Artificial intelligence and pediatric acute kidney injury: a mini-review and white paper

Acute kidney injury (AKI) in pediatric and neonatal populations poses significant diagnostic and management challenges, with delayed detection contributing to long-term complications such as hypertension and chronic kidney disease. Recent advancements in artificial intelligence (AI) offer new avenues for early detection, risk stratification, and personalized care. This paper explores the application of AI models, including supervised and unsupervised machine learning, in predicting AKI, improving clinical decision-making, and identifying subphenotypes that respond differently to interventions. It discusses the integration of AI with existing risk scores and biomarkers to enhance predictive accuracy and its potential to revolutionize pediatric nephrology. However, barriers such as data quality, algorithmic bias, and the need for transparent and ethical implementation are critical considerations. Future directions emphasize incorporating biomarkers, expanding external validation, and ensuring equitable access to optimize outcomes in pediatric AKI care

Renal Manifestations of Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Disruption of either of these genes leads to impaired production of hamartin or tuberin proteins, leading to the manifestation of skin lesions, tumors, and seizures. TSC can manifest in multiple organ systems with the cutaneous and renal systems being the most commonly affected. These manifestations can secondarily lead to the development of hypertension, chronic kidney disease, and neurocognitive declines. The renal pathologies most commonly seen in TSC are angiomyolipoma, renal cysts, and less commonly, oncocytomas. In this review, we highlight the current understanding on the renal manifestations of TSC along with current diagnosis and treatment guidelines

Fluid Overload in Critically Ill Children

Background: A common practice in the management of critically ill patients is fluid resuscitation. An excessive administration of fluids can lead to an imbalance in fluid homeostasis and cause fluid overload (FO). In pediatric critical care patients, FO can lead to a multitude of adverse effects and increased risk of morbidity.Objectives: To review the literature highlighting impact of FO on a multitude of outcomes in critically-ill children, causative vs. associative relationship of FO with critical illness and current pediatric fluid management guidelines.Data Sources: A literature search was conducted using PubMed/Medline and Embase databases from the earliest available date until June 2017.Data Extraction: Two authors independently reviewed the titles and abstracts of all articles which were assessed for inclusion. The manuscripts of studies deemed relevant to the objectives of this review were then retrieved and associated reference lists hand-searched.Data Synthesis: Articles were segregated into various categories namely pathophysiology and sequelae of fluid overload, assessment techniques, epidemiology and fluid management. Each author reviewed the selected articles in categories assigned to them. All authors participated in the final review process.Conclusions: Recent evidence has purported a relationship between mortality and FO, which can be validated by prospective RCTs (randomized controlled trials). The current literature demonstrates that “clinically significant” degree of FO could be below 10%. The lack of a standardized method to assess FB (fluid balance) and a universal definition of FO are issues that need to be addressed. To date, the impact of early goal directed therapy and utility of hemodynamic parameters in predicting fluid responsiveness remains underexplored in pediatric resuscitation

Sociodemographic Disparities in 1-Year Outcomes of Children With Community-Acquired Acute Kidney Injury

IMPORTANCE: Racial disparities have been identified in pediatric community-acquired acute kidney injury (CA-AKI), and they are associated with increased risk of child mortality, morbidity, and progression of kidney disease. OBJECTIVE: To assess clinical outcomes at 1 year among children with CA-AKI, stratified by age, race, and ethnicity. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study is a population-based analysis of deidentified, aggregated electronic health record data collected by 61 large health care organizations from 2003 to 2023 and accessed through the TriNetX platform. Outcomes were assessed at 1 year after a CA-AKI episode. Participants included pediatric patients (aged <18 years) with AKI. Data were accessed in January 2024. EXPOSURE: A diagnosis of CA-AKI and sociodemographic factors such as race, ethnicity, and age, as reported in electronic health records. MAIN OUTCOMES AND MEASURES: The primary end point of this study was to assess differences in clinical outcomes within 1 year of an episode of CA-AKI, including all-cause emergency department (ED) visits, intensive care unit (ICU) admissions, mechanical intubation and ventilation, and mortality. Risk was compared between White children and Asian (including Asian, Native Hawaiian, and Other Pacific Islander), Black, and Hispanic children, stratified by age group. Measures of association, Cox proportional hazard analyses, and Kaplan-Meier survival curves were performed within the TriNetX Advanced Analytics Platform between racial and ethnic groups for each analysis. RESULTS: From the total sample of 18 152 children, those with hospital-acquired AKI, chronic kidney disease, end-stage kidney failure, or dialysis dependence were excluded, leaving a final cohort of 17 125 children (mean [SD] age, 11.2 [5.2] years; 9424 male [55.3%]). Eligible patients were divided into racial and ethnic groups as follows: non-Hispanic Asian, 1169 children (6.5%); non-Hispanic Black, 4636 children (27.3%); Hispanic, 1786 children (10.2%); and non-Hispanic White, 9534 children (55.9%). Patients were further subdivided into groups aged 0 to 9 years (546 Asian children, 1675 Black children, 689 Hispanic children, and 3340 White children) and 10 to 18 years (623 Asian children, 2961 Black children, 1091 Hispanic children, and 6104 White children). Within 1 year of CA-AKI diagnosis, compared with White children, Black children experienced greater rates of ED visits (hazard ratio [HR], 1.53; 95% CI, 1.40-1.67), ICU admissions (HR, 1.31; 95% CI, 1.16-1.47), mechanical ventilation (HR, 1.33; 95% CI, 1.13-1.56), and all-cause mortality (HR, 1.27; 95% CI, 1.09-1.48), as well as the greatest risk for composite outcomes (HR, 1.43; 95% CI, 1.33-1.53). Hispanic children experienced greater rates of ED visits (HR, 1.40; 95% CI, 1.21-1.62) and the greatest risk of all-cause mortality (HR, 1.66; 95% CI, 1.31-2.09), whereas Asian children experienced greater rates of mechanical ventilation (HR, 1.69; 95% CI, 1.26-2.27), compared with White children. Black and Hispanic children aged 0 to 9 years were at greatest risk of experiencing poor clinical outcomes. Black children had a 11.41% lower survival probability and Hispanic children had a 7.14% lower survival probability compared with White children after an initial ED encounter. CONCLUSIONS AND RELEVANCE: Among children with an identified episode of CA-AKI diagnosed in an ED, within 1 year, Black and Hispanic children had a poorer survival probability compared with White children. Future studies are needed to understand these disparities and improve awareness and follow-up after emergency care

Association of pulse pressure, pulse pressure index, and ambulatory arterial stiffness index with kidney function in a cross‐sectional pediatric chronic kidney disease cohort from the CKiD study

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end‐stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1‐16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non‐immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non‐immunological group. There were no significant differences with iohexol‐based glomerular filtration rate (iGFR), LVMI, PPi, or high‐sensitivity C‐reactive protein (hs‐CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non‐immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155967/1/jch13905.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155967/2/jch13905_am.pd

Utility of the Kidney Failure Risk Equation and Estimated GFR for Estimating Time to Kidney Failure in Advanced CKD.

RATIONALE &amp; OBJECTIVE: The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. STUDY DESIGN: Retrospective cohort. SETTING &amp; PARTICIPANTS: CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR&lt;60mL/min/1.73m2 from 34 US nephrology practices (2013-2021). EXPOSURE: 2-year KFRE risk or eGFR. OUTCOME: Kidney failure defined as initiation of dialysis or kidney transplantation. ANALYTICAL APPROACH: Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m2. We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure. RESULTS: Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m2 [IQR 20-37mL/min/1.73 m2]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m2 and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m2. LIMITATIONS: Inability to account for competing risks when estimating time to kidney failure. CONCLUSIONS: Among those with eGFR&lt;15mL/min/1.73m2 or KFRE risk&gt;40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. PLAIN-LANGUAGE SUMMARY: Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR&lt;15mL/min/1.73m2 or KFRE risk &gt; 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis

Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department

Background: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults. Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE). Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(-). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1-3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001). Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs