Publications by authors named "David T Selewski"

92 Publications

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Pediatrics 2022 01;149(1 Suppl 1):S66-S73

Department of Pediatrics, Divisions of Nephrology and Critical Care Medicine, Baylor College of Medicine, Houston, Texas.

Context: Renal dysfunction is associated with poor outcomes in critically ill children.

Objective: To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children.

Data Sources: PubMed and Embase were searched from January 1992 to January 2020.

Study Selection: Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded.

Data Extraction: Data were extracted from included studies into a standard data extraction form by task force members.

Results: The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction.

Limitations: All included studies were observational and many were retrospective.

Conclusions: We present consensus criteria for renal dysfunction in critically ill children.
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http://dx.doi.org/10.1542/peds.2021-052888JDOI Listing
January 2022

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Pediatrics 2022 Jan;149(Supplement_1):S1-S12

Sections of Critical Care and Nephrology.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.
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http://dx.doi.org/10.1542/peds.2021-052888BDOI Listing
January 2022

Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study.

J Perinatol 2021 Nov 13. Epub 2021 Nov 13.

Division of Nephrology, Department of Pediatrics, The Children's Hospital at Montefiore/Albert Einstein College of Medicine, Bronx, NY, USA.

Objective: To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality.

Study Design: A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models.

Result: Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07-4.31), hypernatremia (HR 4.23, 95% CI 2.07-8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01-14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI.

Conclusion: Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.
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http://dx.doi.org/10.1038/s41372-021-01260-xDOI Listing
November 2021

Racial-ethnic differences in health-related quality of life among adults and children with glomerular disease.

Glomerular Dis 2021 Aug 24;1(3):105-117. Epub 2021 Jun 24.

Department of Renal Medicine, Cork University Hospital and University College Cork, Cork, Ireland.

Introduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships between race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease.

Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: 1. Missed school or work due to kidney disease; 2. Responses to Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression.

Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than White or Asian participants. Black adults missed work or school most frequently due to kidney disease (30% versus 16-23% in the other three groups, p=0.04), and had the worst self-reported global physical health (median score 44.1 versus 48.0-48.2, p<0.001) and fatigue (53.8 versus 48.5-51.1, p=0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status were associated with HRQOL.

Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by Black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.
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http://dx.doi.org/10.1159/000516832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553235PMC
August 2021

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

ASAIO J 2021 Oct 12. Epub 2021 Oct 12.

From the Department of Pediatrics, Children's Hospital of Colorado University of Colorado Anschutz Medical Campus Aurora, Colorado, Department of Pediatrics, University of Cincinnati College of Medicine, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, Department of Pediatrics, University of Alabama Birmingham, Birmingham, Alabama, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA, Department of Pediatrics, Toronto Hospital for Sick Children, Toronto, Canada and McGill University Health Centre, Montreal, Canada, Division of Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa Stead Family Children's Hospital, Iowa City, Iowa and Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA Deceased.

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.
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http://dx.doi.org/10.1097/MAT.0000000000001601DOI Listing
October 2021

Advances in Neonatal Acute Kidney Injury.

Pediatrics 2021 11 1;148(5). Epub 2021 Oct 1.

Division of Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.

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.
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http://dx.doi.org/10.1542/peds.2021-051220DOI Listing
November 2021

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.

ASAIO J 2021 May 10. Epub 2021 May 10.

From the Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan Division of Pediatric Critical Care Medicine, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia Department of Pediatrics, University of Alabama Birmingham, Birmingham, Alabama Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee Department of Pediatrics, University of Cincinnati College of Medicine, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio Department of Pediatrics, Toronto Hospital for Sick Children, Toronto, Canada Department of Pediatrics, Children's Hospital of Colorado University of Colorado Anschutz Medical Campus Aurora, Colorado Division of Nephrology, Dialysis and Transplantation, Stead Family Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, Iowa Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.

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.
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http://dx.doi.org/10.1097/MAT.0000000000001471DOI Listing
May 2021

Liposorber® LA-15 system for LDL apheresis in resistant nephrotic syndrome patients.

Pediatr Nephrol 2021 Aug 28. Epub 2021 Aug 28.

Department of Pediatrics, Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.

Background: Steroid-resistant nephrotic syndrome (SRNS) is a major cause of stage 5 chronic kidney disease (CKD 5) in children. LDL apheresis (LDL-A) is now FDA approved for the treatment of pediatric focal segmental glomerulosclerosis (FSGS). Effective management of hyperlipidemia with LDL-A in SRNS patients may prevent progression of kidney disease and lead to remission. We report a case series of patients who received LDL-A for treatment of SRNS METHODS: We describe five children with SRNS who were treated with 12 sessions of LDL-A. Partial remission (PR) is defined as urine protein to creatinine ratio (UPC) of 0.2-2 (g/g) or decrease in UPC ≥ 50%, and complete remission (CR) is defined as UPC < 0.2 (g/g).

Results: One patient achieved CR and three achieved PR. One patient did not respond to therapy. The earliest that a patient achieved PR was at treatment #10 and some did not respond until after LDL-A was completed. Those who responded stayed in either CR or PR for extended periods of time. LDL-A was successful at significantly reducing LDL (p < 0.001), total cholesterol (p < 0.001), and triglyceride (p < 0.001).

Conclusions: LDL-A was able to significantly decrease the lipid levels in these patients and induce CR and PR in the majority. The current study confirms previous studies showing those with a higher glomerular sclerosis burden were less likely to respond. LDL-A should be considered in patients with treatment-resistant SRNS and should be considered before there is a high burden of glomerular sclerosis to provide the best chance of success.
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http://dx.doi.org/10.1007/s00467-021-05211-8DOI Listing
August 2021

The Challenge of Acute Kidney Injury Diagnostic Precision: From Early Prediction to Long-Term Follow-up.

Kidney Int Rep 2021 Jul 19;6(7):1755-1757. Epub 2021 May 19.

Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.

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http://dx.doi.org/10.1016/j.ekir.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258574PMC
July 2021

Epidemiology of Acute Kidney Injury After Neonatal Cardiac Surgery: A Report From the Multicenter Neonatal and Pediatric Heart and Renal Outcomes Network.

Crit Care Med 2021 10;49(10):e941-e951

Department of Pediatric Cardiology, Section of Cardiac Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL.

Objectives: Cardiac surgery-associated acute kidney injury occurs commonly following congenital heart surgery and is associated with adverse outcomes. This study represents the first multicenter study of neonatal cardiac surgery-associated acute kidney injury. We aimed to describe the epidemiology, including perioperative predictors and associated outcomes of this important complication.

Design: This Neonatal and Pediatric Heart and Renal Outcomes Network study is a multicenter, retrospective cohort study of consecutive neonates less than 30 days. Neonatal modification of The Kidney Disease Improving Global Outcomes criteria was used. Associations between cardiac surgery-associated acute kidney injury stage and outcomes (mortality, length of stay, and duration of mechanical ventilation) were assessed through multivariable regression.

Setting: Twenty-two hospitals participating in Pediatric Cardiac Critical Care Consortium.

Patients: Twenty-two-thousand forty neonates who underwent major cardiac surgery from September 2015 to January 2018.

Interventions: None.

Measurements And Main Results: Cardiac surgery-associated acute kidney injury occurred in 1,207 patients (53.8%); 983 of 1,657 in cardiopulmonary bypass patients (59.3%) and 224 of 583 in noncardiopulmonary bypass patients (38.4%). Seven-hundred two (31.3%) had maximum stage 1, 302 (13.5%) stage 2, 203 (9.1%) stage 3; prevalence of cardiac surgery-associated acute kidney injury peaked on postoperative day 1. Cardiac surgery-associated acute kidney injury rates varied greatly (27-86%) across institutions. Preoperative enteral feeding (odds ratio = 0.68; 0.52-0.9) and open sternum (odds ratio = 0.76; 0.61-0.96) were associated with less cardiac surgery-associated acute kidney injury; cardiopulmonary bypass was associated with increased cardiac surgery-associated acute kidney injury (odds ratio = 1.53; 1.01-2.32). Duration of cardiopulmonary bypass was not associated with cardiac surgery-associated acute kidney injury in the cardiopulmonary bypass cohort. Stage 3 cardiac surgery-associated acute kidney injury was independently associated with hospital mortality (odds ratio = 2.44; 1.3-4.61). No cardiac surgery-associated acute kidney injury stage was associated with duration of mechanical ventilation or length of stay.

Conclusions: Cardiac surgery-associated acute kidney injury occurs frequently after neonatal cardiac surgery in both cardiopulmonary bypass and noncardiopulmonary bypass patients. Rates vary significantly across hospitals. Only stage 3 cardiac surgery-associated acute kidney injury is associated with mortality. Cardiac surgery-associated acute kidney injury was not associated with any other outcomes. Kidney Disease Improving Global Outcomes criteria may not precisely define a clinically meaningful renal injury phenotype in this population.
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http://dx.doi.org/10.1097/CCM.0000000000005165DOI Listing
October 2021

Fluid management, electrolytes imbalance and renal management in neonates with neonatal encephalopathy treated with hypothermia.

Semin Fetal Neonatal Med 2021 Aug 12;26(4):101261. Epub 2021 Jun 12.

Department of Pediatrics, University of Alabama-Birmingham, 1600 7th Ave south, Lowder Bldg 502, AL, 35223, Birmingham, USA. Electronic address:

Kidney dysfunction and acute kidney injury (AKI) frequently accompanies neonatal encephalopathy and contributes to neonatal morbidity and mortality. While there are currently no proven therapies for the treatment of AKI, understanding the pathophysiology along with early recognition and treatment of alterations in fluid, electrolyte and metabolic homeostasis that accompany AKI offer opportunity to reduce associated morbidity. Promising new tests and technologies, including urine and serum biomarkers and renal near-infrared spectroscopy offer opportunities to improve diagnosis and monitoring of neonates at risk for kidney injury. Furthermore, recent advances in neonatal kidney supportive therapies such as hemofiltration and hemodialysis may further improve outcomes in this population. This chapter provides an overview of disorders of fluid balance, electrolyte homeostasis and kidney function associated with neonatal encephalopathy and therapeutic hypothermia. Recommendations for fluid and electrolyte management based upon published literature and authors' opinions are provided.
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http://dx.doi.org/10.1016/j.siny.2021.101261DOI Listing
August 2021

Nutrition Considerations in Neonatal Extracorporeal Life Support.

Neoreviews 2021 06;22(6):e382-e391

Department of Pediatrics, Medical University of South Carolina, Charleston, SC.

Extracorporeal life support (ECLS) is a life-saving therapy, but neonates who require ECLS have unique nutritional needs and require aggressive, early nutritional support. These critically ill neonates are at increased risk for long-term feeding difficulties, malnutrition, and growth failure with associated increased morbidity and mortality. Unfortunately, few studies specific to this population exist. Clinical guidelines published by the American Society for Parenteral and Enteral Nutrition are specific to this population and available to aid clinicians in appropriate nutrition regimens, but studies to date suggest that nutrition provision varies greatly from center to center and often is inadequate. Though enteral feedings are becoming more common, aggressive parenteral nutrition is still needed to ensure nutrition goals are met, including the goal of increased protein provision. Long-term complications, including the need for tube feedings and growth failure, are common in neonatal ECLS survivors, particularly those with congenital diaphragmatic hernia. Oral aversion with poor feeding and growth failure must be anticipated and recognized early if present. The nutritional implications associated with the development of acute kidney injury, fluid overload, or the use of continuous renal replacement therapy must be recognized. In this state-of-the-art review, we examine aspects of nutrition for neonates receiving ECLS including nutritional requirements, nutrition provision, current practices, long-term outcomes, and special population considerations.
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http://dx.doi.org/10.1542/neo.22-6-e382DOI Listing
June 2021

Relationship of patent ductus arteriosus management with neonatal AKI.

J Perinatol 2021 06 19;41(6):1441-1447. Epub 2021 Apr 19.

Golisano Children's Hospital, University of Rochester, Rochester, NY, USA.

Objective: Investigate relationship between management of patent ductus arteriosus (PDA) and acute kidney injury (AKI) in very low birthweight neonates.

Study Design: Retrospective cohort study of neonates, <1500 g, admitted to 24 NICUs, 1/1/14 - 3/31/14. AKI diagnosed using the neonatal modified KDIGO definition; diagnosis and treatment of PDA extracted from the medical record. Demographics, clinical characteristics, and AKI stage compared using chi-square and analysis of variance. A general estimating equation logistic regression used to estimate adjusted odds ratios.

Results: Of 526 neonates with sufficient data to diagnose AKI, 157 (30%) had PDA (61 conservative management, 62 pharmacologic treatment only, 34 surgical ligation). In analyses adjusted for sex, birthweight, gestational age, caffeine, nephrotoxin exposure, vasopressor and mechanical ventilation use, with conservative management as reference, there were no differences among treatment cohorts in the odds of AKI.

Conclusion: The underlying physiology of PDA, not management strategy, may determine the likelihood of AKI in neonates <1500 g.
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http://dx.doi.org/10.1038/s41372-021-01054-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238821PMC
June 2021

Continuous renal replacement therapy in patients treated with extracorporeal membrane oxygenation.

Semin Dial 2021 Nov 25;34(6):537-549. Epub 2021 Mar 25.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy utilized for patients with severe life-threatening cardiorespiratory failure. Patients treated with ECMO are among the most severely ill encountered in critical care and are at high-risk of developing multiple organ dysfunction, including acute kidney injury (AKI) and fluid overload. Continuous renal replacement therapy (CRRT) is increasingly utilized inpatients on ECMO to manage AKI and treat fluid overload. The indications for renal replacement therapy for patients on ECMO are similar to those of other critically ill populations; however, there is wide practice variation in how renal supportive therapies are utilized during ECMO. For patients requiring both CRRT and ECMO, CRRT may be connected directly to the ECMO circuit, or CRRT and ECMO may be performed independently. This review will summarize current knowledge of the epidemiology of AKI, indications and timing of CRRT, delivery of CRRT, and the outcomes of patients requiring CRRT with ECMO.
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http://dx.doi.org/10.1111/sdi.12965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250911PMC
November 2021

Use of the Selective Cytopheretic Device in Critically Ill Children.

Kidney Int Rep 2021 Mar 19;6(3):775-784. Epub 2020 Dec 19.

University of Michigan, Ann Arbor, Michigan, USA.

Introduction: Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa) is maintained at <0.40 mmol/l with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa <0.40 mmol/l had improved survival/dialysis independence. We conducted a US Food and Drug Administration (FDA)-sponsored study to evaluate safety and feasibility of the SCD in 16 critically ill children.

Methods: Four pediatric intensive care units (ICUs) enrolled children with AKI and multiorgan dysfunction receiving CKRT to receive the SCD integrated post-CKRT membrane. RCA was used to achieve a circuit iCa level <0.40 mmol/l. Subjects received SCD treatment for 7 days or CKRT discontinuation, whichever came first.

Results: The FDA target enrollment of 16 subjects completed the study from December 2016 to February 2020. Mean age was 12.3 ± 5.1 years, weight was 53.8 ± 28.9 kg, and median Pediatric Risk of Mortality II was 7 (range 2-19). Circuit iCa levels were maintained at <0.40 mmol/l for 90.2% of the SCD therapy time. Median SCD duration was 6 days. Fifteen subjects survived SCD therapy; 12 survived to ICU discharge. All ICU survivors were dialysis independent at 60 days. No SCD-related adverse events (AEs) were reported.

Conclusion: Our data demonstrate that SCD therapy is feasible and safe in children who require CKRT. Although we cannot make efficacy claims, the 75% survival rate and 100% renal recovery rate observed suggest a possible favorable benefit-to-risk ratio.
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http://dx.doi.org/10.1016/j.ekir.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938071PMC
March 2021

Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge.

Front Pediatr 2020 5;8:619548. Epub 2021 Feb 5.

Division of Pediatric Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.

Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations. After informed consent, parents/guardians of 153 pediatric patients (<18 years old) diagnosed with NS from 2005 to 2018 and 50 pediatric nephrologists from 11 participating centers completed anonymous surveys to evaluate immunization practices among pediatric nephrologists, assess the vaccine education provided to families of children with NS, assess the parental knowledge of immunization recommendations, and assess predictors of polysaccharide pneumococcal vaccine adherence. The Advisory Committee on Immunization Practices (ACIP) Immunization 2019 Guideline for those with altered immunocompetence was used to determine accuracy of vaccine knowledge and practices. Forty-four percent of providers self-reported adherence to the ACIP guidelines for inactive vaccines and 22% to the guidelines for live vaccines. Thirty-two percent of parents/guardians reported knowledge that aligned with the ACIP guidelines for inactive vaccines and 1% for live vaccines. Subjects residing in the Midwest and provider recommendations for vaccines were positive predictors of vaccine adherence ( < 0.001 and 0.02, respectively). Vaccine recommendation by medical providers is paramount in vaccine adherence among pediatric patients with NS. This study identifies potential educational opportunities for medical subspecialty providers and family caregivers about immunization recommendations for immunosuppressed patients.
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http://dx.doi.org/10.3389/fped.2020.619548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901920PMC
February 2021

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

Blood Purif 2021 18;50(6):808-817. Epub 2021 Jan 18.

Pediatrics, University of Alabama Birmingham, Birmingham, Alabama, USA.

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.
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http://dx.doi.org/10.1159/000512538DOI Listing
January 2022

Acute kidney injury after in-hospital cardiac arrest.

Resuscitation 2021 03 12;160:49-58. Epub 2021 Jan 12.

Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, United States.

Aim: Determine 1) frequency and risk factors for acute kidney injury (AKI) after in-hospital cardiac arrest (IHCA) in the Therapeutic Hypothermia after Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) trial and associated outcomes; 2) impact of temperature management on post-IHCA AKI.

Methods: Secondary analysis of THAPCA-IH; a randomized controlled multi-national trial at 37 children's hospitals.

Eligibility: Serum creatinine (Cr) within 24 h of randomization.

Outcomes: Prevalence of severe AKI defined by Stage 2 or 3 Kidney Disease Improving Global Outcomes Cr criteria. 12-month survival with favorable neurobehavioral outcome. Analyses stratified by entire cohort and cardiac subgroup. Risk factors and outcomes compared among cohorts with and without severe AKI.

Results: Subject randomization: 159 to hypothermia, 154 to normothermia. Overall, 80% (249) developed AKI (any stage), and 66% (207) developed severe AKI. Cardiac patients (204, 65%) were more likely to develop severe AKI (72% vs 56%,p = 0.006). Preexisting cardiac or renal conditions, baseline lactate, vasoactive support, and systolic blood pressure were associated with severe AKI. Comparing hypothermia versus normothermia, there were no differences in severe AKI rate (63% vs 70%,p = 0.23), peak Cr, time to peak Cr, or freedom from mortality or severe AKI (p = 0.14). Severe AKI was associated with decreased hospital survival (48% vs 65%,p = 0.006) and decreased 12-month survival with favorable neurobehavioral outcome (30% vs 53%,p < 0.001).

Conclusion: Severe post-IHCA AKI occurred frequently especially in those with preexisting cardiac or renal conditions and peri-arrest hemodynamic instability. Severe AKI was associated with decreased survival with favorable neurobehavioral outcome. Hypothermia did not decrease incidence of severe AKI post-IHCA.
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http://dx.doi.org/10.1016/j.resuscitation.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902429PMC
March 2021

Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study.

Kidney Int Rep 2020 Oct 23;5(10):1679-1689. Epub 2020 Jul 23.

Division of Nephrology, Providence Health Care, University of Washington, Spokane, Washington, USA.

Introduction: Prior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status.

Methods: Cure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status.

Results: A total of 469 children and 1146 adults with PROMIS scores were included in the analysis. HRQOL improved over time in nearly all domains, though group-level changes were modest. Edema was most consistently associated with worse HRQOL across domains among children and adults. A greater number of symptoms also predicted worse HRQOL in all domains. Sex, age, obesity, and serum albumin were associated with some HRQOL domains. The estimated glomerular filtration rate (eGFR) was only associated with fatigue and adult physical health; proteinuria was not associated with any HRQOL domain in adjusted models.

Conclusion: HRQOL measures were responsive to changes in disease activity, as indicated by edema. HRQOL over time was not predicted by laboratory-based markers of disease. Patient-reported edema and number of symptoms were the strongest predictors of HRQOL, highlighting the importance of the patient experience in glomerular disease. HRQOL outcomes inform understanding of the patient experience for children and adults with glomerular diseases.
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http://dx.doi.org/10.1016/j.ekir.2020.06.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569685PMC
October 2020

Inpatient Pediatric CKD Health Care Utilization and Mortality in the United States.

Am J Kidney Dis 2021 04 12;77(4):500-508. Epub 2020 Oct 12.

Division of Pediatric Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI.

Rationale & Objective: The impact of chronic kidney disease (CKD) on inpatient health care use is unknown. This study aimed to describe the prevalence of pediatric CKD among children hospitalized in the United States and examine the association of CKD with hospital outcomes.

Study Design: Cross-sectional national survey of pediatric discharges.

Setting & Participants: Hospital discharges of children (aged>28 days to 19 years) with a chronic medical diagnosis included in the Healthcare Cost and Utilization Project Kids' Inpatient Database for 2006, 2009, 2012, and 2016.

Predictor: Presence of primary or coexisting CKD as identified by diagnosis codes.

Outcomes: Length of stay (LOS), cost, and mortality.

Analytical Approach: Multivariable analysis using Poisson, gamma, and logistic regressions were performed for LOS, cost, and mortality, respectively.

Results: A chronic medical condition was present in 6,524,745 estimated discharges during the study period and CKD was present among 3.9% of discharges (96.1% without CKD). Those with CKD had a longer LOS (median of 2.8 [IQR, 1.4-6.0] days compared with 1.8 [IQR, 1.0-4.4] days for those without a CKD diagnosis; P<0.001). Median cost was higher in the CKD group compared with the group without CKD, at $8,755 (IQR, $4,563-18,345) and $5,016 (IQR, $2,860-10,109) per hospitalization, respectively (P<0.001). Presence of CKD was associated with a longer LOS (29.9% [95% CI, 27.2%-32.6%] longer than those without CKD), higher cost (61.3% [95% CI, 57.4%-65.4%] greater than those without CKD), and higher risk for mortality (OR, 1.51 [95% CI, 1.40-1.63]).

Limitations: Lack of access to and adjustment for confounders including patient readmission and laboratory data.

Conclusions: Pediatric CKD was associated with longer LOS, higher costs, and higher risk for mortality compared with hospitalizations with other chronic illnesses. Further studies are needed to better understand the health care needs and delivery of care to hospitalized children with CKD.
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http://dx.doi.org/10.1053/j.ajkd.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485635PMC
April 2021

The longitudinal relationship between patient-reported outcomes and clinical characteristics among patients with focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network.

Clin Kidney J 2020 Aug 5;13(4):597-606. Epub 2019 Aug 5.

Division of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS).

Methods: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied.

Results: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P  0.03).

Conclusions: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.
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http://dx.doi.org/10.1093/ckj/sfz092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467600PMC
August 2020

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

J Perinatol 2021 02 5;41(2):185-195. Epub 2020 Sep 5.

Department of Pediatrics, University of Alabama Birmingham, Birmingham, AL, USA.

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.
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http://dx.doi.org/10.1038/s41372-020-00810-zDOI Listing
February 2021

Time to Initiation of Antihypertensive Therapy After Onset of Elevated Blood Pressure in Patients With Primary Proteinuric Kidney Disease.

Kidney Med 2020 Mar-Apr;2(2):131-138. Epub 2020 Jan 17.

Division of Pediatric Nephrology, Levine Children's Hospital at Atrium Health, Charlotte, NC.

Rationale & Objective: The objective of the study was to estimate the prevalence of hypertension in patients with proteinuric kidney disease and evaluate blood pressure (BP) control.

Study Design: Retrospective cohort study.

Setting & Participants: Data from adults and children with proteinuric kidney disease enrolled in the multicenter Kidney Research Network Registry were used for this study.

Exposure: Proteinuric kidney disease.

Outcomes: Hypertension and BP control.

Analytical Approach: Patients with white-coat hypertension were excluded. Patients were censored at end-stage kidney disease onset. Patients were defined as hypertensive either by hypertension diagnosis code, having 2 or more encounters with elevated BPs, or treatment with antihypertensive therapy excluding renin-angiotensin-aldosterone system blockade. Elevated BP was defined as greater than 95th percentile for children and >140/90 mm Hg in adults. Sustained BP control was defined as 2 or more consecutive encounters with BPs lower than 95th percentile for children and <140/90 mm Hg for adults. Kaplan-Meier and Cox proportional hazards analyses were used to evaluate the time to initiation of antihypertensive therapy.

Results: 842 patients, 69% adults and 31% children, with a total observation period of 6,722 patient-years were included in the analysis. 644 (76%) had hypertension during observation. There was no difference in the prevalence of hypertension between children and adults (74% vs 78%;  = 0.3). Hypertension was most common among those of African American race compared with other races (90% vs 72%-75%;  = 0.003). 504 (78%) patients with hypertension achieved BP control but only 51% achieved control within 1 year. 140 (22%) patients with hypertension never achieved BP control during a median of 41 (IQR, 24-73) months of observation.

Limitations: Differing BP control goals that may lead to overestimation of the controlled patient population.

Conclusions: Hypertension affects most patients with proteinuric kidney disease regardless of age. Time to BP control exceeded 1 year in 50% of patients with hypertension and 22% did not demonstrate control. This study highlights the need to address hypertension early and completely in disease management of patients with proteinuric kidney disease.
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http://dx.doi.org/10.1016/j.xkme.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380443PMC
January 2020

Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study.

J Clin Med 2020 Jul 26;9(8). Epub 2020 Jul 26.

Pediatric Nephrology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium's Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1-21). The percentage of crescents was 3-100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1-11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival ( = 0.003) and a 2% decrease in log odds of renal survival at last follow-up ( < 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials.
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http://dx.doi.org/10.3390/jcm9082385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464981PMC
July 2020

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

Pediatr Nephrol 2020 05 17;35(5):871-882. Epub 2020 Jan 17.

Department of Pediatric, Medical University of South Carolina, Charleston, SC, USA.

Objective: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort.

Methods: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007, to December 31, 2011, at six tertiary care children's hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis.

Measurements And Main Results: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p = 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p = 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p = 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p = 0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00-1.18, p = 0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03-1.19, p = 0.01) were independently associated with hospital mortality.

Conclusions: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.
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http://dx.doi.org/10.1007/s00467-019-04468-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517652PMC
May 2020

Steroid-Associated Side Effects in Patients With Primary Proteinuric Kidney Disease.

Kidney Int Rep 2019 Nov 9;4(11):1608-1616. Epub 2019 Sep 9.

Division of Nephrology, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Introduction: The goal of this study was to assess the occurrence of steroid-associated adverse events (SAAE) in patients with primary proteinuric kidney disease.

Methods: The Kidney Research Network Registry consists of children and adults with primary proteinuric kidney disease. SAAEs of interest were hypertension, hyperglycemia and diabetes, overweight and obesity, short stature, ophthalmologic complications, bone disorders, infections, and psychosis. Events were identified using codes, blood pressures, growth parameters, laboratory values, and medications. Poisson generalized estimating equations tested the association between steroid onset and dose on SAAE risk.

Results: A total of 884 participants were included in the analysis; 534 (60%) were treated with steroids. Of these, 62% had at least one SAAE. The frequency of any SAAE after initiation of steroids was 293 per 1000 person-years. The most common SAAEs were hypertension (173.7 per 1000 person-years), diabetes (78.7 per 1000 person-years), obesity (66.8 per 1000 person-years), and infections (46.1 per 1000 person-years). After adjustment for demographics, duration of kidney disease, estimated glomerular filtration rate (eGFR), proteinuria, and other therapies, steroid exposure was associated with a 40% increase in risk of any SAAE (Relative risk [RR]: 1.4; 95% confidence interval [CI]: 1.3-1.6). A 1-mg/kg per day increase in steroid dose was associated with a 2.5-fold increase in risk of any SAAE.

Conclusion: Most patients with primary proteinuric kidney disease treated with steroids experienced at least one SAAE. Steroid therapy increased risk of hypertension, diabetes, weight gain, short stature, fractures, and infections after adjusting for disease-related factors. This study highlights the importance of surveillance and management of SAAE and provides rationale for the development of steroid minimization protocols.
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http://dx.doi.org/10.1016/j.ekir.2019.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933464PMC
November 2019

Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN).

Kidney Int Rep 2019 Dec 16;4(12):1725-1734. Epub 2019 Sep 16.

Division of Nephrology, Maisonneuve-Rosemont Hospital, Department of Medicine, University of Montreal, Montreal, Quebec, Canada.

Introduction: The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)-based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown.

Methods: We evaluated prescribing practice among patients with primary MN (diagnosed 2010-2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era.

Results: Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST <6 months after biopsy. Of these, 1 in 5 had no indication for (i.e., urine protein-to-creatinine ratio [uPCR] <4 g/g) or an apparent contraindication to (i.e., an estimated glomerular filtration rate [eGFR] <30 ml/min per 1.73 m) IST. As first-line IST, half of treated patients received either CYC (16% of adults; 0% of children) or a CNI (40% and 46%, respectively), whereas 1 in 5 received corticosteroid monotherapy (20% and 27%, respectively) and 1 in 6 rituximab (15% and 15%, respectively). More than 80% of surveyed centers had access to PLA2R testing.

Conclusion: These findings suggest that providers are not aware of, or lack confidence in, current KDIGO guidelines for MN. Treatment patterns observed in this cohort might critically inform the drafting of planned updates to KDIGO guidelines.
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http://dx.doi.org/10.1016/j.ekir.2019.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895579PMC
December 2019

Nephrotoxic medications and acute kidney injury risk factors in the neonatal intensive care unit: clinical challenges for neonatologists and nephrologists.

Pediatr Nephrol 2020 11 12;35(11):2077-2088. Epub 2019 Oct 12.

Stead Family Department of Pediatrics, Division of Nephrology, Dialysis, and Transplantation, University of Iowa, 200 Hawkins Drive, 2027 BT, Iowa City, IA, 52241, USA.

Neonatal acute kidney injury (AKI) is common. Critically ill neonates are at risk for AKI for many reasons including the severity of their underlying illnesses, prematurity, and nephrotoxic medications. In this educational review, we highlight four clinical scenarios in which both the illness itself and the medications indicated for their treatment are risk factors for AKI: sepsis, perinatal asphyxia, patent ductus arteriosus, and necrotizing enterocolitis. We review the available evidence regarding medications commonly used in the neonatal period with known nephrotoxic potential, including gentamicin, acyclovir, indomethacin, vancomycin, piperacillin-tazobactam, and amphotericin. We aim to illustrate the complexity of decision-making involved for both neonatologists and pediatric nephrologists when managing infants with these conditions and advocate for ongoing multidisciplinary collaboration in the development of better AKI surveillance protocols and AKI mitigation strategies to improve care for these vulnerable patients.
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http://dx.doi.org/10.1007/s00467-019-04350-3DOI Listing
November 2020

Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children.

Pediatr Crit Care Med 2020 02;21(2):170-177

Division of Pediatric Critical Care, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA.

Objectives: Evaluate the independent and synergistic associations of fluid overload and acute kidney injury with outcome in critically ill pediatric patients.

Design: Secondary analysis of the Acute Kidney Injury in Children Expected by Renal Angina and Urinary Biomarkers (NCT01735162) prospective observational study.

Setting: Single-center quaternary level PICU.

Patients: One-hundred forty-nine children 3 months to 25 years old with predicted PICU length of stay greater than 48 hours, and an indwelling urinary catheter enrolled (September 2012 to March 2014). Acute kidney injury (defined by creatinine or urine output on day 3) and fluid overload (≥ 20% on day 3) were used as outcome variables and risk factors for ICU endpoints assessed at 28 days.

Interventions: None.

Measurements And Main Results: Acute kidney injury and fluid overload occurred in 19.4% and 24.2% respectively. Both acute kidney injury and fluid overload were associated with longer ICU length of stay but neither maintained significance after multivariate regression. Delineation into unique fluid overload/acute kidney injury classifications demonstrated that fluid overload patients experienced a longer ICU and hospital length of stay and higher rate of mortality compared with fluid overload patients, regardless of acute kidney injury status. Fluid overload/acute kidney injury patients had increased odds of death (p = 0.013). After correction for severity of illness, ICU length of stay remained significantly longer in fluid overload/acute kidney injury patients compared with patients without both classifications (17.4; 95% CI, 11.0-23.7 vs 8.8; 95% CI, 7.3-10.9; p = 0.05). Correction of acute kidney injury classification for net fluid balance led to acute kidney injury class switching in 29 patients and strengthened the association with increased mechanical ventilation and ICU length of stay on bivariate analysis, but reduced the increased risk conferred by fluid overload for mortality.

Conclusions: The current study suggests the effects of significant fluid accumulation may be delineable from the effects of acute kidney injury. Concurrent fluid overload and acute kidney injury significantly worsen outcome. Correction of acute kidney injury assessment for net fluid balance may refine diagnosis and unmask acute kidney injury associated with deleterious downstream sequelae. The unique effects of fluid overload and acute kidney injury on outcome in critically ill patients warrant further study.
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http://dx.doi.org/10.1097/PCC.0000000000002107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007847PMC
February 2020
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