Cardiovascular risk factors after liver transplantation: analysis of related factors

Aims

We sought to analyze the cardiovascular risk factors (CVRF) in liver transplantation and their relation to immunosuppression and hepatitis C virus (HCV) infection.

Patients and Methods

The study included all 158 liver transplants performed between January 2005 and December 2008 that had a minimum follow-up of 1 year. There were 104 men (64%) and 54 women (36%). Data were recorded on both the pretransplant prevalence as well as new cases of diabetes mellitus (DM), hypertension, hypertriglyceridemia, hypercholesterolemia, and hyperuricemia, defined by the need for drug therapy, after a mean follow-up period of 38 months (range, 12-64). We also examined the influence on CVRF of immunosuppression and HCV.

Results

Tacrolimus was prescribed for 61% of the patients and cyclosporine, 39%. Upon univariate analysis only hypertension was significantly associated with the use of cyclosporine (P < .03). There was a trend to a greater incidence of hypercholesterolemia with cyclosporine (P = .1) and DM with tacrolimus (P = .1). The presence of HCV was significantly associated with a greater incidence of de novo DM (P < .01), as was a severe relapse of hepatitis C (P < .03). Multivariate analysis showed a 4.4 times greater risk for developing de novo DM among patients with a severe relapse of HCV.

Conclusion

The development of CVRF after liver transplantation was manifested, mainly during the first 3 months posttransplantation. Special attention should be given to the risk for de novo DM among HCV positive patients.     

Cardiovascular disease after renal transplantation

Cardiovascular disease is a major hazard limiting the life expectancy of renal transplant recipients and the most frequent cause of late allograft loss. Patients with renal disease have usually been exposed for both traditional, and for them unique, risk factors over a prolonged period of time and may carry the burden of advanced atherosclerotic disease already at the time of transplantation. The observed survival benefit of transplantation is probably from elimination of the numerous uremia-related risk factors. However, immunosuppressive therapy and the chronic inflammatory state, together with genetic susceptibility and not infrequently impaired renal function, may bring about new potentially atherogenic conditions. Metabolic risk factors may jeopardize both patient and graft survival. Several observational studies provide evidence for the negative impact of preexisting metabolic abnormalities on long-term outcomes. Identification of modifiable cardiovascular risk factors may enable risk reduction also in renal transplant recipients. Results of ongoing intervention trials are awaited. The observed improvement of patient survival after renal transplantation during the past decade may reflect the increasing awareness and more optimal care of patients throughout the course of renal disease.     

Cardiovascular disease after renal transplantation

Cardiovascular disease (CVD) is common after renal transplantation. In the absence of controlled intervention trials, the strength of evidence that modifying a risk factor will reduce the incidence of CVD in renal transplant recipients must rest on: (1) evidence from studies in the general population, (2) observational studies linking the risk factor to CVD in renal transplant recipients, and (3) studies showing that the risk factor can be safely and effectively treated in transplant patients. Accordingly, the evidence is strong that hyperlipidemia should be treated after renal transplantation. Evidence is very suggestive that pretransplant screening for CVD, treatment of hypertension, the use of low-dose aspirin, and smoking cessation will also help to reduce the incidence of posttransplant CVD. Less compelling are data suggesting that intensive glucose control in diabetics will safely decrease the incidence of CVD. Although there is little evidence that treatment of erythrocytosis will reduce CVD, hematocrits above 55% to 60% should probably be treated to prevent venous thrombosis. Vitamins for reducing homocysteine, antioxidant vitamins, and prophylaxis for potentially atherogenic infections are therapies that warrant additional study. In summary, the best current approach to reducing the high incidence of posttransplant CVD is to aggressively identify, and then systematically treat modifiable risk factors.     

Changes in cardiovascular risk factors after renal transplantation

Authors examined the serum concentration of creatinine, uric acid, homocysteine, cystatine C, total cholesterol and triglyceride in 115 male and 77 female patients six months after the transplantation. The change of the BMI (Body Mass Index) was studied, fat and water body weight was determined by bioelectrical impedance analysis, and the ratio of intra- and extracellular volume was calculated. Both creatinine and cystatine C levels decreased significantly compared to the levels before the transplantation (p < 0.001) because of the good renal function, and there was a good correlation between creatinine, cystatine C and homocysteine levels (r = 0.5315 in females, r = 0.3189 in males). Elevated BMI (36.49%) and hypercholesterolaemia along with moderate hyperhomocysteinaemia was found in a considerable part of the patients. Increase in body weight was confirmed by the increase in fat body weight and volume determined by bioelectrical impedance analysis. In patients with adequate compliance the ratio of intra- and extracellular volume was between 1.67 and 1.79. Blood pressure values showed frequently the non-dipper phenomenon despite appropriate antihypertensive therapy, and negative diurnal index was found with high nocturnal blood pressure levels. The mean blood pressure was 148/81 +/- 13.2/4.8 mmHg in males and 133/84 +/- 15.3/9.8 mmHg in females. Authors enhance the importance of regular monitoring of cardiovascular risk factors in the prevention of cardiovascular complications.     

Cardiovascular risk factors in kidney transplantation

Classical and non-classical cardiovascular risk factors are common after renal transplantation, and they are effectively associated with the development of cardiovascular disease. Despite the absence of large, controlled clinical trials examining the effect of prevention strategies, therapies should not be withheld from renal transplant recipients with significant risk factors, because their risk of developing cardiovascular disease is at least as high as that of the general population.     

Cardiovascular risk profile in patients treated with sirolimus after renal transplantation

Renal transplant patients are inherently predisposed to cardiovascular disease (CVD) as a result of prolonged exposure to multiple cardiovascular risk factors. Approximately one half of all late graft losses are due to death with a functioning graft, and CVD is the most frequent cause of death with a functioning graft among these patients. Immunosuppressive therapies associated with a reduced burden of risk for CVD would therefore greatly decrease post-transplantation morbidity and mortality. The nephrotoxic effects observed with the use of calcineurin inhibitors (CNIs), such as cyclosporine (CsA), run counter to the goal of renal transplant therapy. Sirolimus, a more recent immunosuppressive agent with a unique mechanism of action, offers an alternative to CsA. Recent data from a 4-year study investigating early CsA withdrawal from a sirolimus-CsA-steroid (SRL-CsA-ST) combination demonstrated significantly better renal function, lower blood pressure, and improved graft survival after CsA withdrawal. During that trial, the increase in serum lipids induced by sirolimus was generally manageable with lipid-lowering therapy. Further investigation is warranted to evaluate the value of CNI-free therapy compared with CNI-based regimens in reducing cardiovascular risk factors and improving patient and graft survival.     

Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors

Cardiovascular mortality is increased in transplant recipients. However, studies including non-fatal events are critical to assess the burden of disease and to identify novel risk factors. We described the incidence of fatal and non-fatal events, and explored associations and interactions among traditional and transplant-specific risk factors and cardiovascular events (CVE) in a cohort of 922 patients transplanted between 1993 and 1998. One hundred and seventy-six patients experienced 201 CVE (111 cardiac, 48 cerebrovascular, 42 peripheral-vascular). Most CVE were non-fatal. Factors associated with cardiac events were (adjusted hazard ratios) tobacco (3.53; P<0.001), obesity (2.92; P<0.001), diabetes (2.63; P<0.001), multiple rejections (2.19; P=0.008), prior CVE (2.0; P=0.004), dialysis >1 year (1.91; P=0.007), and overweight status (1.68; P=0.04); with cerebrovascular events: diabetes and peritoneal dialysis (11.95; P<0.001), age >45 (6.77; P<0.001), diabetes (4.87; P<0.001), prior CVE (3.73; P<0.001), creatinine >141 micromol/l (3.16; P=0.001), peritoneal dialysis (3.06; P=0.027), and obesity (0.32; P=0.046); with peripheral-vascular events: diabetes (8.48; P<0.001), tobacco and cytomegalovirus (3.88; P<0.001), age >45 (2.31; P=0.019), and prior CVE (2.25; P=0.016); with mortality: tobacco and deceased-donor (3.52; P<0.001), age >45 (1.81; P=0.002), diabetes (1.76; P=0.002), pulse pressure (1.64; P=0.029), prior CVE (1.52; P=0.04), and dialysis >1 year (1.47; P=0.04). The majority of CVE post-transplant were non-fatal. Previous CVE was strongly associated with CVE post-transplant. Interactions among transplant-specific and traditional risks impacted significantly the incidence of CVE. Modifiable factors such as duration of dialysis, deceased-donor transplantation, and acute rejection should be viewed as cardiovascular risks.     

Cardiovascular complications after renal transplantation and their prevention

By the time of renal transplantation, end-stage renal disease patients have a huge burden of cardiovascular disease (CVD) and are heavily saturated with atherosclerotic risk factors. Worsening of preexisting risk factors or new CVD risk factors may develop in the posttransplant period consequent in part to the diabetogenic and atherogenic potential of immunosuppressive drugs. The annual risk of a fatal or non-fatal CVD event of 3.5 to 5% in kidney transplant recipients is 50-fold higher than the general population. Renal allograft dysfunction, proteinuria, anemia, moderate hyperhomocysteinemia and elevated serum C-reactive protein concentrations, each dependently confer greater risk of CVD morbidity and mortality in the posttransplant period. Long-term care of renal transplant recipients should programmatically incorporate the recommendations of the National Kidney Foundation Working Groups and European Best Practice Guidelines Expert Group on Renal Transplantations into the management of hypertension, dyslipidemia, smoking, and posttransplant diabetes mellitus. Timely utilization of coronary revascularization procedures should be undertaken as these treatments are equally effective in the kidney transplant population.     

Incidence and risk factors of new-onset diabetes mellitus after renal transplantation

PURPOSE: New-onset diabetes mellitus (PTDM), a major metabolic complication after renal transplantation, examined for incidence and risk factors. METHODS: The records of 358 renal transplant recipients with functioning grafts, from 1986 to 2006, were categorized into two groups according to the usage of tacrolimus (FK): FK-based (n = 120 patients) and non-FK-based (n = 238). Using Kaplan-Meier survival analysis and a Cox regression model, this study analyzed the cumulative incidence of PTDM and risk factors, including gender, age, and presence of hepatitis. RESULTS: Cumulative incidences of PTDM after 1, 3, and 5 years posttransplantation in the FK-based group were 11%, 18%, and 22%, respectively. In the non-FK-based group, the cumulative incidences were 5%, 9%, and 12% (P = .01). Taking into account the risk factors, the cumulative incidence of PTDM was significant among patients 51 years or older (odds ratio, 3.965; P = .005), but not with regard to gender or presence of hepatitis B and/or C. Overall cumulative incidence of PTDM in our series was 15% (54/358), including 44% (24/54) of cases that occurred within 1 year after renal transplantation. CONCLUSION: FK is more diabetogenic than cyclosporine or sirolimus. Older age (>==51 years) is a significant risk factor, in contrast to hepatitis and gender. About half of these cases of PTDM occurred within 1 year after transplantation. These results suggest that aggressive monitoring of blood sugar is necessary for early detection of PTDM.     

Cardiovascular risk estimates and risk factors in renal transplant recipients

Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease.     

Recurrent glomerular diseases after renal transplantation

INTRODUCTION: Recurrent glomerular diseases are important causes of graft dysfunction after renal transplantation. As the outcomes of transplantation continue to improve, the problem of recurrent diseases in the transplanted kidney have become evident. The purpose of our study was to determine the risk factors for and the incidence of recurrence in the posttransplant period as well as their impact on graft survival rates. METHOD: We retrospectively analyzed 49 patients with glomerular diseases due to membranoproliferative glomerulonephritis (n = 26); focal segmental glomerulosclerosis (FSGS, n = 18); and systemic lupus erythematosus (n = 5). The mean follow-up was 9.5 years. RESULTS: Recurrent disease was detected in 30 of 49 patients after a mean posttransplant follow-up of 28.1 months (range = 1 to 157) and their average graft survival was 41.3 months. Nineteen patients were recurrence-free with a mean graft survival of 79.4 (range = 15 to 158) months (P < .05). One patient with FSGS, showed disease-recurrence in her third transplant after having experienced recurrences in the former grafts. In all six patients with HLA haplotype B8, recurrence was observed at a mean of 19.5 +/- 9.8 months. The only risk factor that was identified was this HLA haplotype. CONCLUSION: Recurrent disease a significant problem after renal transplantation is associated with decreased graft survival. The donor HLA type may be associated with risk, which should be clearly discussed with both the living donor and the recipient candidate.     

肾移植术后切口疝发生的相关危险因素及治疗分析

切口疝是腹部手术最常见的术后并发症之一。腹部器官移植后,由于患者长期使用免疫抑制疗法及其他原因导致切口愈合缓慢且易感染,发生切口疝的风险也随之增加。肾移植术后切口疝的形成通常不会对患者产生致命的影响,因此并没有得到外科医师的重视。然而,并发切口疝可导致患者住院时间延长以及费用的增加。此外,若不及时治疗,疝内容物与疝囊黏连,可导致肠梗阻,并发循环及呼吸功能紊乱,不仅损害了患者的生活质量,严重时甚至会威胁患者生命。因此,对肾移植术后患者并发切口疝的研究显得尤为重要。     

肾移植术后新发糖尿病危险因素分析

目的 探讨肾移植术后新发糖尿病(new-onset diabetes mellitus after renal transplantation,NODAT)的危险因素.方法 术前未患糖尿病接受同种尸体肾移植的患者706例,根据入选时有否NODAT分为NODAT组和非NODAT组.统计NODAT发生率,对两组患者可能存在...     

肾移植术后高水平BK病毒尿症危险因素分析

目的  分析肾移植术后高水平BK病毒尿症的危险因素及其对预防BK病毒相关性肾病（BKVAN）的意义。方法  回顾性分析262例保留规律随访资料的肾移植受者的临床资料。根据受者BK病毒DNA载量分为高水平BK病毒尿症组（35例）和非高水平BK病毒尿症组（227例）。总结肾移植术后高水平BK病毒尿症的发生情况;采用单因素和多因素分析肾移植术后发生高水平BK病毒尿症的危险因素;采用Kaplan-Meier法绘制生存曲线,对受者进行生存分析。结果  262例肾移植受者中,35例发生高水平BK病毒尿症,发生率为13.4%。发生中位时间181（126,315）d,发生率在移植术后6个月内最高,6个月至2年逐渐降低,2年后有所回升。单因素分析结果提示抗胸腺细胞球蛋白（ATG）治疗史、急性排斥反应（AR）、捐献类型及移植物功能延迟恢复（DGF）是肾移植术后发生高水平BK病毒尿症的危险因素（均为P < 0.05）。多因素Cox回归分析结果显示脑-心双死亡器官捐献（DBCD）、AR及DGF是肾移植术后发生高水平BK病毒尿症的独立危险因素。有ATG治疗史、发生AR、发生DGF以及捐献类型为DBCD的受者的1、3、5年生存率分别低于无ATG治疗史、无发生AR、无发生DGF及其他捐献类型[脑死亡器官捐献（DBD）、心脏死亡器官捐献（DCD）和活体器官捐献]的受者（均为P < 0.05）。结论  DBCD、AR及DGF是肾移植术后发生高水平BK病毒尿症的独立危险因素,加强对此类受者的术后监测并给予早期干预可能是预防BKVAN的有效方式。     

Incidence and risk factors of renal dysfunction after liver transplantation in Korea

Renal dysfunction, one of the most common complications after liver transplantation, influences patient outcomes. Little is known, however, about it in Korea. The aims of this study were to determine the incidence and to identify the risk factors for renal dysfunction after liver transplantation. Sixty-two patients who survived over 6 months after transplantation were enrolled. Renal function was classified by creatinine clearance (Ccr, mL/min), which was estimated using the Cockcroft-Gault formula. Twenty-seven patients (44%) showed mild renal dysfunction (60 < or = Ccr < 90), and 27 patients (44%), moderate dysfunction (30 < or = Ccr < 60). The others were found to have normal function (Ccr > or = 90). None displayed severe dysfunction (Ccr < 30). Compared to a control group (Ccr > or = 60), the renal dysfunction group showed lower preoperative Ccr (91 +/- 28.6, 63 +/- 21.9, respectively, P < .01) and lower Ccr at 3 months after transplantation (72 +/- 17.1, 49 +/- 14.6, respectively, P < .05). Age, sex, immunosuppressive drug usage, serum tacrolimus levels, and the frequency of postoperative acute renal failure did not affect the postoperative renal dysfunction. Twenty-six patients received mycophenolate mofetil while reducing the dose of calcineurin inhibitors because of compromised renal function. With mycophenolate mofetil treatment, the renal function seemed to improve, although the difference was not statistically significant (P = .057). These data demonstrate that renal dysfunction is common after liver transplantation and that preoperative renal function is the important factor predicting postoperative renal dysfunction.     

Cardiovascular risk factors in 116 patients 5 years or more after liver transplantation

We assessed the cardiovascular risk factors (CVRFs) in 116 stable liver transplant patients surviving for 5 years or more (median: 102 months). The prevalence of smokers was 29.3%, hypertension 49.1%, obesity 22.4%, hypercholesterolemia 34.5%, hypertriglyceridemia 11.2%, and hyperhomocysteinemia 57.8%. Diabetes was found in 21.5% of the patients, being more frequent in patients with hepatitis-C-virus infection (31.8% vs 15.3%; P=0.03). Patients on cyclosporine therapy had a higher prevalence of hypertension, hypercholesterolemia and hyperhomocysteinemia than those treated with tacrolimus. Multivariate analysis showed only an association between cyclosporine therapy and cholesterol concentrations (odds ratio:1.02; 95% confidence interval (CI): 1.00-1.03; P=0.01). The prevalence of hypertension, diabetes, hypercholesterolemia and hypertriglyceridemia was lower at the time of the study than at 1 and 3 years after transplantation ( P<0.05), probably related to steroid withdrawal. Comparing 87 patients' CVRFs with the general Spanish population, we found that the age-gender standardized prevalence ratio was not different: smoking 1.46 (95% CI: 0.88-1.76), obesity 1.16 (95% CI: 0.60-1.44), hypertension 1.55 (95% CI: 0.98-1.81), and hypercholesterolemia 0.64 (95%CI: 0.35-1.90). We conclude that the prevalence of CVRFs in liver transplant patients after 5 years or more is lower that found in the first years after the transplantation, and no different from that found within the Spanish population.     

Cardiovascular disease risk factors in chronic renal insufficiency

BACKGROUND: Coronary heart disease (CHD) is an important cause of morbidity and mortality in end-stage renal disease (ESRD). Prevention of CHD in ESRD requires identification and treatment of coronary risk factors in chronic renal insufficiency (CRI). METHODS: We evaluated the prevalence of "traditional coronary risk factors" in CRI in 1,795 patients enrolled in the baseline period of Modification of Diet in Renal Disease (MDRD) Study. Using a cross-sectional design, we determined the relationship of these risk factors to the level of glomerular filtration rate (GFR) and proteinuria. We also predicted the CHD risk in the MDRD Study baseline cohort using the coronary point score. RESULTS: 64.0% had blood pressure > or = 130/85 mmHg despite antihypertensive therapy. 64.2% had LDL cholesterol > or = 130 mg/dl, while 38.3% had HDL cholesterol < 35 mg/dl. After adjustment for age, gender and the presence of diabetes, GFR was inversely associated with systolic blood pressure and positively associated with HDL cholesterol, but not associated with total or LDL cholesterol. After adjustment for age. gender and the presence of diabetes, proteinuria was positively associated with systolic and diastolic blood pressure, total serum cholesterol and LDL cholesterol, and inversely associated with HDL cholesterol. Nonetheless, the predicted CHD risk, even at a very low GFR, was similar to the risk in the general population and lower than the observed rate of de novo CHD in incident dialysis patients. CONCLUSIONS: "Traditional coronary risk factors" are highly prevalent in CRI and vary with the level of renal function. However, the coronary point score does not appear to explain the extent of increased CHD risk in ESRD. Non-traditional risk factors may also contribute to CHD in ESRD.     

Non-immunological risk factors in paediatric renal transplantation

In paediatric renal transplantation, non-immunological risk factors account for about one-third of graft losses. Recurrence of original disease is observed mainly in primary hyperoxaluria and glomerulopathies such as steroid-resistant nephrotic syndrome and membranoproliferative glomerulonephritis. In both glomerulopathies, 20% of grafts are lost from recurrence. Vascular thrombosis is, in most series, the second cause of graft loss in children, particularly in young recipients or with young donors (under 5 years of age). Non-compliance with treatment is a common non-immunological factor in adolescent recipients, which may trigger a severe rejection process resulting in graft loss. The role of factors related to graft preservation and intra- and post-operative management (ischaemia time, delayed graft function) or to cytomegalovirus infection is less obvious in our series. Prevention of vascular thrombosis and of non-compliance is most important in order to improve the results of paediatric renal transplantation.