Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Utilizing electronic medical records alert to improve documentation of neonatal acute kidney injury.

BACKGROUND: Neonatal acute kidney injury (AKI) is a common yet underdiagnosed condition in neonates with significant implications for long-term kidney health. Lack of timely recognition and documentation of AKI contributes to missed opportunities for nephrology consultation and follow-up, potentially leading to adverse outcomes. METHODS: We conducted a quality improvement (QI) project to address this by incorporating an automated real-time electronic medical record (EMR)-AKI alert system in the Neonatal Intensive Care Unit (NICU) at Le Bonheur Children's Hospital. Our primary objective was to improve documentation of neonatal AKI (defined as serum creatinine (SCr) > 1.5 mg/dL) by 25% compared to baseline levels. The secondary goal was to increase nephrology consultations and referrals to the neonatal nephrology clinic. We designed an EMR-AKI alert system to trigger for neonates with SCr > 1.5 mg/dL, automatically adding AKI diagnosis to the problem list. This prompted physicians to consult nephrology, refer neonates to the nephrology clinic, and consider medication adjustments. RESULTS: Our results demonstrated a significant improvement in AKI documentation after implementing the EMR-AKI alert, reaching 100% compared with 7% at baseline (p < 0.001) for neonates with SCr > 1.5 mg/dL. Although the increase in nephrology consultations was not statistically significant (p = 0.5), there was a significant increase in referrals to neonatal nephrology clinics (p = 0.005). CONCLUSIONS: Integration of an EMR alert system with automated documentation offers an efficient and economical solution for improving neonatal AKI diagnosis and documentation. This approach enhances healthcare provider engagement, streamlines workflows, and supports QI. Widespread adoption of similar approaches can lead to improved patient outcomes and documentation accuracy in neonatal AKI care.

Nutrition in Critically Ill Children with AKI on Continuous RRT: Consensus Recommendations.

BACKGROUND: Nutrition plays a vital role in the outcome of critically ill children, particularly those with AKI. Currently, there are no established guidelines for children with AKI treated with continuous RRT (CRRT). A thorough understanding of the metabolic changes and nutritional challenges in AKI and CRRT is required. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with AKI receiving CRRT. METHODS: PubMed, MEDLINE, Cochrane, and Embase databases were searched for articles related to the topic. Expertise of the authors and a consensus of the workgroup were additional sources of data in the article. Available articles on nutrition therapy in pediatric patients receiving CRRT through January 2023. RESULTS: On the basis of the literature review, the current evidence base was examined by a panel of experts in pediatric nephrology and nutrition. The panel used the literature review as well as their expertise to formulate clinical practice points. The modified Delphi method was used to identify and refine clinical practice points. CONCLUSIONS: Forty-four clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with AKI and on CRRT on the basis of the existing literature and expert opinions of a multidisciplinary panel.

Nutrition in critically ill children with acute kidney injury on continuous kidney replacement therapy: a 2023 executive summary.

OBJECTIVES: Nutrition plays a vital role in the outcome of critical illness in children, particularly those with acute kidney injury. Currently, there are no established guidelines for children with acute kidney injury treated with continuous kidney replacement therapy. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with acute kidney injury receiving continuous kidney replacement therapy. METHODS: An electronic search using PubMed and an inclusive academic library search (including MEDLINE, Cochrane, and Embase databases) was conducted to find relevant English-language articles on nutrition therapy for children (<18 y of age) receiving continuous kidney replacement therapy. RESULTS: The existing literature was reviewed by our work group, comprising pediatric nephrologists and experts in nutrition. The modified Delphi method was then used to develop a total of 45 clinical practice points. The best methods for nutritional assessment are discussed. Indirect calorimetry is the most reliable method of predicting resting energy expenditure in children on continuous kidney replacement therapy. Schofield equations can be used when indirect calorimetry is not available. The non-intentional calories contributed by continuous kidney replacement therapy should also be accounted for during caloric dosing. Protein supplementation should be increased to account for the proteins, peptides, and amino acids lost with continuous kidney replacement therapy. CONCLUSIONS: Clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with acute kidney injury and on continuous kidney replacement therapy based on the existing literature and expert opinions of a multidisciplinary panel.

Artificial intelligence in early detection and prediction of pediatric/neonatal acute kidney injury: current status and future directions.

Acute kidney injury (AKI) has a significant impact on the short-term and long-term clinical outcomes of pediatric and neonatal patients, and it is imperative in these populations to mitigate the pathways leading to AKI and be prepared for early diagnosis and treatment intervention of established AKI. Recently, artificial intelligence (AI) has provided more advent predictive models for early detection/prediction of AKI utilizing machine learning (ML). By providing strong detail and evidence from risk scores and electronic alerts, this review outlines a comprehensive and holistic insight into the current state of AI in AKI in pediatric/neonatal patients. In the pediatric population, AI models including XGBoost, logistic regression, support vector machines, decision trees, naïve Bayes, and risk stratification scores (Renal Angina Index (RAI), Nephrotoxic Injury Negated by Just-in-time Action (NINJA)) have shown success in predicting AKI using variables like serum creatinine, urine output, and electronic health record (EHR) alerts. Similarly, in the neonatal population, using the "Baby NINJA" model showed a decrease in nephrotoxic medication exposure by 42%, the rate of AKI by 78%, and the number of days with AKI by 68%. Furthermore, the "STARZ" risk stratification AI model showed a predictive ability of AKI within 7 days of NICU admission of AUC 0.93 and AUC of 0.96 in the validation and derivation cohorts, respectively. Many studies have reported the superiority of using biomarkers to predict AKI in pediatric patients and neonates as well. Future directions include the application of AI along with biomarkers (NGAL, CysC, OPN, IL-18, B2M, etc.) in a Labelbox configuration to create a more robust and accurate model for predicting and detecting pediatric/neonatal AKI.

Maternal Hypertension Disorders and Neonatal Acute Kidney Injury: Results from the AWAKEN Study.

OBJECTIVE: This study aimed to examine the association between maternal hypertension (HTN) exposure and neonatal acute kidney injury (AKI). STUDY DESIGN: Retrospective cohort study of 2,162 neonates admitted to 24 neonatal intensive care units (NICUs). Neonates were classified into the following exposure groups: any maternal HTN, chronic maternal HTN, preeclampsia/eclampsia, both, or neither. Demographics, clinical characteristics, and AKI status were compared using Chi-square and analysis of variance. General estimating logistic regression was used to estimate adjusted odds ratios and included a stratified analysis for site of delivery. RESULT: Neonates exposed to any maternal HTN disorder had a tendency toward less overall and early AKI. When stratified by inborn versus outborn, exposure to both maternal HTN disorders was associated with a significantly reduced odds of early AKI only in the inborn neonates. CONCLUSION: Exposure to maternal HTN, especially preeclampsia/eclampsia superimposed on chronic HTN, was associated with less likelihood of early AKI in the inborn group. KEY POINTS: · Maternal HTN is associated with less neonatal AKI.. · Maternal HTN category is variably associated with AKI.. · Inborn status is an important contributor to this association..

Low albumin levels are independently associated with neonatal acute kidney injury: a report from AWAKEN Study Group.

BACKGROUND: Data from adult and pediatric literature have shown an association between albumin levels and AKI. Whether hypoalbuminemia and neonatal AKI are associated has not been studied. METHODS: We evaluated the association of albumin with early (during the first postnatal week) and late (after the first postnatal week) AKI for 531 neonates from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database and for 3 gestational age (GA) subgroups: < 29, 29 to < 36, and ≥ 36 weeks GA. RESULTS: Low albumin levels were associated with increased odds of neonatal AKI; for every 0.1 g/dL decrease in albumin, the odds of late AKI increased by 12% on continuous analysis. After adjustment for potential confounders, neonates with albumin values in the lowest quartiles (< 2.2 g/dL) had an increased odds of early [Adjusted Odd Ratio (AdjOR) 2.5, 95% CI = 1.1-5.3, p < 0.03] and late AKI [AdjOR 13.4, 95% CI = 3.6-49.9, p < 0.0001] compared to those with albumin in the highest quartile (> 3.1 g/dL). This held true for albumin levels 2.3 to 2.6 g/dL for early [AdjOR 2.5, 95% CI = 1.2-5.5, p < 0.02] and late AKI [AdjOR 6.4, 95% CI = 1.9-21.6, p < 0.01]. Albumin quartiles of (2.7 to 3.0 g/dL) were associated with increased odds of late AKI. Albumin levels of 2.6 g/dL and 2.4 g/dL best predicted early (AUC = 0.59) and late AKI (AUC = 0.64), respectively. Analysis of albumin association with AKI by GA is described. CONCLUSIONS: Low albumin levels are independently associated with early and late neonatal AKI. Albumin could be a potential modifiable risk factor for neonatal AKI.

Pediatric Onco-Nephrology: Time to Spread the Word-Part II: Long-Term Kidney Outcomes in Survivors of Childhood Malignancy and Malignancy after Kidney Transplant.

Onco-nephrology is a recent and evolving medical subspecialty devoted to the care of patients with kidney disease and unique kidney-related complications in the context of cancer and its treatments, recognizing that management of kidney disease as well as the cancer itself will improve survival and quality of life. While this area has received much attention in the adult medicine sphere, similar emphasis in the pediatric realm has not yet been realized. As in adults, kidney involvement in children with cancer extends beyond the time of initial diagnosis and treatment. Many interventions, such as chemotherapy, stem cell transplant, radiation, and nephrectomy, have long-term kidney effects, including the development of chronic kidney disease (CKD) with subsequent need for dialysis and/or kidney transplant. Thus, with the improved survival of children with malignancy comes the need for ongoing monitoring of kidney function and early mitigation of kidney-related comorbidities. In addition, children with kidney transplant are at higher risk of developing malignancies than their age-matched peers. Pediatric nephrologists thus need to be aware of issues related to cancer and its treatments as they impact their own patients. These facts emphasize the necessity of pediatric nephrologists and oncologists working closely together in managing these children and highlight the importance of bringing the onco-nephrology field to our growing list of pediatric nephrology subspecialties.

Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group.

BACKGROUND: Studies in adults showed a relationship between low hemoglobin (Hb) and acute kidney injury (AKI). We performed this study to evaluate this association in newborns. METHODS: We evaluated 1891 newborns from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database. We evaluated the associations for the entire cohort and 3 gestational age (GA) groups: <29, 29-<36, and ≥36 weeks' GA. RESULTS: Minimum Hb in the first postnatal week was significantly lower in neonates with AKI after the first postnatal week (late AKI). After controlling for multiple potential confounders, compared to neonates with a minimum Hb ≥17.0 g/dL, both those with minimum Hb ≤12.6 and 12.7-14.8 g/dL had an adjusted increased odds of late AKI (aOR 3.16, 95% CI 1.44-6.96, p = 0.04) and (aOR 2.03, 95% CI 1.05-3.93; p = 0.04), respectively. This association was no longer evident after controlling for fluid balance. The ability of minimum Hb to predict late AKI was moderate (c-statistic 0.68, 95% CI 0.64-0.72) with a sensitivity of 65.9%, a specificity of 69.7%, and a PPV of 20.8%. CONCLUSIONS: Lower Hb in the first postnatal week was associated with late AKI, though the association no longer remained after fluid balance was included. IMPACT: The current study suggests a possible novel association between low serum hemoglobin (Hb) and neonatal acute kidney injury (AKI). The study shows that low serum Hb levels in the first postnatal week are associated with increased risk of AKI after the first postnatal week. This study is the first to show this relationship in neonates. Because this study is retrospective, our observations cannot be considered proof of a causative role but do raise important questions and deserve further investigation. Whether the correction of low Hb levels might confer short- and/or long-term renal benefits in neonates was beyond the scope of this study.

Pediatric onco-nephrology: time to spread the word : Part I: early kidney involvement in children with malignancy.

Onco-nephrology has been a growing field within the adult nephrology scope of practice. Even though pediatric nephrologists have been increasingly involved in the care of children with different forms of malignancy, there has not been an emphasis on developing special expertise in this area. The fast pace of discovery in this field, including the development of new therapy protocols with their own kidney side effects and the introduction of the CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy, has introduced new challenges for general pediatric nephrologists because of the unique effects of these treatments on the kidney. Moreover, with the improved outcomes in children receiving cancer therapy come an increased number of survivors at risk for chronic kidney disease related to both their cancer diagnosis and therapy. Therefore, it is time for pediatric onco-nephrology to take its spot on the expanding subspecialties map in pediatric nephrology.

The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. OUTCOME: Mechanical ventilation (MV) at postnatal day 7. RESULTS: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35). CONCLUSIONS: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group.

BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates. METHODS: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME: mechanical ventilation (MV) on postnatal day 7. RESULTS: The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7. CONCLUSIONS: We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.

Acute kidney injury in the fetus and neonate.

Acute kidney injury (AKI) is an under-recognized morbidity of neonates; the incidence remains unclear due to the absence of a unified definition of AKI in this population and because previous studies have varied greatly in screening for AKI with serum creatinine and urine output assessments. Premature infants may be born with less than half of the nephrons compared with term neonates, predisposing them to chronic kidney disease (CKD) early on in life and as they age. AKI can also lead to CKD, and premature infants with AKI may be at very high risk for long-term kidney problems. AKI in neonates is often multifactorial and may result from prenatal, perinatal, or postnatal insults as well as any combination thereof. This review focuses on the causes of AKI, the importance of early detection, the management of AKI in neonates, and long-term sequela of AKI in neonates.