Theresa Mottes

Pediatric acute renal failure: outcome by modality and disease

Abstract. Two hundred and twenty-six children who underwent renal replacement therapy (RRT) from 1992 to 1998 were retrospectively reviewed. The mean age, at the onset of RRT, was 74±11.7 months and weight was 25.3±9.7 kg. RRT therapies included hemofiltration (HF; n=106 children for an average of 8.7±2.3 days), hemodialysis (HD; n=61 children for an average of 9.5±1.7 days), and peritoneal dialysis (PD; n=59 children for an average of 9.6±2.1 days). Factors influencing patient survival included: (1) low blood pressure (BP) at onset of RRT (33% survival with low BP, vs 61% with normal BP, vs 100% with high BP; P<0.05), (2) use of pressors anytime during RRT (35% survival in those on pressors vs 89% survival in those not requiring pressors; P<0.01), (3) diagnosis (primary renal failure with a high likelihood of survival vs secondary renal failure; P<0.05), (4) RRT modality (40% survival with HF, vs 49% survival with PD, vs 81% survival with HD; P<0.01 HD vs PD or HF), and (5) pressor use was significantly higher in children on HF (74%) vs HD (33%) or PD (81%; P<0.05 HD vs HF or PD). In conclusion, pressor use has the greatest prediction of survival, rather than RRT modality. Patient survival in children with the need for RRT for ARF is similar to in adults and, as in adults, is best predicted by the underlying diagnosis and hemodynamic stability.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy.

Objective:In pediatric patients, fluid overload at continuous renal replacement therapy initiation is associated with increased mortality. The aim of this study was to characterize the association between fluid overload at continuous renal replacement therapy initiation, fluid removal during continuous renal replacement therapy, the kinetics of fluid removal and mortality in a large pediatric population receiving continuous renal replacement therapy while on extracorporeal membrane oxygenation. Design:Retrospective chart review. Setting:Tertiary children’s hospital. Patients:Extracorporeal membrane oxygenation patients requiring continuous renal replacement therapy from July 2006 to September 2010. Interventions:None. Measurements and Main Results:Overall intensive care unit survival was 34% for 53 patients that were initiated on continuous renal replacement therapy while on extracorporeal membrane oxygenation during the study period. Median fluid overload at continuous renal replacement therapy initiation was significantly lower in survivors compared to nonsurvivors (24.5% vs. 38%, p = .006). Median fluid overload at continuous renal replacement therapy discontinuation was significantly lower in survivors compared to nonsurvivors (7.1% vs. 17.5%, p = .035). After adjusting for percent fluid overload at continuous renal replacement therapy initiation, age, and severity of illness, the change in fluid overload at continuous renal replacement therapy discontinuation was not significantly associated with mortality (p = .212). Models investigating the rates of fluid removal in different periods, age, severity of illness, and fluid overload at continuous renal replacement therapy initiation found that fluid overload at continuous renal replacement therapy initiation was the most consistent predictor of survival. Conclusions:Our data demonstrate an association between fluid overload at continuous renal replacement therapy initiation and mortality in pediatric patients receiving extracorporeal membrane oxygenation. The degree of fluid overload at continuous renal replacement therapy discontinuation is also associated with mortality, but appears to reflect the effect of fluid overload at initiation. Furthermore, correction of fluid overload to ⩽10% was not associated with improved survival. These results suggest that intervening prior to the development of significant fluid overload may be more clinically effective than attempting fluid removal after significant fluid overload has developed. Our findings suggest a role for earlier initiation of continuous renal replacement therapy in this population, and warrant further clinical studies.

Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): study protocol for a prospective observational study

BackgroundAcute kidney injury (AKI) is associated with poor outcome in critically ill children. While data extracted from retrospective study of pediatric populations demonstrate a high incidence of AKI, the literature lacks focused and comprehensive multicenter studies describing AKI risk factors, epidemiology, and outcome. Additionally, very few pediatric studies have examined novel urinary biomarkers outside of the cardiopulmonary bypass population.Methods/DesignThis is a prospective observational study. We anticipate collecting data on over 5000 critically ill children admitted to 31 pediatric intensive care units (PICUs) across the world during the calendar year of 2014. Data will be collected for seven days on all children older than 90 days and younger than 25 years without baseline stage 5 chronic kidney disease, chronic renal replacement therapy, and outside of 90 days of a kidney transplant or from surgical correction of congenital heart disease. Data to be collected includes demographic information, admission diagnoses and co-morbidities, and details on fluid and vasoactive resuscitation used. The renal angina index will be calculated integrating risk factors and early changes in serum creatinine and fluid overload. On days 2–7, all hemodynamic and pertinent laboratory values will be captured focusing on AKI pertinent values. Daily calculated values will include % fluid overload, fluid corrected creatinine, and KDIGO AKI stage. Urine will be captured twice daily for biomarker analysis on Days 0–3 of admission. Biomarkers to be measured include neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). The primary outcome to be quantified is incidence rate of severe AKI on Day 3 (Day 3 – AKI). Prediction of Day 3 – AKI by the RAI and after incorporation of biomarkers with RAI will be analyzed.DiscussionThe Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study, creates the first prospective international pediatric all cause AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children.Trial registrationClinicalTrials.gov: NCT01987921

A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury

Exposure to nephrotoxic medication is among the most common causes of acute kidney injury (AKI) in hospitalized patients. Here we conducted a prospective quality improvement project implementing a systematic Electronic Health Record screening and decision support process (trigger) in our quaternary pediatric inpatient hospital. Eligible patients were noncritically ill hospitalized children receiving an intravenous aminoglycoside for more than 3 days or more than 3 nephrotoxins simultaneously (exposure) from September 2011 through March 2015. Pharmacists recommended daily serum creatinine monitoring in exposed patients after appearance on the trigger report and AKI was defined by the Kidney Disease Improving Global Outcomes AKI criteria. A total of 1749 patients accounted for 2358 separate hospital admissions during which a total of 3243 episodes of nephrotoxin exposure were identified with 170 patients (9.7%) experiencing 2 or more exposures. A total of 575 individual AKI episodes occurred over the 43-month study period. Overall, the exposure rate decreased by 38% (11.63-7.24 exposures/1000 patient days), and the AKI rate decreased by 64% (2.96-1.06 episodes/1000 patient days). Assuming initial baseline exposure rates would have persisted without our project implementation, we estimate 633 exposures and 398 AKI episodes were avoided. Thus, systematic surveillance for nephrotoxic medication exposure and near real-time AKI risk can lead to sustained reductions in avoidable harm. These interventions and outcomes are translatable to other pediatric and nonpediatric hospitalized settings.

Improving delivery of continuous renal replacement therapy: Impact of a simulation-based educational intervention

Purpose: To describe our experience with transitions in both nursing model and educational training program for delivery of continuous renal replacement therapy. There have been very few comparisons between different care and educational models, and the optimal approach remains uncertain. In particular, we evaluated our experience with introducing a simulation-based educational model. Design: Prospective quality control observational study. Setting: The ICU of a tertiary care pediatric referral center. Patients: All patients undergoing CRRT between July 2007 through July 2010 were included. Measurements and Main Results: We monitored CRRT filter life during a transition from a collaborative to critical care nursing model, and subsequently during a transition from a didactic education program to simulation-based training. During the study period, 80 patients underwent continuous renal replacement therapy with use of 343 filters. Process control charts demonstrated a significant increase in filter life and a decrease in unplanned filter changes. Both of these signals emerged at the same time and corresponded with the introduction of the simulation-based education program. Further statistical analysis showed that filter life improved from 42.5 hours (18.2–66.4 hr) during the didactic education program to 59.4 hours (22.2–76.4 hr) during the simulation-based education program (p = 0.008). This relationship persisted when excluding nonpreventable premature filter discontinuations and in a multivariate model that accounted for other potential influences on filter life. Conclusions: We report on the impact of transitioning between different educational programs for continuous renal replacement therapy, specifically with the introduction of a simulation-based approach. We observed a significant and sustained improvement in the delivery of continuous renal replacement therapy as demonstrated by a marked increase in filter lifespan.

Biology of sepsis: Its relevance to pediatric nephrology

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.

Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy

Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis.

Immunomodulatory Device Therapy in a Pediatric Patient with Acute Kidney Injury and Multiorgan Dysfunction

David T. Selewski, Stuart L. Goldstein, Erin Fraser, Katie Plomaritas, Theresa Mottes, Tara Terrell and H. David Humes University of Michigan Health System, C.S. Mott Children’s Hospital, Ann Arbor, Michigan, USA; Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA; Innovative BioTherapies, Inc., Ann Arbor, Michigan, USA; and CytoPherx, Inc., Ann Arbor, Michigan, USA