Continuous renal replacement therapy and therapeutic plasma exchange in pediatric liver failure.

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients. Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48 h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1-5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: •  Pediatric acute liver failure is associated with high mortality. •  Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Acute Kidney Injury.

Acute kidney injury (AKI) has been shown to occur commonly in hospitalized children. AKI is associated with multiple complications, including elevated blood urea nitrogen level, electrolyte dyscrasias, acidosis, and fluid balance disorders. During the past 10 years, multiple multicenter studies have shown that AKI occurs commonly and is associated with adverse outcomes across a variety of populations in pediatrics. This state-of-the-art review provides a detailed overview and update on AKI, including definition, epidemiology, outcomes, differential diagnosis, diagnostics, and management of complications.

Dialysis disequilibrium on CKRT: avoiding the steep slippery slope.

BACKGROUND: Current guidelines for initiation of kidney replacement do not include specific recommendations for prescription parameters and monitoring. CASE OUTLINE: A 16-year-old girl presented with kidney failure with creatinine of 19.8 mg/dL and BUN of 211 mg/dL. She initiated continuous kidney replacement therapy (CKRT) with clearance of 1,300 mL/min/1.73 m2 which was increased to 1,950 mL/min/1.73 m2 at 17 h of stable therapy. COMPLICATIONS: At 31 h of therapy, she developed generalized seizure activity. CT imaging was negative for acute intracranial process, and EEG demonstrated diffuse encephalopathy. CKRT was discontinued, and BUN was noted to be 47 mg/dL at that time (a 79% reduction from presenting BUN). KEY MANAGEMENT POINTS: • The potential for development of DDS is not isolated to intermittent hemodialysis and may occur later in presentation. • A decreased clearance rate should be considered in those with risk factors for development of dialysis disequilibrium syndrome (DDS). • Frequent monitoring of BUN/serum osmolality is important to allow for adjustment of the KRT prescription following initiation of therapy. • Additional research is needed to guide risk assessment for DDS and therapeutic timing and goals in the early stages of KRT initiation. • Inclusion of more specific guidelines surrounding DDS would assist in providing important support for nephrologists. LIST OF RELEVANT GUIDELINES: KDIGO clinical practice guideline for acute kidney injury [1] Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease [2] The Renal Association Clinical Practice Guideline Acute Kidney Injury (AKI) [3] The Japanese Clinical Practice Guideline for Acute Kidney Injury [4].

Healthcare recommendations for Joubert syndrome.

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan.

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.

C septicum Complicating Hemolytic Uremic Syndrome: Survival Without Surgical Intervention.

Clostridium septicum is an anaerobic bacterium that causes rapidly progressive myonecrosis, bacteremia, and central nervous system infection. It has been reported as a complication of Escherichia coli hemolytic uremic syndrome (HUS) in 8 children worldwide; 5 children died, and the 3 reported survivors had surgically treated disease. We present 3 cases of C septicum complicating HUS in children, including the first 2 reported cases of survival without surgical intervention. All patients presented with classic cases of HUS with initial clinical improvement followed by deterioration. Patient 1 had rising fever, tachycardia, and severe abdominal pain 24 hours after admission. She developed large multifocal intraparenchymal cerebral hemorrhages and died 12 hours later. Autopsy revealed C septicum intestinal necrosis, myonecrosis, and encephalitis. Patient 2 had new fever, increasing leukocytosis, and severe abdominal pain on hospital day 4. She was diagnosed with C septicum bacteremia and treated with metronidazole, meropenem, and clindamycin. Patient 3 had new fever and increasing leukocytosis on hospital day 3; blood cultures grew C septicum, and she was treated with penicillin. Patients 2 and 3 improved rapidly and did not require surgery. C septicum is a potential co-infection with E coli It thrives in the anaerobic environment of E coli-damaged intestinal mucosa and translocates to cause systemic infection. Fever, tachycardia, a rising white blood cell count, and abdominal pain out of proportion to examination are key findings for which physicians should be vigilant. Timely evaluation by anaerobic blood culture and early initiation of antibiotics are necessary to prevent fatalities.

Pediatric nephrologists' beliefs regarding randomized controlled trials.

BACKGROUND: Pediatrics and pediatric nephrology lag behind adult medicine in producing randomized controlled trials (RCTs). Physician attitudes have been shown to play a significant role in RCT enrollment. METHODS: We surveyed members of the American Society of Pediatric Nephrology regarding beliefs about RCTs and factors influencing decisions to recommend RCT enrollment. Regression analyses were used to identify the effects of variables on an aggregate score summarizing attitudes toward RCTs. RESULTS: One hundred thirty replies were received. Sixty-six percent had enrolled patients in RCTs. Respondents in practice for more than 15 years were more likely to have recruited a patient to an RCT than those in practice for less than 5 years. Respondents were more willing to recommend RCT enrollment if the study was multicenter, patients were sicker or had a poorer prognosis, or if the parent or participant received a financial incentive versus the provider. In multiple regression analysis, history of enrolling patients in an RCT was the only significant predictor of higher aggregate RCT-friendly attitude. CONCLUSIONS: Many pediatric nephrologists have never enrolled a patient in an RCT, particularly those in practice for less than 5 years. Respondents who have not enrolled patients in RCTs have a less RCT-friendly attitude. Provision of improved training and resources might increase participation of junior providers in RCTs.

Moving beyond supportive care--current status of specific therapies in pediatric acute kidney injury.

Acute kidney injury (AKI) remains a significant challenge, leading to increased morbidity, mortality, and medical costs. Therapy for AKI to this point has largely been supportive; specific interventions to treat established AKI have had minimal effect. Review of the pathogenesis of AKI reveals complex, interacting mechanisms, including changes in microcirculation, the immune system, and inflammation, and cell death from both necrosis and apoptosis. Past definitions of AKI have been imprecise; newer methods for AKI identification and classification, including novel biomarkers and improved criteria for defining AKI, may permit earlier intervention with greater potential for success. With improved understanding of pathophysiology and the opportunity for intervention before AKI is fully established, clinicians may be able to move beyond supportive care and improve outcomes.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

Acute kidney injury: can we improve prognosis?

The incidence of pediatric acute kidney injury (AKI) is increasing. AKI has been found to be independently associated with increased mortality, and current management options are limited in that they are mainly supportive. The use of various definitions of AKI can still be found in the literature, making it difficult to discern the epidemiology behind pediatric AKI. The use of a more uniform definition is a necessary first step to clarify AKI epidemiology and direct our research efforts, and it will ultimately improve prognosis. There is evidence that neonates and infants may be at higher risk for AKI than adults. However, the least amount of research is found for this youngest age group, and more focused efforts on this population are necessary. This paper reviews existing data on and definitions for pediatric AKI, general preventive and treatment strategies, as well as ongoing research efforts on AKI. We are hopeful that the prognosis of AKI will improve with collaboration on a multicenter, multinational scale in the form of prospective, long-term studies on pediatric AKI.

Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry.

BACKGROUND: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. PREDICTOR: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%. OUTCOME & MEASUREMENTS: The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. RESULTS: 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7). LIMITATIONS: This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. CONCLUSIONS: Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. DESIGN: Retrospective database study. SETTING: Multicenter study in pediatric critical care units. PATIENTS: Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. INTERVENTIONS: None. MEASUREMENTS: Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. RESULTS: One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). CONCLUSIONS: Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Acute kidney injury and dialysis in children: illustrative cases.

Pediatric nephrologists and critical care physicians are faced with a heterogeneous patient population with varied epidemiology caring for children with acute kidney injury or other diseases that may require renal replacement therapy provision. We have composed 4 detailed case scenarios to highlight the challenges and interdisciplinary approach required for optimal care provision to children, and that serve to direct the different articles contained in this special issue of Seminars of Nephrology devoted to acute kidney injury in children.

Continuous renal replacement therapy (CRRT) after stem cell transplantation. A report from the prospective pediatric CRRT Registry Group.

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 mmH(2)O, 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.

Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry.

BACKGROUND: This article reports demographic characteristics and intensive care unit survival for 344 patients from the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry, a voluntary multicenter observational network. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Ages were newborn to 25 yr, 58% were male, and weights were 1.3 to 160 kg. Patients spent a median of 2 d in the intensive care unit before CRRT (range 0 to 135). At CRRT initiation, 48% received diuretics and 66% received vasoactive drugs. Mean blood flow was 97.9 ml/min (range 10 to 350 ml/min; median 100 ml/min); mean blood flow per body weight was 5 ml/min per kg (range 0.6 to 53.6 ml/min per kg; median 4.1 ml/min per kg). Days on CRRT were <1 to 83 (mean 9.1; median 6). A total of 56% of circuits had citrate anticoagulation, 37% had heparin, and 7% had no anticoagulation. RESULTS: Overall survival was 58%; survival differed across participating centers. Survival was lowest (51%) when CRRT was started for combined fluid overload and electrolyte imbalance. There was better survival in patients with principal diagnoses of drug intoxication (100%), renal disease (84%), tumor lysis syndrome (83%), and inborn errors of metabolism (73%); survival was lowest in liver disease/transplant (31%), pulmonary disease/transplant (45%), and bone marrow transplant (45%). Overall survival was better for children who weighed >10 kg (63 versus 43%; P = 0.001) and for those who were older than 1 yr (62 versus 44%; P = 0.007). CONCLUSIONS: CRRT can be used successfully for a wide range of critically ill children. Survival is best for those who have acute, specific abnormalities and lack multiple organ involvement; sicker patients with selected diagnoses may have lower survival. Center differences might suggest opportunities to define best practices with future study.

Multi-centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT).

BACKGROUND: Heparin (hepACG) and regional citrate anticoagulation (citACG) remain the most commonly reported continuous renal replacement therapy (CRRT) ACG methods employed. No prospective multi-centre published data exist that compare different ACG methods with respect to CRRT filter life span or patient complications. METHODS: A total of 138 patients from seven US centres receiving 18 208 h of CRRT comprising a total of 442 CRRT circuits were utilized to assess filter life span and ACG-related complications in patients receiving CRRT with hepACG, citACG or no ACG (noACG). RESULTS: Mean circuit life was 41.2+/-30.8 h. Mean circuit survival was no different for circuits receiving hepACG (42.1+/-27.1 h) and citACG (44.7+/-35.9 h), but was significantly lower for circuits with noACG (27.2+/-21.5 h, P<0.005). Kaplan-Meier analyses revealed no survival difference between hepACG and citACG circuits, but significantly lower survival for noACG circuits (P<0.001). Log-rank analysis showed that 69% of hepACG and citACG circuits whereas only 28% of noACG were functional at 60 h. Clotting rates were similar for hepACG circuits (58 out of 230, 25%) and citACG circuits (43 out of 158, 27%), but were significantly higher for noACG circuits (27 out of 54, 50%, P < 0.001). Life-threatening bleeding complications attributable to ACG were noted in the hepACG group but were absent in the citACG group. CONCLUSIONS: The current analysis represents the largest evaluation of CRRT ACG methods to date. While the standard hepACG and citACG methods studied in the prospective paediatric CRRT registry led to similar filter life spans and were superior to noACG, our data suggest that citACG may result in less life-threatening complications.

Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy.

BACKGROUND: Critical illness leading to multi-organ dysfunction syndrome (MODS) and associated acute renal failure (ARF) is less common in children compared to adult patients. As a result, many issues plague the pediatric ARF outcome literature, including a relative lack of prospective study, a lack of modality stratification in subject populations and inconsistent controls for patient illness severity in outcome analysis. METHODS: We now report data from the first multicenter study to assess the outcome of pediatric patients with MODS receiving continuous renal replacement therapy (CRRT). One hundred twenty of 157 Registry patients (63 male/57 female) experienced MODS during their course. RESULTS: One hundred sixteen patients had complete data available for analysis. The most common causes leading to CRRT were sepsis (N= 47; 39.2%) and cardiogenic shock (N= 24; 20%). Overall survival was 51.7%. Pediatric Risk of Mortality (PRISM 2) score, central venous pressure (CVP), and% fluid overload (%FO) at CRRT initiation were significantly lower for survivors versus nonsurvivors. Multivariate analysis controlling for severity of illness using PRISM 2 at CRRT initiation revealed that%FO was still significantly lower for survivors versus nonsurvivors (P < 0.05) even for patients receiving both mechanical ventilation and vasoactive pressors. We speculate that increased fluid administration from PICU admission to CRRT initiation is an independent risk factor for mortality in pediatric patients with MODS receiving CRRT. CONCLUSION: We suggest that after initial resuscitative efforts, an increased emphasis should be placed on early initiation of CRRT and inotropic agent use over fluid administration to maintain acceptable blood pressure.