Acute kidney injury surveillance in the high-risk neonatal population following implementation of creatinine screening protocol.

AIM: Acute kidney injury (AKI) in neonates is associated with longer hospital stays and higher mortality rates. However, there is significant variability in prevalence rates of AKI and the true burden is incompletely understood. In November 2020, the University of Iowa Stead Family Children's Hospital Neonatal Intensive Care Unit implemented a creatinine screening protocol to enhance kidney function monitoring. We sought to evaluate adherence to the protocol to determine if increased surveillance led to increased detection of AKI events. METHODS: A retrospective chart review was conducted for neonates born at <30 weeks' gestation admitted between 2015 and 2020. We reviewed 100 charts in both the pre (2015-2016) and post (2020-2021) implementation era of the AKI surveillance protocol. AKI was defined according to neonatal modified KDIGO criteria. RESULTS: Following implementation of the protocol, neonates were significantly more likely to have creatinine checked (p < 0.001). Serum creatinine was drawn according to protocol guidelines 68% of the time, and 42% of patients (34/82) had an 80% or higher adherence to the protocol. There was a significant increase in detection of AKI in the post-protocol cohort (13/82, incidence of 16%) compared to the pre-protocol cohort (5/83, incidence of 6%), (p = 0.047). CONCLUSION: The implementation of a serum creatinine screening protocol increased the frequency of creatinine draws and detection of AKI.

Fluid and electrolyte management in the neonate and what can go wrong.

PURPOSE OF REVIEW: This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload and acute kidney injury contributing to poor clinical outcomes. Particular attention is given towards the care of extremely preterm infants. RECENT FINDINGS: Emerging data demonstrate (i) disproportionally large transepidermal water loss in the extremely preterm population, (ii) the relationship between postnatal weight loss (negative fluid balance) and improved outcomes, (iii) the frequency and negative effects of dysnatremias early in life, (iv) the role of sodium homeostasis in optimizing postnatal growth, and (v) the deleterious effects of fluid overload and acute kidney injury. SUMMARY: As clinicians care for an increasing number of preterm infants, understanding progress in approaches to fluid and electrolyte management and avoidance of fluid overload states will improve the care and outcomes of this vulnerable population. Further translational and clinical studies are needed to address remaining knowledge gaps and improve current approaches to fluid and electrolyte management.

Gestational age-specific clinical correlates of acute kidney injury in preterm infants with necrotizing enterocolitis.

BACKGROUND: To study the gestational age-specific risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis (NEC). METHODS: Retrospective cohort study comparing gestational age (GA)-specific clinical data between infants without severe AKI (stage 0/1 AKI) and those with severe AKI (stages 2 and 3 AKI) stratified by GA ≤27 and >27 weeks. RESULTS: Infants with GA ≤27 weeks had double the rate of severe AKI (46.3% vs. 20%). In infants with GA >27 weeks, male sex, outborn, and nephrotoxic medication exposure were associated with severe AKI. On multivariable logistic regression, in infants with GA ≤27 weeks, surgical NEC (OR 35.08 (CI 5.05, 243.73), p < 0.001) and ostomy (OR 6.2(CI 1.29, 29.73), p = 0.027) were associated with significantly higher odds of severe AKI. Surgical NEC infants with GA >27 weeks and severe AKI were significantly more likely to be outborn, have later NEC onset, need dopamine, and have longer hospitalization (158 days [110; 220] vs.75.5 days [38.8; 105]; p = 0.007 than those with non-severe AKI. CONCLUSION: In neonates with NEC, surgical intervention was associated with moderate-to-severe AKI in infants with GA ≤27 weeks and with longer hospitalization in infants with GA >27 weeks. IMPACT: In both cohorts need for surgery, stoma, cholestasis, and mechanical ventilation were associated with severe AKI; however, the infants with GA <27 weeks had twice the risk of severe AKI than GA >27 weeks group. The longer exposure to nephrotoxic medication and referral need were significant risk factors for AKI in GA >27 weeks group. GA-specific kidney protective and monitoring strategies to prevent AKI and its consequences are needed to improve the clinical outcomes in neonates with NEC. Understanding the risk factors and short- and long-term outcomes unique to different GA groups will help inform those strategies.

Kidney support for babies: building a comprehensive and integrated neonatal kidney support therapy program.

Kidney support therapy (KST), previously referred to as Renal Replacement Therapy, is utilized to treat children and adults with severe acute kidney injury (AKI), fluid overload, inborn errors of metabolism, and kidney failure. Several forms of KST are available including peritoneal dialysis (PD), intermittent hemodialysis (iHD), and continuous kidney support therapy (CKST). Traditionally, extracorporeal KST (CKST and iHD) in neonates has had unique challenges related to small patient size, lack of neonatal-specific devices, and risk of hemodynamic instability due to large extracorporeal circuit volume relative to patient total blood volume. Thus, PD has been the most commonly used modality in infants, followed by CKST and iHD. In recent years, CKST machines designed for small children and novel filters with smaller extracorporeal circuit volumes have emerged and are being used in many centers to provide neonatal KST for toxin removal and to achieve fluid and electrolyte homeostasis, increasing the options available for this unique and vulnerable group. These new treatment options create a dramatic paradigm shift with recalibration of the benefit: risk equation. Renewed focus on the infrastructure required to deliver neonatal KST safely and effectively is essential, especially in programs/units that do not traditionally provide KST to neonates. Building and implementing a neonatal KST program requires an expert multidisciplinary team with strong institutional support. In this review, we first describe the available neonatal KST modalities including newer neonatal and infant-specific platforms. Then, we describe the steps needed to develop and sustain a neonatal KST team, including recommendations for provider and nursing staff training. Finally, we describe how quality improvement initiatives can be integrated into programs.

Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

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..

Fluid Balance Management Informs Renal Replacement Therapy Use During Pediatric Extracorporeal Membrane Oxygenation: A Survey Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Group.

Fluid overload (FO) and acute kidney injury (AKI) occur commonly in children supported with extracorporeal membrane oxygenation (ECMO). Continuous renal replacement therapy (CRRT) may be used to manage AKI and FO in children on ECMO. In 2012, our group surveyed ECMO centers to begin to understand the practice patterns around CRRT and ECMO. Since then, more centers are initiating ECMO for increasingly diverse indications and an increased volume of research quantifies the detrimental impacts of AKI and FO. We, therefore, investigated practice patterns of CRRT utilization during ECMO in children. A multi-point survey instrument was distributed to 116 international neonatal and pediatric ECMO centers. Sixty of 116 (51.7%) international neonatal and pediatric ECMO centers responded. All reports using CRRT on ECMO, compared with 75% from the 2012 survey. Eighty-five percent use CRRT to treat or prevent FO, an increased from 59%. The modality of CRRT therapy differed between in-line (slow continuous ultrafiltration, 84.4%) and machine-based (continuous venovenous hemodiafiltration, 87.3%) methods. Most (65%) do not have protocols for fluid management, AKI, or CRRT on ECMO. Trialing off CRRT is dictated by physician preference in 90% (54/60), with varying definitions of success. In this survey study, we found that CRRT use during pediatric ECMO has increased since 2012 with fluid management representing the predominant indication for initiation. Despite the expanded utilization of CRRT with ECMO, there remains significant practice variation in terms of method, modality, indication, the timing of initiation, fluid management, and discontinuation.

Acute Kidney Injury and Fluid Overload in Pediatric Extracorporeal Cardio-Pulmonary Resuscitation: A Multicenter Retrospective Cohort Study.

Acute kidney injury (AKI) and fluid overload (FO) are common complications of extracorporeal membrane oxygenation (ECMO). The purpose of this study was to characterize AKI and FO in children receiving extracorporeal cardiopulmonary resuscitation (eCPR). We performed a multicenter retrospective study of children who received eCPR. AKI was assessed during ECMO and FO defined as <10% [FO-] vs. ≥10% [FO+] evaluated at ECMO initiation and discontinuation. A composite exposure, defined by a four-group discrete phenotypic classification [FO-/AKI-, FO-/AKI+, FO+/AKI-, FO+/AKI+] was also evaluated. Primary outcome was mortality and hospital length of stay (LOS) among survivors. 131 patients (median age 29 days (IQR:9, 242 days); 51% men and 82% with underlying cardiac disease) were included. 45.8% survived hospital discharge. FO+ at ECMO discontinuation, but not AKI was associated with mortality [aOR=2.3; 95% CI: 1.07-4.91]. LOS for FO+ patients was twice as long as FO- patients, irrespective of AKI status [(FO+/AKI+ (60 days; IQR: 49-83) vs. FO-/AKI+ (30 days, IQR: 19-48 days); P = 0.01]. FO+ at ECMO initiation and discontinuation was associated with an adjusted 66% and 50% longer length of stay respectively. Prospective studies that target timing and strategy of fluid management, including its removal in children receiving ECPR are greatly needed.

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.

Advances in Neonatal Acute Kidney Injury.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.

Safety, Feasibility, and Impact of Enalapril on Cardiorespiratory Physiology and Health in Preterm Infants with Systemic Hypertension and Left Ventricular Diastolic Dysfunction.

Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was started in neonates with systemic hypertension and echocardiography signs of LV diastolic dysfunction. A total of 11 patients were included with birth weight of 785 ± 239 grams and gestational age of 25.3 (24, 26.1) weeks. Blood pressure improvement was noticed within 2 weeks of treatment. Improvement in LV diastolic function indices were observed with a reduction in Isovolumic Relaxation Time (IVRT) from 63.1 ± 7.2 to 50.9 ± 7.4 msec and improvement in the left atrium size indexed to aorta (LA:Ao) from1.73 (1.43, 1.88) to 1.23 (1.07, 1.29). Neonatal systemic hypertension is often underappreciated in ex-preterm infants and may be associated with important maladaptive cardiac changes with long term implications. It is biologically plausible that identifying and treating LV diastolic dysfunction in neonates with systemic hypertension may have a positive modulator effect on cardiovascular health in childhood and beyond.

Fluid Balance in the Critically Ill Child Section: "How Bad Is Fluid in Neonates?"

Fluid overload (FO) in neonates is understudied, and its management requires nuanced care and an understanding of the complexity of neonatal fluid dynamics. Recent studies suggest neonates are susceptible to developing FO, and neonatal fluid balance is impacted by multiple factors including functional renal immaturity in the newborn period, physiologic postnatal diuresis and weight loss, and pathologies that require fluid administration. FO also has a deleterious impact on other organ systems, particularly the lung, and appears to impact survival. However, assessing fluid balance in the postnatal period can be challenging, particularly in extremely low birth weight infants (ELBWs), given the confounding role of maternal serum creatinine (Scr), physiologic weight changes, insensible losses that can be difficult to quantify, and difficulty in obtaining accurate intake and output measurements given mixed diaper output. Although significant FO may be an indication for kidney replacement therapy (KRT) in older children and adults, KRT may not be technically feasible in the smallest infants and much remains to be learned about optimal KRT utilization in neonates. This article, though not a meta-analysis or systematic review, presents a comprehensive review of the current evidence describing the effects of FO on outcomes in neonates and highlights areas where additional research is needed.

Neonatal Acute Kidney Injury: Understanding of the Impact on the Smallest Patients.

The study of neonatal acute kidney injury (AKI) has transitioned from small, single-center studies to the development of a large, multicenter cohort. The scope of research has expanded from assessment of incidence and mortality to analysis of more specific risk factors, novel urinary biomarkers, interplay between AKI and other organ systems, impact of fluid overload, and quality improvement efforts. The intensification has occurred through collaboration between the neonatology and nephrology communities. This review discusses 2 case scenarios to illustrate the clinical presentation of neonatal AKI, important risk factors, and approaches to minimize AKI events and adverse long-term outcomes.

Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

Improving the quality of neonatal acute kidney injury care: neonatal-specific response to the 22nd Acute Disease Quality Initiative (ADQI) conference.

With the adoption of standardized neonatal acute kidney injury (AKI) definitions over the past decade and the concomitant surge in research studies, the epidemiology of and risk factors for neonatal AKI have become much better understood. Thus, there is now a need to focus on strategies designed to improve AKI care processes with the goal of reducing the morbidity and mortality associated with neonatal AKI. The 22nd Acute Dialysis/Disease Quality Improvement (ADQI) report provides a framework for such quality improvement in adults at risk for AKI and its sequelae. While many of the concepts can be translated to neonates, there are a number of specific nuances which differ in neonatal AKI care. A group of experts in pediatric nephrology and neonatology came together to provide neonatal-specific responses to each of the 22nd ADQI consensus statements.

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.