Francisco X. Flores

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.

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.

Vasopressin-elicited water and urea permeabilities are altered in IMCD in hypercalcemic rats

To investigate how hypercalcemia blunts renal concentrating ability, alterations in basal and arginine vasopressin (AVP)-elicited osmotic water ( P f) and urea ( P urea) permeabilities were measured in isolated perfused terminal inner medullary collecting ducts (IMCD) from control and chronically hypercalcemic rats after dihydrotachysterol (DHT) (M. Levi, L. Peterson, and T. Berl. Kidney Int. 23: 489-497, 1983) treatment. The IMCD P f of DHT-treated rats did not increase significantly after AVP and was accompanied by a significant 87 ± 4% reduction in aquaporin-2 (AQP-2) protein but not mRNA. In contrast, both basal and AVP-elicited IMCD P urea from DHT rats were significantly increased and accompanied by a significant 41 ± 11% increase in AVP-regulated urea transporter protein content. Immunoblotting with anti-calcium/polyvalent cation-sensing receptor protein (CaR) antiserum revealed specific alterations in CaR bands in endosomes purified from the apical membranes of inner medulla of DHT rats. These data are the first detailed analyses of hypercalcemia-induced alterations in AVP-regulated permeabilities and membrane transporters in IMCD. We conclude that selective alterations in IMCD transport occur in hypercalcemia, permitting the body to dispose of excess calcium without forming calcium-containing renal stones.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

Purpose Well-functioning vascular access is essential for the provision of adequate CRRT However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. Methods Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. Results Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). Conclusions Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

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 m2 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 ≥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.

Outcome of management strategies for BK virus replication in pediatric renal transplant recipients

Abstract:  Management of BKV infection is not well defined. Eighteen pediatric renal transplant patients with BKV‐PCR (+) were divided into three groups; Group 1: Viruria only (6), Group 2: Viremia with stable GFR (4), Group 3: Viremia with >25% decline in GFR and BKVAN on biopsy (8). With initial BKV‐PCR(+), Group 1 received no treatment; Group 2 had MMF reduced 30%; Group 3: 6/8 had CNI discontinuation, 2/8 had reduced MMF and cidofovir. BKV, GFR and histology were compared pre‐ and post‐treatment. In Group 1 viruria decreased in all patients; GFR remained stable. Group 2 showed reduced viremia with no GFR change. Group 3 showed reduced viremia in 8/8 patients. Patients with >50% decline in GFR from baseline (6/8) showed worse histology: 2/6 lost grafts despite no BKV on follow‐up biopsy. Our results show that with viruria alone no treatment is necessary; with viremia and stable GFR, reduced immunosuppression decreases viremia and maintains GFR. With viremia and reduced GFR, immunosuppression reduction with or without cidofovir decreases viremia and stabilizes GFR in most patients. Greater than 50% reduction in GFR at BKVAN diagnosis correlates with risk for graft loss. Serial monitoring of BKV viremia with early intervention may prevent BKVAN graft loss in children.

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 m2/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 m2/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.

Immune response to Escherichia coli O157:H7 in hemolytic uremic syndrome following salmonellosis

Abstract.Escherichia coli O157:H7, a Shiga-like toxin (SLT)-producing enteric pathogen, has been implicated in most cases of post-diarrheal hemolytic uremic syndrome (D+HUS). Infection with other bacterial pathogens such as Salmonella has also preceded D+HUS episodes, leading to speculation that these organisms may also be etiological. We present two children with unrelated D+HUS following salmonellosis. Both children had negative stool cultures on sorbitol-MacConkey agar soon after the onset of diarrhea. After the diagnosis of HUS, both patients had repeat stool cultures positive for Salmonella alone. Polymerase chain reactions for SLT I and II gene sequences in Salmonella isolates were negative. Enzyme-linked imunosorbent assay for specific humoral response to E. coli O157:H7 lipopolysaccharide in acute and convalescent serum samples revealed evidence of heretofore undetected E. coli O157:H7 infection contemporaneous with each D+HUS episode. These cases demonstrate that isolation of only non-SLT-producing microbes from children with D+HUS should raise suspicion of concurrent undetected infection with SLT-producing organisms. Assaying specific immune response to E. coli O157:H7 can be an important epidemiological adjunct. Bacterial infection with non-SLT-producing Salmonella may represent concomitant enteric pathology rather than D+HUS-instigating infection.

Acute kidney injury and critical cardiac disease.

The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. The survival of patients with critical congenital heart disease is seldom in question. Consequently, the focus has now shifted to that of morbidity reduction and eventual elimination. Acute kidney injury (AKI) after cardiac surgery is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality. Acute kidney injury occurs frequently, complicating 30% to 40% of adult and pediatric cardiac surgeries. Patients who require dialysis are at high risk of mortality, but even minor degrees of postoperative AKI portend a significant increase in mortality and morbidity.

Hypercalcemia Selectively Decreases Rat Inner Medullary Collecting Duct(IMCD) Vasopressin (AVP)-Elicited Water Permeability (P f ) and Aquaporin-2 (AQP-2) Water Channel Protein Content While Increasing Its Urea Permeability (P urea ) and the UT-2 Urea Channel Protein Content • 1650

Hypercalcemia Selectively Decreases Rat Inner Medullary Collecting Duct(IMCD) Vasopressin (AVP)-Elicited Water Permeability (P f ) and Aquaporin-2 (AQP-2) Water Channel Protein Content While Increasing Its Urea Permeability (P urea ) and the UT-2 Urea Channel Protein Content • 1650