Association of Obesity with Cardiovascular Risk Factors and Kidney Disease Outcomes in Primary Proteinuric Glomerulopathies.

BACKGROUND/AIMS: Obesity is a known risk factor for cardiovascular disease and contributes to the development and progression of kidney disease. However, the specific influence of obesity on outcomes in primary glomerular disease has not been well characterized. METHODS: In this prospective cohort study, data were from 541 participants enrolled in the Nephrotic Syndrome Study Network (NEPTUNE), between 2010 and 2019, at 23 sites across North America. Blood pressure, lipids, and kidney disease outcomes including complete proteinuria remission, kidney failure, and chronic kidney disease progression were evaluated. Data were analyzed using linear and logistic regression with generalized estimating equations and time-varying Cox regression with Kaplan-Meier plots. RESULTS: The prevalence of obesity at baseline was 43.3% (N = 156) in adults and 37.6% (N = 68) in children. In adults, obesity was longitudinally associated with higher systolic BP (ß = 6.49, 95% CI: 2.41, 10.56, p = 0.002), dyslipidemia (OR = 1.74, 95% CI: 1.30, 2.32, p < 0.001), triglycerides (ß = 41.92, 95% CI: 17.12, 66.71, p = 0.001), and lower HDL (ß = -6.92, 95% CI: -9.32, -4.51, p < 0.001). In children, obesity over time was associated with higher systolic BP index (ß = 0.04, 95% CI: 0.02, 0.06, p < 0.001) and hypertension (OR = 1.43, 95% CI: 1.04, 1.98, p = 0.03). In both adults and children, obesity was associated with a significantly lower hazard of achieving complete remission of proteinuria (adult HR = 0.80, 95% CI: 0.69, 0.88, p < 0.001; pediatric HR = 0.72, 95% CI: 0.61, 0.84, p < 0.001). CONCLUSION: Obesity was associated with higher cardiovascular risk and less proteinuria remission from nephrotic syndrome in adults and children with proteinuric glomerulopathies. Weight-loss strategies may forestall cardiovascular disease and progressive kidney function decline in this high-risk patient group.

Medication adherence in pediatric renal transplant patients: The role of family functioning and parent health locus of control.

Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio-emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers' perspectives, in predicting medication non-adherence for adolescents (ages 12-19 years) 1 year post-transplant. Non-adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers' perceptions of poorer overall family functioning predicted missed medication doses (ΔR2  = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem-solving (ß = -0.795, t(21) = -2.927, P = 0.008) and affective involvement (ß = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR2  = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family-based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.

Blood Pressure and Visit-to-Visit Blood Pressure Variability Among Individuals With Primary Proteinuric Glomerulopathies.

Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE (Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years [interquartile range, 32-57.8 years], 61.5% male) and 147 children (11 years [interquartile range, 5-14 years], 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. Histological diagnosis was associated with hypertensive status in adults (P=0.036). In adults, hypertensive status was associated with lower hazard of complete remission (hazard ratio, 0.36; 95% confidence interval, 0.19-0.68) and greater hazard of achieving the composite end point (end-stage renal disease or estimated glomerular filtration rate decline >40%; hazard ratio, 4.1; 95% confidence interval, 1.4-12). Greater systolic and diastolic SD and average real variability were also associated with greater hazard of reaching the composite end point in adults (all P<0.01). In children, greater BPV was an independent predictor of composite end point (determined by systolic SD and average real variability) and complete remission (determined by systolic and diastolic average real variability; all P<0.05). Hypertensive status was common among adults and children enrolled in NEPTUNE. Differences in hypertensive status prevalence, BPV, and treatment were found by age and histological diagnosis. In addition, hypertensive status and greater BPV were associated with poorer clinical outcomes.

Vascular Stiffness in Children With Chronic Kidney Disease.

Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m2 Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.

Complete Remission in the Nephrotic Syndrome Study Network.

BACKGROUND AND OBJECTIVES: This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC) <0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. RESULTS: We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m(2) (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. CONCLUSIONS: In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission.

Neonatal atypical hemolytic uremic syndrome from a factor H mutation treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) results from an inherited dysregulation of the alternative complement pathway leading to thrombotic microangiopathy consisting of hemolytic anemia, thrombocytopenia, and renal injury. The complement inhibitor eculizumab is an approved treatment, but its reported use in neonates - who have an inherently high risk of infection - is limited. CASE DIAGNOSIS/TREATMENT: A 28-day-old female presented with gross hematuria and hypertension. aHUS was suspected based on anemia with schistocytes, thrombocytopenia, low C3, and acute kidney injury requiring peritoneal dialysis. A septic work-up initiated on day 2 for hypothermia and respiratory failure was negative. There was no improvement after 6 days of plasma therapy. Despite being < 6 weeks old she was vaccinated with pneumococcal-13 conjugate, meningococcal (groups C and Y) polysaccharide, and Haemophilus b tetanus toxoid conjugate vaccines and started on penicillin prophylaxis. After 1 dose of eculizumab 300 mg, dialysis was discontinued and her hematological parameters improved. Genetic testing revealed a complement factor H mutation. After 11 months of follow-up, she remains on eculizumab and penicillin without recurrence of aHUS or any infectious complications. CONCLUSIONS: Eculizumab is a safe and effective treatment option for aHUS even in neonates at high risk for infection.

Fertility preservation in paediatric nephrology: results of a physician survey.

OBJECTIVE: Fertility preservation (FP) is a widespread practice in paediatric oncology when gonadotoxic medications such as cyclophosphamide (CPO) are used. FP practice outside of oncology has not been studied, although nephrologists regularly use CPO. This is the first study to explore FP practice by paediatric nephrologists when CPO is used. DESIGN: Survey study. Descriptive statistics and chi-squared analyses were employed to analyse the data. PARTICIPANTS: US paediatric nephrologists were sent a survey via email. The survey queried participants about FP practice behaviours, FP attitudes and barriers to practice. MAIN OUTCOME MEASURES: Of 579 nephrologists invited, 32% responded to the survey. RESULTS: CPO was dosed in mg/kg by 23% of physicians, g/m(2) by 40% and both by 37%. About 80% agreed that pubertal females should be offered a fertility referral, while 58% report that they actually refer. Factors negatively associated with referral include lack of training, lack of referral network and adherence to gonadotoxic dose limits. Results were similar for male patients. CONCLUSION: The survey showed that FP practice in the United States is widespread among nephrologists. Lack of referral networks is a notable barrier for nephrologists. Perceived adherence to dose limits may be problematic given the variable dosing regimens utilised. This is due to the risk of unintended overdose in large adolescents dosed in mg/kg whose cumulative dose exceeds gonadotoxic limits in g/m(2) . This paper has implications for nephrology care providers and other specialists who utilise CPO, generalists who care for these patients and oncologists with extant FP referral networks.

Streptococcal infection as possible trigger for dense deposit disease (C3 glomerulopathy).

UNLABELLED: Dense deposit disease (DDD, formerly known as membranoproliferative glomerulonephritis (MPGN) type II) is a subtype of C3 glomerulopathy (C3G). Electron-dense deposits in the glomerular basement membrane characterize this glomerulonephritis. DDD typically presents with a nephritic syndrome that progresses to end-stage renal failure in 50 % of patients despite treatment. The pathogenic basis of DDD is uncontrolled activation of the alternative complement cascade although the potential triggering events that precipitate the development of complement dysregulation are typically unknown. There are isolated reports of an apparent association between streptococcal infection and DDD, as well as with MPGN types I and III. However, this association has not been deemed compelling, perhaps because so few cases have been reported or because of a current lack of evidence for a plausible hypothesis to connect a streptococcal infection with subsequent disease. In this report, we describe two patients with DDD who definitely had an antecedent streptococcal infection with the phenotype of acute post-streptococcal glomerulonephritis and whose initial kidney biopsy findings on light microscopy were indistinguishable from acute post-streptococcal glomerulonephritis. These patients had additional points of interest: recurrence of gross hematuria with recurrent streptococcal infections, slowly progressive course, persistently low serum C3 concentration, positive C3 nephritic factor, and positive risk alleles in the complement factor H (CFH) gene. CONCLUSION: We suggest that streptococcal infection may trigger DDD in individuals genetically predisposed by virtue of a disorder in complement regulation.

Blood pressure variability of two ambulatory blood pressure monitors.

OBJECTIVE: There are no data on the evaluation of blood pressure (BP) variability comparing two ambulatory blood pressure monitoring monitors worn at the same time. Hence, this study was carried out to compare variability of BP in healthy untreated adults using two ambulatory BP monitors worn at the same time over an 8-h period. METHODS: An Accutorr device was used to measure office BP in the dominant and nondominant arms of 24 participants.Simultaneous 8-h BP and heart rate data were measured in 24 untreated adult volunteers by Mobil-O-Graph (worn for an additional 16 h after removing the Spacelabs monitor) and Spacelabs with both random (N=12) and nonrandom (N=12) assignment of each device to the dominant arm. Average real variability (ARV), SD, coefficient of variation, and variation independent of mean were calculated for systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure (PP). RESULTS: Whether the Mobil-O-Graph was applied to the dominant or the nondominant arm, the ARV of mean systolic (P=0.003 nonrandomized; P=0.010 randomized) and PP (P=0.009 nonrandomized; P=0.005 randomized) remained significantly higher than the Spacelabs device, whereas the ARV of the mean arterial pressure was not significantly different. The average BP readings and ARVs for systolic blood pressure and PP obtained by the Mobil-O-Graph were considerably higher for the daytime than the night-time. CONCLUSION: Given the emerging interest in the effect of BP variability on health outcomes, the accuracy of its measurement is important. Our study raises concerns about the accuracy of pooling international ambulatory blood pressure monitoring variability data using different devices.

Arterial Stiffness in Children: Pediatric Measurement and Considerations.

BACKGROUND: Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. METHODS: There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for pediatric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). CONCLUSIONS: The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure.

A comparison of two ambulatory blood pressure monitors worn at the same time.

There are limited data in the literature comparing two simultaneously worn ambulatory blood pressure (BP) monitoring (ABPM) devices. The authors compared BPs from two monitors (Mobil-O-Graph [I.E.M., Stolberg, Germany] and Spacelabs 90207 [Spacelabs Medical, Issequah, WA]). In the nonrandomized component of the study, simultaneous 8-hour BP and heart rate data were measured by Mobil-O-Graph, consistently applied to the nondominant arm, and Spacelabs to the dominant arm on 12 untreated adults. Simultaneous 8-hour BP and heart data were obtained by the same monitors randomly assigned to a dominant or nondominant arm on 12 other untreated adults. Oscillometric BP profiles were obtained in the dominant and nondominant arms of the above 24 patients using an Accutorr (Datascope, Mahwah, NJ) device. The Spacelabs monitor recorded a 10.2-mm Hg higher systolic pressure in the nonrandomized (P=.0016) and a 7.9-mm Hg higher systolic pressure in the randomized studies (P=.00008) compared with the Mobil-O-Graph. The mean arterial pressures were 1 mm Hg to 2 mm Hg different between monitors in the two studies, and heart rates were nearly identical. Our observations, if confirmed in larger cohorts, support the concern that ABPM device manufacturers consider developing normative databases for their devices.

Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary study program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy for detailed clinical, histopathological, and molecular phenotyping at the time of clinically indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and biannually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histological data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for nephrotic syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in childhood.

BACKGROUND: We identified a mitochondrial tRNA mutation (m.586 G > A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance due to the absence of consistent reports of linkage to specific disease phenotypes and any data pertaining to its effects on mitochondrial function. CASE-DIAGNOSIS/TREATMENT: A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency, and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with the need for peritoneal dialysis. Evaluation of her muscle and blood led to the identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G > A. CONCLUSIONS: The m.586 G > A mutation is pathogenic and a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNA(Phe) and affects the translation of mitochondrial proteins and the stability of the electron transport chain.

Endothelin antagonists in hypertension and kidney disease.

The endothelin (ET) system seems to play a pivotal role in hypertension and in proteinuric kidney disease, including the micro- and macro-vascular complications of diabetes. Endothelin-1 (ET-1) is a multifunctional peptide that primarily acts as a potent vasoconstrictor with direct effects on systemic vasculature and the kidney. ET-1 and ET receptors are expressed in the vascular smooth muscle cells, endothelial cells, fibroblasts and macrophages in systemic vasculature and arterioles of the kidney, and are associated with collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis. Experimental evidence and recent clinical studies suggest that endothelin receptor blockade, in particular selective ETAR blockade, holds promise in the treatment of hypertension, proteinuria, and diabetes. Concomitant blockade of the ETB receptor is not usually beneficial and may lead to vasoconstriction and salt and water retention. The side-effect profile of ET receptor antagonists and relatively poor antagonist selectivity for ETA receptor are limitations that need to be addressed. This review will discuss what is currently known about the endothelin system, the role of ET-1 in the pathogenesis of hypertension and kidney disease, and summarize literature on the therapeutic potential of endothelin system antagonism.

Living donor kidney donation: another form of white coat effect.

BACKGROUND/AIMS: Living donor nephrectomy can be associated with increases in blood pressure several years following the procedure, but the best method to assess blood pressure during the living donor evaluation process is unclear. METHODS: Living kidney donors underwent casual clinic and ambulatory blood pressure monitoring (ABPM) and measurement of central aortic pressures at baseline and 6 months following donor nephrectomy. RESULTS: There was a significant decline in clinic systolic blood pressure (SBP; p = 0.001) and central aortic systolic pressure (p = 0.011) during the study period. However, average ABPM was unchanged and other measures of central arterial pressures and Augmentation Index were unchanged at 6 months compared to baseline. CONCLUSIONS: The remarkable differences between clinic SBP and ambulatory SBP prior to donation, and the disappearance of these differences 6 months later, suggest a substantial white coat effect on SBP associated with living kidney donor evaluation. Also, ABPM represents a better way to assess blood pressure prior to kidney donation.

The efficacy and safety of valsartan in obese and non-obese pediatric hypertensive patients.

This post hoc analysis assessed the efficacy and tolerability of valsartan for the treatment of hypertension in obese vs non-obese children and adolescents. After a 1-week antihypertensive washout period, 142 obese and 119 non-obese hypertensive children and adolescents aged 6 to 16 years were randomized to 2 weeks of once-daily treatment with valsartan 10 to 20 mg, 40 to 80 mg, or 80 to 160 mg, followed by re-randomization to either valsartan or placebo for an additional 2 weeks. Patients could continue to receive valsartan during an optional 52-week, open-label extension. Valsartan resulted in statistically significant (P<.05) and clinically relevant reductions in mean sitting blood pressure (BP), ranging from approximately 7/4 mm Hg (valsartan 10-20 mg) to 13/9 mm Hg (valsartan 80-160 mg) in both obese and non-obese patients. BP control was achieved in 44% of obese and 56% of non-obese patients. Following re-randomization, non-obese patients experienced an increase in BP during placebo treatment, albeit levels remained below baseline, whereas BP reductions were maintained in valsartan recipients (P<.05). The most frequent adverse events during the open-label phase were headache and fever. Valsartan provides similar antihypertensive efficacy in obese and non-obese hypertensive children and adolescents, with good tolerability in both patient populations.

Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension.

The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight-stratified low- (10/20 mg), medium- (40/80 mg), or high-dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2-week placebo-controlled withdrawal phase. Dose-dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, -7.9/-4.6 mm Hg; medium dose, -9.6/-5.8 mm Hg; high dose, -11.5/-7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, -2.7 mm Hg [P=.0368]; SDBP, -3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases.

Valsartan use in pediatric hypertension.

Hypertension affects up to 5% of school-aged children and is defined by an average systolic or diastolic blood pressure greater than the 95th percentile for age, sex and height. In prepubertal children a secondary cause for hypertension including renal disease, coarctation of the aorta or endocrine disease should be excluded by appropriate evaluation. The incidence and prevalence of essential hypertension in adolescents has increased together with the increase in obesity and now accounts for at least 50% of hypertension in this age group. Many children with primary hypertension and most children with secondary causes for hypertension require drug therapy. There are numerous drug classes that are presently used to treat hypertensive pediatric patients, which include ß-blockers, peripheral α-blockers, direct vasodilators, ACE inhibitors, calcium channel blockers, diuretics and ARBs. This article will review the pharmacology of the ARB valsartan with respect to its efficacy, tolerability and safe use in hypertensive pediatric patients.

Solid-organ transplantation in childhood: transitioning to adult health care.

Pediatric solid-organ transplantation is an increasingly successful treatment for solid-organ failure. With dramatic improvements in patient survival rates over the last several decades, there has been a corresponding emergence of complications attributable to pretransplant factors, transplantation itself, and the management of transplantation with effective immunosuppression. The predominant solid-organ transplantation sequelae are medical and psychosocial. These sequelae have a substantial effect on transition to adult care; as such, hurdles to successful transition of care arise from the patients, their families, and pediatric and adult health care providers. Crucial to successful transitioning is the ongoing development of a sense of autonomy and responsibility for one's own care. In this article we address the barriers to transitioning that occur with long-term survival in pediatric solid-organ transplantation. Although a particular transitioning model is not promoted, practical tools and strategies that contribute to successful transitioning of pediatric patients who have received a transplant are suggested.