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Point-of-care ultrasound (POCUS) has evolved in recent years in clinical practice, helping in early bedside diagnosis of important etiologies. Many medical schools and training programs are integrating POCUS into their curriculum. Especially with the technological advances of newer handheld ultrasound devices, POCUS has now become a component adjunct to clinical examination, in the clinic and bedside in critical care units. The diagnostic utility of POCUS lies both in early identification of critical kidney disease, and also extra-renal pathologies from a focused cardiac ultrasound, lung ultrasound, and integrated fluid assessment. There is a need to incorporate POCUS in training in pediatric nephrology and establish competency standard criteria. This review shall cover how POCUS helps in enhancing patient care in pediatric kidney disorders and critical children, and the recent advances., Author(s): Sidharth Kumar Sethi [sup.1] , Rupesh Raina [sup.2] , Abhilash Koratala [sup.3] , Afagh Hassanzadeh Rad [sup.4] , Ananya Vadhera [sup.5] , Hamidreza Badeli [sup.4] Author Affiliations: (1) grid.429252.a, [...]

Background AKI is an important complication post cardiac surgery in children. An early diagnosis can help in mitigating complications and allow for prognostication. Urinary albumin:creatinine ratio (ACR) as a biomarker can provide a cheaper and more accessible AKI risk assessment and prediction. There is a paucity of paediatric literature regarding its utility. Methods This was a prospective observational study, enrolling all children aged 1 month to 18 years, who underwent cardiac surgery, with use of cardiopulmonary bypass. Cohort was divided into groups 75.8 mg/g) predicted post-operative AKI after adjusting for clinical variables (adjusted RR, 11.71; 1.85-16.59). In the group aged 141.3 mg/g) predicted post-operative AKI in unadjusted analysis but not after adjusting for clinical variables (RR, 2.78; 0.70-6.65). For AKI risk prediction, AUC (95% CI) was highest after combining clinical model and pre-operative ACR for groups aged < 2 years [0.805 (0.713-0.896)] and [greater than or equal to] 2 years [0.872 (0.772-0.973)]. Conclusions This study provides evidence for use of albuminuria as a feasible biomarker in AKI prediction in children post cardiac surgery, especially when added to a clinical model. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Arushi Nautiyal [sup.1] , Sidharth Kumar Sethi [sup.2] , Rajesh Sharma [sup.3] , Rupesh Raina [sup.4] , Abhishek Tibrewal [sup.4] , Romel Akole [sup.3] , Aditi Gupta [sup.5] , [...]

Background and objectives Dialysis disequilibrium syndrome (DDS) is a rare neurological complication, most commonly affecting patients undergoing new initiation of hemodialysis (HD), but can also be seen in patients receiving chronic dialysis who miss regular treatments, patients having acute kidney injury (AKI), and in those treated with continuous kidney replacement therapy (CKRT) or peritoneal dialysis (PD). Although the pathogenesis is not well understood, DDS is likely a result of multiple physiological abnormalities. In this systematic review, we provide a synopsis of the data available on DDS that allow for a clear picture of its pathogenesis, preventive measures, and focus on effective management strategies. Methods We conducted a literature search on PubMed/Medline and Embase from January 1960 to January 2021. Studies were included if the patient developed DDS irrespective of age and gender. A summary table was used to summarize the data from individual studies and included study type, population group, age group, sample size, patient characteristics, blood and dialysate flow rate, and overall outcome. A descriptive analysis calculating the frequency of population size, symptoms, and various treatments was performed using R software version 3.1.0. Results A total of 49 studies (321 samples) were identified and analyzed. Out of the included 49 studies, a total of 48 studies reported the presence of DSS among patients (1 study reported based on number of dialysis and therefore was not considered for analysis). Among these 48 studies, 74.3% (226/304) patients were reported to have DSS. The most common symptoms were nausea (25.2%), headache (24.8%), vomiting (23.9%), muscle cramps (18.1%), affected level of consciousness (8.8%), confusion (4.4%), and seizure (4.9%) among the 226 DDS patients. Furthermore, 12 studies decided to switch from HD to alternative dialysis modalities including continuous venovenous hemofiltration/hemodiafiltration (CVVH/CVVHDF) or PD which reported no DDS symptoms. Conclusion Early recognition and timely prevention are crucial for DDS patients. We have provided comprehensive clinical practice points for pediatric, adolescent, and young adult populations. However, it is essential to recognize that DDS was reported more frequently in the early dialysis era, as there was a lack of advanced dialysis technology and limited resources., Author(s): Rupesh Raina [sup.1] [sup.2] [sup.3] , Andrew Davenport [sup.4] , Bradley Warady [sup.5] , Prabhav Vasistha [sup.1] , Sidharth Kumar Sethi [sup.6] , Ronith Chakraborty [sup.1] [sup.2] , Prajit [...]

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

Author(s): Sidharth Kumar Sethi [sup.1] , Abhyuday Rana [sup.2] , Shyam Bihari Bansal [sup.2] , Alka Rana [sup.3] , Dinesh Kumar Yadav [sup.2] , Kritika Soni [sup.2] , Marie-Agnès Dragon-Durey [...]

This article discusses a case study of a 7-year-old girl who presented with a hypertensive crisis and thrombotic microangiopathy (TMA). The study found that severe hypertension led to TMA in this case, which is rare in children. The patient was treated with intravenous eculizumab and antihypertensive agents, which resulted in improvement in her condition. The article emphasizes the importance of evaluating hypertension-associated TMA for complement defects and initiating aggressive hypertension control and targeted therapies for better outcomes. It also highlights the potential association between severe hypertension and TMA, and the role of complement activation in the pathogenesis. [Extracted from the article]

Background Acute kidney injury (AKI) is associated with increased morbidity/mortality. With artificial intelligence (AI), more dynamic models for mortality prediction in AKI patients have been developed using machine learning (ML) algorithms. The performance of various ML models was reviewed in terms of their ability to predict in-hospital mortality for AKI patients. Methods A literature search was conducted through PubMed, Embase and Web of Science databases. Included studies contained variables regarding the efficacy of the AI model [the AUC, accuracy, sensitivity, specificity, negative predictive value and positive predictive value]. Only original studies that consisted of cross-sectional studies, prospective and retrospective studies were included, while reviews and self-reported outcomes were excluded. There was no restriction on time and geographic location. Results Eight studies with 37   032 AKI patients were included, with a mean age of 65.3 years. The in-hospital mortality was 18.0% in the derivation and 15.8% in the validation cohorts. The pooled [95% confidence interval (CI)] AUC was observed to be highest for the broad learning system (BLS) model [0.852 (0.820–0.883)] and elastic net final (ENF) model [0.852 (0.813–0.891)], and lowest for proposed clinical model (PCM) [0.765 (0.716–0.814)]. The pooled (95% CI) AUC of BLS and ENF did not differ significantly from other models except PCM [Delong's test P = .022]. PCM exhibited the highest negative predictive value, which supports this model's use as a possible rule-out tool. Conclusion Our results show that BLS and ENF models are equally effective as other ML models in predicting in-hospital mortality, with variability across all models. Additional studies are needed. [ABSTRACT FROM AUTHOR]

Background: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. Design: Prospective observational quality improvement initiative cohort study. Setting and Participants: A prospective single‐center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. Quality Improvement Plan: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%–30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. Measures: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long‐term outcomes were assessed at the 1‐year follow‐up including adherence to dialysis, renal transplantation, death, and loss to follow‐up. Results: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long‐term outcomes showed 88% adherence to dialysis and 38% renal transplantation. Limitations: This study is characterized by a single‐center design, nonrandomized approach, and limited sample size. Conclusions: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome. [ABSTRACT FROM AUTHOR]

Wide ranges of age and weight in pediatric patients makes renal replacement therapy (RRT) in acute kidney injury (AKI) challenging, particularly in the pediatric intensive care unit (PICU), wherein children are often hemodynamically unstable. Standard hemodialysis (HD) is difficult in this group of children and continuous veno-venous hemofiltration/dialysis (CVVH/D) has been the accepted modality in the developed world. Unfortunately, due to cost constraints, CVVH/D is often not available and peritoneal dialysis (PD) remains the common mode of RRT in resource-poor facilities. Acute PD has its drawbacks, and intermittent HD (IHD) done slowly over a prolonged period has been explored as an alternative. Various modes of slow sustained IHD have been described in the literature with the recently introduced term prolonged intermittent RRT (PIRRT) serving as an umbrella terminology for all of these modes. PIRRT has been widely accepted in adults with studies showing it to be as effective as CVVH/D but with an added advantage of being more cost-effective. Pediatric data, though scanty, has been promising. In this current review, we elaborate on the practical aspects of undertaking PIRRT in children as well as summarize its current status., Author(s): Rajiv Sinha [sup.1] , Sidharth Kumar Sethi [sup.2] , Timothy Bunchman [sup.3] , Valentine Lobo [sup.4] , Rupesh Raina [sup.5] Author Affiliations: (1) 0000 0004 1801 0469, grid.414710.7, Institute [...]

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) defined by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury. Microthrombi develop in the glomerular capillaries secondary to endothelial damage and exert shear stress on red blood cells, consume platelets, and contribute to renal dysfunction and failure. Per current understanding of pathophysiology, HUS is classified into infectious, secondary, and atypical disease. The most common etiology is infectious sequelae of Shiga toxin-producing Escherichia coli (STEC); other causative organisms include shigella and salmonella. Secondary HUS arises from cancer, chemotherapy, solid organ and hematopoietic stem cell transplant, pregnancy, or autoimmune disorders. Primary atypical hemolytic-uremic syndrome (aHUS) is associated with genetic mutations in complement and complement regulatory proteins. Under physiologic conditions, complement regulators keep the alternative complement system continuously active at low levels. In times of inflammation, mutations in complement-related proteins lead to uncontrolled complement activity. The hyperactive inflammatory state leads to glomerular endothelial damage, activation of the coagulation cascade, and TMA findings. Atypical hemolytic-uremic syndrome is a rare disorder with a prevalence of 2.21 to 9.4 per million people aged 20 years or younger; children between the ages of 0 and 4 are most affected. Multidisciplinary health care is necessary for timely management of its extra-renal manifestations. These include vascular disease of the heart, brain, and skin, pulmonary hypertension and hemorrhage, and pregnancy complications. Adequate screening is required to monitor for sequelae. First-line treatment is the monoclonal antibody eculizumab, but several organ systems may require specialized interventions and coordination of care with sub-specialists. [ABSTRACT FROM AUTHOR]

Introduction: Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step‐down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low‐efficiency daily dialysis with pre‐filter replacement (SLED‐f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED‐f as a transition step‐down therapy after CKRT in critically ill pediatric patients with acute kidney injury. Methods: A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi‐organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED‐f. Results: Eleven patients underwent 105 SLED‐f sessions (mean of 9.55 +/− 4.90 sessions per patient), as a part of step‐down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED‐f, urea reduction ratio was 64.1 +/− 5.3%, Kt/V was 1.13 +/− 0.1, and beta‐2 microglobulin reduction was 42.5 +/−4%. Incidence of hypotension and requirement of escalation of inotropes during SLED‐f was 18.18%. Filter clotting occurred twice in one patient. Conclusion: SLED‐f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a commonly encountered comorbidity in critically ill children. The coexistence of AKI disturbs drug pharmacokinetics and pharmacodynamics, leading to clinically significant consequences. This can complicate an already critical clinical scenario by causing potential underdosing or overdosing giving way to possible therapeutic failures and adverse reactions. Current available studies offer little guidance to help maneuver such complex dosing regimens and decision-making in pediatric patients as most of them are done on heterogeneous groups of adult populations. Though there are some studies on drug dosing during continuous renal replacement therapy (CRRT), their utility is in question because of the recent advances in CRRT technology. Our review aims to discuss the principles of pharmacokinetics pertinent for honing the existing practices of drug dosing in critically ill children with AKI, and the various complexities and intricate challenges involved. This in turn will provide a framework to help enable caretakers to tailor dosing regimens in complex clinical setups with further ease and precision. [ABSTRACT FROM AUTHOR]

Author(s): Sidharth Kumar Sethi [sup.1] , Norma Maxvold [sup.2] , Timothy Bunchman [sup.2] , Pranaw Jha [sup.1] , Vijay Kher [sup.1] , Rupesh Raina [sup.3] Author Affiliations: (1) grid.429252.a, 0000000417644857, [...]

Background: The SARS‐CoV‐2 pandemic and corresponding acute respiratory syndrome have affected all populations and led to millions of deaths worldwide. The pandemic disproportionately affected immunocompromised and immunosuppressed adult patients who had received solid organ transplants (SOTs). With the onset of the pandemic, transplant societies across the world recommended reducing SOT activities to avoid exposing immunosuppressed recipients. Due to the risk of COVID‐19‐related outcomes, SOT providers adapted the way they deliver care to their patients, leading to a reliance on telehealth. Telehealth has helped organ transplant programs continue treatment regimens while protecting patients and physicians from COVID‐19 transmission. This review highlights the adverse effects of COVID‐19 on transplant activities and summarizes the increased role of telehealth in the management of solid organ transplant recipients (SOTRs) in both pediatric and adult populations. Methods: A comprehensive systematic review and meta‐analysis were conducted to accentuate the outcomes of COVID‐19 and analyze the efficacy of telehealth on transplant activities. This in‐depth examination summarizes extensive data on the clinical detriments of COVID‐19 in transplant recipients, advantages, disadvantages, patient/physician perspectives, and effectiveness in transplant treatment plans via telehealth. Results: COVID‐19 has caused an increase in mortality, morbidity, hospitalization, and ICU admission in SOTRs. Telehealth efficacy and benefits to both patients and physicians have increasingly been reported. Conclusions: Developing effective systems of telehealth delivery has become a top priority for healthcare providers during the COVID‐19 pandemic. Further research is necessary to validate the effectiveness of telehealth in other settings. [ABSTRACT FROM AUTHOR]

Author(s): Rupesh Raina [sup.1] [sup.2] , Sidharth Kumar Sethi [sup.3] , Timothy Bunchman [sup.4] Author Affiliations: (1) grid.413473.6, 0000 0000 9013 1194, Department of Nephrology, Akron Children's Hospital, , Akron, [...]

Background: Pediatric sepsis is a significant public health issue. This condition is exacerbated by rising serum creatinine and inflammatory cytokines that lead to deleterious effects upon the body. The current standard of care involves the use of continuous kidney replacement therapy to remove harmful cytokines until the body returns to homeostasis. In order to promote faster clearance and reduced stay in the ICU, high-volume hemofiltration (HVHF) has shown promise. However, there is a paucity of studies to fully elucidate its benefits. Methods: A literature search was done using PubMed/ MEDLINE and Embase. The literature was reviewed by two independent reviewers, who independently assessed the quality of randomized controlled trials by using the Cochrane risk of bias tool for RCTs and Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized controlled trials. Data were combined from studies with a similar design. Results: The primary endpoint of all-cause mortality was found to be reduced by 40% across all of the pooled studies. For secondary endpoints, significant reductions of serum creatinine were found. Additionally, duration of ICU stays and treatment course was found to be significantly shorter in HVHF patients than the current standard of care. The rate of adverse effects was analyzed, and there was no difference in the proportion of patients developing hypokalemia, hyperkalemia, hypernatremia, or hyponatremia. The proportion of patients developing hyperglycemia was higher in patients undergoing HVHF, whereas the proportions of patients developing bleeding were significantly less in patients undergoing HVHF. One study reported a total number of adverse events between the two groups which were significantly lesser in patients undergoing HVHF. Conclusion: HVHF shows promise as a modality to treat pediatric patients with sepsis. In order to confirm the benefits of this modality, future studies need significantly more patients for analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7–19) vs. 7 (5–10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74–14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934–0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives. [ABSTRACT FROM AUTHOR]