By Katarina Zorcic and Simi Juriasingani 

Disclaimer: The intent of this article is to raise awareness about the complications that MAY occur with prolonged immunosuppression after transplant. Individuals are advised to speak to their doctors about any specific concerns or medications.

Immunosuppression is one of the most important aspects of modern transplantation. It is what allows the recipient’s body to accept and work with the donor organ, a foreign entity, rather than reject it. Transplant recipients take immunosuppressive medications daily for life and herein lies the paradox. The pills that allow them to live improved lives after their transplants also put them at risk for other conditions with prolonged immunosuppression. The aim of this piece is to raise awareness about the complications caused by chronic immunosuppression, which is an important concern as the population of immunosuppressed transplant recipients grows.   

1. Infections

Complications due to infections are the most common cause of post-transplant mortality. Bacteria, viruses, and fungi are responsible for a larger number of these post-transplant infections. Cytomegalovirus, Epstein-Barr virus, Herpes simplex, Adenovirus, Polyoma, and Rotavirus are the viruses responsible for causing the most common viral infections. Most bacterial infections within the first  month post-transplant are acquired in the hospital Listeria monocytogenes and Nocardia supp cause the majority of bacterial infections in the first six months post-transplant. After that, community-acquired bacterial infections caused by E. coli and S. pneumonia are more common. These bacterial infections mainly affect the urinary tract, respiratory tract, and bloodstream. Furthermore, the most common invasive fungal infections are caused by Candida supp. (infecting wounds and the bloodstream) and Aspergillus supp (infecting the lungs and brain). Invasive fungal infections occur at a rate of 40-59% in intestinal transplant recipients, 5-42% in liver transplant recipients, 7-14% in pancreas transplant recipients, and 15-35% in lung transplant recipients. 

2. Renal Dysfunction

One of the main complications of solid organ transplantations is renal dysfunction. Prolonged use of calcineurin inhibitors, a class of immunosuppressive medications, is linked to the development of chronic kidney disease (CKD). Post-transplant kidney (renal) failure increases the risk of mortality by 4 times when compared with the general population. The level and duration of calcineurin inhibitor administration dictates the incidence and the severity of renal dysfunction observed. Calcineurin inhibitors are known to cause both chronic and acute nephrotoxicity. Therefore, calcineurin inhibitor reduction and avoidance have been suggested as strategies to reduce the risk of nephrotoxicity following a transplant. 

3. Cancer

The incidence of developing a cancerous growth, or malignancy, increases in transplant recipients 3-to 5-fold when compared to the general population due to chronic suppression of the immune defences. After 25 years of immunosuppression, half of transplant recipients are at risk for developing a tumour. The effects of cancer are exacerbated in kidney transplant recipients seeing as it is the third most common cause of death following cardiovascular incidents and infections. The most common de-novo malignancies (i.e., the first occurrence of cancer in the body) are squamous and basal cell carcinomas of the skin, with squamous cell carcinomas being more aggressive and having the possibility to metastasize in transplant recipients. Age, exposure to ultraviolet radiation, and skin type are all risk factors for post-transplant skin cancer in addition to prolonged immunosuppression. 

4. Diabetes Mellitus 

New-onset diabetes after transplantation (NODAT) is another growing concern among immunosuppressed transplant recipients. The incidence of NODAT varies by the organ transplanted. The approximate rates of NODAT one year post-transplant are 20% for lung transplant recipients, 9-21% for liver transplant recipients, and 20-50% for kidney transplant recipients. The main immunosuppressive medications that are a risk factor for NODAT are corticosteroids, calcineurin inhibitors, and sirolimus. Calcineurin inhibitors might be responsible for damaging pancreatic beta cells as they have been associated with reduced insulin release. In addition, NODAT and pre-existing diabetes both increase the risk of cardiovascular disease 2 to 5-fold when compared with recipients without diabetes.

5. Cardiovascular Disease

The most common cause of death in transplant patients is cardiovascular disease. Hypertension, hyperglycemia, and dyslipidemia are all pre-existing risk factors that get amplified after a transplant. This amplification results in quickened atherosclerosis (i.e., buildup of fats and cholesterol on arterial walls) which leads to ischemic heart attacks, congestive heart failure, and/or strokes. It is important to consider lifestyle changes (diet, exercise, etc) to correct any modifiable risk factors in order to reduce the impact of post-transplant cardiovascular disease.

Overall, transplant recipients are living longer today, but that provides them with more time to manifest these chronic immunosuppression complications. It is important that reliable methods are developed to identify and limit the impact of chronic immunosuppression. At the end of the day it is all about finding and keeping the balance between infection and rejection.

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