BACKGROUND: Acute kidney injury is common among critically ill children and independently associated with morbidity and mortality, particularly in those receiving kidney replacement therapy (KRT). As KRT is not innocuous...BACKGROUND: Acute kidney injury is common among critically ill children and independently associated with morbidity and mortality, particularly in those receiving kidney replacement therapy (KRT). As KRT is not innocuous, standardizing its delivery is critical for accurate outcome tracking. Establishing key performance indicators (KPIs) is essential to guide quality improvement and support decision-making through ongoing monitoring of KRT processes. OBJECTIVES: This systematic review evaluated existing evidence on KPIs related to KRT delivery in critically ill pediatric populations. DATA SOURCES: A comprehensive search of Ovid MEDLINE, Ovid Embase, CINAHL, and the Cochrane Library was conducted for studies published from inception to February 2025. STUDY ELIGIBILITY CRITERIA: Eligible studies reported KPIs related to dialysis processes in critically ill children receiving KRT. PARTICIPANTS AND INTERVENTIONS: Critically ill children receiving all KRT modalities were assessed for KPIs according to the Donabedian framework, with each KPI stratified based on whether it measured a process related to KRT care. STUDY APPRAISAL AND SYNTHESIS METHODS: Six reviewers independently screened, selected, and appraised studies using the risk-of-bias tool appropriate for each study design. Data were summarized narratively. RESULTS: Of 7,111 citations screened, 107 studies met inclusion criteria, comprising 57 retrospective cohorts, 27 case series, 16 prospective cohorts, 4 case reports, 2 randomized controlled trials, and 1 audit. Most studies (66.7%) were of moderate quality. Six KPIs were identified across 240 instances: solute clearance (n = 59), filter life (n = 52), downtime (n = 43), fluid management (n = 36), hypotension (n = 25), and prescription (n = 24). KPI definitions were heterogeneous. KPIs were categorized as important (n = 242, 52.1%), scientifically acceptable (n = 107, 23.1%), and feasible (n = 115, 24.8%). LIMITATIONS: This systematic review is limited by heterogeneity in study quality, with most evidence derived from observational or clinical studies rather than structured quality improvement initiatives. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS : Multiple potential KPIs for pediatric KRT were identified; however, definitions and validation were inconsistent. Standardizing and prioritizing a set of concise KPIs are needed to measure, benchmark, and improve KRT quality in critically ill children. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42023474374 (October 30, 2023).
Pediatric acute kidney injury (AKI) often presents insidiously and progresses rapidly. Traditional diagnostic criteria based on serum creatinine and urine output are markedly delayed and insufficient to capture injury pa...Pediatric acute kidney injury (AKI) often presents insidiously and progresses rapidly. Traditional diagnostic criteria based on serum creatinine and urine output are markedly delayed and insufficient to capture injury patterns across different etiologies. This paper aims to summarize recent advances in pediatric AKI biomarker research since the release of the ADQI 23 (2020) consensus. Focusing on three major clinical scenarios-cardiac surgery, sepsis, and nephrotoxic drugs-it reviews early biomarker evidence and explores their potential applications in risk stratification. At the mechanistic level, this paper outlines key pathological pathways in pediatric AKI progression: oxygenation-perfusion imbalance after cardiac surgery, endothelium-immune dysregulation driven by sepsis, and tubular-mitochondrial injury associated with nephrotoxic exposure. In CS-AKI, uNGAL shows the earliest elevation within hours after cardiopulmonary bypass, followed by sequential changes in IL-18, L-FABP, and KIM-1. [TIMP-2] × [IGFBP7] and exosomal miRNA aid in identifying high-risk or severe AKI. In SA-AKI, suPAR and glycocalyx/endothelial injury markers (e.g., syndecan-1, Angpt-2/sTM/Tie-2), combined with urinary DKK3 and complement Ba, can be used for early risk stratification and predicting poor outcomes. In NT-AKI, uNGAL has high negative predictive value for excluding severe AKI, while uKIM-1, uCysC, uOPN, and multi-biomarker combinations can indicate subclinical tubular injury earlier after drug exposure. Overall, single biomarkers struggle to cover AKI heterogeneity. Future efforts should integrate functional dynamic assessments (e.g., FST, RRI), scenario-based multi-biomarker combinations, and AI dynamic models to propose evidence-based, scenario-stratified identification pathways. These will serve as structured references for prospective studies and clinical workflow optimization.
Condit PE, Nightingale NM, Anderson BJ
… +4 more, Miller IJ, Coon JJ, Overmyer KA, Harer MW
Pediatr Nephrol
· 2026 May · PMID 42084626
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BACKGROUND: Diagnosing acute kidney injury (AKI) in preterm neonates remains difficult, and its underlying causes are not well understood. This study aimed to compare urinary metabolite profiles in preterm neonates with...BACKGROUND: Diagnosing acute kidney injury (AKI) in preterm neonates remains difficult, and its underlying causes are not well understood. This study aimed to compare urinary metabolite profiles in preterm neonates with and without AKI. METHODS: We conducted a prospective observational study of neonates born at < 32 weeks' gestation. AKI was staged using the modified neonatal definition. Urine samples were collected every six hours using cotton in diapers. Metabolomic profiling was performed via liquid chromatography mass spectrometry (LC-MS). Data were acquired in polarity switching mode and processed using Compound Discoverer 3.3. RESULTS: Among 32 enrolled neonates (median birth weight 1.25 kg, gestational age 29 weeks), five developed AKI. A total of 987 urine samples were collected, with 522 age- and sex-matched samples from 16 individuals included in the final analysis. Principal component (PC) analysis revealed that PC1 and PC2 accounted for 15.82% and 11.61% of sample variance, respectively. Comparison of samples from neonates with and without AKI identified significantly elevated levels of furosemide, acesulfame, kynurenic acid, and hexaethylene glycol in the AKI group (p < 0.05, log2 fold change > 1) and with significant differences between metabolites within biochemical pathways including branch chain fatty acid oxidation, tyrosine metabolism, and carnitine synthesis. Longitudinal analysis also revealed metabolite changes preceding AKI onset, with distinct profiles compared to neonates who did not develop AKI. CONCLUSIONS: Preterm neonates with AKI exhibit distinct urinary metabolomic profiles compared to those without AKI. These findings suggest potential for metabolomic signatures to aid in early AKI detection, phenotype classification, and identification of therapeutic targets. Further research is needed to refine compound identification and timing of metabolite changes.
Anti-glomerular basement membrane (anti-GBM) nephritis is a rare but highly aggressive cause of rapidly progressive glomerulonephritis (RPGN). Early recognition is essential, as delayed diagnosis leads to irreversible ki...Anti-glomerular basement membrane (anti-GBM) nephritis is a rare but highly aggressive cause of rapidly progressive glomerulonephritis (RPGN). Early recognition is essential, as delayed diagnosis leads to irreversible kidney damage and poor prognosis. We report an 8-year-old girl with anti-GBM nephritis initially misattributed to kidney involvement of IgA vasculitis (IgAV). Diagnosis was confirmed by markedly elevated anti-GBM antibodies and kidney biopsy findings. Despite plasma exchange and immunosuppressive therapy, kidney function deteriorated to kidney failure within several months. This case provides an important clinical insight for pediatric nephrologists: worsening urinary findings or kidney function during follow-up of IgAV should prompt consideration of RPGN and appropriate serological screening, as well as timely kidney biopsy, rather than being attributed solely to IgAV nephritis.
BACKGROUND: Sickle cell nephropathy is a common complication of sickle cell disease that begins in childhood and can progress silently to chronic kidney disease. In the Democratic Republic of Congo (DRC), data on early k...BACKGROUND: Sickle cell nephropathy is a common complication of sickle cell disease that begins in childhood and can progress silently to chronic kidney disease. In the Democratic Republic of Congo (DRC), data on early kidney damage in children with sickle cell disease remain limited. In 2017, studies conducted in the same context reported separately on the prevalence of microalbuminuria and glomerular hyperfiltration (GHF). This study aimed to update the prevalence of albuminuria and GHF and to determine their associated factors in children with sickle cell disease in the DRC. METHODS: We conducted a cross-sectional study including 175 children with sickle cell disease, followed up in four hospitals in Kinshasa. High albuminuria and GHF, the main evaluation criteria, were defined respectively by an albuminuria/creatinine ratio (ACR) ≥ 30 mg/g and an estimated glomerular filtration rate (eGFR) > 130 ml/min/1.73 m in girls and > 140 ml/min/1.73 m in boys, according to the Schwartz formula. RESULTS: Among the 175 children included, 28.5% had high albuminuria and 38.3% had GHF. Factors significantly associated with early renal involvement were frequent blood transfusions (≥ 9/year), recurrent vaso-occlusive crises (≥ 3/year), low fetal hemoglobin levels (< 15%), and markers of hemolysis (LDH > 400 IU/L and elevated indirect bilirubin). These results reflect a high persistence of early renal impairment nearly nine years after the first data were published. CONCLUSIONS: Early markers of kidney damage remain very common in children with homozygous sickle cell disease in the DRC. This persistence highlights the lack of effective kidney prevention strategies and the urgent need for systematic screening using simple and accessible tools in resource-limited settings.
Despite modest improvement, the lifespan of a child on dialysis continues to be 40 years shorter compared to healthy children. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patient...Despite modest improvement, the lifespan of a child on dialysis continues to be 40 years shorter compared to healthy children. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Risk factors for CVD are present even in early stages of chronic kidney disease (CKD) and accelerate as the child's renal function deteriorates. As a result, the highest burden of CVD exists in patients on chronic dialysis. Although dialysis is life-sustaining, the dialysis procedure promotes cardiovascular damage. Both traditional and non-traditional CVD risk factors drive this acceleration. More concerning, the dialysis procedure itself is cardiotoxic. Because of coexisting poor cardiac reserve and altered sympathetic tone in this patient population, dialysis induces repetitive contractile, ischemic injury termed myocardial stunning. This ischemia-reperfusion injury is reversible at first. However, with repetitive episodes, this injury will trigger alterations in cardiac function that decrease contractile function in order to preserve viability. Ultimately, these adaptations lead to remodeling and fibrosis. There is no targeted therapy available to reverse cardiovascular damage in these patients. Intensive monitoring and management of modifiable risks such as hypertension and anemia in the early stages of CKD to optimize cardiovascular health is imperative. However, in late CKD, especially in those patients who are not candidates for preemptive renal transplantation, optimization of the dialysis procedure is critical to prevent acceleration of their CVD burden. Improved assessment of dry weight as well as data-driven fluid management programs may decrease some risk. More importantly, standard implementation of intensified dialysis prescriptions by increasing time or through the addition of convective clearance may mitigate progressive cardiovascular damage and enhance survival. In this review, the pathophysiology of dialysis-induced cardiovascular damage will be reviewed. The management strategies to limit the cardiovascular burden in our patients are also discussed.
BACKGROUND: Renal Fanconi syndrome (RFS) refers to a generalized dysfunction of the proximal tubule, including impaired 1-α hydroxylation of vitamin D. Consequently, rickets is a typical complication. Clinical observatio...BACKGROUND: Renal Fanconi syndrome (RFS) refers to a generalized dysfunction of the proximal tubule, including impaired 1-α hydroxylation of vitamin D. Consequently, rickets is a typical complication. Clinical observations in children with severe nutritional vitamin D deficiency sometimes include proximal tubular dysfunction, raising the possibility that lack of vitamin D could not only be a consequence of RFS but also a cause of it, although this has never been confirmed. Observations in Mendelian disorders with their genetically defined pathophysiology can provide clearer insights. METHODS: We performed a retrospective review of 2 cases with vitamin D deficiency due to loss-of-function variants in CYP27B1. Additionally, we performed an in silico search for vitamin D-responsive elements (VDRE) in the promoter region of genes encoding proximal tubular transporters. RESULTS: Both cases presented with clinical rickets that had been resistant to supplementation with cholecalciferol. Biochemistries at presentation showed a non-anion gap metabolic acidosis, generalized aminoaciduria and urinary phosphate wasting consistent with proximal tubular dysfunction. Symptoms resolved upon treatment with active vitamin D. VDRE motifs were identified in the promoters of SLC34A1 and SLC34A3. CONCLUSIONS: Our observations support the notion of vitamin D deficiency as a cause of RFS and suggest that unresolved cases of RFS should be actively investigated for it.
BACKGROUND: This study aimed to characterize practices and decision-making for extracorporeal membrane oxygenation (ECMO) for congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: General practices (GP)...BACKGROUND: This study aimed to characterize practices and decision-making for extracorporeal membrane oxygenation (ECMO) for congenital anomalies of the kidney and urinary tract (CAKUT). METHODS: General practices (GP) section inquired about institutional practices and barriers, ECMO criteria, and dialysis. The hypothetical cases (HC) illustrated four clinical scenarios with varying degrees of renal severity for ECMO candidacy. RESULTS: Then, 99 (42 centers) and 91 (38 centers) physicians completed the GP and HC components, respectively. The majority considered ECMO on a case-by-case basis (66%). Bilateral renal agenesis was the most common diagnosis for exclusion (52%). Prenatal markers used for ECMO exclusion included anhydramnios (43%) and lung volumes (43%). The majority of centers had nephrology involved in ECMO decision-making. Challenges for implementing ECMO included disease heterogeneity (79%) and poor evidence on outcomes (66%). HC responses demonstrated variability in considering ECMO for CAKUT. CONCLUSIONS: Variability among providers and institutes underscores the need for consensus-based guidelines to optimize decision-making and outcomes.
BACKGROUND: This study characterizes a pediatric case of fibronectin glomerulopathy (FNG) caused by a novel FN1 variant and investigates the evidence for systemic involvement and genotype-phenotype correlations through a...BACKGROUND: This study characterizes a pediatric case of fibronectin glomerulopathy (FNG) caused by a novel FN1 variant and investigates the evidence for systemic involvement and genotype-phenotype correlations through a comprehensive literature review. METHODS: We report a female child diagnosed with FNG in February 2017 based on kidney biopsy and genetic testing at our institution. Clinical data and genetic reports were retrospectively analyzed. Fibronectin immunohistochemistry was performed on both kidney and gastric mucosal biopsy specimens. In addition, a literature review of Chinese and English databases was conducted to summarize genetically confirmed FNG cases. RESULTS: The patient was a 9-year-old girl who presented with nephrotic-range proteinuria, microscopic hematuria, hypertension, and progressive kidney decline, culminating in kidney failure ten years after onset. Initial kidney pathology suggested atypical membranoproliferative glomerulonephritis (MPGN). Genetic analysis identified a novel de novo heterozygous deletion in the FN1 gene (NM_212482.5: c.5749_5751delACT; p.Thr1917del). Gastric mucosal immunohistochemistry revealed specific fibronectin deposition within the extracellular matrix, indicating systemic involvement. The comprehensive literature review of 72 patients revealed that the heparin-binding domain is a mutational hotspot, a finding consistent with the variant location in our case. The review also summarized disease management, progression, and post-transplant recurrence risk. CONCLUSION: This study presents the first reported pediatric FNG case internationally associated with the FN1 p.Thr1917del mutation and offers histological evidence suggestive of a possible systemic extracellular matrix proteinopathy. Our findings underscore the value of fibronectin staining and FN1 genetic testing in patients with atypical MPGN and broaden the disease's clinical and genetic profile.
BACKGROUND: Hypertensive emergency in children often exhibits neurological symptoms indicative of hypertensive encephalopathy (HE). The risk factors concerning HE development remain unclear, motivating the objective of t...BACKGROUND: Hypertensive emergency in children often exhibits neurological symptoms indicative of hypertensive encephalopathy (HE). The risk factors concerning HE development remain unclear, motivating the objective of this study to identify risk factors and formulate an equation for forecasting HE in hospitalized pediatric patients. METHODS: This retrospective case-control study focused on pediatric patients aged 1-18 years diagnosed with hypertension from 2011 to 2021. Logistic regression analysis was utilized to identify variables associated with HE. A HE predictive equation was developed based on significant factors, with sensitivity, specificity, and predictive values assessed using receiver operating characteristics curves. RESULTS: Three hundred thirty-two patients with mean age 9.3 years were recruited. 12.3% developed HE. Univariable analysis revealed risk factors for HE, including central nervous system symptoms, peak systolic and diastolic blood pressure z-score (Z-SBP and Z-DBP), corticosteroid and calcineurin inhibitor use, and leukemia/lymphoma. Logistic regression formed the equation predicting HE occurrence as follows: 2.162 (vomiting) + 2.921 (headache/dizziness) + 2.363 (leukemia/lymphoma) + 1.807 (corticosteroid) + 0.783 (peak Z-SBP). The equation demonstrated robust correlation with predicted probability of developing HE and had AUC of 0.95. A cutoff score of 4 showed high sensitivity (97.6%) and negative predictive value (99%), identifying 98% of HE cases. CONCLUSIONS: This study pinpointed key risk factors and introduced an accurate predictive equation, underscoring the significance of assessing multiple factors beyond blood pressure levels for HE prediction in hypertensive pediatric patients.
BACKGROUND: Neonates with kidney failure require placement of a peritoneal dialysis catheter (PD-C) shortly after birth. PD-C malfunction and peritonitis, both common in this population, are associated with PD failure. T...BACKGROUND: Neonates with kidney failure require placement of a peritoneal dialysis catheter (PD-C) shortly after birth. PD-C malfunction and peritonitis, both common in this population, are associated with PD failure. The aim of this study was to describe our center's PD-C-related practices and outcomes in neonates with kidney failure. METHODS: We performed a retrospective chart review of neonates who required kidney replacement therapy (KRT) within the first 30 days of life from 01/2018-12/2023. We evaluated for PD-C duration, PD-C replacement or revision, and peritonitis. RESULTS: Twenty-four neonates had PD-C placed for chronic dialysis at a median of 9.7 days and 3 kg. Peritoneal dialysis (PD) was initiated a median of 14 days after PD-C placement, at a median age of 26.5 days. During a median follow-up time of 26.2 months, there were 42 PD-Cs tracked. Initial PD-C lasted a median of 355 days (IQR 165-632, range 50-953). Reasons for removal of initial PD-C included mechanical complications (38%), kidney transplant (25%), and infection (21%). There were 44 episodes of peritonitis in 19 patients. Seventeen of these episodes (39%) occurred within four weeks of a surgical procedure, despite all patients but one receiving perioperative antibiotic prophylaxis for all surgical procedures. The overall rate of peritonitis was 0.34 per 100-catheter days. CONCLUSIONS: PD-C complications are common in this highly complex population, despite mitigation attempts with perioperative antibiotics. Future work should focus on neonatal-specific recommendations for surgery timings and prophylaxis to reduce the risk of infection and PD failure in the neonatal kidney failure population.
BACKGROUND: Syndrome of inappropriate antidiuresis (SIAD) is a common cause of euvolaemic hyponatraemia. Moderate-to-severe hyponatraemia, particularly in the neurosurgical setting, often necessitates administration of c...BACKGROUND: Syndrome of inappropriate antidiuresis (SIAD) is a common cause of euvolaemic hyponatraemia. Moderate-to-severe hyponatraemia, particularly in the neurosurgical setting, often necessitates administration of correctional fluids, typically hypertonic saline. However, predicting changes in plasma sodium levels following fluid administration is challenging and often inaccurate. In adults, the Voets equation has been shown to be superior to the classical Adrogué-Madias formula in predicting sodium levels achieved with correctional fluids, however, no studies have investigated its efficacy in children. Recent advancements in accurately estimating total body water in young children may improve this process. The current study was performed to compare the predictive accuracy of the Adrogué-Madias and Voets equations in estimating the change in plasma sodium levels following administration of correctional intravenous fluids. METHODS: This prospective observational hospital-based study was conducted in paediatrics and neurosurgical intensive care units from August 2022 to August 2024. Children aged 2 months to 18 years who satisfied the inclusion criteria for SIAD were enrolled. The predictive accuracy of Voets and Adrogué-Madias equations were calculated and compared. RESULTS: Analysis of predicted sodium correction using the Adrogué-Madias equation showed a p-value of 0.026 and an intraclass correlation coefficient (ICC) of 0.399. By contrast, the Voets equation demonstrated a p-value of < 0.001 and an ICC of 0.926. CONCLUSION: Both Adrogué-Madias and Voets equations were found to be effective in the prediction of hyponatraemia in patients with SIAD. However, the Voets equation was found to be more reliable and accurate in predicting the change in plasma sodium.