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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.

Hematuria or proteinuria may be just a normal transient finding in children, usually accompanying a non-specific viral infection, or it can be an indicator of a kidney or urinary tract disorder. In this chapter, the various causes and significance of discolored urine, hematuria and proteinuria in children are discussed. A pragmatic clinical approach to evaluate a child with isolated hematuria or isolated proteinuria is suggested to reduce unnecessary extensive workup in benign cases and yet not miss the cases with significant glomerular or urinary tract disease. Early detection and treatment of significant disorders would hopefully delay or prevent the onset of renal insufficiency in children.

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.

Rituximab is an important second line therapy in difficult nephrotic syndrome (NS), especially given toxicity of long-term glucocorticoid or calcineurin inhibitor (CNI) use. However, clinical response to rituximab is heterogenous. We hypothesized that this was underpinned by immunological differences amongst patients with NS. We recruited a cohort of 18 subjects with glucocorticoid-dependent or glucocorticoid-resistant childhood-onset minimal change NS who received rituximab either due to CNI nephrotoxicity, or due to persistent glucocorticoid toxicity with inadequate response to cyclophosphamide or CNIs. Immunological subsets, T-cell activation assays and plasma cytokines were measured at baseline and 6-months post-rituximab. Time to relapse was bifurcated: 56% relapsed within one year ("early relapse"), while the other 44% entered remission mainly lasting ≥3 years ("sustained remission"). At baseline, early relapse compared to sustained remission group had lower regulatory T-cells (Tregs) [2.94 (2.25, 3.33)% vs 6.48 (5.08, 7.24)%, P

After nearly three years of the COVID-19 pandemic, research has affirmed that COVID-19 is more than just a respiratory virus. There have been significant breakthroughs made surrounding the development of acute kidney injury (AKI) and chronic kidney disease (CKD), in pediatric populations. Additionally, patient populations susceptible to renal complications consist of pediatric transplant recipients, multisystem inflammatory syndrome (MIS-C), and dialysis. Although research is gradually becoming more available surrounding this prevalent topic, knowledge is sparse on the deleterious effects of COVID-19 on pediatric patients with kidney disease and requires more in-depth analysis. The virtual international conference, Pediatric Critical Care Nephrology & Dialysis Course, on August 7th, 2021, reviewed the severe cases of COVID-19 in the global pediatric population. By integrating international perspectives, statistics, techniques, and treatments for managing renal complications, we further develop scientific understanding of the renal complications seen in children with COVID-19 globally.

Background More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. Methods Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology—Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8–21 years) and caregivers (of children ages 0–21 years) pertaining to blood pressure. Results Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). Conclusions For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD.

Decline in skills and knowledge among patients and/or caregivers contributes to peritoneal-dialysis (PD)-related peritonitis. Re-training is important, but no guidelines exist. We describe the implementation of a structured re-training program to decrease peritonitis rates. This is a prospective quality improvement study involving pediatric patients on long-term home automated PD at National University Hospital, Singapore, between 2012 and 2018. With increasing peritonitis rates, systematic root cause analysis was performed, and based on the contributory factors identified, a structured re-training program was implemented from 2015. This was conducted in 5 cycles, each consisting of 4 modules (hand hygiene, exit site care, peritonitis, and PD troubleshooting). Peritonitis rates were analyzed in 2 phases: Phase 1 (2012–2014) when no re-training was performed and Phase 2 (2016–2018) after re-training was instituted. Fifty-nine patients were included. Of these, 45 patients were in Phase 1, 32 in Phase 2, and 18 in both phases. Peritonitis rates decreased from 0.37 ± 0.67 episodes per patient-year in Phase 1 to 0.13 ± 0.32 episodes per patient-year in Phase 2. After adjusting for age at kidney failure onset, PD vintage, years of nursing experience, and the average patient-to-nurse ratio over the study period for each patient, the adjusted peritonitis rates decreased by 0.38 episodes per patient-year (95% CI, 0.09 to 0.67, p = 0.011) from Phase 1 to Phase 2. Despite an improvement in staffing ratio, peritonitis rates only improved significantly after intensive structured re-training was instituted.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

Peritonitis- and catheter-related infections due to nontuberculous mycobacteria (NTM) including Mycobacterium abscessus have been reported among adults on peritoneal dialysis (PD). There is no recommended antimicrobial regimen for the treatment of M. abscessus peritonitis. Clofazimine has emerged as an important adjuvant antimicrobial treatment of M. abscessus lung infection. We report, to our knowledge, the first case of M. abscessus PD peritonitis in a child treated successfully using clofazimine as a novel adjuvant therapy to amikacin and clarithromycin. Her clinical features were similar to those of bacterial peritonitis, but she had persistence of symptoms and high inflammatory markers despite empirical therapy for peritonitis. Bacterial culture of PD effluent became positive for M. abscessus after 5 days. There was complete symptom resolution after 6 days of multidrug therapy. Due to ototoxicity, amikacin was discontinued after 6 weeks, while clarithromycin and clofazimine were continued for 9 months to ensure complete pathogen eradication before a planned renal transplant. A high index of suspicion in refractory or culture-negative cases is important for the diagnosis of NTM peritonitis. Multidrug therapy is recommended for M. abscessus infections. Clofazimine was chosen as a novel adjunct antimicrobial because of its pharmacokinetics, ease of administration, cost-effectiveness, and lack of serious adverse events.

International audience; Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods.

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6–13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3–7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P

Background: Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support. Methods: Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically. Results: We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child’s suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood). Conclusions: Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. Graphical Abstract: A higher resolution version of the Graphical abstract is available as Supplementary information. [Figure not available: see fulltext.]

Introduction The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic. Methods Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians. Results We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier than in-person visits. Patients also felt that the quality of their visits were equivalent to what they would receive in person. Physicians used a wide variety of online systems to conduct synchronous telemedicine with Zoom (23%), EPIC (9%), Doxy.me (7%), services not specified (37%), or a mix of local or smaller services (24%). Most physicians' concerns were related to technological issues and the ability to procure physical exams and/or laboratory results. Conclusions There is a paucity of published trials on telemedicine services in pediatric nephrology. Virtual care was feasible and acceptable for patients, caregivers, and providers during the COVID-19 pandemic., Graphical abstract

Circulating factors have been implicated in the pathogenesis of minimal change disease (MCD), and may have direct effects on cholesterol metabolism. This study investigated the pathogenesis of hypercholesterolemia in an IL-13 overexpression rat model of MCD prior to the onset of proteinuria, so as to establish the direct contribution of IL-13, especially with regard to hepatic cholesterol handling. In this model of MCD, the temporal relationship between hypercholesterolemia and proteinuria was first identified. Plasma proprotein convertase subtilisin/kexin type 9 (Pcsk9) and liver ATP-binding cassette sub-family G member 5 (Abcg5) were measured using ELISA. Liver Ldlr and liver X receptor alpha (Lxra) were quantified with Western blot. Abcg5-mediated cholesterol efflux in IL-13-stimulated rat primary hepatocytes was measured using taurocholate as cholesterol acceptor. The role of Lxra was validated using a luciferase assay in Lxre-luciferase-transfected IL-13-stimulated hepatocytes. IL-13-transfected rats developed hypercholesterolemia prior to proteinuria, with 35% of rats hypercholesterolemic but only 11% proteinuric by Day 20 (P = 0.04). These pre-proteinuric hypercholesterolemic rats showed elevations in total and LDL-cholesterol, but not hypertriglyceridemia or hepatic steatosis. The hypercholesterolemia was associated with increased hepatic Pcsk9 synthesis and enhanced circulating Pcsk9 levels, which correlated strongly with plasma total cholesterol (r = 0.73, P

Intentional or unintentional ingestions among children and adolescents are common. There are a number of ingestions amenable to renal replacement therapy (RRT). We systematically searched PubMed/Medline, Embase, and Cochrane databases for literature regarding drugs/intoxicants and treatment with RRT in pediatric populations. Two experts from the PCRRT (Pediatric Continuous Renal Replacement Therapy) workgroup assessed titles, abstracts, and full-text articles for extraction of data. The data from the literature search was shared with the PCRRT workgroup and two expert toxicologists, and expert panel recommendations were developed. We have presented the recommendations concerning the use of RRTs for treatment of intoxications with toxic alcohols, lithium, vancomycin, theophylline, barbiturates, metformin, carbamazepine, methotrexate, phenytoin, acetaminophen, salicylates, valproic acid, and aminoglycosides.

Rationale & Objective: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers. Study Design: We used the nominal group technique whereby participants identified and ranked outcomes and explained their priorities. Settings & Participants: Young people with CKD (stages 1-5, dialysis, or transplantation) and their caregivers were purposively sampled from 6 centers across Australia, the United States, and Canada. Analytical Approach: Importance scores were calculated (scale of 0-1), and qualitative data were analyzed thematically. Results: 34 patients (aged 8-21 years) and 62 caregivers participated in 16 groups and identified 48 outcomes. The 5 highest ranked outcomes for patients were survival (importance score, 0.25), physical activity (0.24), fatigue (0.20), lifestyle restrictions (0.20), and growth (0.20); and for caregivers, kidney function (0.53), survival (0.28), infection (0.22), anemia (0.20), and growth (0.17). 12 themes were identified reflecting their immediate and current priorities (wanting to feel normal, strengthening resilience, minimizing intrusion into daily life, imminent threats to life, devastating family burdens, and seeking control over health) and considerations regarding future impacts (protecting health/development, remaining hopeful, concern for limited opportunities, prognostic uncertainty, dreading painful and invasive procedures, and managing expectations). Limitations: Only English-speaking participants were recruited. Conclusions: Kidney function, infection, survival, and growth were the highest priorities for patients with CKD and their caregivers. Young people with CKD also prioritized highly the outcomes that directly affected their lifestyle and sense of normality, while caregiver's highest priorities concerned the long-term health of their child, current health problems, and the financial and family burdens of caring for a child with CKD.

Rationale & Objective: Clinical decision-making priorities may differ among children, their parents, and their clinicians. This study describes clinicians’ perspectives on shared decision making in pediatric chronic kidney disease (CKD) and identifies opportunities to improve shared decision making and care for children with CKD and their families. Study Design: Semistructured interviews. Setting & Participants: Fifty clinicians participated, including pediatric nephrologists, nurses, social workers, surgeons, dietitians, and psychologists involved in providing care to children with CKD. They worked at 18 hospitals and 4 university research departments across 11 countries (United States of America, Canada, Australia, People's Republic of China, United Kingdom, Germany, France, Italy, Lithuania, New Zealand, and Singapore). Analytical Approach: Interview transcripts were analyzed thematically. Results: We identified 4 themes: (1) striving to blend priorities (minimizing treatment burden, emphasizing clinical long-term risks, achieving common goals), (2) focusing on medical responsibilities (carrying decisional burden and pressure of expectations, working within system constraints, ensuring safety is foremost concern), (3) collaborating to achieve better long-term outcomes (individualizing care, creating partnerships, encouraging ownership and participation in shared decision making, sensitive to parental distress), and (4) forming cumulative knowledge (balancing reassurance and realistic expectations, building understanding around treatment, harnessing motivation for long-term goals). Limitations: Most clinicians were from high-income countries, so the transferability of the findings to other settings is uncertain. Conclusions: Clinicians reported striving to minimize treatment burden and working with children and their families to manage their expectations and support their decision making. However, they are challenged with system constraints and sometimes felt the pressure of being responsible for the child's long-term outcomes. Further studies are needed to test whether support for shared decision making would promote strategies to establish and improve the quality of care for children with CKD.

BACKGROUND Acute kidney injury (AKI) develops in 4% of hospitalized patients and is a marker of clinical deterioration and nephrotoxicity. AKI onset is highly variable in hospitals, which makes it difficult to time biomarker assessment in all patients for preemptive care. OBJECTIVE The study sought to apply machine learning techniques to electronic health records and predict hospital-acquired AKI by a 48-hour lead time, with the aim to create an AKI surveillance algorithm that is deployable in real time. METHODS The data were sourced from 20,732 case admissions in 16,288 patients over 1 year in our institution. We enhanced the bidirectional recurrent neural network model with a novel time-invariant and time-variant aggregated module to capture important clinical features temporal to AKI in every patient. Time-series features included laboratory parameters that preceded a 48-hour prediction window before AKI onset; the latter’s corresponding reference was the final in-hospital serum creatinine performed in case admissions without AKI episodes. RESULTS The cohort was of mean age 53 (SD 25) years, of whom 29%, 12%, 12%, and 53% had diabetes, ischemic heart disease, cancers, and baseline eGFR 2, respectively. There were 911 AKI episodes in 869 patients. We derived and validated an algorithm in the testing dataset with an AUROC of 0.81 (0.78-0.85) for predicting AKI. At a 15% prediction threshold, our model generated 699 AKI alerts with 2 false positives for every true AKI and predicted 26% of AKIs. A lowered 5% prediction threshold improved the recall to 60% but generated 3746 AKI alerts with 6 false positives for every true AKI. Representative interpretation results produced by our model alluded to the top-ranked features that predicted AKI that could be categorized in association with sepsis, acute coronary syndrome, nephrotoxicity, or multiorgan injury, specific to every case at risk. CONCLUSIONS We generated an accurate algorithm from electronic health records through machine learning that predicted AKI by a lead time of at least 48 hours. The prediction threshold could be adjusted during deployment to optimize recall and minimize alert fatigue, while its precision could potentially be augmented by targeted AKI biomarker assessment in the high-risk cohort identified.

Objective We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. Methods Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. Results The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03–0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002–0.000001). Conclusion The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Although the use of telemedicine in rural areas has increased steadily over the years, its use was rapidly implemented during the onset of the coronavirus disease 2019 (COVID-19) crisis. Due to this rapid implementation, there is a lack of standardized work flows to assess and treat for various nephrotic conditions, symptoms, treatment modalities, and transition processes in the pediatric population. To provide a foundation/suggestion for future standardized work flows, the authors of this report have developed standardized work flows using the Delphi method. These work flows were informed based on results from cross-sectional surveys directed to patients and providers. Most patients and providers were satisfied, 87% and 71%, respectively, with their telemedicine visits. Common issues that were raised with the use of telemedicine included difficulty procuring physical laboratory results and a lack of personal warmth during telemedicine visits. The work flows created based on these suggestions will both enhance safety in treating patients and allow for the best possible care.

Worldwide, the number of end-stage renal disease (ESRD) patients has been rapidly increasing, with more than a million patients receiving dialysis therapy. Coverage of renal replacement therapy (RRT) is usually directly related to country-specific gross national income (GNI). In pediatrics, global data from the International Pediatric Peritoneal Dialysis Network (IPPN) showed that dialysis patient survival was associated with GNI status, being significantly higher in high-income economies (94.1% at 5 years), compared to middle- and low-income countries combined (88.7%). The provision of RRT, funding, dialysis modality, ESRD etiology, technical resources, and trained healthcare professionals also show important variation across regions around the world, most of the cases directly related to economic and cultural factors. The IPPN data also showed that these differences do have an impact on growth, nutrition, biochemical status, and dialysis-related complications such as peritonitis, especially in children with chronic kidney disease in the developing world. This chapter provides an analysis of the differences in RRT around the world, allowing a better understanding of the ways to improve dialysis programs for children and adolescents in developing regions.

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.

Acute kidney injury continues to be a highly occurring disease in the intensive care unit, specifically affecting up to a third of critically ill neonates as per various studies. Although first-line treatments of acute kidney injury are noninvasive, kidney replacement therapy (KRT) is indicated when conservative management modes fail. There are various modalities of KRT which can be used for neonatal populations, including peritoneal dialysis, hemodialysis, and continuous KRT. However, these KRT modalities present their own challenges in this specific patient population Thus, it is the aim of this review to introduce each of these KRT modalities in terms of their challenges, advances, and future directions, with specific emphasis on new technology including the Cardio-Renal Pediatric Emergency Dialysis Machine, Newcastle infant dialysis and ultrafiltration system, and the Aquadex system for ultrafiltration.

Kidney disease is a global public health concern across the age spectrum, including in children. However, our understanding of the true burden of kidney disease in low-resource areas is often hampered by a lack of disease awareness and access to diagnosis. Chronic kidney disease (CKD) in low-resource settings poses multiple challenges, including late diagnosis, the need for ongoing access to care and the frequent unavailability of costly therapies such as dialysis and transplantation. Moreover, children in such settings are at particular risk of acute kidney injury (AKI) owing to preventable and/or reversible causes - many children likely die from potentially reversible kidney disease because they lack access to appropriate care. Acute peritoneal dialysis (PD) is an important low-cost treatment option. Initiatives, such as the Saving Young Lives programme, to train local medical staff from low-resource areas to provide care for AKI, including acute PD, have already saved hundreds of children. Future priorities include capacity building for both educational purposes and to provide further resources for AKI management. As local knowledge and confidence increase, CKD management strategies should also develop. Increased awareness and advocacy at both the local government and international levels will be required to continue to improve the diagnosis and treatment of AKI and CKD in children worldwide.

A lack of consensus exists as to the timing of kidney biopsy in children with steroid-dependent nephrotic syndrome (SDNS) where minimal change disease (MCD) predominates. This study aimed at examining the applicability of a biomarker-assisted risk score model to select SDNS patients at high risk of focal segmental glomerulosclerosis (FSGS) for biopsy. Fifty-five patients with SDNS and biopsy-proven MCD (n = 40) or FSGS (n = 15) were studied. A risk score model was developed with variables consisting of age, sex, eGFR, suPAR levels and percentage of CD8+ memory T cells. Following multivariate regression analysis, total risk score was calculated as sum of the products of odds ratios and corresponding variables. Predictive cut-off point was determined using receiver operator characteristics (ROC) curve analysis. Plasma suPAR levels in FSGS patients were significantly higher, while percentage of CD45RO+CD8+CD3+ was significantly lower than in MCD patients and controls. ROC analysis suggests the risk score model with threshold score of 16.7 (AUC 0.84, 95% CI 0.72–0.96) was a good predictor of FSGS on biopsy. The 100% PPV cut-off was >24.0, while the 100% NPV was

Coronavirus disease 2019 (COVID-19) has rapidly spread not only in China but throughout the world. Children with kidney failure (chronic kidney disease (CKD) stage 5) are at significant risk for COVID-19. In turn, a set of recommendations for the prevention and control of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 in pediatric hemodialysis (HD) centers and in home peritoneal dialysis (PD) settings have been proposed. The recommendations are based on the epidemiological features of the SARS-CoV-2 virus and COVID-19 disease, susceptibility factors, and preventive and control strategies. These recommendations will be updated as new information regarding SARS-CoV-2 and COVID-19 becomes available.

Objective The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6–17 years, with or without chronic kidney disease (CKD). Methods This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram. Results Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (− 14.9 mmHg and − 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients. Conclusions Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.

Background: Peritoneal dialysis (PD) remains the most widely used modality for chronic dialysis in children, particularly in younger children and in lower and middle income countries (LMICs). We present guidelines for dialysis initiation, modality selection, small solute clearance, and fluid removal in children on PD. A review of the literature and key studies that support these statements are presented. Methods: An extensive Medline search for all publications on PD in children was performed using predefined search criteria. Results: High-quality randomized trials in children are scarce and current clinical practice largely relies on data extrapolated from adult studies or drawn from observational cohort studies in children. The evidence and strength of the recommendation is GRADE-ed, but in the absence of high-quality evidence, the opinion of the authors is provided and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate. We discuss the timing of dialysis initiation, factors to be considered when selecting a dialysis modality, the assessment and management of volume status on PD, achieving optimal small solute clearance, and the importance of preserving residual kidney function. While optimal dialysis must remain the goal for every patient, a careful discussion with fully informed patients and caregivers is important to understand the patient and family’s expectations of dialysis and reasonable adjustments to the dialysis program may be considered in accordance with a philosophy of shared decision-making. Conclusions: There continues to be very poor evidence in the field of chronic PD in children and these recommendations can at best serve to guide clinical decision-making. In LMICs, every effort should be made to conform to the framework of these statements, taking into account resource limitations.

Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.

Rationale & Objective: The inconsistency in outcomes reported and lack of patient-reported outcomes across trials in children with chronic kidney disease (CKD) limits shared decision making. As part of the Standardized Outcomes in Nephrology (SONG)-Kids initiative, we aimed to generate a consensus-based prioritized list of critically important outcomes to be reported in all trials in children with CKD. Study Design: An online 2-round Delphi survey in English, French, and Hindi languages. Settings & Participants: Patients (aged 8-21 years), caregivers/family, and health care professionals (HCPs) rated the importance of outcomes using a 9-point Likert scale (7-9 indicating critical importance) and completed a Best-Worst Scale. Analytical Approach: We assessed the absolute and relative importance of outcomes. Comments were analyzed thematically. Results: 557 participants (72 [13%] patients, 132 [24%] caregivers, and 353 [63%] HCPs) from 48 countries completed round 1 and 312 (56%) participants (28 [40%] patients, 64 [46%] caregivers, and 220 [56%] HCPs) completed round 2. Five outcomes were common in the top 10 for each group: mortality, kidney function, life participation, blood pressure, and infection. Caregivers and HCPs rated cardiovascular disease higher than patients. Patients gave lower ratings to all outcomes compared with caregivers/HCPs except they rated life participation (round 2 mean difference, 0.1), academic performance (0.1), mobility (0.4), and ability to travel (0.4) higher than caregivers and rated ability to travel (0.4) higher than HCPs. We identified 3 themes: alleviating disease and treatment burden, focusing on the whole child, and resolving fluctuating and conflicting goals. Limitations: Most participants completed the survey in English. Conclusions: Mortality, life participation, kidney function, and blood pressure were consistently highly prioritized by patients, caregivers, and HCPs. Patients gave higher priority to some lifestyle-related outcomes compared with caregivers/HCPs. Establishing critically important outcomes for all trials in children with CKD may improve consistent reporting of survival, kidney health, and clinical and life impact outcomes that are meaningful for decision making.

Our established interleukin-13 (IL-13) overexpression rat model of minimal change-like nephropathy provided a platform to study the molecular signalling pathways in T-helper 2 (Th2) cytokine associated minimal change nephrotic syndrome (MCNS). We hypothesized that IL-13 may act directly on podocytes, causing podocyte foot process effacement and hence proteinuria in our rat model of minimal change-like nephropathy. The present study aimed firstly to delineate the glomerular ‘gene signature’ associated with IL-13-mediated dysregulation of podocyte-related proteins, and subsequently to investigate the role of the differentially regulated genes (DEGs) in IL-13-mediated podocyte injury. Glomerular transcriptional profile of IL-13-overexpressed rats showed characteristic features of podocyte injury with 87% of podocyte-related genes being significantly down-regulated. Gene expression of Vav1 was shown to be highly up-regulated in the glomeruli of IL-13-overexpressed rats and pathway analysis of the DEGs suggested a possible novel role of Vav1 in podocyte cytoskeleton remodelling. Immunofluorescence examination demonstrated glomerular expression of Vav1 in rats which co-localized with synaptopodin, confirming podocyte expression. However, positive staining for the phosphorylated form of Vav1 (p-Vav1) was only seen in IL-13-overexpressed rats. Moreover, in vitro IL-13 stimulation of human podocytes resulted in phosphorylation of Vav1. This was associated with Rac1 activation and actin cytoskeleton rearrangement, which was abrogated in Vav1 knockdown podocytes. In conclusion, we have demonstrated the role of Vav1-Rac1 pathway characterized by phosphorylation of Vav1, activation of Rac1 and the subsequent actin cytoskeleton rearrangement in IL-13-induced podocyte injury, possibly explaining the podocyte foot process effacement seen in our IL-13 overexpression rat model.

The incidence of acute kidney injury (AKI) especially among critically ill infants and children is on the rise. Improved acute care has contributed to the increased prevalence of pediatric AKI survivors who are at risk for long-term adverse patient and renal outcomes. Recent studies both in adult and pediatric AKI survivors from either community or hospital settings have demonstrated that mortality risk persists even after hospital discharge. In addition, proteinuria, hypertension, incident or progressive chronic kidney disease, and end-stage kidney disease have been shown to occur among survivors of AKI. Despite the compelling evidence, there is no universal system in place addressing post-discharge care and long-term follow-up for risk stratification and management of adverse outcomes.