title: Challenges in pediatric transplantation: the impact of chronic kidney disease and cardiovascular risk factors on long-term outcomes and recommended management strategies.
abstract: Barriers to successful outcomes following pediatric transplantation have shifted from ischemic reperfusion injury and rejection to more long-term complications. Of particular concern is the high prevalence of CKD owing to preexisting damage and nephrotoxicity, as well as other CV complications such as hypertension and cardiomyopathy. All of these contribute to graft loss and shortened life expectancy, thereby limiting the success story of solid-organ transplantation. Managing CKD and related CV morbidity should be integral to the care of pediatric transplant patients, and timely detection of any irregularities would increase the chances of restoring lost kidney function. GFR is still the widely accepted indicator of renal function, and nuclear medicine techniques are the gold standard measurement methods. These methods are limited by costs, radiation exposure and substrate injection, and current practice still uses the Schwartz estimate, despite its well-documented limitations. Newer endogenous markers of GFR, such as cystatin C clearance, give a more accurate measure of true GFR but have not been embraced in the management of pediatric transplant recipients. Furthermore, indirect markers (e.g., microalbuminuria and hypertension) could also aid early detection of renal damage. The effects of mainstay immunosuppressants on kidney and heart function are varied, with available data indicating favorable outcomes with tacrolimus compared with ciclosporin. There is a need for appropriately designed and powered randomized controlled trials to validate innovative concepts for tailored immunosuppression in the pediatric population. To date, very few studies have generated long-term data in pediatric renal transplant patients - results of 1-4-yr study favored tacrolimus over ciclosporin, but other immunosuppressive agents also need to be evaluated.
authors.affiliation: Department of Paediatrics, London Health Science Centre, Children's Hospital, University of Western Ontario, London, ON, Canada. guido.filler@lhsc.on.ca
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
mesh_terms: D002318:Cardiovascular Diseases / Q000150:complications* / Q000175:diagnosis; D002908:Chronic Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation / Q000379:methods*; D016377:Organ Transplantation / Q000379:methods*; D010372:Pediatrics / Q000379:methods*; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus