Defining systolic blood pressure normative values in hospitalized pediatric patients: a single center experience.

BACKGROUND: Normative blood pressure (BP) values and definition of hypertension (HTN) in children in outpatient setting cannot be reliably used for inpatient therapy initiation. No normative exists to describe HTN in hospitalized pediatric populations. We aimed to study the prevalence of hypertension and produce normative BP values in hospitalized children. METHODS: Cross sectional observational study of all children hospitalized on acute care floors, ≥2 and <18 years age, at Stanford Children's Hospital, from Jan-01-2014 to Dec-31-2018. Cohort included 7468 hospital encounters with a total of 118,423 automated, oscillometric, BPs measured in the upper extremity during a hospitalization of >24 hours. RESULTS: Overall prevalence of HTN, defined by outpatient guidelines, was 12-48% in boys and 6-39% in girls, stage 1 systolic HTN in 12-38% of boys and 6-31% of girls, stage 2 systolic HTN in 3-10% of boys and 1-8% of girls. Centile curves were derived demonstrating overall higher BP reading for hospitalized patients compared to the outpatient setting. CONCLUSION: Higher blood pressures are anticipated during hospitalization. Thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances. IMPACT: Hospitalized children have higher blood pressures compared to patients in the ambulatory setting, hence outpatient normative blood pressure values cannot be reliably used for inpatient therapy initiation. No normative exists to describe hypertension in hospitalized pediatric populations. The thresholds provided by the centile curves generated in this study may provide the clinician with some guidance on how to manage hospitalized pediatric patients based on clinical circumstances.

COVID-19 in pediatric kidney transplantation: a follow-up report of the Improving Renal Outcomes Collaborative.

BACKGROUND: We report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC). METHODS: Patient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test. RESULTS: From September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age > 12 years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19. CONCLUSIONS: Despite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in < 1% of COVID-19-positive patients and in less than < 0.1% of all transplant patients within the IROC cohort. A higher resolution version of the Graphical abstract is available as Supplementary information.

Complement-Binding Donor-Specific Anti-HLA Antibodies: Biomarker for Immunologic Risk Stratification in Pediatric Kidney Transplantation Recipients.

Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody (DSA) monitoring. Included in the study were children who underwent kidney transplantation between January 1, 2010 and March 1, 2018 at Stanford, with at least 12-months follow-up. A total of 233 patients were included with a mean follow-up time of 45 (range, 9-108) months. Median age at transplant was 12.3 years, 46.8% were female, and 76% had a deceased donor transplant. Fifty-two (22%) formed C1q-binding de novo donor-specific antibodies (C1q-dnDSA). After a standardized augmented immunosuppressive protocol was implemented, C1q-dnDSA disappeared in 31 (58.5%). Graft failure occurred in 16 patients at a median of 54 (range, 5-83) months, of whom 14 formed dnDSA. The 14 patients who lost their graft due to rejection, all had persistent C1q-dnDSA. C1q-binding status improved the individual risk assessment, with persistent; C1q binding yielding the strongest independent association of graft failure (hazard ratio, 45.5; 95% confidence interval, 11.7-177.4). C1q-dnDSA is more useful than standard dnDSA as a noninvasive biomarker for identifying patients at the highest risk of graft failure.

Patterns in Tacrolimus Variability and Association with De Novo Donor-Specific Antibody Formation in Pediatric Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: High tacrolimus intrapatient variability has been associated with inferior graft outcomes in patients with kidney transplants. We studied baseline patterns of tacrolimus intrapatient variability in pediatric patients with kidney transplants and examined these patterns in relation to C1q-binding de novo donor-specific antibodies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All tacrolimus levels in participants who underwent kidney-only transplantation at a single pediatric center from 2004 to 2018 (with at least 12-month follow-up, followed until 2019) were analyzed to determine baseline variability. Intrapatient variability was defined using the coefficient of variation (SD/mean ×100%) of all samples in a 6-month moving window. Routine de novo donor-specific antibody measurements were available for a subgroup of patients transplanted in 2010-2018. Cox proportional hazards models using tacrolimus intrapatient variability as a time-varying variable were used to examine the association between intrapatient variability and graft outcomes. The primary outcome of interest was C1q-binding de novo donor-specific antibody formation. RESULTS: Tacrolimus intrapatient variability developed a steady-state baseline of 30% at 10 months post-transplant in 426 patients with a combined 31,125 tacrolimus levels. Included in the outcomes study were 220 patients, of whom 51 developed C1q-binding de novo donor-specific antibodies. De novo donor-specific antibody formers had higher intrapatient variability, with a median of 38% (interquartile range, 28%-48%) compared with 28% (interquartile range, 20%-38%) for nondonor-specific antibody formers (P<0.001). Patients with high tacrolimus intrapatient variability (coefficient of variation >30%) had higher risk of de novo donor-specific antibody formation (hazard ratio, 5.35; 95% confidence interval, 2.45 to 11.68). Patients in the top quartile of tacrolimus intrapatient variability (coefficient of variation >41%) had the strongest association with C1q-binding de novo donor-specific antibody formation (hazard ratio, 11.81; 95% confidence interval, 4.76 to 29.27). CONCLUSIONS: High tacrolimus intrapatient variability was strongly associated with de novo donor-specific antibody formation.

Update on COVID-19 vaccination in pediatric solid organ transplant recipients.

BACKGROUND: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group. METHODS: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues. RESULTS: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. CONCLUSIONS: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.

Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls.

OBJECTIVES: Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery-related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI. DESIGN: This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure. SETTING: Patients underwent cardiac surgery and postoperative care at Lucile Packard Children's Hospital Stanford. PATIENTS: There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7-3.8 yr) for WS and 1.7 years (IQR, 0.8-3.1 yr) for controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1-16; p = 0.034). Higher RPP at postoperative hours 9-16 was associated with decreased OR of CS-AKI (0.88 [0.8-0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14-1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13-3.17]; p = 0.015). CONCLUSIONS: The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.

Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients.

BACKGROUND: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy. METHODS: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1 year. RESULTS: A total of 166 patients met inclusion criteria. Age of patients was 12 years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5 mg/kg (n = 52) versus the higher cumulative dose of > 3.5 mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12 months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival. CONCLUSIONS: Reduced rATG dosing (≤ 3.5 mg/kg) when compared to higher dosing (> 3.5 mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States.

BACKGROUND AND OBJECTIVES: In December 2014, the Kidney Allocation System (KAS) was implemented to improve equity in access to transplantation, but preliminary studies in children show mixed results. Thus, we aimed to assess how the 2014 KAS policy change affected racial and ethnic disparities in pediatric kidney transplantation access and related outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of children <18 years of age active on the kidney transplant list from 2008 to 2019 using the Scientific Registry of Transplant Recipients. Log-logistic accelerated failure time models were used to determine the time from first activation on the transplant list and the time on dialysis to deceased donor transplant, each with KAS era or race and ethnicity as the exposure of interest. We used logistic regression to assess odds of delayed graft function. Log-rank tests assessed time to graft loss within racial and ethnic groups across KAS eras. RESULTS: All children experienced longer wait times from activation to transplantation post-KAS. In univariable analysis, Black and Hispanic children and other children of color experienced longer times from activation to transplant compared with White children in both eras; this finding was largely attenuated after multivariable analysis (time ratio, 1.16; 95% confidence interval, 1.01 to 1.32; time ratio, 1.13; 95% confidence interval, 1.00 to 1.28; and time ratio, 1.17; 95% confidence interval, 0.96 to 1.41 post-KAS, respectively). Multivariable analysis also showed that racial and ethnic disparities in time from dialysis initiation to transplantation in the pre-KAS era were mitigated in the post-KAS era. There were no disparities in odds of delayed graft function. Black and Hispanic children experienced longer times with a functioning graft in the post-KAS era. CONCLUSIONS: No racial and ethnic disparities from activation to deceased donor transplantation were seen before or after implementation of the KAS in multivariable analysis, whereas time on dialysis to transplantation and odds of short-term graft loss improved in equity after the implementation of the KAS, without compromising disparities in delayed graft function. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_07_CJN06740521.mp3.

COVID-19 vaccination in pediatric solid organ transplant recipients-Current state and future directions.

BACKGROUND: Population-level COVID-19 immunization will play a key role in slowing down the SARS-CoV-2 pandemic on a global scale and protect the most at-risk individuals. Thanks to a formidable universal effort, several SARS-CoV-2 vaccines have been marketed less than a year since the first documented COVID-19 case, with promising safety, efficacy, and immunogenicity results in adults. As children were not included in the initial trials, no vaccine is currently approved for individuals <16 years of age. Similarly, immunosuppressed individuals, such as solid organ transplant recipients, were excluded from initial vaccine trials, limiting the understanding of vaccine immunogenicity and safety in this at-risk population. Thus, data regarding COVID-19 vaccination in pediatric solid organ transplantation recipients are currently lacking. METHODS: Members of the International Pediatric Transplant Association review the current general status of COVID-19 vaccines focusing on pediatric-specific issues. RESULTS: This review provides an overview of COVID-19 vaccines in pediatric SOT recipients and highlights the current paucity of data in both pediatric and transplant settings in terms of safety, immunogenicity, and clinical efficacy. CONCLUSIONS: Vaccine trials including children and transplant recipients are underway and will be necessary to characterize COVID-19 vaccine safety, immunogenicity, and efficacy, which will determine potential future research directions.

SARS-CoV-2 and pediatric solid organ transplantation: Current knowns and unknowns.

The COVID-19 pandemic has proven to be a challenge in regard to the clinical presentation, prevention, diagnosis, and management of SARS-CoV-2 infection among children who are candidates for and recipients of SOT. By providing scenarios and frequently asked questions encountered in routine clinical practice, this document provides expert opinion and summarizes the available data regarding the prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients and highlights ongoing knowledge gaps requiring further study. Currently available data are still lacking in the pediatric SOT population, but data have emerged in both the adult SOT and general pediatric population regarding the approach to COVID-19. The document provides expert opinion regarding prevention, diagnosis, and management of SARS-CoV-2 infection among pediatric SOT candidates and recipients.

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative.

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.

Diarrhea in the pediatric solid organ transplantation recipient: A multidisciplinary approach to diagnosis and management.

Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high-risk population, focusing on timely diagnosis of both infectious and non-infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes.

Management and prevention of varicella and measles infections in pediatric solid organ transplant candidates and recipients: An IPTA survey of current practice.

BACKGROUND: Varicella and measles infections can be life-threatening after solid organ transplantation (SOT) but may be preventable with live-attenuated vaccines (LAV). METHODS: This survey conducted in January 2019 among subscribers of the International Pediatric Transplantation Association listserv aimed to explore the current strategies to prevent and manage both infections in the pediatric SOT population, including recommending LAV after SOT. RESULTS: The answers given by 95 pediatric SOT healthcare workers show that these strategies are not yet optimal and call for further education. In particular, 59% of respondents are unnecessarily waiting for a SOT candidate to be >1 year of age to start administrating LAV before SOT. Interestingly, most respondents are willing to administer LAV after SOT (57%), and a fifth (21%) are already doing so, off-label. The survey queried the precautions taken to improve safety evaluations after LAV, and identified knowledge gaps and practitioners' concerns. CONCLUSION: The results of this survey could be used as a starting point for education and promotion of the safe administration of LAV in carefully selected SOT recipients; in turn, this would increase available data that would contribute to the development of evidence-based guidelines by the transplant societies and ultimately prevent these infections after SOT.

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients. METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions. RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits. CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.

Peak blood pressure and prediction of posterior reversible encephalopathy syndrome in children.

BACKGROUND: Hypertension is a risk factor for posterior reversible encephalopathy syndrome (PRES), but the timing and severity of hypertension relative to PRES are unknown. The objective was to identify a clinically meaningful blood pressure (BP) threshold that predicts PRES development in high-risk children. METHODS: We recorded peak systolic BP, diastolic BP, BP z-scores, and mean arterial pressure over the 14 days preceding clinical concern for PRES in 35 subjects who developed PRES, compared to 14 controls who had normal brain magnetic resonance imaging and similar underlying disease, renal function, and medications. We used multivariable logistic regression models adjusted for fluid overload and obesity to estimate the association of peak BP with PRES. We used receiver operating characteristic curves to determine which peak BP thresholds best predicted PRES and calculated the corresponding sensitivity, specificity, and positive and negative predictive values. RESULTS: Peak systolic BP z-score was most strongly associated with PRES (OR 3.97, 95% CI 1.62-9.74), and peak systolic BP z-score ≥ 3.0 predicted PRES (area under the curve 0.95, 95% CI 0.88-1.0) with 91% sensitivity and 85% specificity, indicating 94% positive predictive value and 79% negative predictive value. CONCLUSIONS: We demonstrated that peak systolic BP z-score ≥ 3.0 in the preceding 14 days predicted PRES development in cases compared with controls in children at high risk. Our study suggests that stage 2 hypertension, corresponding to a z-score ≥ 3.0, could help define hypertensive emergency in high-risk children and indicate when more aggressive treatment is warranted to prevent neurologic injury.

Ureterostomy as an alternative to ileal conduits in pediatric kidney transplantation.

INTRODUCTION: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction. METHODS: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009 to 2017. RESULTS: All patients with ileal conduits developed at least one urinary tract infection (UTI) within 1 year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI. CONCLUSION: In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.

Infections among pediatric transplant candidates: An approach to decision-making.

INTRODUCTION: The presence of infections in the immediate pretransplant period poses challenges in decision-making. Delaying transplantation because of these infections may be required, but is associated with a risk to the potential recipient. The aim of this project was to develop a structured framework based on expert opinion to guide decision-making regarding the safety of transplantation for candidates with infection immediately before transplant, and to show how this framework can be applied to clinical scenarios. METHODS: Categories were created as follows: Category A: no delay; Category B: brief delay (≤1 week); Category C: intermediate delay (>1 week); and Category D: more prolonged or indefinite delay. A survey containing 59 clinical scenarios was sent to members of the IPTA ID CARE committee. Answers were reviewed, and the level of agreement was characterized as follows: Level 1: ≥75% agreement; Level 2:51%-74% agreement; and Level 3: ≤50% agreement. 95% CIs were calculated for the mean overall agreement across 59 scenarios. RESULTS: Among the panel, the agreement level ranged from 33% to 92% with the mean overall agreement across the 59 scenarios being 61%. For 7/59 scenarios, the lower bound of 95% CI was greater than 50%, indicating a difference at the 5% level of significance between the observed proportion and the chance level of 0.5. SUMMARY: The document provides expert opinion regarding the need to delay transplantation in the setting of different infections. The most important points in the decision to proceed to SOT included the urgency of transplantation and the severity of infection.

Evaluation and management of elevated blood pressures in hospitalized children.

Elevated blood pressures (BP) are common among hospitalized children and, if not recognized and treated promptly, can lead to potentially significant consequences. Even though we have normative BP data and well-developed guidelines for the diagnosis and management of hypertension (HTN) in the ambulatory setting, our understanding of elevated BPs and their relationship to HTN in hospitalized children is limited. Several issues have hampered our ability to diagnose and manage HTN in the inpatient setting including the common presence of physiologic conditions, which are associated with transient BP elevations (i.e., pain or anxiety), non-standard approaches to BP measurement, a lack of clarity regarding appropriate diagnostic and therapeutic thresholds, and marginal outcome data. The purpose of this review is to highlight the issues and challenges surrounding BP monitoring, assessment of elevated BPs, and the diagnosis of HTN in hospitalized children. Extrapolating from currently available clinical practice guidelines and utilizing the best data available, we aim to provide guidelines regarding evaluation and treatment of elevated BP in hospitalized children.

DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS.

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300 mg/d) for 8 weeks, followed by open-label sparsentan only. End points at week 8 were reduction from baseline in UP/C (primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C: ≤1.5 g/g and >40% reduction [secondary]). RESULTS: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients did when all doses (45% versus 19%; P=0.006) or the 400 and 800 mg doses (47% versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. CONCLUSIONS: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated.

Superior Hypertension Management in Pediatric Kidney Transplant Patients After Native Nephrectomy.

BACKGROUND: Native nephrectomy in pediatric kidney transplant recipients is performed for multiple indications. Posttransplant hypertension requiring medical management is common, and the effect of native nephrectomy on posttransplant hypertension is poorly studied. Our aim is to evaluate the impact of native nephrectomy on posttransplant hypertension. METHODS: One hundred thirty-six consecutive pediatric kidney transplant recipients from 2007 to 2012 were studied at a single institution and divided into 2 groups: no nephrectomy and native nephrectomy (unilateral and bilateral nephrectomy). Antihypertensive medication use was evaluated before nephrectomy/transplant, at discharge from transplant and at 1, 3, and 5 years posttransplant. RESULTS: In a bivariate analysis, nephrectomy was associated with a significant reduction in the percentage of patients requiring antihypertensive medication at the time of discharge (27.3%) and 1 year posttransplant (10.7%) as compared with patients without nephrectomy (71.7%, and 50%, respectively, P < 0.05). This trend toward reduction in antihypertensive medication in the nephrectomy group as compared with the no nephrectomy group persisted at 3 (18.6% versus 43.2%) and 5 years (19.7% versus 37.5%) posttransplant. Multivariable logistic regression demonstrated that patients without native nephrectomy had higher odds of requiring antihypertensive medication at the time of discharge (3.3) and 1 year (5.2) as compared with patients who underwent native nephrectomy (P = 0.036 and P = 0.013, respectively). CONCLUSIONS: Native nephrectomy reduces the odds of needing antihypertensive medication after transplant. The impact of native nephrectomy is crucial to the comprehensive management of pediatric transplant recipients where medication compliance is challenging and lifelong hypertension is known to negatively impact cardiovascular health.