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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Beyond the Kidney: Combating the Risks of Infectious Disease and Malignancy in Renal Transplant Recipients


GOAL
To provide nephrologists, nephrology nurses, and transplant coordinators with up-to-date information on the challenges of renal transplantation.

TARGET AUDIENCE
This activity is designed for nephrologists and nephrology nurses working in renal transplant centers, in addition to transplant coordinators. No prerequisites required.

LEARNING OBJECTIVES
At the conclusion of this activity, the participant should be able to:

  • Outline the latest data on infectious complications in renal transplant recipients and apply these data to infection diagnosis and management.
  • Identify immunosuppressive therapies to minimize infectious risk while optimizing graft survival in the renal transplant patient.
  • Summarize the risk of malignancy in renal transplant recipients.
  • Propose protocols for cancer prevention and screening to improve patient outcomes.

The Johns Hopkins University School of Medicine, The Institute for Johns Hopkins Nursing, and the American Board for Transplant Certification take responsibility for the content, quality, and scientific integrity of this CE activity.

ACCREDITATION STATEMENT
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of The Johns Hopkins University School of Medicine, The Institute for Johns Hopkins Nursing, and the American Board for Transplant Certification.

The Institute for Johns Hopkins Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

The American Board for Transplant Certification (ABTC) has established a continuing certification program whereby certified coordinators meeting the eligibility requirements may seek to maintain certification through the Continuing Education Points for Transplant Certification (CEPTC) program. The ABTC has approved this educational offering.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

This 2 contact hour Educational Activity (Provider Directed/Learner Paced) is provided by The Institute for Johns Hopkins Nursing. Claim only those contact hours actually spent in the activity.

The American Board for Transplant Certification (ABTC) has approved this educational offering for up to 2.0 Category I Continuing Education Points for Transplant Certification (CEPTCs).

The estimated time to complete this educational activity: 2 hours.

Release date: October 15, 2007. Expiration date: October 15, 2009.

This program is supported by an educational grant from Wyeth Pharmaceuticals.

Full Disclosure Policy Affecting CE Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:

PROGRAM DIRECTORS

Hamid Rabb, MD
Physician Director, Kidney and Pancreas Transplantation
Professor of Medicine
Division of Nephrology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Rabb reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Flavio G. Vincenti, MD
President, American Society of Transplantation
Professor of Clinical Medicine
University of California, San Francisco
San Francisco, California
Dr Vincenti reports having no significant financial or advisory relationships with corporate organizations related to this activity.

PARTICIPATING FACULTY

Stuart M. Flechner, MD, FACS
Professor of Surgery
Cleveland Clinic Lerner College of Medicine
Transplant Center/Glickman Urological Institute
Cleveland, Ohio
Dr Flechner reports receiving grants/research support from Bristol-Myers Squibb, Novartis, and Wyeth Pharmaceuticals; serving as a consultant for Genzyme, Roche Pharmaceuticals, and Wyeth Pharmaceuticals; and serving on the speakers’ bureau for Novartis, Roche Pharmaceuticals, and Wyeth Pharmaceuticals.

Sundaram Hariharan, MD
Professor of Medicine
Chief, Division of Nephrology
Medical College of Wisconsin
Milwaukee, Wisconsin
Dr Hariharan reports serving as a consultant for Alexion, Bristol-Myers Squibb, and Genentech; and serving on the speakers’ bureau for Astellas.

Notice: Faculty have indicated that they have not referenced unlabeled or unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Beyond the Kidney: Combating the Risks of Infectious Disease and Malignancy in Renal Transplant Recipients
Hamid Rabb, MD,* and Flavio G. Vincenti, MD†

The patient undergoing kidney transplantation has a significantly higher chance of survival and good graft function today than in the early 1960s when kidney transplantation was first performed. Successful kidney transplantation increases life expectancy by 10 to 20 years.1,2 Improved outcomes after kidney transplantation are attributed to advances, such as better surgical techniques, patient selection, and immunosuppressive drug therapy. Although the long-term outlook for renal transplant recipients has improved, the life expectancy of renal transplant recipients remains significantly shorter than that of the general population.3 Factors contributing to excess mortality among renal transplant recipients include cardiovascular disease, type 2 diabetes, infectious disease, and cancer. Prevention and management of these factors, previously not a major focus in care for the renal transplant recipient, have become important components of transplantation-associated healthcare. Effective prevention and management of cardiovascular and metabolic disease, infectious disease, and malignancy are among the important challenges in improving prognosis after renal transplantation, and transplant clinicians play an integral role in meeting these challenges. This issue of Johns Hopkins Advanced Studies in Medicine , which is the fourth module in a 5-module educational series titled, “Filtering Through the Evidence: A Multi-Modular Educational Initiative on Renal Transplantation,” discusses the prevention, recognition, and management of infectious disease and malignancy in renal transplant recipients. Prevention, recognition, and management of cardiovascular and metabolic disease in renal transplant patients were discussed in a previous module.

The numerous sources of infection in the renal transplant recipient include donor tissue, latent infection or colonization in the recipient, the hospital setting, and the community. Bacterial, viral, fungal, and protozoal agents pose risks to the renal transplant recipient. Because of the transplant recipient’s immunosuppressed state, pathogens can cause more severe disease than they normally would, and organisms that are not typically pathogenic can cause clinically significant disease. Of the infectious diseases, those caused by viruses cause the greatest morbidity and mortality in transplant recipients, who are particularly vulnerable to the severe manifestations of viral infections. Herpesviruses, including cytomegalovirus, varicella zoster virus, herpes simplex viruses 1 and 2, and human herpesvirus 6 are among the most common and dangerous for renal transplant recipients. These viruses are immunosuppressive and oncogenic.

In his article, Sundaram Hariharan, MD, Professor of Medicine and Chief of the Division of Nephrology at the Medical College of Wisconsin in Milwaukee, emphasizes the importance of preventive therapy and prompt diagnosis in the management of viral infections in renal transplant recipients. Dr Hariharan advocates careful screening of recipients and donors for infectious disease, prophylactic antimicrobial therapy, meticulous postoperative care, and judicious use of immunosuppression as key components of managing infectious risk in the renal transplant recipient. Efforts to prevent infectious complications can begin before transplantation with the treatment of active infections, vaccination against likely posttransplant pathogens, and avoidance of exposure to pathogens during the perioperative period. If prophylactic efforts fail, early and precise diagnosis is crucial in identifying an appropriate course of therapy for posttransplantation infections.

Besides being at high risk for infectious complications, renal transplant recipients face much greater risk of de novo malignancy than the general population. In fact, although the risk of acute graft rejection and other complications of renal transplantation are decreasing, that of transplant-associated malignancies is increasing. Some of this increased risk is attributed to malignancies linked to infectious agents, including Epstein-Barr virus, which is associated with posttransplant lymphoproliferative disorder; human herpesvirus 8, which is associated with Kaposi’s sarcoma; and human papilloma viruses, which are associated with cervical cancer, penile cancer, and nonmelanoma skin cancer. Other causes of posttransplant malignancy are chronic disease and chronic immunosuppressive therapy. In his article Stuart M. Flechner, MD, FACS, Professor of Surgery at the Cleveland Clinic Lerner College of Medicine and Transplant Center/Glickman Urological Institute in Ohio, discusses the incidence of cancer and its most common types after renal transplantation, the etiology of posttransplant malignancy, and prevention and management of cancer in the renal transplant recipient. Dr Flechner advises that nephrology clinicians familiarize themselves with malignancies commonly seen in renal transplant recipients. Some of the risk factors for transplantation-associated cancer can be modified. Stopping smoking, for instance, can significantly decrease the risk of cancer in the renal transplant recipient. Strategies for preventing and managing malignancies include keeping immunosuppressive therapy to the minimum level that maintains good graft function, practicing vigilant cancer surveillance after transplantation, and aggressively treating cancers that are detected.

Although outcomes after renal transplantation have continuously improved over the decades, additional progress is necessary. Among several determinants of the success of the renal transplant, prevention, and management of infectious and malignant complications are crucial to maintaining graft health and prolonging patient survival. The information in this monograph should be useful for nephrology clinicians seeking to improve their ability to provide quality care for their patients at risk of infectious disease and malignancy.

REFERENCES

1.    Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725-1730.
2.    Port FK, Wolfe RA, Mauger EA, et al. Comparison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. JAMA. 1993;270:1339-1343.
3.    Ojo AO, Hanson JA, Wolfe RA, et al. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000;57:307-313.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his article and all its contents.

*Physician Director, Kidney and Pancreas Transplantation, Professor of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

†President, American Society of Transplantation, Professor of Clinical Medicine, University of California, San Francisco.

Address correspondence to: Hamid Rabb, MD, Physician Director, Kidney and Pancreas Transplantation, Professor of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, East Baltimore Campus, Ross 970 Nephrology, 720 Rutland Avenue, Baltimore, MD 21205. E-mail: hrabb1@jhmi.edu.





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