What is the calcineurin inhibitor of choice for pediatric renal transplantation?

Cyclosporine microemulsion (CyA) and tacrolimus (Tac) are the principal immunosuppressants prescribed for adult and pediatric renal transplantation. In the majority of patients, these calcineurin inhibitors have been used in combination with other immunosuppressive drugs, such as azathioprine or mycophenolate mofetil (MMF). In this review we will address the question of what calcineurin inhibitor we should use in an individual pediatric renal transplant patient. Well-designed randomized studies in children showed no difference in short-term patient and graft survival with cyclosporine microemulsion and tacrolimus. However Tac is significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population when used in conjunction with azathioprine and corticosteroids. This difference disappears when calcineurin inhibitors are used in combination with MMF as both Tac and CyA produce similar rejection rates and graft survival. However, Tac is associated with improved graft function at 1 and 2 yr post-transplant. Adverse events of hypomagnesaemia and diarrhea seem to be higher in Tac group whereas hypertrichosis, flu syndrome and gum hyperplasia occurs more frequently in the CyA group. The incidence of post-transplant diabetes mellitus was almost identical between Tac and CyA treated patients. The recommendation drawn from the available data is that both CyA and Tac can be used safely and effectively in children. However Tac may be preferable to CyA because of steroid sparing effect and less hirsutism. We recommend that cyclosporine should be chosen when patients experience Tac-related adverse events. Nevertheless, the best calcineurin inhibitor should be decided on individual patients according to variable risk factors, such as risk of rejection in sensitized patient or delayed graft function. The possibility of adverse events should also be considered.     

What is the role for mycophenolate mofetil in pediatric renal transplantation?

Mycophenolate mofetil (MMF) has gained considerable popularity in pediatric renal transplantation. This popularity is largely a result of data from three large trials of MMF in adult cadaveric transplant patients who demonstrated a decreased rate of acute rejection episodes when treated with cyclosporin A (CsA), prednisone, and MMF compared with those receiving CsA, prednisone, and azathioprine (AZA) or placebo. However, the ability of MMF to reduce acute rejection appears to be limited to the first month post-transplant, and its effectiveness with microemulsion CsA or tacrolimus-based regimens has not been proven. In addition, there are currently no data that convincingly demonstrate that this agent improves graft survival, patient survival, graft function or protects against chronic rejection. Finally, there may be an increased risk for severe cytomegalovirus (CMV) disease and lymphoproliferative disorder with central nervous system involvement in patients treated with MMF. These data call into question the role of MMF in current immunosuppressive regimens.     

Editorial: Can omega‐3 fatty acids improve executive functioning? Will this reduce ADHD and depression?

Families with children who have neurodevelopmental disorders and mental health problems often opt to use nonmainstream and complementary medicines including dietary supplements. One dietary supplement popular with parents seeking treatment for both depression and ADHD is omega‐3 fatty acids. This has led to much research and scientific debate dedicated to examining the efficacy of omega‐3 supplementation as a treatment for both depression and ADHD.     

Outpatient pediatric renal transplant biopsy – Is it safe?

The safe observation time following pediatric renal transplant biopsy is unknown. To predict the safety of day-care pediatric renal transplant biopsy, we retrospectively evaluated the timing, incidence and severity of post-biopsy complications in children observed overnight. Biopsies were performed under real time ultrasound guidance using an 18-gauge Bard Biopty needle. Coagulation screen and platelet counts were measured preprocedure. Hemoglobin (Hb) was measured preprocedure, at 6 h and at 1-day post-procedure. Twenty-eight of 45 children transplanted between January 2002 and May 2004 underwent 65 biopsies. There was gross hematuria following 8 (12%) biopsies; 2/8 occurred after 6 h. Hb fell by >15 g/L in six cases (9%) - three had Hb drop within 6 h post-procedure and three had a steady decline over 24 h. No patient required blood transfusion. Oral analgesia post-procedure was required in seven cases (11%). One of these had gross hematuria. No patient required surgical intervention or transfusion. Three complications were recorded >6 h post-biopsy but none required intervention. Daycare renal transplant biopsy appears to be safe in selected patients.     

HHV‐6 encephalitis in pediatric unrelated umbilical cord transplantation: A role for ganciclovir prophylaxis?

Cheng FWT, Lee V, Leung WK, Chan PKS, Leung TF, Shing MK, Li CK. HHV‐6 encephalitis in pediatric unrelated umbilical cord transplantation: A role for ganciclovir prophylaxis?
Pediatr Transplantation 2010: 14:483–487. © 2009 John Wiley & Sons A/S. Abstract: The role of ganciclovir as HHV‐6 prophylaxis in unrelated HSCT setting remains controversial. We performed an eight‐yr retrospective review of patients received unrelated HSCT from January 2000 to September 2008. From January 2002, ganciclovir prophylaxis 5 mg/kg twice daily for seven days for all unrelated HSCT before transplant was adopted. The prevalence of HHV‐6 encephalitis was studied before and after the change in policy. Fifty‐four unrelated HSCT were performed from January 2000 to September 2008. Four cases (7.4%) of HHV‐6 encephalitis were diagnosed. All of them were due to variant B infection. Two cases out of 16 cases (12.5%) were diagnosed before adoption of the policy; two cases out of 38 cases (5.3%) were diagnosed afterward. All of them were unrelated UCB transplant recipients. They were all seropositive to HHV‐6 before transplant. Two cases complicated with significant residual neurological deficit and refractory seizure. The other two cases died of other transplant‐related mortalities. We conclude that HHV‐6 encephalitis is still a rare complication of unrelated HSCT and may be more common in unrelated UCB transplant. Routine use of ganciclovir as HHV‐6 prophylaxis in all unrelated HSCT recipients may not be justified but may have a role in unrelated UCB transplant.