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

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. [ABSTRACT FROM AUTHOR]

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

Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid–base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8–12 mmol/L or anion gap 23–27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR. [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]

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

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 [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]

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]

Introduction: Acute kidney injury (AKI) is a clinical condition characterized by an abrupt increase in serum creatinine levels due to functional changes in the kidneys from a newfound insult or injury. For supportive treatment, continuous renal replacement therapy (CRRT) is one of the most widely used modalities due to its precise control of fluid balance over extended periods of time. However, its complications include circuit clotting, the most frequent cause for CRRT interruption. Vascular access and circuit management were found to be major determinants of performance efficiency. Anticoagulation required to prevent clotting has the downside of increasing the risk of bleeding, especially in the setting of overdosage. Hence, a delicate balance needs to be maintained consistently. Methods: This study explores the adequacy of non‐anticoagulation measures in the prevention of circuit clotting. A comprehensive literature search was conducted using PubMed/Medline and Embase databases to include all relevant studies. Findings The most‐effective CRRT catheter would be made of nonthrombogenic material, noncuffed and nontunneled with separate lumens for arterial and venous blood. Further, studies show that blood flow during the process is optimized at 200 ml/min, which can be lowered in the pediatric population due to more narrow catheters. Platelet count and hematocrit need to be closely monitored as levels above 450,000 × 106/L and 0.40, respectively, increase risk of clotting. Predilution is a non‐anticoagulation technique to reduce the risk of clotting by returning replacement solution to the blood before it reaches the filter. Also, biocompatible membranes such as polyacrylonitrile or polysulfone activate the coagulation cascade significantly less than the conventional cellulose‐based membranes, thereby reducing clotting chances. Discussions: With the advent of such techniques and maneuvers, anticoagulation can be efficiently maintained in patients undergoing CRRT without increasing the risk of bleeding. [ABSTRACT FROM AUTHOR]

Background: β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.Methods: We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.Results: A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.Conclusions: BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present. [ABSTRACT FROM AUTHOR]

Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning. We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods. A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR. Both dialyzability and clinical data do not support a clinical benefit from ECTRs for CCB poisoning. The EXTRIP workgroup recommends against using extracorporeal methods to enhance the elimination of amlodipine, diltiazem, and verapamil in patients with severe poisoning. [ABSTRACT FROM AUTHOR]

Isoniazid toxicity from self‐poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence‐based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty‐three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence). [ABSTRACT FROM AUTHOR]

Introduction: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost‐effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting. Methods: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence. Results: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT. Conclusion: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population. [ABSTRACT FROM AUTHOR]

In the last three decades, significant advances have been made in the care of children requiring renal replacement therapy (RRT). The move from the use of only hemodialysis and peritoneal dialysis to continuous venovenous hemofiltration with or without dialysis (continuous renal replacement therapy, CRRT) has become a mainstay in many intensive care units. The move to CRRT is the result of greater clinical experience as well as advances in equipment, solutions, vascular access, and anticoagulation. CRRT is the mainstay of dialysis in pediatric intensive care unit (PICU) for critically ill children who often have hemodynamic compromise. The advantages of this modality include the ability to promote both solute and fluid clearance in a slow continuous manner. Though data exist suggesting that approximately 25% of children in any PICU may have some degree of renal insufficiency, the true need for RRT is approximately 4% of PICU admissions. This article will review the history as well as the progress being made in the provision of this care in children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. To assess practice pattern similarities and differences amongst pediatric rheumatologists and nephrologists in the management of pediatric Granulomatosis with Polyangiitis (GPA). Methods. A voluntary survey was distributed to the Midwest Pediatric Nephrology Consortium Group (MWPNC) and an international pediatric rheumatology email listserv in 2016-2017. Data were collected on general practice characteristics and preferences for induction management under three clinical scenarios (A-C): newly diagnosed GPA with glomerulonephritis, GPA with rapidly progressive glomerulonephritis, and GPA with pulmonary hemorrhage. In addition, individual preferences for GPA maintenance medications, disease monitoring, and management of GPA with end-stage renal disease were ascertained. Results. There was a 68% response rate from the MWPNC membership and equal numbers of rheumatology respondents. Survey results revealed Rituximab plus Cyclophosphamide is a more common induction choice for rheumatologists than nephrologists in induction Scenarios A and B, whereas Cyclophosphamide is more commonly chosen by nephrologists in Scenario A. Plasmapheresis rates increased for Scenarios A, B, and C for both specialties, but were overall low. There was no clear consensus on the duration of maintenance therapy nor diagnostic work-up. Rheumatologists more frequently chose Rituximab for maintenance and induction compared to nephrologists. There was also a higher than expected proportion of Mycophenolate Mofetil use for both specialties. Conclusion. This survey has revealed important differences in the way that rheumatologists and nephrologists manage this disease. It highlights the need for well-designed clinical trials in pediatric GPA patients and reveals that both specialties must be represented during consensus-building and clinical trial design efforts. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypothesis: Acute kidney injury (AKI) is a common cause of morbidity and mortality worldwide, with a pediatric incidence ranging from 19.3% to 24.1%. Treatment of pediatric AKI is a source of debate in varying geographical regions. Currently CRRT is the treatment for pediatric AKI, but limitations due to cost and accessibility force use of adult equipment and other therapeutic options such as peritoneal dialysis (PD) and hemodialysis (HD). It was hypothesized that more cost-effective measures would likely be used in developing countries due to lesser resource availability. Methods: A 26-question internet-based survey was distributed to 650 pediatric Nephrologists. There was a response rate of 34.3% (223 responses). The survey was distributed via pedneph and pcrrt email servers, inquiring about demographics, technology, resources, pediatric-specific supplies, and preference in renal replacement therapy (RRT) in pediatric AKI. The main method of analysis was to compare responses about treatments between nephrologists in developed countries and nephrologists in developing countries using difference-of-proportions tests. Results: PD was available in all centers surveyed, while HD was available in 85.1% and 54.1% (p = 0.00), CRRT was available in 60% and 33.3% (p = 0.001), and SLED was available in 20% and 25% (p = 0.45) centers of developed and developing world respectively. In developing countries, 68.5% (p = 0.000) of physicians preferred PD to costlier therapies, while in developed countries it was found that physicians favored HD (72%, p = 0.00) or CRRT (24%, p = 0.041) in infants. Conclusions: Lack of availability of resources, trained physicians and funds often preclude standards of care in developing countries, and there is much development needed in terms of meeting higher global standards for treating pediatric AKI patients. PD remains the main modality of choice for treatment of AKI in infants in developing world. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite abnormal clotting, circuits clot during continuous renal replacement therapy ( CRRT) in children with acute liver failure ( ALF). We report our experience. All children with ALF needing CRRT were studied over 2 years. Patient and circuit factors associated with circuit use were evaluated. Thirty-one children in liver failure (median age 7.4 years) underwent CRRT, of which 17 (54.8%) died. A total of 98 filtration episodes were used. The smallest access catheter was 6.5 Fr, while the largest was 13.5 Fr. The most common filter used was HFO7 (63%). Mean duration ( SD) of circuit use was 33.13(30.83) hours. Of the 98 filtration episodes, circuits blocked in 25, whereas the access catheter blocked in 25. Fifty-two circuits were changed electively for a variety of reasons. Prostacyclin was the anticoagulant in 62 filtration episodes. The remaining filtration episodes had either no anticoagulation or heparin. The mean ( SD) 'downtime' was 5.13 (9.15) hours. We found a significant association between fresh frozen plasma ( FFP) use with circuit blockade. Neither the duration of CRRT nor the 'downtime' influenced mortality. The CRRT circuits blocked in children despite deranged clotting in liver disease. Circuits are changed for a variety of reasons other than clotting. The use of FFP reduces circuit life. [ABSTRACT FROM AUTHOR]

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High A, Moderate B, Low C, Very Low D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic. [ABSTRACT FROM AUTHOR]

lthough rare, renal replacement therapy (RRT) for the treatment of the metabolic, respiratory and hemodynamic complications of intoxications may be required. Understanding the natural clearance of the medications along with their volume of distribution, protein binding and molecular weight will help in understanding the benefit of commencing RRT. This information will aid in choosing the optimal forms of RRT in an urgent setting. Overdose of common pediatric medications are discussed with suggestions on the type of RRT within this educational review. [ABSTRACT FROM AUTHOR]

Low birth-weight infants are at risk for renal disease when renal insults occur in the neonatal period. Renal growth as measured by sonography over time is utilized by many nephrologists as predictors of future renal disease. To identify infants at risk by defining normal renal growth for the very premature infant. Renal growth was evaluated in 30 infants whose birth weight was 1,500 g or less and gestational age was <31 weeks. During a 2-month time period, three US measurements were taken (first week of life, age 28 days, and age 56 days or earlier if discharged). Infants were divided according to birth weight: the extremely low birth-weight group (ELBW) was <1,000 g ( n = 14), and the very low birth-weight group (VLBW) was 1,000–1,500 g ( n = 16). In both groups, the right and left renal lengths were similar. In the ELBW group, the initial mean length was 3.25 cm and grew to 4.16 cm, while the mean volume was 4.85 cm and grew to 10.39 cm. In the VLBW group the initial mean length was 3.69 cm and grew to 4.35 cm while the mean volume was 7.25 cm and grew to 11.83 cm. These data establish normal expected growth for future studies. [ABSTRACT FROM AUTHOR]

Recent data suggest that elevated levels of uric acid (UA) might contribute to the progression of renal disease. Rasburicase, recombinant urate oxidase, is a highly safe and efficacious hypo-uricosuric agent for treatment of elevated UA levels from tumor lysis. We adopted the use of rasburicase for management of hyperuricemia in infants with acute kidney injury (AKI) and, herein, report our experience. We conducted a retrospective chart review of infants with hyperuricemia (UA > 8 mg/dl) secondary to AKI (serum creatinine > 1.5 mg/dl) treated with rasburicase. Seven infants (mean age 34 ± 55 days, six male), with a mean weight of 3.2 ± 1.2 kg, were identified. Rasburicase was administered intravenously as a single, onetime, bolus of 0.17 ± 0.04 mg/kg body weight. Within 24 h, serum UA had decreased from 13.6 ± 4.5 mg/dl to 0.9 ± 0.6 mg/dl ( P < 0.05), creatinine had decreased from 3.2 ± 2.0 mg/dl to 2.0 ± 1.2 mg/dl ( P < 0.05), and urinary output had increased from 2.4 ± 1.2 ml/kg per hour to 5.9 ± 1.8 ml/kg per hour ( P < 0.05). Continued improvements in UA, creatinine, and urinary output were observed in the week following administration of rasburicase, without rebound of the UA. We observed no treatment-related side effects. All patients demonstrated a normalization of uric acid level without need of renal replacement therapy. In conclusion, a single intravenously administered bolus of rasburicase appears to be a novel treatment for hyperuricemia in infants with AKI. [ABSTRACT FROM AUTHOR]

Background. Paediatric patients with systemic lupus erythematosus (SLE) often have severe presentations including lupus nephritis (LN). Few paediatric studies have evaluated the anticardiolipin antibody (aCL) and renal histology. The purpose of this study was to evaluate clinicopathologic features, including aCL, short-term clinical and renal histologic outcomes of paediatric patients with new-onset SLE nephritis. [ABSTRACT FROM PUBLISHER]

Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (±4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin® [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m2 (±19) at 28 months (±14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5–58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at the 5th International Pediatric Continuous Renal Replacement Therapy (PCRRT) Conference in Orlando Florida on June 19-21, 2008 is presented. It highlights the biomarkers in acute kidney injury (AKI) and neonatal AKI. Other topics include high-flux hemodialysis (HFHD), continuous veno-venous hemodiafiltration (CVVHDF), and continuous renal replacement therapy (CRRT). The conference involved nurses, pharmacists, and physicians.

Pediatric stem cell transplant (SCT) recipients commonly develop acute renal failure (ARF). We report the demographic and survival data of pediatric SCT patients enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. Since 1 January 2001, 51/370 (13.8%) patients entered in the ppCRRT Registry had received a SCT. Median age was 13.63 (0.53–23.52) years. The primary reasons for the initiation of continuous renal replacement therapy (CRRT) were treatment of fluid overload (FO) and electrolyte imbalance (49%), FO only (39%), electrolyte imbalance only (8%) and other reasons (4%). The CRRT modalities included continuous veno-veno hemodialysis (CVVHD), 43%, continuous veno-veno hemofiltration (CVVH), 37% and continuous veno-veno hemodiafiltration (CVVHDF), 20%. Seventy-six percent had multi-organ dysfunction syndrome (MODS), 72% received ventilatory support and the mean FO was 12.41 ± 3.70%. Forty-five percent of patients survived. Patients receiving convective therapies had better survival rates (59% vs 27%, P < 0.05). Patients requiring ventilatory support had worse survival (35% vs 71%, P < 0.05). Mean airway pressure (Paw) at the end of CRRT was lower in survivors (8.7 ± 2.94 vs 25.76 ± 2.03 mmH2O, P < 0.05). Development of high mean airway pressure in non-survivors is likely related to non-fluid injury, as it was not prevented by early and aggressive fluid management by CRRT therapy. [ABSTRACT FROM AUTHOR]

Purpose: The acquisition cost of commercially-available (CA) dialysis solutions is higher than manually-compounded (MC) solutions but pharmacy preparation time and medication errors are presumed to be lower. The objective of this study was to compare resource utilization and total cost between CA- and MC-dialysis solutions. Methods: A model was constructed using solution acquisition cost, preparation cost, and the cost of a medication error. Solution preparation costs were obtained by prospectively recording preparation times for 1 month before and after the implementation of a CA-solution protocol. Preparation times were converted to costs using the hourly wage of a pharmacist and pharmacy technician. The presumed error rate was 0.5% for MC and 0.1% for CA solutions. A univariate sensitivity analysis was conducted by varying the incidence of a medication error. Results: Preparation time for an MC solution was significantly longer than for a CA solution (8 ± 3 minutes/bag vs 4 ± 1 minutes/bag, P < .001). Total solution costs (acquisition + preparation) were $11.13 and $26.38 per bag for MC and CA, respectively. When medication errors were considered, the cost per error-free event was $48.14 per bag for MC solutions and $33.77 per bag for CA solutions. The threshold where the cost-ratio became less costly for MC solutions was when the absolute difference in error rate was no more than 0.2%. Conclusion: Despite a higher acquisition cost, CA solutions could result in lower total costs compared with MC solutions. A small difference in medication error rate is required to produce these savings. [ABSTRACT FROM AUTHOR]

An infant with a suspected inborn metabolism error was treated with a metabolic cocktail of intravenous sodium phenylacetate (NaPh) and sodium benzoate (NaBz) for hyperammonemia. Sequential hemodialysis (HD) then hemofiltration (HF) was performed due to hyperammonemia. Dialytic and convective clearance (K; ml/min) of ammonia, NaPh, and NaBz was measured. The K of ammonia was 57 and 37 for HD and HF, respectively. The K of NaBz was 37 and 12 for HD and HF, respectively. The K of NaPh was 38 and 14 ml/min for HD and HF, respectively. Despite high clearance of both NaPh and NaBz by HD and HF, the hyperammonemia was corrected. [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) is commonly used for renal support in the intensive care unit. While the risk of medication errors in the intensive care unit has been described, errors related specifically to CRRT are unknown. The purpose of this study is to characterize medication errors related to CRRT and compare medication errors that occur with manually compounded solutions versus commercially available solutions. We surveyed three separate internet-based, pediatric list serves that are commonly used for communications for programs utilizing CRRT. Data regarding CRRT practices and medication errors were recorded. Medication errors were graded for degree of severity and compared between programs using manually compounded dialysis solutions versus commercially available dialysis solutions. In a survey with 31 program responses, 18 reported medication errors. Two of the 18 were related to heparin compounding, while 16/18 were due to solution compounding errors. Half of the medication errors were classified as causing harm, two of which were fatal. All medication errors were reported by programs that manually compounded their dialysis solutions. Medication errors related to CRRT are associated with a high degree of severity, including death. Industry-based, commercially available solutions can decrease the occurrence of medication errors due to CRRT. [ABSTRACT FROM AUTHOR]

Infants requiring CRRT present a unique challenge due to the large circuit volume to blood volume ratio. Blood priming is often used, but some patients can become unstable during the initiation of CRRT due to electrolyte and acid-base imbalance. We postulated that using Z-BUF we could normalize electrolytes and improve the acid base status of the prime prior to patient connection. To test this we set up a circuit using the Baxter BM-25 CRRT pump, a polysulfone or AN-69 membrane, and a three-way stopcock. The circuit was primed with a 60/40 mix of expired autologous donor pRBCs and 5% albumin. The modalities of CVVH, CVVHD, and CVVHDF were compared for relative efficacy. Electrolytes, lactate, pH, cytokines (TNF-α, IL-1β, bradykinin, and IL-6) were measured. Plasma hemoglobin levels were also measured before and after the Z-BUF procedure. Bradykinin production and elimination in AN-69 membrane circuits were assessed. All lab values equilibrated by 35 minutes. All CRRT modalities were equally efficacious for Z-BUF. Cytokine production or significant hemolysis was not found. In addition, no bradykinin accumulation occurred in AN-69 membrane-containing circuits. We conclude that Z-BUF is a simple and effective way to normalize electrolyte and acid-base status in the CRRT circuit when blood priming is required. [ABSTRACT FROM AUTHOR]

Höcker B, Weber LT, Bunchman T, Rashford M, Tönshoff B for the Tricontinental MMF Suspension Study Group. Mycophenolate mofetil suspension in pediatric renal transplantation: Three-year data from the tricontinental trial. Pediatr Transplantation 2005. © 2005 Blackwell Munksgaard Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adult solid organ transplant recipients, but data in children and adolescents are scarce. This prospective, multicenter, open-labeled, single-arm study investigated the efficacy and safety of an MMF-based immunosuppressive regimen in 100 pediatric renal transplant recipients over a 3-yr period of time. Three age groups were formed (<6 yr, n = 33; 6 to <12 yr, n = 34; 12–18 yr, n = 33). Basic immunosuppression consisted of MMF (600 mg/m2 b.i.d), cyclosporin A microemulsion and corticosteroids. Seventy-three percent of patients were given anti-lymphocyte antibody induction therapy, of whom 74% received anti-thymocyte globulin. Patient and graft survival 3 yr after transplantation amounted to 98 and 95%, respectively. Twenty-five percent of all patients suffered a biopsy-proven acute rejection episode in the first 6 month post-transplant. Children undergoing induction therapy exhibited a numerically lower rejection rate (21 vs. 37%, p = 0.11). Three years after transplantation, the acute rejection rate added up to 30% (26% with induction therapy vs. 41% without induction therapy, p = 0.21). The number of patients with acute rejection was lowest in the youngest age group (18%), in comparison with 39% in the 6 to <12 yr and 33% in the 12–18 yr age group, respectively. For the entire patient population, the rate of patients who withdrew prematurely because of adverse events was low (12%). The present study shows that MMF therapy in pediatric renal transplant recipients leads to an excellent patient and graft survival 3 yr post-transplant with an acceptable safety profile. [ABSTRACT FROM AUTHOR]