12.8 ± 2.4 years, coronary calcification progressed over time (P < 0.001) and the clinical endpoint occurred in 54 patients. In the analysis by the joint model, both the baseline CAC score and the CAC score progression were strongly associated with the incidence rate of the composite event [hazard ratio 1.261 (95% confidence interval 1.119–1.420), P = 0.0001].ConclusionsCAC at baseline and coronary calcification progression robustly predict the risk of death and cardiovascular events in renal transplant recipients. These findings support the hypothesis that the link between the calcifying arteriopathy of renal transplant patients and clinical end points in these patients is causal in nature.

Statin use and incident cardiovascular events in renal transplant recipients.

BackgroundStatins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users.Method622 included RTR (follow‐up 5.4 years) were matched based on propensity scores and dichotomized by statin use. Survival analysis was conducted.ResultsCox regression showed that statin use was not significantly associated with the compound CV endpoint in a fully adjusted model (HR = 0.81, 95% CI = 0.53‐1.24, P = .33). Subgroup analyses in RTR using cyclosporine revealed a strong positive association of statin use with the CV compound outcome in a fully adjusted model (HR = 6.60, 95% CI 1.75‐24.9, P = .005). Furthermore, statin use was positively correlated with cyclosporine trough levels (correlation coefficient 0.11, P = .04).ConclusionIn conclusion, statin use does not significantly decrease incident CV events in an overall RTR cohort, but is independently associated with CV‐specific mortality and events in cyclosporine using RTR, possibly due to a bilateral pharmacological interaction.

Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

The Economic Burden of Post-transplant Events in Renal Transplant Recipients

Kidney transplantation (KT) is considered the optimum treatment choice for end stage renal disease (ESRD) both from a clinical and economic perspective. The incidence of acute rejection (AR) from KD could differ according to different patient and donor characteristic, as well as, the type of immunosuppressant agent allocated. Thus, it is crucial to carefully examine the costs associated with the type of immunosuppressant agents as they directly affect the clinical outcomes of recipients. Tacrolimus which is one of the Calcineurin inhibitors (CI) have proven a huge success in kidney transplantation and are considered the cornerstone therapy post transplantation. Since the expiry of its patent in 2008, generic versions have been introduced in the market. While it has been widely accepted in the medical community to switch from brand to generic drug products provided that they have proven therapeutic bioequivalence, the switch has been documents to be sensitive case with particular products which are characterized by a narrow therapeutic index (NTI). Their concern is that most of the bioequivalence studies are conducted in health volunteers’ whom do not suffer any comorbidity which is not the case in real life settings. González et al., 2017 note that this conversion affected its dose and blood levels which lead to the occurrence of acute rejection episodes due to under immunosuppression and report that infectious adverse events occurred as a result of over immunosuppression. Another important observation that there was a post serum creatinine increase after the formulation conversion and also patients experienced greater incidence of magnesium wasting, and more episodes of rejection which led to greater institutional costs of care. These findings highlight that cost containment policies need to be revisited especially with NTI drugs as their extra monitoring costs might actually off-set the savings of the generic product in the short term.

Incidence of Cardiovascular Events After Renal Transplantation.

Renal transplant recipients may present with transplant-specific risk factors related to end-stage renal disease. Although cardiovascular disease-related deaths may be reduced in renal transplant recipients, this disease is still the leading cause of death in patients with a functioning allograft. In this study, our aim was to determine the incidence of cardiovascular events after renal transplant. This observational retrospective cohort study analyzed renal transplant recipients seen at Başkent University Hospital from 2014 to 2017. Posttransplant cardiovascular events were defined as presence of myocardial infarction, percutaneous coronary interventions, new-onset angina, and death. Patient characteristics, traditionals cardiovascular risk factors, routine biochemistry, and other comorbidities were included in our analyses. In total, 56 renal transplant recipients older than 18 years were included (mean age of 48.4 ± 11.3 years; 21.4% were female patients). In the patient group, 14.2% had coronary artery disease pre-transplant, and 1 patient had an acute myocardial infarction. Mean time from transplant to incidence of cardiovascular events (as shown by coronary angiography) was 9.34 ± 5.2 years. Thirty-six recipients (64.2%) had a cardiovascular event during this posttransplant period, and 6 patients who developed cardiovascular events were women. Five patients (8.9%) required bypass surgery after coronary angiography. Stent implantations were needed in 14 patients. The remaining patients received medical treatment decisions. Twenty-one patients had no acute or chronic cardiovascular events. One patient died because of noncardiac reasons (pulmonary aspergillosis). Two patients died after cardiac surgery, and 1 patient died because of decompensated heart failure. The presence of symptoms of cardiovascular disease is an important prognostic marker that requires cardiac evaluation. As with the general population, modifiable risk factors can reduce the incidence of cardiovascular events in renal transplant recipients.

A High Abdominal Aortic Calcification Score by Dual X-Ray Absorptiometry (DXA) is Associated with Cardiovascular Events after Kidney Transplantation

Introduction It is unknown whether aortic calcification is associated with increased risk for cardiovascular events in renal transplant recipients. Therefore, this study focused on the association of abdominal aortic calcification (AAC) and cardiovascular events, using a dual X-ray absorptiometry (DXA) scoring methodology for AAC. Methods Renal transplant recipients, referred for a DXA procedure within 6 months after transplantation, were included in a single-centre study, between 2008 to 2014, with an end of follow-up at December 2017. Primary endpoint was the occurrence of cardiovascular events, defined as myocardial infarction, cerebrovascular accident or transient ischemic attack, within 36 months after transplantation. AAC was quantified using an 8-score scale system and patients were divided into 3 groups; a control group (AAC = 0), a low-AAC group (AAC = 1 – 3), and a high-AAC group (AAC = 4 – 8). Results We evaluated 701 patients, 267 (38.1%) had detectable calcifications (low-AAC 190 patients; high-AAC 77 patients) and 434 (61.9%) had no calcifications. Univariate Cox proportional hazard analysis of the high-AAC score showed a hazard ratio (HR) of 3.3 (95% CI 1.7 – 6.3, p < 0.01) for cardiovascular events, while results were not significant for the low-AAC score, HR 1.0 (95% CI 0.5 – 2.1, p = 0.91). Multivariate analysis showed an independent significant association between a high-AAC score and cardiovascular events, HR 2.4 (95% CI 1.2 – 5.0), p = 0.02). Conclusions An independent association between a high-AAC score and cardiovascular events was identified and provides an opportunity for physicians for early cardiovascular risk stratification in renal transplant recipients.

A high abdominal aortic calcification score by dual X-ray absorptiometry is associated with cardiovascular events after kidney transplantation.

Aortic calcification is associated with an increased risk for cardiovascular events in renal transplant recipients. This study focused on the association of abdominal aortic calcification (AAC) and cardiovascular events assessed using a dual-energy X-ray absorptiometry (DXA) scoring methodology for AAC. From 2008 to 2014, renal transplant recipients referred for a DXA procedure within 6 months after transplantation were included in a retrospective, single-centre study. The primary endpoint was the occurrence of cardiovascular events, defined as myocardial infarction, cerebrovascular accident or transient ischaemic attack, after transplantation. AAC was quantified using an 8-point scoring system and patients were divided into three groups; a control group (AAC = 0), a low AAC group (AAC = 1-3) and a high AAC group (AAC = 4-8). We evaluated 701 patients, 267 (38.1%) had detectable calcifications (low AAC 190 patients, high AAC 77 patients) and 434 (61.9%) had no calcifications. Cardiovascular events were seen in 37 (8.5%) patients in the control group, in 18 (9.5%) in the low AAC group and in 20 (26.0%) in the high AAC group. Univariate Cox proportional hazards analysis of the high AAC score showed a hazard ratio (HR) of 4.23 [95% confidence interval (CI) 2.44-7.33; P < 0.01] for cardiovascular events, while results were not significant for the low AAC score. Multivariate analysis showed an independent significant association between a high AAC score and cardiovascular events [HR 2.78 (95% CI 1.05-7.64); P = 0.04]. Assessment of the continuous net reclassification index (NRI), comparing the combined clinical variables with a model of both AAC scoring and clinical variables, showed an NRI of 0.76 (95% CI 0.65-0.86; P < 0.01). An independent association between a high AAC score, assessed by DXA, and cardiovascular events was identified and provides an opportunity for early cardiovascular risk stratification in renal transplant recipients.

Is low pre-transplant parathyroid hormone a risk marker for cardiovascular disease in long-term follow-up of renal transplant recipients?

BackgroundSecondary hyperparathyroidism and altered levels of parathyroid hormone (PTH) are associated with vascular events in chronic kidney disease. After renal transplantation, this association is not clear. Pre-transplant parathyroidectomy (PTX) is common, but post-transplant data are scarce. We aimed to study the effect of PTH at the time of transplantation on risk of post-transplant vascular events in renal transplant recipients with and without pre-transplant PTX.Methods258 patients from two Swedish transplant units were followed for 6 years. Separate analyses were made for patients with or without pre-transplant PTX. Patients with no pre-transplant PTX were stratified by quartiles of PTH at time of transplantation and patients with pre-transplant PTX were stratified by above and below median levels of PTH at time of transplantation. Hazard ratios for vascular events, mortality, and graft failure were calculated in adjusted Cox regression models.ResultsIn patients with no pre-transplant PTX, the lowest quartile of PTH at transplantation had a higher risk of cardiovascular events compared to quartile 3 with an adjusted hazard ratio (95% CI) of 2.63 (1.04–6.67). In patients with pre-transplant PTX, the group below median of PTH had a higher risk of cardiovascular events with an adjusted hazard ratio (95% CI) of 18.15 (1.62–203.82) compared to patients above median of PTH.ConclusionLow levels of parathyroid hormone before transplantation were associated with increased risk of post-transplant vascular events both in patients with and without pre-transplant parathyroidectomy. Any conclusions on causal or direct effect of PTH on outcome cannot be drawn from this observational study.

Role of homocysteine level as risk factor in the occurrence of cardiovascular events in renal transplant recipients

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Traditional risk factors like elevated homocysteine levels may not completely explain the higher CVD seen in RTRs. Identification and optimisation of modifiable risk factors may help to reduce the occurrence of CVD in such population. To study the role of homocysteine level as risk factor in the occurrence of cardiovascular events in renal transplant patients. Another objective was to evaluate the other risk factors in the occurrence of CVD in such population.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Thirty renal transplant recipients and thirty healthy controls were studied. Inclusion criteria were transplant duration &amp;gt;6 months and patients with chronic stable renal function over the last 3 months. Samples for fasting plasma homocysteine were collected and plasma homocysteine was then estimated. All the patients were followed up every month for 6 months and evaluated for occurrence of any cardiovascular event.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The mean hornocysteine levels were found to be 27.4±7.902 µmol/L in cases and 10.86±1.98 µmol/L in controls. There was no statistically significant relationship between homocysteine levels and transplant duration, mean IMT levels, proteinuria, and presence of left ventricular hypertrophy or choice of immunosuppressive regimen. Of the 30 patients, 6 patients (20%) had evidence of cardiovascular event. In the absence of other conventional factors, age of the patient, creatinine clearance (index of graft function) and mean intima-media thickness were more closely related with cardiovascular events. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Plasma homocysteine failed to show as an independent risk factor for cardiovascular events. New, emerging cardiovascular risk factors (e.g. Lipoprotein (a), high sensitivity C-reactive protein, fibrinogen, tissue plasminogen activator and plasminogen activator inhibitor-1) should be studied to design effective therapy to delay the progression of atherosclerosis and prolong the life of renal transplant recipients.&lt;/p&gt;

Study of Cardiovascular Outcomes in Renal Transplantation: A Prospective, Multicenter Study to Determine the Incidence of Cardiovascular Events in Renal Transplant Recipients in Ontario, Canada.

Background:Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies.Objective:The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs.Design:Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study.Setting:Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada.Patients:Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded.Measurements:Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist.Methods:CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model.Results:A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years).Limitations:Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada.Conclusions:Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

Pre-Transplant Assessment of Vascular Calcification as a Risk Factor of Mortality, Graft Loss, and Cardiovascular Events in Renal Transplant Recipients

BackgroundVascular calcification (VC) is known as an independent predictor of mortality in patients undergoing hemodialysis; nevertheless, there is a lack of studies about the impact of vascular calcification in renal transplant recipients, and none of them use the Kauppila Index (KI) as a predictor of patient and graft prognosis. MethodsWe conducted an observational, retrospective study of 119 renal transplants, evaluating abdominal aortic calcifications (L4-S1) with the KI. We established 2 categories: absence (KI = 0–2) and presence (KI = 3–24) of VCs before transplantation. We analyzed the impact of calcification in graft and patient survival, new-onset diabetes mellitus, hypertension, cardiovascular events, renal function, and mineral metabolism. ResultsVCs were observed in 50 patients (42%) before renal transplantation. Patients with VCs were older, but no statistical differences were found in the pre-transplant study between sex, diabetes, body mass index, and cardiovascular events. We found a major patient survival (limited to first 2 years after transplantation), graft survival, and death-censored graft survival in those without VCs (P = .037, P = .015, and P = .023, respectively). In line with results, a higher incidence of major cardiovascular events (MACE) and cardiovascular death was observed in the group with preexisting calcification (P = .016/P = .019). In the multivariable analysis, VCs were not an independent predictor for graft loss, death-censored graft loss, or major cardiovascular events. ConclusionsSimple evaluation of VCs with the use of the KI at the time of transplantation relates with graft and patient survival and with MACE after renal transplantation.

Coronary artery calcification and large artery stiffness in renal transplant recipients

PurposeCoronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in renal transplant recipients (RTR). Carotid-femoral pulse wave velocity (PWV), a non-invasive measure of large artery stiffness, also predicts CV events in RTR. The study investigated the relationship between CAC and PWV in RTR and assessed the performance of PWV measurement in predicting CAC. Patients/methodsThe study was performed as cross-sectional analysis in 104 RTR. CAC was determined as total calcium score (CS) and calcium mass (CM). Carotid-femoral PWV was also measured. Sensitivity, specificity and receiver operating characteristic (ROC) curve were used to assess the performance of PWV as diagnostic test for presence of CAC. ResultsCAC was found in 69% of participants. PWV was higher in RTR with CAC than in RTR without CAC (10.2±2.2 vs. 8.6±15; p<0.001). In univariate analysis CS was significantly correlated with age, duration of hypertension, waist circumference, PWV, hemoglobin concentration, and serum glucose. In multiple linear regression analysis CS was independently associated with age only, but not with PWV. Sensitivity and specificity of PWV>7.6m/s as cut-off for detecting CAC>0 was 0.889 and 0.406, respectively. Sensitivity and specificity of PWV>10.2m/s as cut-off for detecting severe CAC (CS>400) was 0.319 and 0.969, respectively. ConclusionsThe study confirmed high prevalence of coronary artery calcification in renal transplant recipients. The study does not support the hypothesis that aortic stiffness is independently associated with coronary artery calcification in RTR. PWV measurement may be useful in excluding severe CAC in RTR.

Cardiovascular risk factors following renal transplant.

Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.

The economic burden of posttransplant events in renal transplant recipients in Europe.

This study aims to describe the healthcare resource utilization and costs of managing renal posttransplant patients over 3 years posttransplant in nine European countries and to stratify them by year 1 glomerular filtration rate (GFR). A retrospective observational and database analysis of renal transplant patients and a physician questionnaire study were conducted to collect recipient and donor characteristics, posttransplant events, and healthcare resource utilization related to these posttransplant events. In each country, local published costs were applied to the resource use identified. The results were stratified by the patient GFR reading at a time point 1 year after renal transplant. The database study identified 3,181 patients who met the inclusion criteria, along with 2,818 transplants carried out in the centers surveyed by questionnaire. Total 3-year costs derived from the questionnaire analysis vary depending on local treatment practices, from a minimum of &OV0556;33,602 per patient in the Czech Republic to &OV0556;77,461 per patient in the Netherlands. Consistently across countries, estimated costs appear to decrease with improved graft functioning status (increased GFR) at 1 year. The average 3-year costs, discounting immunosuppression therapy and certain posttransplant events, per patient with a GFR greater than or equal to 60 at 1 year are estimated to be around 35% lower than those with 15≤GFR<30. This study demonstrates that in Europe, worsening posttransplant renal function may contribute to substantive increases in resource use, with some variation across regions. Therefore, management strategies that promote renal function after transplantation have the potential to provide important resource savings.

Post-transplant Renal Function and Cardiovascular Events Are Closely Associated With the Aortic Calcification Index in Renal Transplant Recipients

IntroductionThe aortic calcification index (ACI) is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in renal transplant recipients has not been well examined. In this study, we investigated the relationship between pretransplant ACI, ACI progression, post-transplant renal function, and post-transplant cardiovascular events in renal transplant recipients. Patients and methodsThe study from June 1996 to Jan 2012 included 61 renal transplant recipients (living donors, 47; cadaveric donors, 14). The median follow-up period was 60 months. ACI was quantitatively measured on abdominal computed tomography. The relationship between age, dialysis period, estimated glomerular filtration rate (eGFR), and pre- and post-transplant ACI was longitudinally evaluated. Risk factors for post-transplant ACI progression were determined by logistic regression analysis. Patient background and the incidence of post-transplant cardiovascular events were also assessed. ResultsThe pretransplant ACI (median 4.2%) significantly correlated with age at transplant, dialysis period, and diabetes mellitus. ACI gradually increased up to 2.8 times at 10 years after transplantation. Post-transplant eGFR significantly correlated with ACI progression in patients with chronic kidney disease of stage ≥3. Logistic regression analyses showed that age at transplantation, post-transplant period, cadaveric donors, and post-transplant chronic kidney disease stage 3 were risk factors for post-transplant ACI progression. The pretransplant ACI was higher (median 66%) in 3 patients who experienced post-transplant cardiovascular events. ConclusionsACI progression closely correlates with age and post-transplant renal function. A high pretransplant ACI is a risk factor for post-transplant cardiovascular events in renal transplant recipients.

Treatment with everolimus is associated with a procoagulant state

Renal transplant recipients are at increased risk of venous thromboembolic events, which is in part caused by their treatment with maintenance immunosuppressive drugs. Because we observed an increased incidence of venous thromboembolic events in renal transplant recipients treated with the mTOR inhibitor (mTORi) everolimus, we aimed to identify prothrombotic mechanisms of this immunosuppressive drug. In a single center study, nested in a multi-center randomized controlled trial, we measured parameters of coagulation, anti-coagulation and fibrinolysis in renal transplant recipients, receiving the mTORi everolimus (n=16, mTOR group) and compared them to a similar patient group, receiving a calcineurin inhibitor and/or mycophenolate sodium (n=20, non-mTOR group). All patients were at least 6 months following transplantation with a stable transplant function. The use of an mTORi was associated with significantly higher levels of von Willebrand factor, prothrombin fragment 1+2, thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 as compared to a non-mTORi based immunosuppressive regimen. Treatment with an mTORi leads to increased endothelial activation, thrombin formation and impaired fibrinolysis in renal transplant recipients. This suggests an increased risk of thrombotic events in renal transplant recipients treated with mTOR inhibitors. A prospective study to establish the precise risk of thrombotic events in these patients is urgently needed.