TreatmentUpdate
183

2011 March 

Selected complications that can occur after transplantation

Over the long-term, if immunosuppressive drugs are successful in helping to minimize the immune system’s attack on transplanted tissue, there are several health issues that can occur. It is difficult to untangle the specific cause(s) of some of these long-term issues for several reasons.

Preexisting issues

People who receive transplanted livers and kidneys often have traditional risk factors for cardiovascular disease prior to transplantation. These risk factors include poor dietary habits, smoking tobacco or engaging in substance use, being overweight, not getting sufficient exercise and so on. Not all of these bad habits are eliminated after transplantation.

Immunosuppressive drugs may amplify some of the effects of preexisting cardiovascular disease risk factors. Because transplant recipients are often given combinations of immunosuppressive drugs, it is sometimes difficult to link every adverse effect to a specific drug.

Cardiovascular complications

Bearing in mind some of these points, note that premature cardiovascular disease—including the development of higher-than-normal blood pressure and abnormal levels of lipids in the blood—is a common complication after transplantation.

Diabetes

Within a year after transplantation, and depending on the study, between 5% and 20% of transplant recipients develop type 2 diabetes. Tacrolimus (Prograf) decreases the body’s production of insulin (a hormone needed to help control blood sugar levels) and this drug appears to have greater potential to cause diabetes than cyclosporine (Neoral, Sandimmune). The use of sirolimus (rapamycin, Rapamune) also appears to be linked to an increased risk for developing this complication.

Cancer

In general, as HIV-negative people live longer, their immune system gradually weakens and therefore their risk for cancer increases. As people who have transplanted organs live longer, their risk for developing cancer also increases because of the immunosuppressive therapies that they must continuously take. Researchers in Australia and New Zealand who have been monitoring HIV-negative transplant recipients have found that while deaths from heart attack and stroke have decreased—likely because these are preventable—deaths from infections and cancers have increased. Indeed, overall, compared to the average HIV-negative person without a transplant, HIV-negative people who do get transplants are between three and five times more likely to develop cancer.

The rate of cancers that are relatively common in non-transplanted HIV-negative people—colon, breast, lung and prostate tumours—is only slightly increased in people who receive a transplant. Other cancers, particularly those affecting the skin and immune system, are ones that tend to occur in transplant recipients. Studies of immunosuppressive drugs in HIV-positive people have not lasted long enough for researchers to be certain about their effects.

In HIV-negative people, exposure to cyclosporine has been associated with an increased risk for cancer, while exposure to mycophenolate (CellCept) has not. Studies that have assessed exposure to the mTOR inhibitors sirolimus or everolimus (Certican, Zortress) suggest that, at least for now, these drugs appear to be associated with a reduced risk for cancer.

Transplant teams are conducting clinical trials using different doses and combinations of immunosuppressive medicines to try to find the most effective and safest ones over the long term.

REFERENCES:

  1. Alberú J. Clinical insights for cancer outcomes in renal transplant patients. Transplantation proceedings. 2010 Nov;42(9 Suppl):S36-40.
  2. Geissler EK. Can immunosuppressive strategies be used to reduce cancer risk in renal transplant patients? Transplantation Proceedings. 2010 Nov;42(9 Suppl):S32-5.
  3. Rama I, Grinyó JM. Malignancy after renal transplantation: the role of immunosuppression. Nature Reviews Nephrology. 2010 Sep;6(9):511-9.
  4. Chak E, Saab S. Risk factors and incidence of de novo malignancy in liver transplant recipients: a systematic review. Liver International. 2010 Oct;30(9):1247-58.
  5. Carpenter CB, Milford EL, Sayegh MH. Chapter 276. Transplantation in the Treatment of Renal Failure. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
  6. Finberg R, Fingeroth J. Chapter 126. Infections in Transplant Recipients. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.
  7. Dienstag JL, Chung RT. Chapter 304. Liver Transplantation. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Companies, Inc.; 2008.