Care of the Kidney Transplant Recipient

Kidney transplantation is a successful treatment modality for end-stage real disease and the preferred mode of renal replacement therapy. Both patient and allograft survival at 1 yr are >90% in most transplant centers. The success of transplantation has in fact led to an increased demand for organs and an increased waiting time for deceased donor kidneys. This in turn has stimulated increased living donation and the use of extended-criteria deceased donor kidneys, including those donated after cardiac death. Moreover, although more potent and complex immunosuppressive strategies have reduced the rates of acute rejection and improved short-term graft survival, long-term graft survival rates have not improved as dramatically. This is due in part to continued graft failure caused by allograft fibrosis and atrophy (also known as chronic allograft nephropathy or CAN) as well as death with a functioning graft. Transplant nephrologists are now focusing on the medical management of their patients with more attention to the details of the medical management of comorbidities. Thus, this supplement of the Clinical Journal of the American Society of Nephrology will explore the leading medical complications after kidney transplant, with attention to etiology, detection, and management.

Although cardiovascular disease is believed to be the leading cause of death in renal transplant recipients, there is ample evidence to support the idea that transplantation reduces the risk of cardiovascular disease. Understanding the contribution of pre- and posttransplant factors on the development of cardiovascular disease will help with rational study design and treatment strategies aimed at reducing the impact of these factors. In his article, Gill explores the impact of traditional and nontraditional risk factors, including the role of immunosuppressive drugs on the development of cardiovascular disease after transplantation.

One major contributor to cardiovascular disease in the transplant population is diabetes mellitus. Moreover, diabetes in and of itself has a significant negative impact on both patient and graft survival. Crutchlow and Bloom discuss the factors that contribute to the development of new-onset diabetes after transplantation, including the relevance of viral infections. Key steps in management including the use of noninsulin therapy are discussed in the context of the transplant setting. Aggressive detection and management may be critical to improve long-term outcomes.

The development of anemia after transplantation is more common than would be expected if extrapolated from the degree of renal dysfunction when compared with native kidney disease. In their article, Winkelmayer and Chandraker discuss the pathogenesis and how if may be different from anemia in native CKD. The difficulty in providing treatment guidelines as a result of a lack of evidence is also discussed. Management strategies used and their impact on the basis of center-specific reports will be discussed.

Whereas acute graft loss may be all but conquered, little progress on the long-term survival of renal allografts appears to have been made. Jevnikar and Mannon tackle the issues in a disease once simply labeled as CAN. They present an update in the histological considerations and describe the potential role of alloantibody. The impact of tubular cell injury and the role of epithelial-mesenchymal transformation is discussed in the context of identifying new biomarkers and strategies for management.

The steady decline in acute rejection episodes has not come without some cost. The increased use of induction therapy and the introduction of more potent immunosuppressive agents have contributed significantly to the reduction of acute rejection episodes, but it has also lead to an increase in infectious complications after transplantation. The most obvious correlation between increased immunosuppression and the infection is the emergence of the BK polyoma virus as a cause of renal transplant dysfunction. Dall and Hariharan review the incidence, pathogenesis, and treatment of this infection. Although described >40 yr ago, BK was virtually unknown before 1995, after which time it has rapidly emerged as a bete-noir of many transplant centers. Although still difficult to treat once established within the allograft, screening for its presence coupled with the judicious reduction of immunosuppression appear to have gone a long way toward limiting graft loss by this invasive viral infection.

There is also a changing landscape of other viral infections seen after transplantation. Cytomegalovirus, before effective antiviral prophylaxis, was a significant cause of morbidity and mortality in renal allograft recipients. The availability of newer monitoring assays and the increased awareness of potential viral infectious agents have led to an increased detection of a wider spectrum of viral infectious agents in transplants recipients. These issues as well as prevention strategies and treatment are discussed in the article by Weikert and Blumberg.

The impact of immunosuppression is also evident as malignancy rates after transplantation are increasing and the contribution of malignancy to recipient mortality growing. In their comprehensive review, Wong et al. summarize the current evidence for cancer screening in general populations and evaluate the efficacy of these strategies in the posttransplant population. Critically, they identify an insufficiency of evidence to apply current screening practices in the immunosuppressed patient population and recommend that additional studies be considered to find cost-effective and efficacious methods to screen for cancer after transplant.

The negative contributory role of immunosuppressive agents to both patient and allograft survival has led to increased interest in strategies aimed at reduction or elimination of immunosuppressive agents after transplantation. Steroids have been targeted because of their contribution to a wide variety of conditions that contribute to increased morbidity after transplantation. Calcineurin inhibitors on the other hand are well known to cause acute and chronic nephrotoxicity. Srinivas and Meier-Kriesche argue that, despite the recent popularity particularly of steroid elimination strategies among US transplant centers, the long-term safety, benefit, and effectiveness of these strategies are far from proven.

Finally, recognizing that a fundamental goal of transplantation is to return patients to more healthy and productive lives, McKay and Josephson present a comprehensive review of the data on reproduction after transplantation. As discussed in their review, fertility often improves after successful transplantation. As a number of immunosuppressants are contraindicated in pregnancy, recipients and their physicians must balance the desire of having children with alterations in therapy that may affect graft function and outcome. Successful pregnancies are now a part of the posttransplant management. Being able to conceive after kidney transplantation may be the ultimate indicator of the success of this transplant as a treatment modality.

We are delighted to present this series of articles that review the major issues of posttransplant care, providing an up-to-date understanding of etiology, management, and therapy. By recognizing these comorbidities after transplantation and implementing the respective management strategies, we can continue to maintain a precious resource while avoiding unnecessary loss at a time that we can simply not afford to take any kidney transplant for granted.

• Copyright © 2008 by the American Society of Nephrology