Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

http://www.jsht.jp/uploads/ISHLT_GL_TaskForce2_110810.pdf

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

The pediatric transplant community stands at a time of unprecedented choice of immunosuppressive agents - and with a legacy of morbidity from those agents used in the previous two decades. This review considers the clinical utility and side-effect profiles of immunosuppressants used widely in current practice (e.g., glucocorticoids, azathioprine, ciclosporin, tacrolimus, mycophenolate, and sirolimus) and those agents which are in increasing use or in evaluation (e.g., IL-2 receptor antibodies, everolimus, FTY720, LEA29Y, and deoxyspergualin). Further consideration is given to the wider drug interactions likely during the use of new immunosuppressant regimens and to our growing awareness of the influences of genetic heterogeneity on drug efficacy and handling. Finally, we consider the new demands being placed on the use of drug monitoring to regulate dosage of this new repertoire of immunosuppressants.

Immunosuppression in pediatric solid organ transplantation : Opportunities, risks, and management

Background Hypertension is recognized as prevalent in pediatric cardiac transplant recipients. This study investigated risk factors for this complication and, in particular, the role of immunosuppression. Methods Results of 24-hour ambulatory blood pressure monitoring of children surviving more than 1 year after cardiac transplantation were analyzed retrospectively. Subjects were designated either hypertensive or normotensive by comparison with published normal values. To identify factors associated with hypertension, clinical data contemporaneous with 24-hour ambulatory blood pressure monitoring were collected and compared between the groups. Results In the 51 children studied, the incidence of hypertension was 49%. Hypertensive and normotensive recipients were similar for sex, age at transplantation, time between transplantation and 24-hour ambulatory blood pressure results, and choice of calcineurin inhibitor. In contrast, hypertensive patients were taking significantly more immunosuppressive agents (2.92 vs 2.12 p p = 0.03), and were more likely to be on maintenance prednisone therapy (64% vs 23%, p p = 0.03). Multiple regression analysis controlling for tacrolimus level showed a combination of prednisone and sirolimus was more strongly associated with hypertension than either agent alone, with an odds ratio of 7.3 (95% confidence interval, 1.5–36.1) vs 4.1 (95% confidence interval, 0.85–26.3). Conclusions Hypertension after pediatric cardiac transplantation is a common problem and primarily associated with immunosuppressive regimen.

Hypertension after pediatric heart transplantation is primarily associated with immunosuppressive regimen.

Arterial hypertension is a major risk factor for cardiovascular disease after solid organ transplantation, emphasizing the need for blood pressure (BP) monitoring. The authors studied 24-hour ambulatory BP monitoring (ABPM) parameters (index, load, dipping) and their predictive value with regard to hypertension as well as correlations with graft function and metabolic parameters such as obesity and dyslipidemias. The ABPM profiles of 111 renal, 29 heart, and 13 liver transplant recipients were retrospectively analyzed 5 to 10 years after transplant (median 5.1 years). The BP profiles among the different transplant groups were similar. The BP index and load were abnormal especially at nighttime and the nocturnal BP dipping was often blunted (in 49% to 83% of the patients). The BP variables were found to be equally valued when assessing hypertension. BP load of 50% instead of 25% seems to be a more adequate cutoff value. The BP variables correlated poorly with the metabolic parameters and kidney function. Antihypertensive medication did not notably change the ABPM profile in renal transplant recipients. Hypertension, including nocturnal hypertension, is present in children receiving solid organ transplant, underlining the importance of use of ABPM in the follow-up of these patients.

Blood pressure profiles 5 to 10 years after transplant in pediatric solid organ recipients.

The management of non-renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post-transplantation follow-up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non-renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24-h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non-renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m(2) .

Practice recommendations for the monitoring of renal function in pediatric non-renal organ transplant recipients.

Background There has been little formal study of blood pressure in children after cardiac transplantation. Methods Twenty-four-hour and clinical blood pressure (BP) were measured in 28 children (>6 months after transplantation) and compared with a large amount of normal data. Results Conventional (clinical) systolic BP (SBP) was elevated in 9 (32.1%) of 28 (95% confidence interval [CI] 15.8 to 52.3), and conventional diastolic BP (DBP) was elevated in 5 (17.8%) of 28 (95% CI 6.0 to 36.8). Mean 24-hour BP was >97.5 percentile in 2 (7.7%) of 26 (95% CI 0.9 to 25.1) for SBP and in 7 (28.0%) of 25 (95% CI 12.1 to 49.4) for DBP. In comparison with the control population, mean nighttime SBP was 8.9 mm Hg higher in the transplanted group (95% CI 4.8 to 13.1), but daytime and mean 24-hour SBP were similar. Mean day, night, and 24-hour DBP was significantly higher in the transplanted patients. The nighttime decrease in BP was significantly less than controls for SBP, but not for DBP. Conventional BP measurement was poorly predictive of 24-hour BP. There was a significant association between mean 24-hour SBP and interventricular septal thickness ( r 2 = 0.35; p = 0.01). DBP was not associated with interventricular septal thickness ( r 2 = 0.07; p = 0.20) but was significantly correlated with the time since transplantation ( r = 0.42; p = 0.03 for conventional DBP and r = 0.43; p = 0.04 for 24-hour DBP). Conclusions The elevation of DBP in children after cardiac transplantation is unexplained. The elevation in nighttime SBP has possible important therapeutic implications and is not predicted by conventional (clinical) BP measurement.

Blood pressure after cardiac transplantation in childhood.

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Blood pressure after cardiac transplantation in childhood.