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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]

Kidney replacement therapy (KRT) is used to provide supportive therapy for critically ill patients with severe acute kidney injury and various other non-renal indications. Modalities of KRT include continuous KRT (CKRT), intermittent hemodialysis (HD), and sustained low efficiency daily dialysis (SLED). However, circuit clotting is a major complication that has been investigated extensively. Extracorporeal circuit clotting can cause reduction in solute clearances and can cause blood loss, leading to an upsurge in treatment costs and a rise in workload intensity. In this educational review, we discuss the pathophysiology of the clotting cascade within an extracorporeal circuit and the use of various types of anticoagulant methods in various pediatric KRT modalities. [ABSTRACT FROM AUTHOR]

COVID‐19 has challenged the global healthcare system through rapid proliferation and lack of existing treatment resulting in over 180 million cases and 3.8 million deaths since December 2019. Although pediatric patients only comprise 1%–2% of diagnosed cases, their incidence of acute kidney injury ranges from 8.2% to 18.2% compared to 49% in adults. Severe infection, initiated by dysregulated host response, can lead to multiorgan failure. In this review, we focus on the use of various blood filters approved for use in pediatric kidney replacement therapy to mitigate adverse effects of severe illness. Therapeutic effects of these blood filters range from cytokine removal (CytoSorb, HA330, HCO/MCO), endotoxin removal (Toraymyxin, CPFA), both cytokine and endotoxin removal (oXiris), and nonspecific removal of proteins (PMMA) that have already been established and can be used to mitigate the various effects of the cytokine storm syndrome in COVID‐19. [ABSTRACT FROM AUTHOR]

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: The recent worldwide pandemic of COVID-19 has been a serious, multidimensional problem that has left a detrimental worldwide impact on individuals of all ages and several organ systems. The typical manifestation of kidney involvement is acute kidney injury (AKI); however, there is a lack of consensus data regarding AKI epidemiology in COVID-19. This systematic literature review aims to bridge this knowledge gap. Design, Setting, Participants, and Measurements: MEDLINE and Cochrane library were systematically searched for the literature related to AKI in COVID-19 patients of all ages. MedRxIV was searched for relevant unpublished manuscripts. Two reviewers independently assessed the literature on the incidence of AKI and mortality, extracting the need for kidney replacement therapy (KRT). Results: Sixty studies (n = 43,871 patients) were included in this review. The pooled incidence of AKI among COVID-19 patients was 19.45% (95% confidence intervals [95% CI]: 14.63–24.77%), while the pooled incidence of AKI COVID-19 patients requiring KRT was 39.04% (16.38–64.57%). The pooled proportion of COVID+ patients was significantly lower at 8.83% (5.64% to 12/66%). The overall mortality of COVID-19 patients was calculated to be 17.71% (95% CI: 11.49–24.93%), while the mortality among patients with AKI was higher at 54.24% (95% CI: 44.70–63.63%). Conclusion: This comprehensive systematic review summarizes the available literature pertaining to AKI epidemiology in COVID-19 patients and highlights the incidence, associated mortality, and the need for KRT in this susceptible population. [ABSTRACT FROM AUTHOR]

Background: Despite extensive research into acute kidney injury (AKI) in adults, research into the epidemiology, associated risk factors, treatment, and mortality of AKI in pediatric COVID-19 patients is understudied. Advancing understanding of this disease is crucial to further developing treatment and preventative care strategies to reduce morbidity and mortality. Methods: This is a retrospective analysis of 2,546 COVID-19 pediatric patients (age ≤ 21 years) who were admitted the ICU in North America. Analysis of the Virtual Pediatric Systems (VPS) COVID-19 database was conducted between January 1, 2020, and June 30, 2021. Results: Out of a total of 2,546 COVID positive pediatric patients, 10.8% (n = 274) were diagnosed with AKI. Significantly higher continuous and categorical outcomes in the AKI subset compared to the non-AKI cohort included: length of stay at the hospital (LOS) [9.04 (5.11–16.66) vs. 5.09 (2.58–9.94) days], Pediatric Index of Mortality (PIM) 2 probability of death [1.20 (0.86–3.83) vs. 0.96 (0.79–1.72)], PIM 3 probability of death [0.98 (0.72–2.93) vs. 0.78 (0.69–1.26)], mortality [crude OR (95% CI): 5.01 (2.89–8.70)], airway and respiratory support [1.63 (1.27–2.10)], cardio-respiratory support [3.57 (1.55–8.23)], kidney support [12.52 (5.30–29.58)], and vascular access [4.84 (3.70–6.32)]. Conclusions: This is one of the first large scale studies to analyze AKI among pediatric COVID-19 patients admitted to the ICU in North America. Although the course of the COVID-19 virus appears milder in the pediatric population, renal complications may result, increasing the risk of disease complication and mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and objectives: COVID-19 is responsible for the 2019 novel coronavirus disease pandemic. Despite the vast research about the adult population, there has been little data collected on acute kidney injury (AKI) epidemiology, associated risk factors, treatments, and mortality in pediatric COVID-19 patients admitted to the ICU. AKI is a severe complication of COVID-19 among children and adolescents. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE and Cochrane Center Trials to find all published literature related to AKI in COVID-19 patients, including incidence and outcomes. Results: Twenty-four studies reporting the outcomes of interest were included. Across all studies, the overall sample size of COVID positive children was 1,247 and the median age of this population was 9.1 years old. Among COVID positive pediatric patients, there was an AKI incidence of 30.51%, with only 0.56% of these patients receiving KRT. The mortality was 2.55% among all COVID positive pediatric patients. The incidence of multisystem inflammatory syndrome in children (MIS-C) among COVID positive patients was 74.29%. Conclusion: AKI has shown to be a negative prognostic factor in adult patients with COVID-19 and now also in the pediatric cohort with high incidence and mortality rates. Additionally, our findings show a strong comparison in epidemiology between adult and pediatric COVID-19 patients; however, they need to be confirmed with additional data and studies. [ABSTRACT FROM AUTHOR]

Kidney replacement therapy (KRT) is a common supportive treatment for renal dysfunction, especially acute kidney injury. However, critically ill or immunosuppressed patients with renal dysfunction often have dysfunction in other organs as well. To improve patient outcomes, clinicians began to initiate kidney replacement therapy in situations where nonrenal conditions may lead to acute kidney injury, such as septic shock, hematopoietic stem cell transplantation, veno‐occlusive renal disease, cardiopulmonary bypass, chemotherapy, tumor lysis syndrome, hyperammonemia, and various others. In this review, we discuss the use of various modes of kidney replacement therapy in treating renal and nonrenal complications to illustrate why kidney support therapy is a more appropriate terminology than kidney replacement therapy. [ABSTRACT FROM AUTHOR]

Background: There are similarities in hemodialysis (HD) between adults and children and also unique pediatric aspects. In this systematic review, we evaluated the existing HD literature, including vascular access, indications, parameters, and outcomes as a reflection on real-life HD practices. Methods: Medline, Embase, CINAHL, Web of Science, and Cochrane Library were systematically searched for literature on HD in children (1–20 years). Two reviewers independently assessed the literature and data on indications; vascular access, outcomes, and specific parameters for HD were extracted. Results: Fifty-four studies (8751 patients) were included in this review. Studies were stratified into age groups 1–5, 6–12, and 13–20 years based on median/mean age reported in the study, as well as era of publication (1990–2000, 2001–2010, and 2011–2019). Across all age groups, both arteriovenous fistulas and central venous catheters were utilized for vascular access. Congenital abnormalities and glomerulopathy were the most common HD indications. HD parameters including HD session duration, dialysate and blood flow rates, urea reduction ratio, and ultrafiltration were characterized for each age group, as well as common complications including catheter dysfunction and intradialytic hypotension. Median mortality rates were 23.3% (3.3), 7.6% (14.5), and 2.0% (3.0) in ages 1–5, 6–12, and 13–20 years, respectively. Median transplantation rates were 41.6% (38.3), 52.0% (32.0), and 21% (25.6) in ages 1–5, 6–12, and 13–20, respectively. Conclusion: This comprehensive systematic review summarizes available literature on HD in children and young adults, including best vascular access, indications, technical aspects, and outcomes, and reflects on HD practices over the last three decades. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the preferred treatment of end‐stage renal disease in children. However, time to transplant varies, making a well‐functioning long‐term vascular access essential for performing hemodialysis efficiently and without disruption until a kidney becomes available. However, establishing long‐term vascular access in pediatric patients can present distinct challenges due to this population's unique characteristics, such as smaller body size and lower‐diameter blood vessels. There are three main pediatric long‐term vascular access options, which include central venous catheters (CVC), arteriovenous fistula (AVF), and arteriovenous graft (AVG). CVC are currently the most widely used modality, although various studies and guidelines recommend AVF or AVG as the preferred option. Although AVF should be used whenever possible, it is crucial that clinicians consider factors such as patient size, physical exam findings, comorbidities, predicted duration of treatment to decide on the most optimal long‐term vascular access modality. This article reviews the three long‐term vascular access methods in children and the benefits and complications of each. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common in critically ill children and affects nearly 30–40% of patients admitted to the pediatric intensive care unit (ICU). Even with technological advances in critical care and dialysis, there is a high mortality rate of 66.8% to 90% in ICU patients. Renal replacement therapy (RRT) is often performed to treat patients with AKI. However, for optimal RRT treatment, it is crucial to consider the indications, modes of access, and prescription of each RRT method. Therefore, this review aims to discuss the various modalities of RRT in pediatric patients, which include peritoneal dialysis (PD), hemodialysis (HD), continuous RRT (CRRT), and sustained low-efficiency dialysis (SLED). [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is one of the most frequent and severe glomerular kidney disease with frequent progression to end-stage renal disease and a high rate of recurrence in renal transplantations. Due to intolerance or resistance to the current immunomodulatory treatments, the management of FSGS is a therapeutic challenge. Over the last few years, development in extracorporeal therapies has shown potential beneficial outcomes in drug-resistant and recurrent FSGS patients. Thus, this study reviews the current literature on the use of extracorporeal therapies, such as plasma exchange therapy, immunoadsorption, and low-density lipoprotein apheresis, for the treatment of FSGS in the pediatric population. [ABSTRACT FROM AUTHOR]

Background. In recent years, the use of adrenocorticotropic hormone (ACTH) therapy for treatment of proteinuria due to nephrotic syndrome (NS) has been heavily explored. ACTH therapy, which comes in the natural (H. P. Acthar Gel) or synthetic (tetracosactide) form, has resulted in remission in patients with immunosuppressive and steroid-resistant NS. However, the exact efficacy of ACTH therapy in the NS etiologies, such as membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), lupus nephritis (LN), IgA nephropathy (IgAN), and membranoproliferative glomerulonephritis (MPGN), has not been determined. Objective. This systematic review analyzed the published literature on ACTH therapy in various NS etiologies to determine its efficacy. Methods. A comprehensive search of MEDLINE, EMBASE, and Cochrane databases was conducted for articles through June 2019. An additional search was performed on clinicaltrials.gov to search for additional trials and cross reference the results of our database search. The literature which studied synthetic or natural ACTH treatment in patients with known etiologies of NS was included. Studies were excluded when they consisted of a single case report or did not analyze the lone effect of ACTH in NS. Results. The initial search yielded a total of 411 papers, and 22 papers were included. In 214 MN patients, there was an overall remission of 40% (85/214) and an overall remission of 43% (42/98) in FSGS patients. In other etiologies, there were overall remissions of 78% (11/14), 31% (5/16), 40% (16/40), and 62% (8/13) in MCD, LN, IgAN, and MPGN patients, respectively. Conclusion. ACTH showed benefits in proteinuria reduction across all etiologies of NS. However, more randomized controlled studies with larger population sets and longer follow-ups are imperative to establish causal benefits. New studies into its efficacy in children are also necessary. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chronic kidney disease and end-stage renal disease (ESRD) in children are major health concerns worldwide with increasing incidence and prevalence. Renal replacement therapies and kidney transplants have remarkably improved the management of patients with ESRD in both adult and pediatric populations. Kidney transplant has the best patient outcomes, but many a time it has a considerable waiting period. In the meantime, the majority of patients with pediatric ESRD are dependent on dialysis. The conventionally utilized hemodialysis regimen is the three times weekly, in-center hemodialysis. Many studies have demonstrated the unfavorable long-term morbidity associated with the conventional regimen. Intensified dialysis programs, which include extended nocturnal hemodialysis or short daily hemodialysis, are being increasingly advocated over the past two decades. In addition to having much better clinical outcomes as compared with the conventional regimen, the flexibility to provide dialysis at home serves as a great incentive. PubMed/Medline, Embase and Cochrane databases for literature on nocturnal home hemodialysis in children with ESRD were extensively searched. Contrary to the noticeable literature available on adult home hemodialysis, a small number of studies exist in the pediatric population. In this review, the benefits, implementation and associated barriers of nocturnal home hemodialysis in children were addressed. [ABSTRACT FROM AUTHOR]