By Sabrina Candelaria, MPH, RD, CDN

For children and adolescents with chronic kidney disease (CKD), transplantation provides an opportunity to lead healthier, more productive lives, while allowing for a more normal progression of growth and development. In pediatric transplantation, obtaining normal kidney function hinges on the ability of post-transplant care to prevent organ rejection through balanced immune system control. Advancements in recent years have lead to the use of medications that help prevent the immune system from attacking the transplanted organ.¹ However, these medications are not without side effects.

Immunosuppressive Medications

Despite the evolution of immunosuppressive medications that have greatly enhanced organ survival, many drug therapies have adverse effects. Gastrointestinal distress, diabetes mellitus, hypertension, obesity, bone disease, increased susceptibility to infection, elevated triglycerides, kidney damage, and growth retardation are among the multiple effects.^1-4 Raising awareness of these potential consequences becomes a serious concern for pediatric patients whose growth and development are at their peak during childhood and adolescence. It is essential for patients and their caregivers to become informed about side effects of these medications, as well as their management, to ensure optimal post-transplant care and survival.

The combination and use of immunosuppressive medications is dependent on multiple patient-specific factors (underlying disease, responsiveness to steroids, etc.) and varies among treatment centers. Non-compliance with prescribed medication regimens is of major concern and often leads to transplant failure. Thus, controlling unpleasant side effects is of utmost importance as they are influential in the overall outcome and survival of the transplanted kidney.

Side Effects of Immunosuppressive Medications

Adverse side effects have been associated with many commonly prescribed immunosuppressive medications: corticosteroids (prednisone, prednisolone, methylprednisone- Solu-Medrol®); cyclosporine (Sandimmune®, Neoral®); tacrolimus (Prograf®, FK506); azathioprine (Imuran®); mycophenolate mofetil (Cell-Cept®, Myfortic®); sirolimus (Rapamune®); antibiotics (Bactrim®); anti-fungal medications (Mycelex®, Nystatin®); anti-viral medications (Zovirax®, Cytovene®); and diuretics (Lasix®).

Commonly observed physiological side effects of greatest concern can be classified as gastrointestinal or metabolic.4 As evidenced in medical literature and clinical practice, patients typically experience numerous symptoms at some point during their post-operative course. Side effects may include, but are not limited to the following: gastrointestinal problems, such as nausea, vomiting, diarrhea, increased appetite (hyperphagia), loss of appetite (anorexia), and swelling of the gums (gingival hypertrophy); and metabolic problems, such as high blood pressure (hypertension); elevated blood levels of potassium, glucose, and triglycerides (hyperkalemia, hyperglycemia and hyperlipidemia respectively); decreased blood levels of phosphorous and magnesium (hypophosphatemia and hypomagnesaemia); anemia; bone disease (osteoporosis/ osteopenia); kidney damage (nephrotoxicity); headache, tremors, and seizures (neurotoxicity); excessive weight gain (obesity); and growth retardation. The tables below (Source: References ^{1, 2, 4-6}) provide a guide to common side effects of post-transplant medications.

In addition to physiological aspects, it is important to acknowledge the psychosocial impact that side effects such as changes in body image, facial appearance, scarring, short stature, etc., may have in the pediatric population. This is of particular concern during adolescence when self-esteem is easily influenced. Physical changes can be extremely stressful and may result in lowered self-esteem. Therefore, it is advisable to form relationships with all members of the interdisciplinary team, including the social worker and child-life specialist, to minimize effects these issues can have on psychosocial well-being.

Managing Effects of Immunosuppressive Medications

Successful management of symptoms involves a combination of dosage adjustment and medical nutrition therapy. This adjustment is patient specific and depends on the underlying etiology of the patient’s disease, as well as side effects. It is not uncommon for the medical team to alter the dosage and/or combination of medications to minimize side effects. Nutritional approaches include: manipulation of nutrient intake requiring dietary restriction or vitamin/mineral supplementation (i.e. fluid intake; control of caloric, protein and fat intake; and monitoring of sodium, potassium, phosphorous, calcium or magnesium intake); small, frequent meals (up to six small meals per day); and alternative modes of nutrient delivery, such as the gastrointestinal tract (tube feeding) or intravenously (parenteral nutrition). Many adverse effects discussed, such as nausea, vomiting, diarrhea, hyperglycemia, hyperlipidemia and obesity, are examples of side effects whose management has been positively associated with medical nutrition therapy.

Making Use of the Interdisciplinary Transplant Team

To ensure that patients receive the maximum benefit of post-transplant treatment, it is imperative for the interdisciplinary transplant team to establish open communication with patients and caregivers. Typically, this team includes physicians, transplant coordinators, nurses, dietitians, social workers and child-life specialists. Positive interaction between team members and the patient often lead to more effective treatment. Therefore, post-transplant treatment concerns, especially in patients displaying symptoms, should be immediately reported to the transplant team for effective management.

References:

1. Smith JM, Nemeth TL, McDonald RA. Current immunosuppressive agents in pediatric renal transplantation: Efficacy, side-effects and utilization. Pediatr Transplantation 2004: 8: 445-453.

2. Chand DH, Southerland SM, Cunningham RJ III. Tacrolimus: The good, the bad, the ugly. Pediatr Transplantation 2001: 5: 32-36.

3. Fine RN, Alonso EM, Fischel JE, Bucuvalas JC, Enos RA, Gore-Langton RE. Pediatric Transplantation of the kidney, liver and heart: Summary report. Pediatr Transplantation 2004: 8: 75-86.

4. Hasse JM, Blue LS. Comprehensive Guide to Transplant Nutrition. American Dietetic Association, 2002.

5. Pronsky ZM. Food-Medication Interactions Handbook, 13^th Edition. Food-Medication Interactions; Birchrunville, PA; 2005.

6. Saland, JM. Osseous complications of pediatric transplantation. Pediatr Transplantation, 2004: 8: 400-415.

Sabrina Candelaria, MPH, RD, CDN is a pediatric renal dietitian for Pediatric Nephrology & Renal Transplant Services at the Children’s Hospital at Montefiore in Bronx, N.Y.

This article originally appeared in the September 2005 issue of aakpRENALIFE, Vol. 21, No. 2.

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