Elsevier

The Lancet

Volume 378, Issue 9800, 15–21 October 2011, Pages 1419-1427
The Lancet

Series
Prevention of cardiovascular disease in adult recipients of kidney transplants

https://doi.org/10.1016/S0140-6736(11)61334-2Get rights and content

Summary

Although advances in immunosuppression, tissue typing, surgery, and medical management have made transplantation a routine and preferred treatment for patients with irreversible renal failure, successful transplant recipients have a greatly increased risk of premature mortality because of cardiovascular disease and malignancy compared with the general population. Conventional cardiovascular risk factors such as hyperlipidaemia, hypertension, and diabetes are common in transplant recipients, partly because of the effects of immunosuppressive drugs, and are associated with adverse outcomes. However, the natural history of cardiovascular disease in such recipients differs from that in the general population, and only statin therapy has been studied in a large-scale interventional trial. Thus, the management of this disease and the balance between management of conventional risk factors and modification of immunosuppression is complex.

Introduction

Successful developments in immunosuppression and clinical management, which have made kidney transplantation routine in adults with end-stage renal disease, have unmasked a greatly increased risk of premature cardiovascular disease in these patients who are otherwise successfully treated by transplantation.1, 2 Here we examine the pattern and determinants of cardiovascular disease, including management of individual risk factors but excluding pretransplantation management (cardiovascular screening).

The standard management of kidney transplant recipients is combination immunosuppression consisting of a calcineurin inhibitor (tacrolimus or ciclosporin), an inhibitor of proliferation stimulation (mycophenolic acid, mycophenolate mofetil, or azathioprine), or an inhibitor of the mammalian target of rapamycin ([mTOR], sirolimus or everolimus), with or without corticosteroids. Doses are gradually tapered after transplantation to stable maintenance concentrations. Additionally, most patients receive induction treatment with antilymphocyte or antithymocyte globulin, or with an interleukin-2 receptor antibody (eg, basiliximab). The main aims of this approach are to prevent acute cellular rejection—historically the main cause of early graft failure—and to optimise early graft function.3 The incidence of acute rejection is close to 10%, and more than 90% of transplants are functioning after 1 year with an average estimated glomerular filtration rate (eGFR) of about 60 mL/min per 1·73 m2.1, 2, 3

Acute rejection episodes have less effect on long-term graft outcomes than they did previously, indicating the effect of improved maintenance immunosuppression, and effective detection and treatment of rejection episodes. Therefore, the effect of immunosuppressant drugs on long-term patient outcomes (diabetes, cardiovascular disease, and malignancy) and on cardiovascular risk factors has become as much a clinical issue as has their effect on acute rejection (table).4, 5 Reporting of the effect of new immunosuppressant drugs on cardiovascular risk factors can determine their potential use; for example, one of the potential benefits of the costimulation blocker belatacept is its cardiovascular risk profile (table).6, 7

Key messages

  • Cardiovascular disease has an atypical nature in renal transplant recipients when compared with the general and dialysis population

  • Available data support the use of statins, and standard interventions, in the management of coronary disease in transplant recipients

  • In the management of hypertension, there are no data to favour one agent over another, and blood-pressure targets have been adopted from the chronic kidney disease population guidelines

  • New-onset diabetes is a major, potentially modifiable risk factor for cardiovascular disease in transplant recipients

  • Minimisation or avoidance of corticosteroids or calcineurin inhibitors can reduce lipid concentrations, blood pressure, and risk of diabetes, but has a restricted role in the management of cardiovascular disease after transplantation

Section snippets

Premature cardiovascular disease

All patients with end-stage renal disease have an increased risk of premature cardiovascular disease. The risk for those receiving maintenance haemodialysis is between ten and 20 times that of the general population.1, 2 After successful transplantation, and despite use of immunosuppressive drugs (table), this risk is reduced, but remains three to five times that of the general population (figure 1).1, 2 Furthermore, younger adult patients have the greatest increase in cardiovascular risk and,

Nature and determinants of post-transplantation cardiovascular disease

The atypical nature of cardiovascular disease is reinforced by findings from studies of the relations between conventional and non-conventional cardiovascular risk factors and events in kidney transplant recipients. In early studies, Kasiske and colleagues12 did not identify a relation between conventional cardiovascular risk factors—ie, smoking, hypertension, or hyperlipidaemia—and cardiovascular events (termed coronary heart disease, a composite of myocardial infarction, cardiac death, and

Dyslipidaemia

Dyslipidaemia is almost invariably associated with transplantation, with a pattern of raised concentrations of total and LDL cholesterol, triglycerides, and HDL cholesterol1, 22 and with increased concentrations of intermediate (atherogenic) lipoproteins.22 In the first 6 weeks after kidney transplantation, concentrations of total and LDL cholesterol increase by 1–1·5 mmol/L, with smaller increases in concentrations of triglyceride and HDL cholesterol.23 This pattern is driven by

Use of interventions

Management of kidney transplant recipients with coronary artery disease who present with an acute coronary syndrome or with symptomatic coronary artery disease is the same as for the general population. Patients with end-stage renal disease—specifically patients on dialysis—are less likely to undergo intervention than the general population, and are more likely to die after myocardial infarction. However, a report of patients in Medicare in the USA suggests that although intervention is less

Conclusions

In view of the scarcity of evidence from specific trials of cardiovascular interventions in transplant recipients, understanding which information derived from other populations is relevant is essential. The restricted benefit of standard interventions, such as statin therapy, emphasises the atypical nature of cardiovascular disease in kidney transplant recipients (figure 5). A single intervention is unlikely to be of major benefit, and a strategy for multiple risk factor intervention will need

Search strategy and selection criteria

We searched PubMed and Embase, between 2000 and 2011, for the MeSH terms “renal transplant” or “kidney transplant”, “hypertension”, “diabetes”, “lipid”, “cardiovascular”, “vascular”, and “stroke”. We also sought relevant clinical trials using the online library of the Centre for Evidence in Transplantation with the terms “CV”, “cardiovascular”, “hypertension”, “lipid”, “statin”, or “diabetes”. We excluded papers not written in English language.

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