Search

Background: Acute kidney injury (AKI) is common in hospitalized children and increases the risk of chronic kidney disease (CKD) and hypertension, but little is known about the patient level risk factors for pediatric hypertension after AKI. The aims of this study are to evaluate the prevalence and risk factors for new onset hypertension in hospitalized children with AKI and to better understand the role of acute kidney disease (AKD) in the development of hypertension. Methods: This study was an observational cohort of all children ≤ 18 years old admitted to a single tertiary care children's hospital from 2015 to 2019 with a diagnosis of AKI. Hypertension was defined as blood pressure > 95th percentile for sex, age, height, diagnosis of hypertension on the problem list, or prescription of antihypertensive medication for > 90 days after AKI. Results: A total of 410 children were included in the cohort. Of these, 78 (19%) developed hypertension > 90 days after AKI. A multivariable logistic regression model identified AKD, need for kidney replacement therapy, congenital heart disease, and non-kidney solid organ transplantation as risk factors for hypertension after AKI. Conclusions: Incident hypertension after 3 months is common among hospitalized children with AKI, and AKD, need for dialysis, congenital heart disease, and non-kidney solid organ transplant are significant risk factors for hypertension after AKI. Monitoring for hypertension development in these high-risk children is critical to mitigate long-term adverse kidney and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Cardiac surgery‐associated acute kidney injury (CS‐AKI) occurs in approximately 65% of neonates undergoing cardiac surgery on cardiopulmonary bypass and contributes to morbidity and mortality. Caffeine may reduce CS‐AKI by counteracting adenosine receptor upregulation after bypass, but pharmacokinetics (PK) in this population are unknown. The goal of our analysis is to address knowledge gaps in age‐, disease‐, and bypass‐related effects on caffeine disposition and explore preliminary associations between caffeine exposure and CS‐AKI using population PK modeling techniques and an opportunistic, electronic health record‐integrated trial design. We prospectively enrolled neonates receiving preoperative caffeine per standard of care and collected PK samples. We retrospectively identified neonates without caffeine exposure undergoing surgery on bypass as a control cohort. We followed US Food and Drug Administration guidance for population PK model development using NONMEM. Effects of clinical covariates on PK parameters were evaluated. We simulated perioperative exposures and used multivariable logistic regression to evaluate the association between caffeine exposure and CS‐AKI. Twenty‐seven neonates were included in model development. A 1‐compartment model with bypass time as a covariate on clearance and volume of distribution best fit the data. Twenty‐three neonates with caffeine exposure and 109 controls were included in the exposure‐response analysis. Over half of neonates developed CS‐AKI. On multivariable analysis, there were no significant differences between CS‐AKI with and without caffeine exposure. Neonates with single‐ventricle heart disease without CS‐AKI had consistently higher simulated caffeine exposures. Our results highlight areas for further study to better understand disease‐ and bypass‐specific effects on drug disposition and identify populations where caffeine may be beneficial. [ABSTRACT FROM AUTHOR]

Background: Renal damage is a progressive complication of sickle cell disease (SCD). Microalbuminuria is common in children with SCD, while a smaller number of children have more severe renal manifestations necessitating kidney biopsy. There is limited information on renal biopsy findings in children with SCD and subsequent management and outcome. Methods: This is a multicenter retrospective analysis of renal biopsy findings and clinical outcomes in children and adolescents with SCD. We included children and adolescents (age ≤ 20 years) with SCD who had a kidney biopsy performed at a pediatric nephrology unit. The clinical indication for biopsy, biopsy findings, subsequent treatments, and outcomes were analyzed. Results: Thirty-six SCD patients (ages 4–19 years) were identified from 14 centers with a median follow-up of 2.6 years (0.4–10.4 years). The indications for biopsy were proteinuria (92%) and elevated creatinine (30%). All biopsies had abnormal findings, including mesangial hypercellularity (75%), focal segmental glomerulosclerosis (30%), membranoproliferative glomerulonephritis (16%), and thrombotic microangiopathy (2%). There was increased use of hydroxyurea, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers following renal biopsy. At last follow-up, 3 patients were deceased, 2 developed insulin-dependent diabetes mellitus, 6 initiated chronic hemodialysis, 1 received a bone marrow transplant, and 1 received a kidney transplant. Conclusions: Renal biopsies, while not commonly performed in children with SCD, were universally abnormal. Outcomes were poor in this cohort of patients despite a variety of post-biopsy interventions. Effective early intervention to prevent chronic kidney disease (CKD) is needed to reduce morbidity and mortality in children with SCD. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome.Methods: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items.Results: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores.Conclusion: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure. [ABSTRACT FROM AUTHOR]

Purpose Controversy exists regarding the use of continuous antibiotic prophylaxis vs observation in the management of children with vesicoureteral reflux. The reported effectiveness of continuous antibiotic prophylaxis in children with reflux varies widely. We determined whether the aggregated evidence supports use of continuous antibiotic prophylaxis in children with vesicoureteral reflux. Materials and Methods We searched the Cochrane Controlled Trials Register, clinicaltrials.gov , MEDLINE ® , EMBASE ® , Google Scholar and recently presented meeting abstracts for reports in any language. Bibliographies of included studies were then hand searched for any missed articles. The study protocol was prospectively registered at PROSPERO (No. CRD42014009639). Reports were assessed and data abstracted in duplicate, with differences resolved by consensus. Risk of bias was assessed using standardized instruments. Results We identified 1,547 studies, of which 8 are included in the meta-analysis. Pooled results demonstrated that continuous antibiotic prophylaxis significantly reduced the risk of recurrent febrile or symptomatic urinary tract infection (pooled OR 0.63, 95% CI 0.42–0.96) but, if urinary tract infection occurred, increased the risk of antibiotic resistant organism (pooled OR 8.75, 95% CI 3.52–21.73). A decrease in new renal scarring was not associated with continuous antibiotic prophylaxis use. Adverse events were similar between the 2 groups. Significant heterogeneity existed between studies (I 2 50%, p = 0.03), specifically between those trials with significant risk of bias (eg unclear protocol descriptions and/or lack of blinding). Conclusions Compared to no treatment, continuous antibiotic prophylaxis significantly reduced the risk of febrile and symptomatic urinary tract infections in children with vesicoureteral reflux, although it increased the risk of infection due to antibiotic resistant bacteria. Continuous antibiotic prophylaxis did not significantly impact the occurrence of new renal scarring or reported adverse events. [ABSTRACT FROM AUTHOR]

Background and objectives: Nephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents. Design: This cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, socialpeer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema. Results: All 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics. Conclusions: Children and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS. [ABSTRACT FROM AUTHOR]