Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Concurrent use of continuous kidney replacement therapy during extracorporeal membrane oxygenation: what pediatric nephrologists need to know-PCRRT-ICONIC practice points.

Extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support for neonatal, pediatric, and adult patients when traditional management has failed. This lifesaving therapy has intrinsic risks, including the development of a robust inflammatory response, acute kidney injury (AKI), fluid overload (FO), and blood loss via consumption and coagulopathy. Continuous kidney replacement therapy (CKRT) has been proposed to reduce these side effects by mitigating the host inflammatory response and controlling FO, improving outcomes in patients requiring ECMO. The Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup and the International Collaboration of Nephrologists and Intensivists for Critical Care Children (ICONIC) met to highlight current practice standards for ECMO use within the pediatric population. This review discusses ECMO modalities, the pathophysiology of inflammation during an ECMO run, its adverse effects, various anticoagulation strategies, and the technical aspects and outcomes of implementing CKRT during ECMO in neonatal and pediatric populations. Consensus practice points and guidelines are summarized. ECMO should be utilized in patients with severe acute respiratory failure despite the use of conventional treatment modalities. The Extracorporeal Life Support Organization (ELSO) offers guidelines for ECMO initiation and management while maintaining a clinical registry of over 195,000 patients to assess outcomes and complications. Monitoring and preventing fluid overload during ECMO and CKRT are imperative to reduce mortality risk. Clinical evidence, resources, and experience of the nephrologist and healthcare team should guide the selection of ECMO circuit.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Advances in pediatric acute kidney injury.

The objective of this study was to inform the pediatric nephrologists of recent advances in acute kidney injury (AKI) epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities. Studies were identified from PubMed, EMBASE, and Google Scholar for topics relevant to AKI. The bibliographies of relevant studies were also reviewed for potential articles. Pediatric (0-18 years) articles from 2000 to May 2020 in the English language were included. For epidemiological outcomes analysis, a meta-analysis on data regarding AKI incidence, mortality, and proportion of kidney replacement therapy was performed and an overall pooled estimate was calculated using the random-effects model. Other sections were created highlighting pathophysiology, novel biomarkers, changing definitions of AKI, evolving tools for AKI diagnosis, and various management modalities. AKI is a common condition seen in hospitalized children and the diagnosis and management have shown to be quite a challenge. However, new standardized definitions, advancements in diagnostic tools, and the development of novel management modalities have led to increased survival benefits in children with AKI. IMPACT: This review highlights the recent innovations in the field of AKI, especially in regard to epidemiology, pathophysiology, novel biomarkers, diagnostic tools, and management modalities.

Neonatal acute kidney injury risk stratification score: STARZ study.

BACKGROUND: Neonates admitted in the neonatal intensive care unit are vulnerable to acute kidney injury leading to worse outcomes. It is important to identify "at-risk" neonates for early preventive measures. METHODS: The study was a multicenter, national, prospective cohort study done in 11 centers in India. A multivariable logistic regression technique with step-wise backward elimination method was used, and a "Risk Prediction Scoring" was devised [the STARZ score]. RESULTS: The neonates with admission in the NICU within <25.5 h of birth, requirement of positive pressure ventilation in the delivery room, <28 weeks gestational age, sepsis, significant cardiac disease, urine output <1.32 ml/kg/h or serum creatinine ≥0.98 mg/dl during the first 12 h post admission, use of nephrotoxic drugs, use of furosemide, or use of inotrope had a significantly higher risk of AKI at 7 days post admission in the multivariate logistic regression model. This scoring model had a sensitivity of 92.8%, specificity of 87.4% positive predictive value of 80.5%, negative predictive value of 95.6%, and accuracy of 89.4%. CONCLUSIONS: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. IMPACT: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. These neonates with a higher risk stratification score need intense monitoring and daily kidney function assessment. With this intensification of research in the field of AKI risk stratification prediction, there is hope that we will be able to decrease morbidity and mortality associated with AKI in this population.

Anticoagulation in patients with acute kidney injury undergoing kidney replacement therapy.

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.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

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.

Pediatric intradialytic hypotension: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup.

Intradialytic hypotension (IDH) is a common adverse event resulting in premature interruption of hemodialysis, and consequently, inadequate fluid and solute removal. IDH occurs in response to the reduction in blood volume during ultrafiltration and subsequent poor compensatory mechanisms due to abnormal cardiac function or autonomic or baroreceptor failure. Pediatric patients are inherently at risk for IDH due to the added difficulty of determining and attaining an accurate dry weight. While frequent blood pressure monitoring, dialysate sodium profiling, ultrafiltration-guided blood volume monitoring, dialysate cooling, hemodiafiltration, and intradialytic mannitol and midodrine have been used to prevent IDH, they have not been extensively studied in pediatric population. Lack of large-scale studies on IDH in children makes it difficult to develop evidence-based management guidelines. Here, we aim to review IDH preventative strategies in the pediatric population and outlay recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup. Without strong evidence in the literature, our recommendations from the expert panel reflect expert opinion and serve as a valuable guide.

Renal replacement therapy in the management of intoxications in children: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) workgroup.

BACKGROUND: Intentional or unintentional ingestions among children and adolescents are common. There are a number of ingestions amenable to renal replacement therapy (RRT). METHODS: 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. RESULTS AND CONCLUSIONS: 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.

Hemodialysis in neonates and infants: A systematic review.

Hemodialysis (HD) in neonates and infants poses unique challenges due to high risks of mortality attributable to obligatory small blood flow volumes. Although HD is often necessary in neonates, its effectiveness and feasibility are poorly understood. The aim of this review is to describe in detail the few studies reporting on HD in neonates and infants (<12 months old) and then dissertate more broadly on the subject with an emphasis on recent innovations with potential to overcome traditional barriers for effective HD in this population. We detail the clinical characteristics, outcomes, technical considerations, maintenance and complications associated with HD, and provide guidance for addressing challenges associated with HD in this population.

Prolonged intermittent renal replacement therapy in children.

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.

Recommendations on the Indications for RBC Transfusion for the Critically Ill Child Receiving Support From Extracorporeal Membrane Oxygenation, Ventricular Assist, and Renal Replacement Therapy Devices From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To present recommendations and supporting literature for RBC transfusions in critically ill children supported with extracorporeal membrane oxygenation, ventricular assist devices, or renal replacement therapy. DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children. METHODS: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The extracorporeal membrane oxygenation/ventricular assist device/renal replacement therapy subgroup included six experts. We conducted electronic searches of the PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017, using medical subject heading terms and text words to define concepts of RBC transfusion, extracorporeal membrane oxygenation, ventricular assist device, and renal replacement therapy. We used a standardized data extraction form to construct evidence tables and graded the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Recommendations developed and supporting literature were reviewed and scored by all panel members. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. RESULTS: For inpatients requiring extracorporeal membrane oxygenation, ventricular assist device, or renal replacement therapy support, there was expert agreement (> 80%) on five good practice statements aimed to improve accuracy and uniform reporting of RBC transfusion data in pediatric extracorporeal membrane oxygenation, ventricular assist device, and renal replacement therapy studies and quality improvement projects; four clinical recommendations of physiologic metrics and biomarkers of oxygen delivery, in addition to hemoglobin concentration, to guide RBC transfusion, acknowledging insufficient evidence to recommend specific RBC transfusion strategies; and eight research recommendations. CONCLUSIONS: Further research surrounding indications, risks, benefits, and alternatives to RBC transfusion in children on extracorporeal devices is clearly needed. Using a structured literature review and grading process, the Transfusion and Anemia Expertise Initiative panel concluded that there is currently insufficient evidence to recommend specific RBC transfusion variables in children requiring extracorporeal membrane oxygenation, ventricular assist device, or renal replacement therapy support.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Hematopoietic stem cell transplantation and acute kidney injury in children: A comprehensive review.

AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Addressing AKI in the context of sinusoidal obstruction syndrome, chemotherapy, thrombotic microangiopathy and hypertension post chemotherapy, glomerulonephritis, and graft versus host disease provides greater insight into renal impairment associated with these HSCT-related ailments. To obtain a better understanding of AKI among pediatric patients receiving HSCT, we investigated the current literature specifically addressing these areas of concern.

Nutritional management in the critically ill child with acute kidney injury: a review.

Acute kidney injury (AKI) in critically ill children is frequently a component of the multiple organ failure syndrome. It occurs within the framework of the severe catabolic phase determined by critical illness and is intensified by metabolic derangements. Nutritional support is a must for these children to improve outcomes. Meeting the special nutritional needs of these children often requires nutritional supplementation by either the enteral or the parenteral route. Since critically ill children with AKI comprise a heterogeneous group of subjects with varying nutrient needs, nutritional requirements should be frequently reassessed, individualized and carefully integrated with renal replacement therapy. This article is a state-of-the-art review of nutrition in critically ill children with AKI.

The complexity of dialytic therapy in hyperammonemic neonates.

The utilization of renal replacement therapy (RRT) in the setting of hyperammonia is a rare and complicated occurrence. Data demonstrate that the quicker the ammonia level is normalized, the better the neurological outcome. The optimal form of RRT is often decided by local practice. The recent work by Picca and colleagues details a larger series of children who underwent RRT for hyperammonia and adds some credence to the use of peritoneal dialysis (PD) in this population. While these authors conclude that PD is not optimal, they do note that the use of PD may be an option when other forms of RRT are not available. The results reinforce the general maxim that you should continue to do that which you do well and often, which in this context refers to continuing to use your form of RRT until alternative modalities are available.