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Medicine » Urology and Nephrology » "Understanding the Complexities of Kidney Transplantation", book edited by Jorge Ortiz and Jason Andre, ISBN 978-953-307-819-9, Published: September 6, 2011 under CC BY-NC-SA 3.0 license. © The Author(s).

Chapter 6

Cardiovascular Diseases in Kidney Transplantation

By Roberto Marcén and Sara Jiménez
DOI: 10.5772/23210

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Cardiovascular Diseasesin Kidney Transplantation

Roberto Marcén1 and Sara Jiménez

1. Introduction

Cardiovascular diseases that include atherosclerotic diseases; coronary artery disease, cerebrovascular disease and peripheral vascular disease, and cardiac functional diseases; congestive heart failure, left ventricular hypertrophy and arrhythmias, are very common in the general population and are the first cause of mortality (Wilson &Culleton, 1998, Culleton & Wilson, 1998). Moreover, patients with chronic renal failure have an increased risk of cardiovascular disease compared with the general population, and after stratification by age and gender, cardiovascular mortality is 10 to 20 times more frequent independently of treatment; predialysis, dialysis or after kidney transplantation (Foley et al, 1998). Kidney transplantation is the best therapy of end-stage renal disease by reducing cardiovascular mortality (McDonald & Russ, 2002, Ojo et al, 2000, Wolfe et al, 1999). But even after transplantation, a recipient of 25 to 35 years of age has a 10 times higher risk of cardiovascular mortality than an individual of similar sex and gender without renal failure (Foley et al, 1998). Among the cardiovascular diseases, atherosclerotic diseases are the most frequently studied and are associated with patient outcome. Ischaemic heart disease was the cause of 53% of total mortality in a study performed in Scandinavia 15 years ago (Lindholm et al, 1995) and these findings were still prevalent in a later report (Aakhus et al, 2004). However, several authors have recently emphasized the importance of functional cardiopathies such as congestive heart failure on patient outcome (Rigatto et al, 2002).

The high incidence of cardiovacular events and mortality in renal transplant recipients has been attributed to the increased presence of traditional (Ojo, 2006) and nontraditional risk factors (Ducloux et al, 2004, De Mattos et al, 2006). As traditional risk factors do not fully explain the high cardiovascular risk it has been postulated that some of these risk factors, age, diabetes and smoking, could have a higher deleterous impact in transplant recipients than in the general population (Kasiske et al, 2000a). Other authors consider that transplant related (De Mattos et al, 2006) and nontraditional or emergent factors, hyperhomcysteinemia and inflammation, could play a predominant role in the appearance of cardiovascular events (Ducloux et al, 2004). Progressive chronic graft dysfunction and death with functioning graft are the most important causes of graft loss (Matas et al, 2002, Collins et al, 2008) and cardiovascular diseases are the leading cause of mortality in renal transplant recipients dying with a functioning graft (Pilmore et al, 2010). Consequently decreasing cardiovascular mortality could improve patient and graft outcomes (Howard et al, 2002, Marcén et al, 2001, Morales, 2008, Vanrenterghem et al, 2008).

The present chapter reviews the cardiovascular diseases which affect renal transplant recipients and their impact on patient mortality, the risk factors associated with these complications and the therapeutical strategies to improve patient and graft outcomes.

2. Cardiovascular diseases

Renal transplant recipients are not healthy individuals. They have a past history of chronic renal failure and dialysis therapy, both having negative impact on cardiovascular risk and they present variable chronic renal failure stages. All cardiovascular diseases; atheriosclerotic and functional cardiopathies can affect transplant recipients (Table 1).

Atheroesclerotic diseasesFunctional cardiopathies
Coronary artery diseases
Cerebrovascular diseases
Peripheral vascular diseases
Congestive heart failure
Left ventricular hypertrophy

Table 1.

Most common cardiovascular diseases affecting transplant recipients

As in the general population, cardiovascular diseases are important causes of morbidity and mortality in renal transplant recipients. Heart diseases and cerebrovascular diseases accounted for about 35% mortality in our Unit (Figure 1).


Figure 1.

Causes of mortality in 224 renaltransplant recipients with functioning graft( Ramón y Cajal Hospital)

2.1. Atherosclerotic diseases

2.1.1. Coronary artery disease

Coronary artery disease is the most frequent atherosclerotic disease in the general population and a leading cause of cardiovascular mortality. It is generally admitted that coronary artery disease is between 2 and 6 times more frequent in renal transplant recipients than in the general population (Aarkhus et al, 1999, Kasiske, 1988, Lentine et al, 2005a, Marcén et al, 2006, Massy, 2001). A very high number of events occurring during the first weeks after transplantation have been attributed to surgical stress, immunosuppression and silent disease while the patient was on dialysis (Kasiske et al, 2000, 2005, Lentine et al, 2005, Marcén et al, 2006). In a retrospective study from the USA, the prevalence of coronary artery disease, defined as acute myocardial infarction, coronary revascularization procedures, or death due to coronary disease, was 23% at 15 years of follow-up and it was the cause of 18.7% of mortality (Kasiske et al, 1996). In a multicenter, retrospective study performed in Spain, the prevalence of coronary artery disease was 6.8% at 5 years (Marcén et al, 2006) and very similar findings have been reported from France (Doucloux et al, 2004), two low risk countries. Data from the United Network for Organ Sharing (UNOS) and United States Renal Data System (USRDS) registry showed that the prevalence of acute myocardial infarction was between 6% to 11 % at 3 years a 17% lower than that observed on waiting list patients (Kasiske et al, 2006, Lentine et al, 2005). Moreover, myocardial infarction has a poor prognosis and is the cause of high mortality (Herzog et al, 1998, 2000, Morales, 2008).

The diagnostic criteria and therapeutical measures must be those used in the general population and in patients with chronic renal failure (Murphy et al, 1998). As a high percentage of events occur in the first weeks or months after the procedure, efforts have to be made to prevent and treat coronary artery disease before transplantation. Several algorithms have been proposed in which patients are classified according to cardiovascular risk (Lentine et al, 2008b, Wang & Kasiske, 2010), but we have not yet the ideal diagnostic procedure for asymptomatic patients.

2.1.2. Cerebrovascular diseases

Cerebrovascular diseases include transient cerebral ischaemia, when focal neurologic symptoms resolve in 24 hours, and persistent neurological deficits documented by computed tomography or nuclear magnetic resonance. Patients with chronic renal disease have more severe atherosclerotic lesions in carotic arteries than the general population (Kennedy et al 2001). This could explain the 5 to 10 times higher risk of having ischaemic or haemorragic events when compared with the general population (Seliger et al, 2002, 2003a,b). In renal transplant recipients the annual incidence was from 0.5% to 2.3% (Abedini et al, 2009a, Aull-Watschinger et al, 2008, Cosio et al, 2005, Lentine et al, 2008a, Oliveras et al,2003), and ischaemic events predominated in a proportion of 2-3:1 compared with haemorragic events (Aull-Watschinger et al, 2008, Oliveras et al, 2003). In a long-term study, by actuarial analysis, 15% of patients who survived with a functioning graft for 15 years experienced a major crebrovascular event (Kasiske et al, 1996). The evolution of cerebrovascular diseases is poor and a mortality rate around of 50% three months after the event has been reported (Oliveras et al, 2003). In retrospective studies, cerebrovascular diseases were the cause of 5% to 8% of total mortality (Aull-Watschinger et al, 2008, Howard et al, 2002). Only the Assessment of Lescol in Renal Transplantation (ALERT) study has prospectively investigated these complications, the incidence was 8.8% during the 6.7 year follow-up period, and 21% of the cerebrovascular events, 48% of haemorragic and 8% of ischaemic, were fatal and accounted for 9.9% of total mortality (Abedini et al, 2009a).

2.1.3. Peripheral vascular disease

The incidence and clinical outcome of this complication have been seldom studied in renal transplant recipients. The diagnostic criteria include: intermitent claudication, ulceration with long-vessel disease on flow studies, amputations, by-pass or percutaneous angioplasty. The frequency reported was variable. In an old study, in which only amputation or revascularization procedures were included, the cumulative incidence was 15% at 15 years (Kasiske et al, 1996). In other studies, the incidence increased with the length of follow-up, from 2.1% at 1 year to 5.9% at 10 years (Sung et al, 2000). Data from the UNOS registry have shown a cumulative incidence of 20% in diabetic and 5% in nondiabetic patients at 3 years (Snyder et al, 2006). As the disease develops along years it is difficult to distinguish risk factors due to transplantation from those present before. The need of amputation is low about 2 to 3% (Sung et al, 2000). The disease by itself is not a cause of mortality but patients suffering from it have an increased risk of death with a functioning graft (Snyder et al, 2006, Sung et al, 2000).

3. Functional heart diseases

3.1. Congestive heart failure

Congestive heart disease is defined as dysnea plus at least two of the following characteristics; increased yugular venous pressure, basal lung rales, lung hypertension in radiography or pulmonary edema (Harnett et al, 1995). In dialysis patients, congestive heart failure is 36 times more frequent than in the general population and it is a mortality risk factor (Collins 2002, Stack & Bloemberg, 2001). Congestive heart disease has been studied less than coronary artery disease in the renal transplant population and it is associated with coronary artery disease in 30% of cases (Rigatto, 2003a,b). Its annual incidence was 3-5 times that of the general population, reached a cumulative incidence of 18.3% at 3years and was associated with poor graft function (Abbott et al, 2003b, Lentine et al, 2005, Rigatto, 2003a,b). It has a high impact on mortality, similar to that of coronary artery disease (Lentine et al, 2005).

3.2. Left ventricular hypertrophy

There are two types of left ventricular hypertrophy; concentric ventricular hypertrophy and dilatation with or without hypertrophy. The first one is associated with volume overload and the second with aortic insuficiency or severe anemia. Both types are more frequent in patients in renal failure than in the general population, reaching 20-50% in patients with chronic renal failure (Levin et al, 1996, Tucker et al, 1997) and up to 70% in those on dialysis (Foley et al, 1995, Mc Gregor et al, 1998). Several prospective studies have shown that left ventricular hypertrophy improved during the first two years after transplantation but it was still present in about 40% of renal transplant recipients (Rigatto et al, 2000, Teruel et al, 1987). Factors related with no improvement were: age, left ventricular morphology, duration and severity of hypertension and time averaged pulse pressure (Rigatto et al, 2000). Moreover, renal transplant also improved ventricular function in most patients even in those with severe impairment (Parfrey et al 1995, Wali et al, 2005). However these findings have been recently questioned when cardiac structure was assessed by magnetic resonance (Patel et al, 2008). Parameters of ventricular hypertrophy or impaired cardiac function were associated with increased risk of cardiovascular events and cardiovascular mortality in renal transplant recipients (Aull-Watschinger et al, 2008, Mc Gregor et al, 2000). In a nonrandomized study, conversión from CNI to sirolimus regressed left ventricular mass thickness regardless of blood pressure changes, thus suggesting non-hemodynamic-effect mechanisms on the left ventricular mass (Paoletti et al, 2008).

3.3. Arrhythmias

Atrial fibrilation is the most common cardiac rythm disorder in the general population and in patients on dialysis (Harnett et al 1995, Zebe 2001). Data from renal transplant recipients, despite being a high risk population due to the pre-transplant history and the high prevalence of risk factors related to this complication such as hypertension and obesity, have only been recently reported. Registry studies from the USA have shown a cumulative prevalence around 7 % at 3 years (Abbott et al, 2003a, Lentine et al, 2006). Risk factors for postransplantation atrial fibrilation include older age, male gender, renal failure for hypertension, and coronary artery disease. As in the general population atrial fibrilation was associated with an increased cardiovascular mortality, up to 3 times higher than patients without the disease (Abbott et al, 2003b, Lentine et al, 2006).

4. Cardiovascular risk factors

Three types of cardiovascular risk factors are generally identified in transplant recipients (Table 2). 1) Traditional risk factors are those which in the general population are associated with cardiovascular diseases, and their treatment decreases the incidence of these complications. They include; older age, hypertension, hypercholesterolemia, diabetes mellitus, tobacco smoking and obesity. Their incidence is mostly increased in advanced CKD stages (Ansell et al, 2007, Karthikeyan et al, 2004, Marcén et al, 2005). 2) Risk factors associated with the transplant; anaemia, graft dysfunction and related complications, proteinuria, and immunosuppression. Finally, 3) Non-traditional or emergent factors such as hyperhomocysteinemia and chronic inflammation.

Traditional risk factorsTransplant related factorsNontraditional or emergent factors
Graft dysfunction

Table 2.

Cardiovascular risk factors

4.1. Traditional risk factors

4.1.1. Age and sex

Older age is a nonmodifiable cardiovascular risk factor in the general population. In renal transplant recipients it was associated with an increased risk for cardiovascular atherosclerotic diseases; ischemic heart disease, cerebrovascular disease, and peripheral vascular disease (Kasiske et al, 1996, Kasiske et al, 2006, Marcén et al, 2006, Oliveras et al, 2003, Rigatto et al, 2002, Snyder et al, 2006), and also for functional heart diseases; congestive heart failure, left ventricular hypertrophy and arrhythmias (Abbott et al, 2003a, Lentine et al 2006, Rigatto et al, 2000, Rigatto et al, 2002). Male gender is a risk factor for ischemic heart disease and peripheral vascular disease (Kasiske, 1988, Rigatto et al, 2002, Kasiske et al, 2006, Marcén et al, 2006, Snyder et al, 2006) and female gender for cerebrovascular disease and congestive heart failure (Abbott et al, 2003a, Lentine et al, 2008a).

4.1.2. Hypertension

It is a common complication in renal transplant recipients. Its prevalence varies between 70 and 90%. There are several causes and mechanisms of high blood pressure and many patients have several of them. A previous history of hypertension, artery graft stenosis, the own recipient kidneys, overweight, chronic graft dysfunction and immunosuppressive agents such as calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are the conditions generally associated with post-transplant hypertension (Koomans & Ligtenberg, 2001, Zhang et al, 2003). Among CNIs, cyclosporine seems to increase blood pressure more than tacrolimus (Ligtenberg et al, 2001). It has been associated with an increased risk of ischemic heart disease, congestive heart failure, left ventricular hypertrophy (Rigatto 2001) and with mortality (Kasiske et al 2004, Fernández-Fresnedo et al, 2005).

One characteristic of post-transplant hypertension is the lack of control despite treatment. In a study of 1295 patients, only 12.4% had a normal blood pressure one year after grafting and more than 95% of them were on antihypertensive therapy (Kasiske et al, 2004). Others found in their series a higher number of patients with normal blood pressure without therapy (26.0%) but they also reported that 32.0% of patients had uncontrolled blood pressure while they were on treatment (Tutone et al, 2005). Cross-sectional studies have shown that between 60 to 100% of patients according to the stage of graft failure had a blood pressure above 130/80 mm Hg and most of them were on antihypertensive therapy (Karthikeyan et al, 2004, Marcén et al, 2009a).

There are not specific blood pressure levels for renal transplant recipients and the reference values are those of the general population. As the renal transplant recipients are considered a high risk population for cardiovascular diseases, a blood pressure of 130/80 mm Hg has been recommended. Treatment includes changing life style, reducing the diet sodium intake, physical activity, low consumption of alcohol and antihypertensive agents (Choubanian et al, 2003). There are no specific antihypertensive agents to treat post-transplant hypertension and all agents can be used. The prescription has to be done taking into account the characteristic of each patient (KDIGO, 2009, Park & Luan, 2005). Most patients need to be treated with several antihypertensive agents. Studies in which angiotensin converting enzyme inhibitors or angiotensin receptor blockers have been compared with other antihypertensive agents have shown controversial results, and there are no studies in which the superiority of one agent over the others on patient survival has been definitively established (Opelz et al, 2006, Hiremath et al, 2007). There are not randomized, prospective studies that have demonstrated the beneficial effects of controlling blood pressure in renal transplant recipients, but it has been assumed that they would be similar to those obtained in the general population. However, retrospective registry studies have shown that decreasing blood pressure even several years after hypertension appearance was associated with a better patient outcome (Opelz et al, 2005).

4.1.3. Dyslipidemia

Lipid disorders are more common in renal transplant recipients than in the general population and include high levels of cholesterol and triglycerides. Also frequent are high levels of LDL-cholesterol, lipoprotein (a) and apolipoprotein B, while HDL-cholesterol can be high, normal or low. Hypercholesterolemia, total serum cholesterol above 200 mg/dl and LDL-cholesterol above 100 mg/dl, have been observed in up to 90 % of patients (Aakhus et al, 1996, Hricik et al, 1994). Several factors have been associated with hyperlipidemia; genetic predisposition, body weight gain, graft dysfunction, proteinuria, diabetes, immunosuppressive and antihypertensive agents (Massy & Kasiske, 1996).

Among immunosuppressive agents, corticosteroids, CNIs and mammalian target of rapamycin inhibitors (mTORs), sirolimus and everolimus, are those most frequently associated with hyperlipidemia. The mechanisms of corticosteroid-induced hyperlipidemia are through promoting insulin resistence and hyperinsulinism, reduction of lipoprotein lipase activity, overproduction of triglycerides and secretion of VDLD-cholesterol (Hricik et al, 1994). CNIs inhibit bile acid synthesis and binding of the drugs to the LDL-cholesterol receptor with reduction of its activity. Also a decrease in lipoprotein lipase activity and impairment of LDL-cholesterol catabolism may be involved. These effects seem to be more prominent with cyclosporine than with. mTORs are the agents with stronger hyperlipidemic effect, which is more accentuated in those patients also treated with cyclosporine than in those treated with tacrolimus. The pathogenesis of mTOR dyslipidemia is unclear. A reduced catabolism of apo B100 could be the cause of increased triglycerides and cholesterol and decreased lipoprotein lipase activity and increased free fatty acid levels may be contributing factors. Their effects are dose dependent and rapidly reversible.

As in the general population, hypercholesterolemia and low HDL-cholesterol levels are associated with ischemic heart disease. The treatment of this complication may follow the recommendations given to the general population and confirmed by the transplant guidelines (KDIGO, 2009). It is important to begin with a rich diet of monosaturated fats, but diet therapy does not control hyperlipidemia and lipid-lowering agents have to be added. 3-Hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins) are the elective pharmacologic agents in hypercholesterolemic patients. Fluvastatin, pravastatin and atorvastatin seem to have a more favourable safety profile over simvastatin and lovastatin. In patients with hypertriglyceridemia, gemfibrocil is the pharmacological agent of choice. Some observational studies have shown an association between statin therapy and better patient outcome. However, the Assessment of Lescol in Renal Transplantation (ALERT) study did not show differences in the primary compound end point, despite a reduction of 32% in the LDL-cholesterol blood levels at 5 years follow-up, between recipients treated with fluvastatin compared with those on placebo. A later evaluation of the study showed the benefits of the treatment but only when statin therapy started in the first two years after transplantation and in low-risk recipients. In case of statin intolerance or hyperlipidemia of difficult control, ezetimibe that blocks the cholesterol absorption in the brush border, alone or combined with statins, is an efficient and safe alternative.

4.1.4. Diabetes

In the renal transplant recipients, two types of diabetes mellitus can be distinguished, diabetes mellitus as the cause of end-stage renal disease and new onset diabetes mellitus (NODAT). The prevalence of diabetes mellitus as the cause of renal failure is variable among countries. In the USA, more than 20% of the patients on the waiting list or transplanted have diabetes mellitus as the cause of renal failure (Collins et al, 2008). The incidence of NODAT varies between 2% to 50% in the first posttransplantation year according to the criteria used in its definition (Montori et al, 2002). When the American Diabetes Association criteria were used, the incidence of NODAT at 12 months was 13% and of glucose intolerance of 33% in a study performed at the Mayo Clinic. Similar findings have been observed in a prospective study from Spain. As the term NODAT does not include states of impaired fasting glucose and impaired glucose tolerance which pose a cardiovascular threat similar to overt diabetes, the term transplant associated hyperglycemia (TAH) has been proposed. The most common risk factors associated with NODAT or TAH include: race, blacks or hispanics, older age, obesity, family history, hepatitis C virus infection and some immunosuppressive agents such as corticosteroids, CNIs (tacrolimus) and mTORs (Crutchlow & Bloom, 2007).

The effects of immunosuppresive agents on glucose metabolism have been widely reviewed. Both CNIs, cyclosporine and tacrolimus, cause NODAT by inducing insulin resistance or by impaired insulin secretion. Early trials designed to compare the efficacy and security of cyclosporine and tacrolimus, and registry data showed a higher incidence of NODAT in patients treated with tacrolimus and more recent studies have confirmed these findings (Vincenti et al 2007). Also mTORs are associated with an increased risk of NODAT (Johnston et al, 2008). These agents induce hyperglucemia by impairing insulin-mediated suppression of hepatic glucose production, by ectopic triglyceride deposition leading to insulin resistance, or by direct β cell toxicity.

Single centre and registry studies have shown the association of NODAT with acute myocardial infarction, cerebrovascular events and mortality. The treatment has the objective of preventing the symtoms due to uncontrolled hyperglucemia and the microvascular complications as the transplant recipients develop identical complications as the nontransplanted diabetic patients. The guidelines of the American Diabetes Association and the Joint Nacional Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for patients with type 2 diabetes have been recommended.

4.1.5. Tobacco

The effects of tobacco on the health in the general population are well known. It is a risk factor of cardiovacular diseases, malignancies and respiratory diseases. About 25% of the renal transplant population are active smokers after transplantation. In transplant recipients, tobacco was associated with cardiovascular diseases and mortality. It has been reported that the negative impact of tobacco on health disappeared after five years, and some authors emphasize that efforts have to be made to convince the patients about the benefits of avoiding smoking. There are few data about the influence of transplant on toxic habits, but some studies suggest that transplantation constituted a strong reason to give up smoking.

4.1.6. Obesity

Obesity is a growing health problem in the general population. Epidemiological studies have shown its association with a higher morbidity and mortality due to cardiovascular diseases. Transplant recipients have a tendency to gain body weight mostly in the first year after grafting. In a study performed in our Unit, the mean body weight gain in the first year was 5 kg or 8.7 % of the body weight at the time of transplantation and the percentage of obese patients increased nearly two fold, from 6.5% to 11.7%. Inappropriate dietary habits, decreased physical activity, and increased appetite as a result of well-being and corticosteroid therapy are among the causes of owerweight and obesity after transplantation.

Both body weight gain and obesity (body mass index >30 kg/m2) are associated with an increased risk for NODAT, hypertension, hyperlipidemia and metabolic syndrome which are cardiovascular risk factors. The effects of weight gain and obesity on graft and patient outcome are controversial. Some authors do not find that the complication has any impact on patient mortality. However, other studies and registry data have shown their negative impact on patient survival due to an increased cardiovascular and infectious mortality. In our opinion, controlling weight gain and weight reduction in patients with marked obesity seems to be a goal to improve well-being and outcomes in renal transplant recipients.

4.2. Risk factors associated with transplantation

4.2.1. Anaemia

Post-transplant anaemia is a common complication that has only been recently studied and considered. Its prevalence depends greatly on the definition criteria and the time post-transplant. Nowadays, there is a trend toward the use of the World Health Organization criteria which define anaemia as serum haemoglobin less than 12 g/dl in women and less than 13 g/dl in men. The prevalence of anaemia is about 90% during the first posttransplant weeks and decreases to 25% to 35% at 12 months and remains stable or slightly increases thereafter. In cross-sectional studies the prevalence of anaemia reached more than one third of patients and it was severe, serum haemoglobin below 11 g/dl, in about 10%.The origen of anaemia is multifactorial and graft function is the most important factor. However, it does not completely explain post-transplant anaemia, as renal transplant recipients have more severe anaemia for each chronic renal disease stage when compared with nontransplantation subjects. Several immunosuppressive agents such as azathioprine, mycophenolate mofetil (MMF), enteric coated mycophenolic acid (EC-MPA) and mTORs may cause anemia due to bone marrow toxicity or to disorders on iron homeostasis. The combination of MMF or EC-MPA with mTORs is specially toxic for the bone marrow. Other medications as angiotensin converting enzyme inhibitors andangiotensin receptor blockers are known to cause anaemia and should be cautiously used.

Recent studies have shown an association between anaemia and graft survival, cardiovascular diseases and mortality. Post-transplant anaemia seems to be a risk factor of congestive heart failure and of left ventricular hypertrophy but not of ischaemic heart disease. In addition, anaemia has been associated with increased mortality in some studies but not in others. The treatment of anaemia must follow the recommendations given for patients with chronic kidney disease in the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines (KDIGO, 2009). Iron supplementation and erythropoiesis stimulant agents should be administered to maintain serum haemoglobin between 11 and 12 g/dl.

4.2.2. Graft dysfunction

Renal function measured by the estimated glomerular filtration rate (eGFR) is a cardiovascular risk factor in the general population. An important number of renal transplant recipients have different stages of renal failure (Figure 2), and at least two thirds have chronic renal failure defined by an eGFR below 60 ml/min/1.73m2. As cardiovascular diseases are the leading cause of renal transplant recipient mortality, it seems logical to think in the existence of some links between premature cardiovascular death and poor graft function. Registry and prospective studies have demonstrated a correlation betwen serum creatinine and cardiovascular events or cardiovascular mortality. However, for other authors the increased cardiovascular risk of patients with poor graft function is mostly due to the effects of hypertension and anaemia than to graft failure itself. Moreover, uncontrolled hyperparathyroidism mostly in recipients with poor graft function may be a risk factor for progression of coronary artery calcification. The treatment of renal dysfunction includes the control of hypertension and dyslipidemias as well as the use of non-nephrotoxic immunosuppressive agents as MMF, EC-MPA and belatacept and dose reduction or withdrawal of CNIs.

The prevalence of proteinuria in the renal transplant recipients is between 7.5 and 45%. It is a risk factor of progressive renal function loss and of cardiovascular disease in nontransplantation patients. Retrospective studies have reported that proteinuria is an important predictor of cardiovascular events and mortality in renal transplant recipients. It is important to note that proteinuria is frequently associated with graft dysfunction, hypertension and obesity and the effects of proteinuria on cardiovascular events could be mediated by these conditions or viceversa. Treatment of proteinuria includes control of hypertension, maintaning blood pressure levels below 120/80 mm Hg, of dyslipidemias and of overweigth, and avoiding immunosuppressive agents associated with proteinuria as mTORs (Amer & Cosio, 2009). Angiotensin converting enzime inhibitors and angiotensin receptor blockersare the elective agents of treatment of hypertension in patients with proteinuria because of their antiproteinuric effects. However, these agents can deteriorate graft function and increase the severity of anaemia, both cardiovascular risk factors as well. Moreover, there are no definitive studies which support the effectiveness of this treatment.


Figure 2.

Distribution of chronic kidney disease stages at 12 months in 447 renal transplant recipients (Ramón y Cajal Hospital)

4.2.3. Immunosuppression

The effects of immunosuppressive agents in cardiovascular risk factors have been previously reviewed. In addition, the impact of these agents on each cardiovascular risk factor has already been described. Corticosteroids and CNIs are the agents with worst cardiovascular risk profile, increasing the incidence and severity of traditional risk factors such as hypertension, hyperlipidemia, diabetes and obesity. CNIs also are nephrotoxic and cause graft function impairment. mTORs increase the risk of anaemia, hyperlipidemia, diabetes and proteinuria. MMF and EC-MPA may increase the risk of anaemia but have no impact in the other cardiovascular risk factors. Combinations of CNIs with MMF and EC-MPA or with mTOR allow corticosteroid withdrawal without harm. On the other hand, MMF and EC-MPA and mTORs alone or in combination can be used for CNI dose reduction or withdrawal. All these strategies have been shown to be effective in improving cardiovascular risk but there are no prospective studies in which this improvement is followed by a lower incidence of cardiovascular events or mortality. Among the new immunosuppressive agents, belatacept improved short-term cardiovascular risk profile and graft function when compared with cyclosporine. However, phase II trials with tasocitinib have shown no improvement in hyperlipidemia and blood pressure when compared with patients who received tacrolimus (Busque et al, 2009).

4.3. Emergent risk factors

4.3.1. Hyperhomocysteinemia

Homocystein is a sulfur amino acid produced in all cells, and hyperhomocysteinemia has been considered a cardiovascular risk factor in the general population. Hyperhomocysteinemia is present in around 60% to 70% of renal transplant recipients. Homocystein levels are related with graft function, folic acid levels, serum albumin, age, and treatment with CNIs. The impact of homocystein levels on cardiovascular events is controversial. Some authors found an association between the homocystein levels and cardiovascular diseases and a prospective study has shown that homocystein levels above 12 μmol/l were associated with 2.44 times increased mortality. Other authors have not found this association. The treatment consists in the administration of folic acid supplements (5 mg/day) even with normal folic acid levels. The efficacy of this therapy in the prevention of cardiovascular events has been examined in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT).This trial should contribute to answer this question.

4.3.2. Inflammation

C-reactive protein (CRP) is an acute phase marker of inflammation. It is produced by the liver under control of several citokines. In the general population, C-reactive protein is associated with obesity and poor renal function. It is also a negative predictor of acute myocardial infarction, cerebrovascular disease and cardiovascular mortality. In renal transplant recipients, its levels are associated with graft function, waist circumference and smoking. The association between graft function and C-reactive protein levels could be explained by the situation of chronic low-grade inflammation, by being a marker of graft-mediated immune response or by a decreased renal excretion. As in the general population, it has been considered a risk factor of cardiovascular disease and mortality. Data from the ALERT study have confirmed the previous findings, baseline levels of CRP as well as of IL-6, another inflammation marker, were independently associated with major cardiovascular events and all-cause mortality. Results from a retrospective study have shown an association between MMF therapy and less inflammation than other immunosuppressive agents.

5. Therapeutical strategies

The management of each particular cardiovascular disease in renal transplant recipients should be similar to that used in the general population. In addition, clinical trials have demonstrated that cardiovascular events and cardiovascular mortality have been reduced by controlling blood glucose, lipid levels and blood pressure inthe general population. As interventional studies are lacking in the transplant population, it seems reasonable to extrapolate these findings to transplant recipients. However, transplant recipients present differences from the general population, one of them is the high incidence of graft dysfunction. Preserving graft function has to be a goal in the management of transplant recipients and this could be partly accomplished by controlling the traditional cardiovascular risk factors and by a prudent use of immunosuppressive agents. CNIs minimization or withdrawal may be individually considered. Additional interventions such as treatment of anaemia with erytropoyesis stimulating agents could help in the prevention of cardiovascular diseases but the optimal haemoglobin threshold has to be determined. The benefits of lowering homocysteine levels have not been proved. In addition, long-term interventional studies should be performed in order to improve graft and patient outcomes (Table 3).

Control of cardiovascular risk
Preserving graft functionTreating emergent factors
Blood pressure
Minimization/avoidance of CNIs
Control of proteinuria
Folic acid supplements

Table 3.

Preventionand treatment of cardiovascular diseases after transplantation.

6. Summary

Cardiovascular diseases are common after transplantation. Coronary vascular disease, cerebrovascular disease and congestive heart failure are the diseases most commonly associated with mortality. The increased incidence of cardiovascular events could be partly explained by the high prevalence of traditional risk factors which are not adequately controlled and by the presence of renal dysfunction. Pretransplant evaluation of candidates, control of traditional risk factors and preservation of graft function should be the measures taken to improve patient outcome. The control of traditional risk factors has been effective in the reduction of cardiovascular events in the general population and there are no reasons to believe that it does not work in the transplant population. In addition, adequate control of traditional risk factors could preserve progression of graft failure. A prudent use of immunosuppressive agents could also help to improve the cardiovascular risk profile and graft function. The benefits of additional interventions need to be proved.


1 - S. Aakhus, K. Dahl, T. E. Widerøe, 1863Hyperlipidaemia in renal transplant patients.J Intern Med. 2395May 1996), 4074150954-6820
2 - S. Aakhus, K. Dahl, T. E. Wideroe, 1986Cardiovascular morbidity and risk factors in renal transplant patients. Nephrol Dial Transplant. 143March 1999) 6486540931-0509
3 - S. Aakhus, K. Dahl, T. E. Wideroe, 1987Cardiovascular disease in stable renal transplant patients in Norway: morbidity and mortality during a 5-yr follow-up. Clin Transplant. 185October 2004), 5966040902-0063
4 - J. Aalten, MA Christiaans, H. de Fijter, R. Hené, J. H. van der Heijde, J. Roodnat, J. Surachno, A. Hoitsma, 1988The influenceof obesity on short- and long-term graft and patient survival after renal transplantation. Transplant Int. 1911November 2006), 901907ISSN.0934-0874.
5 - K. C. Abbott, J. C. Reynols, A. J. Taylor, L. Y. Agodoa, 2001Hospitalized atrial fibrillation after renal transplantation in the United States. Am J Transplant. 34June 2003a), 4714761600-6135
6 - K. C. Abbott, C. M. Yuan, A. J. Taylor, D. F. Cruess, L. Y. Agodoa, 1990Early renal insufficiency and hospitalized heart disease after renal transplantation in the era of modern immunosuppression. J Am Soc Nephrol 149November 2003b), 235823651046-6673
7 - S. Abedini, I. Holme, B. Fellstrom, A. Jardine, E. Cole, B. Maes, H. Holdaas, on behalf of the ALERT study group. (1963Cerebrovascular events in renal transplant recipients. Transplantation. 871January 2009a), 1121170041-1337
8 - S. Abedini, I. Holme, W. März, G. Weihrauch, B. Fellstróm, A. Jardine, E. Cole, B. Maes, H. Neumayer-H, C. Gronhagen-Riska, P. Ambühl, H. Holdaas, behalf. on, the. A. L. E. R. T. of, group. study, 2006Inflammation in renal transplantation. Clin J Am Soc Nephrol 47July 2009b), 124612541555-9041
9 - D. B. Allison, K. R. Fontaine, J. E. Manson, J. Stevens, T. B. Vantallie, 1883Annual deaths attibutable to obesity in the United States.JAMA 28216October 1999), 15301538ISSN. 0098-7484.
10 - H. Amer, F. G. Cosio, 1990Significance and management of proteinuria in kidney transplant recipients. J Am Soc Nephrol. 2012December 2009), 249024921046-6673
11 - D. Ansell, U. P. Udayarej, R. Steenkamp, C. R. K. Dudley, 2001Chronic renal failure in kidney transplant recipients. Do they receive optimum care?: data from the UK renal registry. Am J Transplant 75May 2007), 116711761600-6135
12 - M. Arias, G. Fernández-Fresnedo, E. Rodrigo, J. C. Ruiz, J. González-Cotorruelo, C. Gómez-Alamillo, 1972Non-Immunologic intervention in chronic allograft nephropathy. Kidney Int 99December 2005), S118S1230085-2538
13 - K. A. Armstrong, S. B. Campbell, C. M. Hawley, D. L. Nicol, D. W. Johnson, N. M. Isbel, 2001Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients Am J Transplant. 511November 2005), 27102718ISSN.1600-6135.
14 - J. J. Augustine, T. C. Knauss, J. A. Schulak, K. A. Bodziak, C. Siegel, D. E. Hricik, 2001Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients. Am J Transplant. 412December 2004), 20012006ISSN.1600-6135.
15 - S. Aull-Watschinger, H. Konstantin, D. Demetriou, M. Schillinger, A. Habicht, W. H. Hörl, B. Watschinger, 1986Pre-transplant predictors of cerebrovascular events after kidney transplantation. Nephrol Dial Transplant 234April 2008), 142914350931-0509
16 - M. C. Banas, B. Banas, J. Wolf, U. Hoffman, B. Krüger, CA Böger, S. R. Orth, B. K. Krämer, 1986Smoking behaviour of patients before and after renal transplantation. Nephrol Dial Transplant 234April 2008), 14421446ISSN.0931-0509.
17 - CE Bartecchi, Kenzie. T. D. Mac, R. W. Schrier, 1812The human cost of tobacco use (first of two parts). New Engl J Med. 33013March 1994), 907912ISSN. 0028-4793.
18 - R. Borrows, M. Loucaidou, G. Chusney, S. Borrows, J. V. Tromp, T. Cairns, M. Griffith, N. Hakim, A. Mc Lean, A. Palmer, V. Papalois, D. Taube, 1986Anaemia and congestive heart failure early post-renal transplantation. Nephrol Dial Transplant. 235May 2008), 3ISSN.0931-0509.
19 - A. G. Bostom, R. Y. Gohh, A. J. Beaulieu, H. Han, P. F. Jacques, J. Selhub, L. Dworkin, I. H. Rosenberg, 1963Determinants of fasting plasma total homocysteine levels among chronic stable renal transplant recipients. Transplantation. 682July 1999), 2572610041-1337
20 - A. G. Bostom, MA Carpenter, L. Hunsicker, P. F. Jacques, J. W. Kusek, AS Levey, J. L. Mc Kenney, R. Y. Mercier, MA . Pfeffer, J. Selhub, 1981Baseline characteristics of participants in the folic acid for vascular outcome reduction in transplantation (FAVORIT) trial. Am J Kidney Dis. 531January 2009), 1211280272-6386
21 - C. Buchanan, L. Smith, J. Corbett, E. Nelson, F. Shihab, 2001A retrospective analysid of ezetimibe treatment in renal transplant recipients. Am J Trasplant 64April 2006), 7707741600-6135
22 - T. E. Burroughs, J. Swindle, S. Takemoto, K. L. Lentine, G. Machnicki, W. D. Irish, D. C. Brennan, MA Schnitzler, 1963Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients. Transplantation 838April 2007), 10271034ISSN. 0041-1337.
23 - S. Busque, J. Leventhal, D. C. Brennan, S. Steinberg, G. Klintmalm, T. Shah, S. Mulgaonkar, J. S. Bromberg, F. Vincenti, S. Harharan, D. Slakey, V. R. Peddi, R. A. Fisher, N. Lawendy, C. Wang, G. Chan, 2001Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in the novo kidney allograft recipients. Am J Transplant. 98August 2009), 193619451600-6135
24 - S. J. Chadban, L. Baines, K. Polkingghome, A. Jefferys, S. Dogra, C. Kanganas, A. Irish, J. Eris, R. Walker, 1981Anemia after kidney transplantation is not completely explained by reduced kidney function. Am J Kidney Dis. 492February 2007), 301309ISSN.0272-6386.
25 - D. Chhabra, M. Grafals, A. I. Skaro, M. Parker, L. Gallon, 2006Impact of anemia after renal transplantation on patient and graft survival and on rate of acute rejection. Clin J Am Soc Nephrol. 34July 2008), 11681174ISSN.1555-9041.
26 - S. H. Chang, P. T. Coates, S. P. Mc Donald, 1963Effects of body mass index at transplant on outcomes of kidney transplantation. Transplantation. 848October 2007), 981987ISSN. 0041-1337.
27 - A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo, D. W. Jones, B. J. Materson, S. Oparil, J. T. . Wright, E. J. Roccella, 1883Seventh report of the joint national comittee on prevention, detection, evaluation, and treatment of high blood pressure. The JNC 7 report. JAMA. 28919December 2003), 256025720098-7484
28 - G. Ciancio, G. W. Burke, J. J. Gaynor, A. Mattiazzi, D. Roth, W. Kupin, M. Nicolas, P. Ruiz, A. Rosen, J. Miller, 1963Arandomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolatemofetil, versus cyclosporine(NEORAL)/sirolimus in renal transplantation II. Survival, function, and protocol compliance at 1 year. Transplantation 772January 2004), 2522580041-1337
29 - Collins AJ.1972Impact of congestive heart failure and other cardiac diseases on patients outcomes. Kidney Int. Suppl 81 (October 2002), S3S70085-2538
30 - A. J. Collins, RN Foley, C. Herzog, BM Chavers, D. Gilbertson, A. Ishani, B. L. Kasiske, J. Liu, L. W. Mau, M. Mc Bean, A. Murray, Peter. W. St, H. Guo, Q. Li, S. Li, S. Li, Y. Peng, Y. Qiu, T. Roberts, M. Skeans, J. Snyder, C. Solid, C. Wang, E. Weinhandl, D. Zaun, C. Arko, S. C. Chen, F. Dalleska, F. Daniels, S. Dunning, J. Ebben, E. Frazier, C. Hanzlik, R. Johnson, D. Sheets, X. Wang, B. Forrest, E. Constantini, S. Everson, P. W. Eggers, L. Agodoa, 2008Excerpts from the United States Renal Data System 2007 annual data report.Am J Kidney Dis. 51Suppl 1, (January 2008), S13200272-6386
31 - F. G. Cosio, M. F. Falkenhaim, T. E. Pesavento, S. Yim, A. Alamir, M. L. Henry, R. M. Ferguson, 1987Patient survival after renal transplantation.II. The impact of smoking. Clin Transplant 134August 1999), 336341ISSN. 0902-0063.
32 - F. G. Cosio, T. E. Pesavento, R. P. Pelletier, M. Henry, R. M. Ferguson, S. Kim, S. Lemeshow, 1981Patient survival after renal transplantation III: the effects of statins, Am J Kidney Dis 403September 2002a), 638643ISSN. 0272-6386.
33 - F. G. Cosio, T. E. Pesavento, S. Kim, K. Osei, M. Henry, R. M. Ferguson, 1972Patient survival after renal transplantation:IV. Impact of post-transplant diabetes. Kidney Int. 624October 2002b), 14401446ISSN. 0085-2538.
34 - F. G. Cosio, Y. Kudva, M. van der Velde, T. S. Larson, S. C. Textor, MD Griffin, MD Stegall, 1972New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 676June 2005), 241524210085-2538
35 - F. G. Cosio, L. J. Hickson, MD Griffin, MD Stegall, Y. Kudva, 2001Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am J Transplant 83March 2008), 593599ISSN. 1600-6135.
36 - Crutchlow MF & Bloom RD.2006Transplant-associated hyperglycemia:a new look at an old problem. Clin J Am Soc NephrolVol.2, 2March 2007), 3433551555-9041
37 - B. F. Culleton, P. W. F. Wilson, 1990Cardiovascular disease: risk factors, secular trends, and therapeutic guidelines. J Am Soc Nephrol. 9suppl, (December 1998), S5S151046-6673
38 - A. M. De Mattos, J. Prather, A. J. Olyaei, Y. Shibagaki, DS Keith, M. Mori, D. J. Norman, Becker. T. et, 1972Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors. Kidney Int. 704August 2006), 7577640085-2538
39 - D. Ducloux, G. Motte, B. Challier, R. Gibey, J. M. Chalopin, 1990Serum total homocysteine and cardiovascular ocurrence in chronic stable renal transplant recipients: a prospective study. J Am Soc Nephrol. 111January 2000), 1341371046-6673
40 - D. Ducloux, A. Kazory, J. M. Chalopin, 1972Predicting coronary heart disease in renal transplant recipients: a prospective study. Kidney Int. 661July 2004), 4414470085-2538
41 - A. Durrbach, J. M. Pestana, T. Pearson, F. Vincenti, C. D. García, J. Campistol, Mde. C. Rial, S. Florman, A. Block, G. Di Russo, J. Xing, P. Garg, J. Grinyo, 2001A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant. 103March 2010), 5475571600-6135
42 - A. E. El -Agroudy, E. W. Wafa, O. E. Greith, A. B. S. El -Dein, MA Ghoneim, 1963Weight gain after renal transplantation is a risk factor for patient and graft outcome. Transplantation. 1577May 2004), 13811385ISSN.0041-1337.
43 - B. Fellström, A. G. Jardine, I. Soveri, E. Cole, H. H. Neumayer, B. Maes, C. Gimpelewicz, H. Holdaas, 1963Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplant trial. Transplantation 797August 2005), 116011630041-1337
44 - G. Fernández-Fresnedo, R. Escallada, E. Rodrigo, A. L. De Francisco, J. G. Cotorruelo, Castro. S. Sanz De, J. A. Zubimendi, J. C. Ruiz, M. Arias, 1963The risk of cardiovascular disease associated with proteinuria in renal transplant patients. Transplantation. 768April 2002), 134513480041-1337
45 - G. Fernández-Fresnedo, R. Escallada, Francisco. A. L. Martin de, J. C. Ruiz, E. Rodrigo, Castro. S. Sanz de, Cotorruelo. Gonzalez, J. , M. Arias, 2001Association between pulse pressure and cardiovascular disease in renal transplant patients. Am J Transplant 52February, 2005), 3943981600-6135
46 - C. Fernandez-Miranda, P. Gómez, P. Díaz-Rubio, J. Estenoz, J. L. Carillo, A. Andrés, J. M. Morales, 1987Plasma homocysteine levels in renal transplanted patients on cyclosporine or tacrolimus therapy: effect of treatment with folic acid. Clin Transplant. 142April 2000), 1101140902-0063
47 - S. Fishbane, D. J. Cohen, D. W. Coyne, A. Djamali, A. K. Singh, J. B. Wish, 1972Posttransplant anemia: the role of sirolimus. Kidney Int. 764August 2009), 376382ISSN.0085-2538.
48 - RN Foley, P. S. Parfrey, JD Harnett, G. M. Kent, D. C. Murray, P. E. Barré, 1990The prognostic importance of left ventricular geometry in uremic cardiomyopathy. J Am Soc Nephrol. 512June 1995), 202420311046-6673
49 - RN Parfrey. P. S. Foley, MJ Sarnak, 1981Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 325suppl.3, (November 1998), S112S1190272-6386
50 - A. N. Friedman, I. H. Rosenberg, J. Selhub, AS Levey, A. G. Bostom, 2001Hyperhomocysteinemia in renal transplant recipients. Am J Trasnsplant. 24April 2002), 3083131600-6135
51 - AS Go, G. M. Chertow, D. Fan, CE Mc Culloch, C. Hsu, 1812Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 35113September 2004), 129613050028-4793
52 - S. M. Haffner, 1978Management of dyslipidemia in adults with diabetes. Diabetes Care 26Suppl 1, (January 2003), S83S86ISSN. 0149-5992.
53 - W. Hagen, M. Födinger, G. Heinz, H. Buchmayer, W. H. Hörl, G. Sunder-Plassman, 1972Effect of MTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients. Kidney Int. 78February 2001), S253S2570085-2538
54 - JD Harnett, RN Foley, G. M. Kent, P. E. Barre, D. Murray, P. S. Parfrey, 1972Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int. 473March 1995), 8848900085-2538
55 - O. Heisel, R. Heisel, R. Balshaw, P. Keown, 2001New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant 44April 2004), 5835951600-6135
56 - CA Herzog, Ma J. Z. , A. J. Collins, 1812Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Enl J Med. 33912September 1998), 7998050028-4793
57 - CA Herzog, Ma J. Z. , A. J. Collins, 1981Long term survival of renal transplant recipients in the United States after acute myocardial infarction. Am J Kidney Dis. 361July 2000), 1451530272-6386
58 - S. Hiremath, D. Ferguson, S. Doucette, A. V. Mulay, G. A. Knoll, 2001Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant. 710October 2007), 235023601600-6135
59 - H. Holdaas, B. Fellström, A. G. Jardina, I. Holme, G. Nyberg, P. Fauchald, C. Frönhagen-Riska, S. Madsen, H. Neumayer-H, E. Cole, B. Maes, P. Ambühl, A. G. Olsson, A. Haertmann, DO Solbu, T. R. Pedersen, on, AG., Haertmann, A., Solbu, DO. & Pedersen, TR. on behalf of the Assessment of Lescol in renal transplantation (ALERT) Study Investigators. (1823Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 3619374June 2003), 202420310140-6736
60 - H. Holdaas, B. Fellström, A. G. Jardine, G. Nyberg, C. Grönhagen-Riska, S. Madsen, H. H. Neumayer, E. Cole, B. Maes, P. Ambühl, J. O. Logan, B. Staffler, C. Gimpelewicz, 1986Beneficial effect of early initiation of lipid-lowering therapy following renaltransplantation. Nephrol Dial Transplant 205May 2005), 9749800931-0509
61 - M. Hornum, K. A. Jorgensen, J. M. Hansen, F. T. Nielsen, K. B. Christensen, E. R. . Mathiesen, B. Feldt-Rasmussen, 1990New-onset diabetes mellitus after kidney transplantation in Denmark. Clin J Am Soc Nephrol 54April, 2010), 709716ISSN. 1555-9041.
62 - R. J. Howard, P. R. Patton, A. I. Reed, A. W. Hemming, W. J. Van der Werf, W. W. Pfaff, T. R. Srinivas, J. C. Scornik, 1963The changing causes of graft loss and death after kidney transplantation. Transplantation. 7312April 2002), 192319280041-1337
63 - D. E. Hricik, 1981Posttransplant hyperlipidemia: the treatment dilemma. Am J Kidney Dis. 235May 1994), 7667710272-6386
64 - D. E. Hricik, 2001Anemia after kidney transplantation-is the incidence increasing?. Am J Transplant. 37July 2003), 771772ISSN.1600-6135.
65 - A. E. Imoagene-Oyedeji, S. E. Rosas, A. M. Doyle, S. Goral, R. D. Bloom, 1990Posttransplantation anemia at 12 months in kidney recipients treated with mycophenolate mofetil: risk factors and implications for mortality. J Am Soc Nephrol.1711November 2006), 32403247ISSN.1046-6673.
66 - A. G. Jardine, H. Holdaas, B. Fellström, E. Cole, G. Nyberg, C. Grönhagen-Riska, S. Madsen, H. H. Neumayer, B. Maes, P. Ambühl, A. G. Olsson, I. Holme, P. Fauchald, C. Gimpelwicz, T. R. Pedersen, 2001Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients: Pos-hoc subgroup analyses of the ALERT study. Am J Transplant 46June 2004), 9889951600-6135
67 - O. Johnston, C. L. Rose, A. C. Webster, J. S. Gill, 1990Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol 197July 2008), 14111418ISSN.1046-6673.
68 - N. Kamar, L. Rostaing, 1963Negative impact of one-year anemia on long-term patient and graft survival in kidney transplant patients receiving calcineurin inhibitors and mycophenolate mofetil. Transplantation. 858April 2008), 11201124ISSN.0041-1337.
69 - V. Karthikeyan, J. Karpinski, R. C. Nair, G. Knol,l, 2001The burden of chronic kidney disease in renal transplant recipients. Am J Transplant. 42February 2004), 262269ISSN.1600-6135.
70 - B. L. Kasiske, 1946Risk factors fos accelerated atheroesclerosis in renal transplant recipients. Am J Med. 846January 1988), 9859920002-9343
71 - B. L. Kasiske, C. Guijarro, Z. A. Massy, M. R. Wiederkehr, Ma J. Z. , 1990Cardiovascular disease after renal transplantation.J Am Soc Nephrol. 71January 1996 ), 1581651046-6673
72 - B. L. Kasiske, H. A. Chakkera, J. Roel, 1990Explained and unexplained ischemic heart disease risk after renal transplantation. J Am Soc Nephrol. 1111September 2000a) 17351743ISSN. 1046-6673.
73 - B. L. Kasiske, D. Klinger, 1990Cigarrette smoking in renal transplant recipients. J Am Soc Nephrol 114April 2000b), 753759ISSN. 1046-6673.
74 - B. L. Kasiske, J. J. Synder, D. Gilberston, A. J. Matas, 2001Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 32February 2003), 178185ISSN.1600-6135.
75 - B. L. Kasiske, S. Anjum, R. Shah, J. Skogen, C. Kandaswamy, B. Danielson, E. A. O’Shaughnessy, D. C. Dahl, J. R. Silkensen, M. Sahadevan, J. J. Snyder, 1981Hypertension after kidney transplantation. Am J Kidney Dis 436April 2004), 107110810272-6386
76 - B. L. Kasiske, MA Malik, CA Herzog, 1963Risk-stratified screening for ischemic heart disease in kidney transplant candidates. Transplantation. 806September 2005), 8158200041-1337
77 - B. L. Kasiske, J. R. Maclean, J. J. Snyder, 1990Acute myocardial infarction and kidney transplantation. J Am Soc Nephrol. 173March 2006), 9009071046-6673
78 - B. L. Kasiske, A. de Mattos, S. M. Flechneer, L. Gallon, H. Meier-Kriesche-U, M. R. Weir, A. Wilkinson, 2001Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients. Am J Transplant 87July 2008), 138413921600-6135
79 - KDIGO clinical practice guideline for the care of kidney transplant recipients.2001Am J Transplant. 9Suppl 3 (November 2009), S1155ISSN.1600-6135.
80 - R. Kennedy, C. Case, R. Fathi, D. Johnson, N. Isbel, T. H. Marwick, 1946Does renal failure cause an atherosclerotic milieu in patients with end-stage renal disease? Am J Med. 1103February 2001), 1982040002-9343
81 - G. A. Knoll, 1981Proteinuria in kidney transplant recipients: prevalence, prognosis and evidence-based management. Am JKidney Dis. 546December 2009), 113111440272-6386
82 - H. E. Koomans, G. Ligtenberg, 1963Mechanism and consequences of arterial hypertension after renal transplantation. Transplantation 72Suppl, (September 2001), S9S120041-1337
83 - A. J. Langone, P. Chuang, 1963Ezetimibe in renal transplant patients with hyperlipidemia resistant to HMG-CoA reductase inhibitors. Transplantation 815March 2006), 8048070041-1337
84 - K. L. Lentine, D. C. Brennan, MA Schnitzler, 1990Incidence and predictors of myocardial infarction after kidney transplantation. J Am Soc Nephrol. 162February 2005), 496506ISSN. 1046-6673.
85 - K. L. Lentine, MA Schnitzler, K. C. Abbott, L. Li, T. E. Burroughs, W. Irish, D. C. Brennan, 1981De novo congestive heart failure after kidney transplantation: a common condition with poor prognostic implications. Am J Kidney Dis 464October 2005), 720733ISSN. 0272-6386.
86 - K. L. Lentine, MA Schnitzler, K. C. Abbott, L. Li, H. Xiao, T. E. Burroughs, S. K. Takemoto, L. M. Willoughby, J. A. . Gavard, D. C. Brennan, 2006Incidence, predictors, and associated outcomes of atrial fibrillation after kidney transplantation. Clin J Am Soc Nephrol 12March 2006), 2882961555-9041
87 - K. L. Lentine, Rey. L. A. Rocca, S. Kolli, G. Bacchi, MA Schnitzler, K. C. Abbott, H. Xiao, D. C. Brennan, 2006Variations in the risk for cerebrovascular events after kidney transplant compared with experience on the waiting list and after graft failure. Clin J Am Soc Nephrol 34July 2008a), 10901101ISSN. 1555-9041.
88 - K. L. Lentine, MA Schnitzler, D. C. Brennan, J. J. Snyder, P. J. Hauptman, K. C. Abbott, D. Axelrod, P. R. Salvalaggio, B. Kasiske, 2006Cardiac evaluation before kidney transplantation: a practice patterns analysis in Medicare-insured dialysis patients. Clin J Am Soc Nephrol. 34April 2008b), 11151124ISSN. 1555-9041.
89 - A. Levin, J. Singer, C. R. Thompson, H. Ross, M. Lewis, 1981Prevalent left ventricular hypertrophy in the predialysis population : identifying opportunities for intervention. Am J Kidney Dis. 273March 1996), 3473540272-6386
90 - G. Ligtenberg, R. J. Hene, P. J. Blankestijn, H. A. Koemans, 1990Cardiovascular risk factors in renal transplant recipients: cyclosporin A versus tacrolimus. J Am Soc Nephrol 122February 2001), 3683731046-6673
91 - A. Lindholm, D. Albrechtsen, L. Frodin, G. Tufveson, N. H. Persson, G. Lundgran, 1963Ischemic heart disease-major cause of death and graft loss alter transplantation in Scandinavia. Transplantation. 605September 1995), 4514570041-1337
92 - R. Marcén, J. Pascual, J. L. Teruel, J. J. Villafruela, ME Rivera, F. Mampaso, F. J. Burgos, J. Ortuño, 1963Outcome ofcadaveric renal transplant patients treated for 10 years with cyclosporine. Is chronic allograft nephropathy the major cause of graft loss?. Transplantation. 721July 2001), 57620041-1337
93 - R. Marcén, J. Pascual, M. Tenorio, J. Ocaña, J. L. Teruel, J. J. Villafruela, M. Fernández, Burgos, F. J. , J. Ortuño, 1969Chronic kidney disease in renal transplant recipients. Transplant Proc. 379November 2005), 371837200041-1345
94 - R. Marcén, J. M. Morales, D. del Castillo, J. M. Campistol, D. Serón, F. Valdés, F. Anaya, A. Andrés, M. Arias, J. Bustamante, L. Capdevila, F. Escuin, S. Gil-Vernet, M. González-Molina, I. Lampreave, F. Oppenheimer, L. Pallardó, the. for, Renal. Spanish, Forum, 1969Posttransplant diabetes mellitus in renal allograft recipients: a prospective multicenter study at 2 years. Transplant Proc 3810December 2006), 353035320041-1345
95 - R. Marcén, J. M. Morales, M. Arias, G. Fernández-Juarez, G. Fernández-Fresnedo, A. Ahdrés, E. Rodrigo, J. Pascual, B. . Dominguez, J. Ortuño, 1990Ischemic heart disease after renal transplantation in patients on cyclosporine in Spain. J Am Soc Nephrol. 17Suppl 3, (December 2006), S286S2901046-6673
96 - R. Marcén, A. Fernández, J. Pascual, J. L. Teruel, J. J. Villafruela, N. Rodríguez, J. Martins, F. J. Burgos, J. Ortuño, 1969High body mass index and posttransplant weigth gain are not risk factors for kidney graft and patient outcomes. Transplant Proc. 397September 2007), 22052207ISSN. 0041-1345.
97 - R. Marcén, D. del Castillo, L. Capdevila, G. Fernandez-Fresnedo, E. Rodrigo, C. Cantarell, A. Fernandez-Rodriguez, M. O. Lópes-Silva, J. Camps, P. Aljama, J. Ortuño, M. Arias, 1963Achieving chronic kidney disease treatment targets in renal transplant recipients: results from a cross-sectional study in Spain. Transplantation 879May 2009a), 13401346ISSN.0041-1337.
98 - R. Marcén, 1971Immunosuppressive drugs in kidney transplantation. Impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs. 6916November 2009b), 22272243ISSN.0012-6667.
99 - N. N. Massarweh, J. L. Clayton, CA Mangum, S. S. Florman, D. P. Slakey, 1963High body mass index and short-and long-term renal allograft survival in adults. Transplantation. 8010November 2005), 14301434ISSN. 0041-1337.
100 - Z. A. Massy, 1963Hyperlipidemia and cardiovascular disease after organ transplantation. Transplantation. 72suppl.6, (September 2001), S13S150041-1337
101 - Z. A. Massy, B. L. Kasiske, 1990Post-transplant hyperlipidemia: mechanism and management. J Am Soc Nephrol. 77July 1996), 9719771046-6673
102 - A. J. Matas, A. Humar, K. J. Gillingham, W. D. Payne, R. W. G. Gruessner, R. Kandaswamy, D. L. Dunn, J. S. . Najasrian, D. E. R. Sutherland, 1972Five preventable causes of kidney graft loss in the 1990s: A single-center analysis. Kidney IntVol. 62, 2August 2002), 7047140085-2538
103 - A. D. Mayer, J. Dmitrewski, J. P. Squifflet, T. Besse, B. Grabensee, B. Klein, F. W. Eigler, U. Heemann, R. Pichlmayr, M. Behrend, Y. Vanrenterghem, J. Donck, J. van Hooff, M. Christiaans, J. M. Morales, A. Andres, R. W. Johnson, C. Short, B. Buchholz, N. Rehmert, W. Land, S. Schleibner, J. L. Forsythe, D. Talbot, . Pohanka, E. , 1963Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection. A report of the European tacrolimus multicenter renal study group. Transplantation 643August 1997), 436443ISSN. 0041-1337.
104 - S. Mazzaferro, M. Pascquali, F. Taggi, M. Baldinelli, C. Conte, M. L. Muci, N. Pirozzi, I. Carbone, M. Francone, F. Pugliese, 2006Progression of coronary artery calcification inrenal transplantation and the role of secondary hyperparathyroidism and inflammation. Clin J Am Soc Nephrol 43March 2009), 6856901555-9041
105 - S. P. Mc Donald, G. R. Russ, 1986Survival of recipients of cadaveric kidney transplants compared with those receiving dialysis treatment in Australia an New Zealand 1991-2001. Nephrol Dial Transplant. 1712December 2002) 221222190931-0509
106 - E. Mc Gregor, A. G. Jardine, L. S. Murray, H. J. Dargie, R. S. Rodger, B. J. Junor, MA Mc Millan, JD Briggs, 1986Pre-operative echocardiographic abnormalities and adverse outcome following renal transplantation. Nephrol Dial Transplant. 136June 1998), 149915050931-0509
107 - E. Mc Gregor, G. Steward, S. C. Rodger, A. G. Jardine, 1986Early echocardiographic changes and survival following transplantation. Nephrol Dial Transplant. 151January 2000), 93930931-0509
108 - H. U. Meier-Kriesche, M. Vaghela, R. Thambuganipalle, G. Friedman, M. Jacobs, B. Kaplan, (163, The effect of body mass index on long-term renal allograft. Transplantation. 689November 1999129412970041-1337
109 - H. U. Meier-Kriesche, J. A. Arndorfer, B. Kaplan, 1963The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death.Transplantation. 731January 2002), 7074ISSN.0041-1337.
110 - H. U. Meier-Kriesche, R. Baliga, B. Kaplan, 1963Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation 758April 2003), 129112050041-1337
111 - Miller LW.2001Cardiovascular toxicities of immunosuppressive agents. Am J Transplant. 29October 2002), 8078181600-6135
112 - M. Z. Molnar, M. Czira, C. Ambrus, A. C. Kovacs, J. Pap, A. Remport, L. Szeifer, I. Mucsi, 2001Anemia is associated with mortality in kidney-transplanted patients- a prospective cohort study. Am J Transplant. 74April 2007), 818824ISSN.1600-6135.
113 - V. M. Montori, A. Basu, P. J. Erwin, J. A. Velosa, S. E. Gabriel, Y. C. Kudva, 1978Posttransplantation diabetes. A systematic review of the literature. Diabetes Care 253March, 2002), 5385920149-5992
114 - R. Moore, D. Hernandez, H. Valantine, 1990Calcineurin inhibitors and post-transplant hyperlipidaemias. Drugs SafVol.24, 10755766
115 - J. M. Morales, B. Dominguez-Gil, 1990Impact of tacrolimus and mycophenolate mofetil combination on cardiovascular risk profile after transplantation. J Am Soc Nephrol 17Suppl 3, (December 2006), S296S3031046-6673
116 - J. M. Morales, R. Marcén, A. Andrés, M. González-Molina, D. del Castillo, M. Cabello, L. Capdevila, J. M. Campistol, F. Oppenheimer, D. Serón, S. Gil-Vernet, I. Lampreave, F. Valdés, F. Anaya, F. Escuin, M. Arias, L. . Pallardó, J. Bustamente, 1972Renal transplantation in the moderm immunosuppresive era in Spain: four-year results from a multicenter database focus on post-transplant cardiovascular disease. Kidney Int Suppl. 111December 2008), S94S990085-2538
117 - S. W. Murphy, RN Foley, P. S. Parfrey, 1981Screening and treatment for cardiovascular disease in patients with chronic renal disease. Am J Kidney Dis. 32Suppl 3, (November 1998), S184S1990272-6386
118 - A. O. Ojo, J. A. Hanson, R. A. Wolfe, A. B. Leichtman, L. Y. Agodoa, F. K. Port, 1972Long-term survival in renal transplant recipients with graft function. Kidney Int. 571January 2000), 3073130085-2538
119 - A. O. Ojo, 1963Cardiovascular complications after renal transplantation and their prevention. Transplantation. 825September 2006), 6036110041-1337
120 - A. Oliveras, J. Roquer, J. M. Puig, A. Rodriguez, M. Mir, A. Orfila, J. Masramon, J. Loveras, 1987Stroke in renal transplant recipients: epidemiology, predictive risk factors and outcome. Clin Transplant 171February 2003), 180902-0063
121 - G. Opelz, B. Döhler, for the Collaborative Transplant Study. (2001Improved long-term outcomes after renal transplantation associated with blood pressue control. Am J Transplant.. 511November 2005), 272527310000-1600
122 - G. Opelz, M. Zeier, G. Laux, C. Morath, B. Döhler, 1990No improvement of patients or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: a collaborative transplant study report. J Am Soc Nephrol. 1711November 2006), 325732621046-6673
123 - E. Paoletti, M. Amidore, P. Cassottana, M. Gherzi, L. Marsano, G. Cannella, 1981Effects of sirolimus on left ventricular hypertrophy in kidney transplant recipients: a 1-year nonrandomized controlled trial. Am J Kidney Dis. 522August 2008), 3243300272-6386
124 - P. S. Parfrey, JD Harnett, RN Foley, G. M. Kent, D. C. Murray, P. E. Barre, R. D. Guttmann, 1963Impact of renal transplantation on uremic cardiomyopathy. Transplantation. 609November 1995), 9089140041-1337
125 - J. M. Park, F. L. Luan, 1990Management of hypertension in solid-organ transplantation. Prog Transplant. 151March 2005), 17221526-9248
126 - R. K. Patel, P. B. Mark, N. Jonhston, E. Mc Gregor, H. . Dargie, A. G. Jardine, 2006Renal transplantation is not associated with regression of left ventricular hypertrophy: a magnetic resonance study. Clin J Am Soc Nephrol. 36November 2008), 180718111555-9041
127 - H. Pilmore, H. Dent, S. Chang, S. P. Mc Donald, S. J. Chadban, 1963Reduction in cardiovascular death after kidney transplantation. Transplantation. 897April 2010), 8518570041-1337
128 - P. M. Ridker, M. Cushman, MJ Stampfer, R. P. Tracy, C. H. Hennekens, 1812Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 33614April 1997), 9739790028-4793
129 - C. Rigatto, RN Foley, G. M. Kent, R. Guttman, P. S. Parfrey, 1963Long-term changes in left ventricular hypertrophy after renal transplantation. Transplantation. 704August 2000), 5705750041-1337
130 - C. Rigatto, P. Parfrey, R. Foley, C. Negrijn, C. Tribula, J. Jeffey, 1990Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. J Am Soc Nephrol. 134April 2002), 10841090ISSN.1046-6673.
131 - C. Rigatto, 1990Clinical epidemiology of cardiac disease in renal transplant recipients. Semi in Dial 162March-April 2003a), 1061100152-5139X.
132 - C. Rigatto, R. Foley, J. Jeffery, C. Negrijn, C. Tribula, P. Parfrey, 1990Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia. J Am Soc Nephrol 142February 2003b), 462468ISSN.1046-6673.
133 - C. Rigatto, 2001Anemia, renal transplantation and the anemia paradox. Semin Nephrol. 264July 2006), 3073120270-9295
134 - J. I. Roodnat, P. G. H. Muldr, J. Rischen-Vos, I. C. van Riemsdijk, T. van Gelder, R. Zietse, J. N. Izermans, W. Weimar, 1963Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation. 723August 2001), 4384440041-1337
135 - F. P. Schena, MD Pascoe, J. Aberu, Rial. M. del Carmen, R. Oberbauer, D. C. Brennan, J. M. Campistol, L. Racusen, M. S. Polinsky, R. Goldberg-Alberts, H. Li, J. Scarola, J. F. Neylan, for the sirolimus CONVERT trial study group. (1963Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-months efficacy and safety results from the CONVERT trial. Transplantation. 872January 2009), 2332420041-1337
136 - S. L. Seliger, N. S. Weiss, D. L. Gillen, B. Kestenbaum, A. Ball, D. J. Sherrard, C. O. Stehman-Breen, 1972HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int. 611January 2002), 2973040085-2538
137 - S. L. Seliger, D. L. Gillen, W. T. Longstreth, B. Kestenbaum, C. O. Stehman-Breen, 1972Elevated risk of stroke among patients with end-stage renal disease. Kidney Int. 642August 2003), 6036090085-2538
138 - S. L. Seliger, D. L. Gillen, D. Tirschwell, H. Wasse, B. R. Kestenbaum, C. O. Stehman-Breen, 1990Risk factors for incident stroke among patients with end-stage renal disease. J Am Soc Nephrol 1410October 2003), 262326311046-6673
139 - N. Shah, S. Al-Khoury, B. Afzali, A. Covic, A. Roche, J. Msarsh, I. C. Macdougall, D. J. A. Goldsmirhm, 1963Posttransplantation anemia in adult renal allograft recipients: prevalence and predictors. Transplantation 818April 2006), 11121118ISSN.0041-1337.
140 - J. J. Snyder, B. L. Kasiske, Lean. R. Mac, 1990Peripheral arterial disease and renal transplantation. J Am Soc Nephrol 177July 2006), 205620681046-6673
141 - I. Soveri, H. Holdaas, A. Jardine, C. Gimpelewicz, B. Staffler, B. Fellström, 1986Renal transplant dysfunction-importance quantified in comparison with traditional risk factors for cardiovascular disease and mortality. Nephrol Dial Transplant 218August 2006), 228222890931-0509
142 - A. G. Stack, W. E. Bloembergen, 1981A cross-sectional study of the prevalence and clinical correlates of congestive heart failure among incident U.S. dialysis patients. Am J Kidney Dis 385November 2001), 99210000272-6386
143 - E. M. Stuveling, H. L. Hillege, S. J. Bakker, R. O. Gans, P. E. De Jong, D. de Zeeuw, 1972C-reactive protein is associated with renal function abnormalities in a non-diabetic population. Kidney Int. 632February 2003), 6546610085-2538
144 - R. S. Sung, M. Althoen, T. A. Howell, R. M. Merion, 1963Peripheral vascular occlusive disease in renal transplant recipients: risk factors and impact on kidney allograft survival. Transplantation.707October 2000), 104910540041-1337
145 - J. L. Teruel, Padial. L. Rodriguez, C. Quereda, P. Yuste, R. Marcen, J. Ortuño, 1963Regression of left ventricular hypertrophy after renal transplantation. A prospective study. Transplantation. 432February 1987), 3073090041-1337
146 - B. Tucker, F. Fabbian, M. Giles, R. C. Thuraisingham, A. E. Raine, L. R. Baker, 1997Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic renal failure. Nephrol Dial Transplant 124April 1997), 7247280272-6376
147 - V. K. Tutone, P. B. Mark, G. A. Steward, C. C. Tan, C. C. Geddes, A. G. Jardine, 1987Hypertension, antihypertensive agents andoutcomes following renal transplantation. Clin Transplant 192April 2005), 1811920902-0063
148 - R. M. Van Ree, A. P. J. de Vries, L. H. Oterdoom, T. H. The, R. T. Gansevoort, J. J. H. van der Heide, W. J. van Son, R. J. Ploeg, P. E. de Jong, R. O. B. Gans, S. J. L. Bakker, (1986, 1986Abdominal obesity and smoking are important determinants of C-reactive protein in renal transplant recipients. Nephrol Dial Transplant. 2011November 2005), 252425310931-0509
149 - Y. Vanrenterghem, C. Ponticelli, J. M. Morales, D. Abramowicz, K. Baboolal, B. Eklund, V. Kliem, C. Legendre, Sarmento. A. L. Morais, F. Vincenti, 2001Prevalence and management of anemia in renal transplant recipients: a European survey. Am J Transplant. 37July 2003), 835845ISSN.1600-6135.
150 - Y. F. C. Vanrenterghem, K. Claes, G. Montagnino, S. Fieuws, B. Maes, M. . Villa, C. Ponticelli, 1963Risk factors for cardiovascular events after successful renal transplantation. Transplantation. 852January 2008), 2092160041-1337
151 - F. Vincenti, S. C. Jensik, R. S. Filo, J. Millar, J. Pirsch, 1963A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation 735March 2005), 775782ISSN. 0041-1337.
152 - F. Vincenti, S. Friman, E. Scheuermann, L. Rostaing, T. Jenssen, J. M. Campistol, K.. Uchida, MD Pescovitz, P. Marchetti, M. Tuncer, F. Citterio, A. Wiecek, S. Chadban, M. El -Shahawy, K. Budde, N. Goto, on behalf of the DIRECT investigators. (2001Results of an international, randomised trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transpl 76June 2007), 15061514ISSN.1600-6135.
153 - F. Vincenti, B. Charpentier, Y. Vanrenterghen, L. Rostaing, B. Bresnahan, P. Darji, P. Massari, G. A. Mondragon-Ramirez, M. Agarwal, G. Di Russo, C. S. Lin, P. Garg, CP Larsen, 2001A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 103March 2010), 5355461600-6135
154 - R. K. Wali, G. S. Wang, S. S. Gottlieb, L. Bellumkonda, R. Hansalia, E. Ramos, C. Drachenberg, J. Papadimitriou, MA Brisco, S. Blahut, J. C. Fink, M. L. Fisher, S. T. . Bartlett, M. R. Weir, 1983Effect of kidney transplantation on left ventricular systolic dysfunction and congestive heart failure in patients with end-stage renal disease. J Am Coll Cardiol, 457April 2005), 105110600735-1097
155 - K. Wang, H. Zhang, Y. Li, Q. Wei, H. Li, Y. Yang, Y. Lu, 1969Safety of mycophenolate mofetil versus azathioprine in renal transplantation: a systematic review.Transplant Proc. 367September 2004), 20682070ISSN.0041-1345.
156 - J. H. Wang, B. L. Kasiske, 1992Screening and management of pretransplant cardiovascular disease. Curr Opin Nephrol Hypertens. 196November 2010), 5865911473-6543
157 - A. C. Webster, V. W. S. Lee, J. R. Chapman, J. C. Craig, 1963Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients; a systemsatic review meta-analysis of randomized trials. Transplantation 819May 2006), 123412480041-1337
158 - F. Wiesbauer, G. Heinze, C. Mitterbauer, F. Harnoncourt, W. H. Hörl, R. Oberbauer, 1990Statin use is associated with prolonged survival of renal transplant recipients. J Am Soc Nephrol 1911November 2008), 221122181046-6673
159 - P. W. F. Wilson, B. F. Culleton, Epidemiology of cardiovascular disease in the United States. A J Kidney Dis. 325suppl 3. (November 1998S56S650272-6386
160 - W. C. Winkelmayer, M. Lorenz, R. Kramar, M. Fodinger, W. H. Hörl, G. Sunder-Plassmann, 2001C-reactive protein and body mass index independently predict mortality in kidney transplant recipients. Am J Transplant. 47July 2004), 114811541600-6135
161 - W. C. Winkelmayer, R. Kramar, G. C. Curhan, A. Chandraker, G. Endler, M. Födinger, W. H. Hörl, Plassmann. G. Sunder, 1990Fasting plasma total homocysteine levels and mortality and allograaft loss in kidney transplant recipients: a prospective study. J Am Soc Nephrol. 161January 2005), 2552601046-6673
162 - W. C. Winkelmayer, A. Chandraker, MA Brookhart, R. Kramar, G. Sunder-Plassmann, 1986A prospective stydy of anaemia and long-term outcomes in kidney transplant recipients. Nephrol Dial Transplant. 2112December 2006), 35593566ISSN.0931-0509.
163 - R. A. Wolfe, V. B. Ashby, E. L. Milford, A. O. Ojo, R. E. Ettenger, L. Y. Agodoa, P. J. Held, F. K. Port, 1812Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 34123December 1999), 172517300028-4793
164 - BM Wong, M. Huang, J. S. Zaltzman, G. V. Prasad, 1963Mycophenolate mofetil and C-reactive protein in renal transplant recipients. Transplantation. 831January 2007), 48530041-1337
165 - P. D. Yorgin, JD Scandling, A. Belson, J. Sanchez, S. R. Alexander, K. A. Andreoni, 2001Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem? Am J Transplant. 25May 2002), 429435ISSN.1600-6135.
166 - R. Zhang, B. Leslie, J. P. Boudreaux, D. Frey, E. Reisin, 1827Hypertension after kidney transplantation: impact, pathogenesis and therapy. Am J Med Sci 3254April 2003), 2022081538-2990
167 - H. Zebe, 1986Atrial fibrillation in dialysis patients. Nephrol Dial Transplant. 165June 2001), 7657680931-0509
168 - N. Zitt, B. Kollerits, U. Neyer, W. Mark, D. Heininger, G. Mayer, F. Kronenberg, K. Lhotta, 1986Cigarette smoking and chronic allograft nephropathy. Nephrol Dial Transplant. 2210October 2007), 30343034ISSN. 0931-0509