Implementation of a tier system for IVIG indications to address IVIG shortage at a tertiary care pediatric medical center.

BACKGROUND: Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. OBJECTIVE: To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. METHODS: Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. RESULTS: Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. CONCLUSION: Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.

Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium.

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study.

BACKGROUND: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. METHODS: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. RESULTS: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). CONCLUSIONS: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.

Alterations in diastolic function and cardiac geometry in children: a longitudinal study across the spectrum of dialysis and transplant.

BACKGROUND: Children with kidney failure have increased risk for cardiovascular morbidities before and after transplantation. Ejection fraction is often preserved, masking cardiac dysfunction until severe. Data on longitudinal changes in diastolic function and cardiac geometry are limited. METHODS: A prospective study was conducted to investigate longitudinal changes in diastolic function and structure pre- and post-kidney transplant compared with healthy peers. Transplant recipients (n = 41) had echocardiograms pre-transplant, 1, 18, 30, and 42 months post-transplant. The controls (n = 26) underwent one echocardiogram. Diastolic function and cardiac geometry were assessed by E/e' lateral, E/A, interventricular septal end diastole diameter, left ventricular internal end diastole diameter, left ventricular posterior wall end diastole diameter, and left atrial dimension. RESULTS: E/e' of patients remained worse than controls until 30 months post-transplant, and E/A was impaired at all time points compared to the controls. Left ventricular geometry was abnormal in 46% pre-transplant and remained altered in 44.7%, 32.3%, 30.7%, and 27.2% at 1, 18, 30, and 42 months post-transplant. Determinants of diastolic dysfunction included hemodialysis, uncontrolled hypertension, steroid exposure, and metabolic syndrome; abnormal geometry was associated with glomerular diagnosis, dialysis duration, obesity, steroids, and metabolic syndrome. Abnormal diastolic function and structure were associated with left ventricular hypertrophy. CONCLUSION: Diastolic dysfunction and geometry partially improve after transplant but remain abnormal in a subset of patients compared to healthy peers. Traditional indicators of systolic function are preserved. Modifiable risk factors include dialysis modality and duration, uncontrolled hypertension, corticosteroids, obesity, and metabolic syndrome. Attention to diastolic changes provides opportunity for early intervention. A higher resolution version of the Graphical abstract is available as Supplementary information.

Plant-based diets: a fad or the future of medical nutrition therapy for children with chronic kidney disease?

Plant-based diets are growing in popularity worldwide due to the importance of reducing the population's ecological footprint as well as an emerging role in the prevention and treatment of chronic human diseases. In adults, plant-based diets have been shown to be beneficial for preventing and controlling conditions that are common in patients with chronic kidney disease (CKD), such as obesity, hypertension, type 2 diabetes, dyslipidemia, and metabolic acidosis. Emerging evidence suggests that the higher fiber content of plant-based diets may help to modulate production of uremic toxins through beneficial shifts in the gut microbiome. The effects of the plant-based diet on progression of CKD remain controversial, and there are no data to support this in children. However, knowledge that the bioavailability of potassium and phosphorus from plant-based foods is reduced has led to recent changes in international kidney-friendly diet recommendations for children with CKD. The new guidelines advise that high potassium fruits and vegetables should no longer be automatically excluded from the kidney-friendly diet. In fact, a plant-based diet can be safely implemented in children with CKD through building the diet around whole, high fiber foods, avoiding processed foods and using recommended cooking methods to control potassium. The health benefits of the plant-based diet compared to omnivorous diets in children with CKD need investigation.

Social Determinants of Cardiovascular Health in African American Children With CKD: An Analysis of the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: To identify differences in socioeconomic factors (SES) and subclinical cardiovascular disease (CVD) markers by race among Chronic Kidney Disease in Children (CKiD) participants and determine whether differences in CVD markers persist after adjusting for SES. STUDY DESIGN: Analysis of 3,103 visits with repeated measures from 628 children (497 White participants; 131 African American participants) enrolled in the CKiD study. SETTING & PARTICIPANTS: Children with mild-moderate CKD with at least 1 cardiovascular (CV) parameter (ambulatory blood pressure, left ventricular mass index [LVMI], or lipid profile) measured. EXPOSURE: African American race. OUTCOMES: Ambulatory hypertension, LVMI, triglycerides, high-density lipoprotein cholesterol. ANALYTICAL APPROACH: Due to increased CV risks of glomerular disease, the analysis was stratified by CKD cause. Inverse probability weighting was used to adjust for SES (health insurance, household income, maternal education, food insecurity, abnormal birth history). Linear and logistic regression were used to evaluate association of race with CV markers. RESULTS: African American children were disproportionately affected by adverse SES. African Americans with nonglomerular CKD had more instances of ambulatory hypertension and higher LVMI but more favorable lipid profiles. After adjustment for SES, age, and sex, the magnitude of differences in these CV markers was attenuated but remained statistically significant. Only LVMI differed by race in the glomerular CKD group, despite adjustment for SES. LIMITATIONS: Study design limits causal inference. CONCLUSION: African American children with CKD are disproportionately affected by socioeconomic disadvantages compared with White children. The degree to which CV markers differ by race is influenced by disease etiology. African Americans with nonglomerular CKD have increased LVMI, more ambulatory hypertension, and favorable lipid profile, but attenuation in magnitude after adjustment for SES was observed. African Americans with glomerular CKD had increased LVMI, which persisted after SES adjustment. As many social determinants of health were not captured, future research should examine effects of systemic racism on CV health in this population.

Practice patterns and influence of allograft nephrectomy in pediatric kidney re-transplantation: A pediatric nephrology research consortium study.

INTRODUCTION: There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re-listing, donor source at re-transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post-graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re-transplant (18% vs 7%; P = .03) and multiple rejections in first year after re-transplant (7% vs 1%; P = .03). CONCLUSIONS: Practices pertaining to failed renal allografts are inconsistent-40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re-transplant.

Effect of levocarnitine supplementation on myocardial strain in children with acute kidney injury receiving continuous kidney replacement therapy: a pilot study.

BACKGROUND: Carnitine plays a key role in energy production in the myocardium and is efficiently removed by continuous kidney replacement therapy (CKRT). Effects of levocarnitine supplementation on myocardial function in children receiving CKRT have not been investigated. METHODS: This controlled pilot cohort study of 48 children investigated effects of levocarnitine supplementation on myocardial strain in children receiving CKRT for acute kidney injury (AKI). Children (n = 9) with AKI had total (TC) and free plasma carnitine (FC) measurements and echocardiogram for longitudinal and circumferential strain at baseline (prior to CKRT) and follow-up (on CKRT for > 1 week with intravenous levocarnitine supplementation, 20 mg/kg/day). Intervention group was compared with three controls: (1) CKRT controls (n = 10) received CKRT > 1 week (+AKI, no levocarnitine), (2) ICU controls (n = 9) were parenteral nutrition-dependent for > 1 week (no AKI, no levocarnitine), and (3) healthy controls (n = 20). RESULTS: In the Intervention group, TC and FC increased from 36.0 and 18 µmol/L to 93.5 and 74.5 µmol/L after supplementation. TC and FC of unsupplemented CKRT controls declined from 27.2 and 18.6 µmol/L to 12.4 and 6.6 µmol/L, which was lower vs. ICU controls (TC 32.0, FC 26.0 µmol/L), p < 0.05. Longitudinal and circumferential strain of the Intervention group improved from - 18.5% and - 18.3% to - 21.1% and - 27.6% after levocarnitine supplementation; strain of CKRT controls (-14.4%, -20%) remained impaired and was lower vs. Intervention and Healthy Control groups at follow-up, p < 0.05. CONCLUSIONS: Levocarnitine supplementation is associated with repletion of plasma carnitine and improvement in myocardial strain and may benefit pediatric patients undergoing prolonged CKRT.

Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients.

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12-17 years receiving a stable calcineurin inhibitor-based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein-Barr virus were enrolled; all completed the 6-month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [Cmax ] and area under the serum concentration-time curve from time zero extrapolated to infinity [AUC0-INF ] were 20% and 25%, respectively). Mean half-life (T1/2 ) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady-state (Vss ) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.

The prevalence and outcome of children with failure to thrive after pediatric kidney transplantation.

BACKGROUND: Prior to transplantation, effects of advanced CKD contribute to malnutrition and impaired growth. After transplant, children are expected to thrive, however, in a subset of transplant recipients this does not occur. Factors associated with post-transplant FTT are poorly understood. OBJECTIVE: A retrospective cohort study was conducted to determine factors associated with FTT and association of FTT with infections and hospitalizations. METHODS: Records of 119 children transplanted between 2005 and 2016 were reviewed. FTT was defined by ≥2 of the following post-transplant criteria: (a) low BMI or deceleration in BMI z-score, (b) poor growth velocity, and (c) chronic hypoalbuminemia at 1 or 3 years post-transplant. Association of FTT with deceased donor transplant, de novo DSA, intolerance to MMF, anemia, vitamin D deficiency, and CIC was investigated by logistic regression. Poisson regression was used to identify outcomes associated with FTT. RESULTS: Low pre-transplant BMI and post-transplant CIC dependence were independently associated with FTT after transplant. Odds of FTT at 1 year post-transplant decreased by 0.5 for each 1 unit increase in pre-transplant BMI z-score. Requirement for CIC conferred 3.8 and 7.8 higher odds of FTT at 1 and 3 years. Patients with FTT had 2.7 and 2.6 times infections and hospitalizations during the first year, and 4.2 and 4.3 times infections and hospitalizations over 3 years post-transplant. CONCLUSIONS: Children with low BMI prior to transplant and those requiring CIC after transplant are at increased risk for post-transplant FTT. FTT is associated with adverse outcomes, evidenced by increased infections and hospitalizations.

Kidney transplant practice patterns and outcome benchmarks over 30 years: The 2018 report of the NAPRTCS.

The NAPRTCS has collected clinical information on children undergoing renal transplantation since 1987 and now includes information on 12 920 renal transplants in 11 870 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in patient and allograft outcomes after pediatric renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation and also provides historical perspective. This report highlights current practices in an era of major changes in DD kidney allocation and continuing steroid minimization. This report presents outcomes of the patients in the NAPRTCS transplant registry up to end of 2017. In particular, an increase in the cumulative incidence of late first AR has occurred in the most recent cohort, while all prior cohorts had a lower cumulative incidence of late first AR.

Prevalence and outcomes of fragility: a frailty-inflammation phenotype in children with chronic kidney disease.

BACKGROUND: Frailty is a condition of decreased physiologic reserve and increased vulnerability to stressors. Frailty in combination with inflammation has been associated with increased mortality risk in adults with advanced chronic kidney disease (CKD). This study aimed to investigate prevalence and outcomes associated with a frailty-inflammation phenotype, or "fragility," in children with CKD. METHODS: We analyzed 557 children (age 6-19 years, eGFR 30-90 ml/min/1.73 m2) from the Chronic Kidney Disease in Children (CKiD) study. Based on adult models, the CKiD fragility model included four indicators: (1) suboptimal growth/weight gain (BMI < 5th percentile-for-height-age, deceleration ≥ 10 BMI-for-height-age percentiles/1 year, height-for-age percentile < 3rd or deceleration ≥ 10 height percentiles/1 year); (2) low muscle mass (mid-upper-arm circumference < 5th percentile or deceleration ≥ 10 percentiles/1 year); (3) fatigue (parent/child report); (4) inflammation (CRP > 3 mg/l). Logistic regression was used to evaluate association of fragility indicators with three adverse outcomes: frequent infection (> 1 per year/3 years), hospitalization (any), and rapid CKD progression (decline in eGFR > 30% or initiation of renal replacement therapy within 3 years). RESULTS: Prevalence of fragility indicators 1 year after study entry were 39% (suboptimal growth/weight gain), 62% (low muscle mass), 29% (fatigue), and 18% (inflammation). Prevalence of adverse outcomes during the subsequent 3 years were 13% (frequent infection), 22% (hospitalization), and 17% (rapid CKD progression). Children with ≥ 3 fragility indicators had 3.16-fold odds of frequent infection and 2.81-fold odds of hospitalization, but did not have rapid CKD progression. CONCLUSIONS: A fragility phenotype, characterized by the presence of ≥ 3 indicators, is associated with adverse outcomes, including infection and hospitalization in children with CKD.

Results of early treatment for de novo donor-specific antibodies in pediatric kidney transplant recipients in a cross-sectional and longitudinal cohort.

The development of dnDSA anti-HLA antibodies has been shown to be a significant risk factor for graft failure. In 2008, we instituted a routine protocol of standardized monitoring and treatment of dnDSA in pediatric kidney transplant recipients. Of 67 first-time pediatric kidney transplant recipients, 26 (38%) developed dnDSA after 1.36 (IQ 1-2.14) years. Coefficient of variance of tacrolimus, a surrogate marker of non-adherence, was found to be the single most important risk factor for dnDSA development. Overall, there was a significant reduction in dnDSA with treatment in 19 (76%) children. No difference in graft survival and estimated glomerular filtration rate was noted between dnDSA negative and those treated for dnDSA. There was an increased risk of hospitalization in those treated for dnDSA. This study suggests that early detection and treatment of dnDSA can help to prevent graft failure and preserve graft function in the short term. Future studies and longer follow-up are needed to fully elucidate the effect of early detection and treatment of dnDSA in pediatric kidney transplant recipients.

Comparison of BMI, waist circumference, and waist-to-height ratio for identification of subclinical cardiovascular risk in pediatric kidney transplant recipients.

BACKGROUND: Kidney transplant recipients are at high risk for CV morbidity. However, the measure of obesity that best predicts CV risk has not been established. OBJECTIVE: A prospective, controlled study was conducted to compare the ability of BMI, WC, and WHr to identify CV risk in pediatric kidney transplant recipients. METHODS: Transplant recipients, aged 3-20 years, had echocardiogram, CIMT, BMI, WC, WHr, blood pressure, lipids, and leptin measured. Receiver operating characteristic analysis was used to compare the ability of BMI, WC, and WHr to detect a composite adverse CV outcome. Presence of the composite outcome was defined by ≥3 of the following five criteria: (a) LVH, (b) high CIMT, (c) impaired myocardial strain, (d) dyslipidemia, and/or (e) hypertension. Multivariate analysis was conducted by generalized estimating equation regression. RESULTS: We analyzed 108 visits of 42 transplant recipients. Prevalence of obesity by WHr (43.5%) was higher than BMI (24.1%) and WC (12.0%). Proportion of WHr-obese who met criteria for the adverse CV outcome was higher (62.2%) than BMI (34.6%) and WC-obese (33.3%). Leptin levels were higher in children with obesity. Area under the ROC curve for WHr-obese (0.77) was higher compared to BMI (0.47) and WC (0.48) to detect the CV outcome, P = 0.0006. WHr-obesity was associated with 5.72 increased odds of having the adverse CV outcome, P = 0.0001, while BMI and WC were not significant. CONCLUSION: WHr is more sensitive than BMI or WC to detect subclinical CV risk and should be included in screening of pediatric kidney transplant recipients.

Increased carotid intima-media thickness in African American pediatric kidney transplant recipients.

Early signs of subclinical CV dysfunction can be detected by ultrasound for CIMT. Although A-A are at high risk for CV disease, CIMT of A-A kidney transplant recipients has not been previously investigated. The aim of this prospective, controlled, longitudinal study was to investigate determinants of CIMT in a multiracial pediatric kidney transplant population, with a focus on A-A. Transplant recipients (n = 42) had BMI, waist-to-height ratio, fasting glucose, lipid panel, HbA1c%, and CIMT measured at 1, 18, and 30 months post-transplant. Twenty-four healthy children (14 A-A) served as controls. CIMT of A-A transplant (0.49, 0.49, and 0.48 mm) was higher than non-AA transplant (0.43, 0.44, and 0.44 mm) at 1, 18, and 30 months and higher than A-A controls (0.47 mm). Hyperparathyroidism prior to transplant predicted high CIMT-for-race. A-A race was associated with 10% higher CIMT vs non-A-A transplant. Metabolic syndrome was associated with 0.03 ± 0.01 mm increase in CIMT among A-A transplant recipients only. In conclusion, A-A kidney transplant recipients have increased CIMT. Metabolic syndrome disproportionately affects CIMT of A-A children post-transplant. Identification of subclinical CV damage, detected by CIMT, may provide an opportunity for early detection of CV risk in this vulnerable population.

Correction to: Effects of obesity and metabolic syndrome on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study.

As originally published, this article contained errors owing to oversights in typesetting. The article has now been amended accordingly.

Effects of obesity and metabolic syndrome on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study.

BACKGROUND: Obesity and metabolic syndrome (MS) are common after kidney transplantation, but their contribution to adverse cardiovascular (CV) outcomes in children are not well known. A prospective, controlled, longitudinal cohort study was conducted to investigate the effects of obesity and MS on left ventricular hypertrophy (LVH) and myocardial strain in pediatric kidney transplant recipients. METHODS: Transplant recipients (n = 42) had anthropometrics [body mass index (BMI), waist circumference, waist-to-height ratio], biochemical parameters (fasting glucose, lipid panel, HbA1c%), and echocardiogram with speckle tracking analysis for strain measured at 1, 18, and 30 months post-transplant. Additionally, 35 pre-transplant echocardiograms were analyzed retrospectively. Healthy children (n = 24) served as controls. RESULTS: Waist-to-height ratio detected abdominal obesity in 46% of transplant patients, whereas only 8.1% were identified as obese by waist circumference. Ejection fraction and fractional shortening of the transplant group were normal. Prevalence of LVH was 35.2%, 17.1%, and 35.5% at 1, 18, and 30 months respectively. The longitudinal strain of transplant group was worse than controls at all time points (p < 0.001). Hemodialysis was independently associated with 21% worse longitudinal strain during the pre-transplant period (p = 0.04). After transplantation, obesity, MS, and systolic hypertension predicted increased odds of LVH (p < 0.04). Worse longitudinal strain was independently associated with obesity, MS, hypertension, and the combination of MS with elevated low density lipoprotein (LDL) cholesterol (p < 0.04), whereas higher estimated glomerular filtration rate (eGFR) conferred a protective effect (p < 0.001). CONCLUSION: Obesity and MS adversely affect CV outcomes after transplantation. Further studies are needed to investigate speckle tracking echocardiography as a tool for early detection of subclinical myocardial dysfunction in this population.

Waist-to-height ratio, body mass index, and cardiovascular risk profile in children with chronic kidney disease.

BACKGROUND: Cardiovascular (CV) risk is high in children with chronic kidney disease (CKD), and further compounded in those who are overweight. Children with CKD have a unique body habitus not accurately assessed by body mass index (BMI). Waist-to-height ratio (WHr), a better predictor of CV risk in populations with short stature, has not been investigated in children with CKD. METHODS: Analysis of 1723 visits of 593 participants enrolled in the Chronic Kidney Disease in Children (CKiD) study was conducted. CKiD participants had BMI and WHr measured and classified as follows: (1) lean (WHr ≤ 0.49, BMI < 85th percentile); (2) WHr-overweight (WHr > 0.49, BMI < 85th percentile); (3) BMI-overweight (WHr ≤ 0.49, BMI ≥ 85th percentile); or (4) overweight by both BMI and WHr. Left ventricular mass index (LVMI), fasting lipids, fibroblast growth factor 23 (FGF23), blood pressure, and glucose were measured as markers of CV risk. Linear mixed-effects regression was used to evaluate differences in CV markers between overweight and lean groups. RESULTS: Participants were 12.2 years old, 60% male, and 17% African-American. Approximately 15% were overweight by WHr but not by BMI. Overweight status by WHr-only or both WHr and BMI was associated with lower high-density lipoprotein (HDL) and higher LVMI, triglycerides, and non-HDL cholesterol compared to lean. CV markers of participants overweight by BMI-only were similar to those of lean children. CONCLUSIONS: WHr-adiposity is associated with an adverse CV risk profile in children with CKD. A significant proportion of children with central adiposity are missed by BMI. WHr should be utilized as a screening tool for CV risk in this population.