Multisite Retrospective Review of Outcomes in Renal Replacement Therapy for Neonates with Inborn Errors of Metabolism.

OBJECTIVE: To assess the outcomes of neonates in a contemporary multi-institutional cohort who receive renal replacement therapy (RRT) for hyperammonemia. STUDY DESIGN: We performed a retrospective analysis of 51 neonatal patients with confirmed inborn errors of metabolism that were treated at 9 different children's hospitals in the US between 2000 and 2015. RESULTS: Twenty-nine patients received hemodialysis (57%), 21 patients received continuous renal replacement therapy (41%), and 1 patient received peritoneal dialysis (2%). The median age at admission of both survivors (n = 33 [65%]) and nonsurvivors (n = 18) was 3 days. Peak ammonia and ammonia at admission were not significantly different between survivors and nonsurvivors. Hemodialysis, having more than 1 indication for RRT in addition to hyperammonemia, and complications during RRT were all risk factors for mortality. After accounting for multiple patient factors by multivariable analyses, hemodialysis was associated with a higher risk of death compared with continuous renal replacement therapy. When clinical factors including evidence of renal dysfunction, number of complications, concurrent extracorporeal membrane oxygenation, vasopressor requirement, and degree of hyperammonemia were held constant in a single Cox regression model, the hazard ratio for death with hemodialysis was 4.07 (95% CI 0.908-18.2, P value = .067). To help providers caring for neonates with hyperammonemia understand their patient's likelihood of survival, we created a predictive model with input variables known at the start of RRT. CONCLUSIONS: Our large, multicenter retrospective review supports the use of continuous renal replacement therapy for neonatal hyperammonemia.

Practice patterns and influence of allograft nephrectomy in pediatric kidney re-transplantation: A pediatric nephrology research consortium study.

INTRODUCTION: There are no guidelines regarding management of failed pediatric renal transplants. MATERIALS & METHODS: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. RESULTS: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty-three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P < .001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P = .04). Nephrectomy of allografts did not affect time to re-listing, donor source at re-transplant but significantly decreased time to (P = .009) and incidence (P = .0002) of complete cessation of immunosuppression post-graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re-transplant (18% vs 7%; P = .03) and multiple rejections in first year after re-transplant (7% vs 1%; P = .03). CONCLUSIONS: Practices pertaining to failed renal allografts are inconsistent-40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re-transplant.

A retrospective review of outcomes in the treatment of hyperammonemia with renal replacement therapy due to inborn errors of metabolism.

BACKGROUND: Outcomes for severe hyperammonemia treated with renal replacement therapy (RRT) reported in the literature vary widely. This has created differing recommendations regarding when RRT is beneficial for hyperammonemic patients. METHODS: To evaluate our institution's experience with RRT in pediatric patients with inborn errors of metabolism (IEMs) and potential prognostic indicators of a better or worse outcome, we performed a retrospective chart review of patients who received RRT for hyperammonemia. Our cohort included 19 patients with confirmed IEMs who received RRT between 2000 and 2017. Descriptive statistics are presented as medians with interquartile ranges with appropriate statistical testing assuming unequal variance. RESULTS: There were 16 males (84%) and 3 females (16%) identified for inclusion in this study. There were 9 survivors (47%) and 10 non-survivors (53%). The average age of survivors was 67 months (age range from 3 days to 15.6 years). The average age of non-survivors was 1.8 months (age range from 2 days to 18.7 months). Peak ammonia, ammonia on admission, and at RRT initiation were higher in non-survivors compared with survivors. Higher ammonia levels and no change in ammonia between admission and RRT initiation were associated with an increased risk of mortality. CONCLUSIONS: Hyperammonemia affects two distinct patient populations; neonates with markedly elevated ammonia levels on presentation and older children who often have established IEM diagnoses and require RRT after failing nitrogen-scavenging therapy. Our experience demonstrates no significant change in mortality associated with neonatal hyperammonemia, which remains high despite improvements in RRT and intensive care.

Immunogenicity of Augmented Compared With Standard Dose Hepatitis B Vaccine in Pediatric Patients on Dialysis: a Midwest Pediatric Nephrology Consortium Study.

BACKGROUND AND OBJECTIVES: Patients on maintenance dialysis have a higher risk of unresponsiveness to hepatitis B vaccination and loss of hepatitis B immunity. Adult guidelines recommend augmented dosing (40 mcg/dose), resulting in improved response in adults. We sought to determine whether children on dialysis mount a similar antibody response when given standard or augmented dosing of hepatitis B vaccine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective review of patients on dialysis aged <19 years from May 1, 2008 to May 1, 2013 at 12 pediatric dialysis units. Hepatitis B surface antibody (HBsAb) titers ≥10 mIU/ml were defined as protective. RESULTS: A total of 187 out of 417 patients received one or more hepatitis B vaccine boosters. The median age was 13 years; the cohort was 57% boys and 59% white. Booster dose or HBsAb titers were missing in 17 patients. Conversion to protective HBsAb titers was achieved in 135 out of 170 patients (79%) after their first single-dose booster or multidose booster series. In patients receiving a single-dose booster, the response rate was 53% (nine out of 17) after a 10 mcg dose, 86% (65 out of 76) after a 20 mcg dose, and 65% (17 out of 26) after a 40 mcg hepatitis B vaccine dose. In patients receiving a multidose booster series, the response rate was 95% (19 out of 20) after a 10 mcg/dose series, 83% (20 out of 24) after a 20 mcg/dose series, and 71% (five out of seven) after a 40 mcg/dose series. Patients receiving a multidose booster series had a response rate of 86% (44 out of 51), compared with 76% (91 out of 119) in patients receiving a single-dose booster (P=0.21). Twenty-seven patients received more than one single-dose booster or multidose series, and 26 out of 27 (96%) eventually gained immunity after receiving one to three additional single-dose boosters or multidose booster series. CONCLUSIONS: There was no clear gradient of increasing seroconversion rate with increasing vaccine dose in this cohort of pediatric patients on dialysis.

Therapeutic plasma exchange may improve hemodynamics and organ failure among children with sepsis-induced multiple organ dysfunction syndrome receiving extracorporeal life support.

OBJECTIVE: To determine the effect of therapeutic plasma exchange on hemodynamics, organ failure, and survival in children with multiple organ dysfunction syndrome due to sepsis requiring extracorporeal life support. DESIGN: A retrospective analysis. SETTING: A PICU in an academic children's hospital. PATIENTS: Fourteen consecutive children with sepsis and multiple organ dysfunction syndrome who received therapeutic plasma exchange while on extracorporeal life support from 2005 to 2013. INTERVENTIONS: Median of three cycles of therapeutic plasma exchange with median of 1.0 times the estimated plasma volume per exchange. MEASUREMENTS AND MAIN RESULTS: Organ Failure Index and Vasoactive-Inotropic Score were measured before and after therapeutic plasma exchange use. PICU survival in our cohort was 71.4%. Organ Failure Index decreased in patients following therapeutic plasma exchange (mean ± SD: pre, 4.1 ± 0.7 vs post, 2.9 ± 0.9; p = 0.0004). Patients showed improved Vasoactive-Inotropic Score following therapeutic plasma exchange (median [25th-75th]: pre, 24.5 [13.0-69.8] vs post, 5.0 [1.5-7.0]; p = 0.0002). Among all patients, the change in Organ Failure Index was greater for early therapeutic plasma exchange use than late use (early, -1.7 ± 1.2 vs late, -0.9 ± 0.6; p = 0.14), similar to the change in Vasoactive-Inotropic Score (early, -67.5 [28.0-171.2] vs late, -12.0 [7.2-18.5]; p = 0.02). Among survivors, the change in Organ Failure Index was greater among early therapeutic plasma exchange use than late use (early, -2.3 ± 1.0 vs late, -0.8 ± 0.8; p = 0.03), as was the change in Vasoactive-Inotropic Score (early, -42.0 [16.0-76.3] vs late, -12.0 [5.3-29.0]; p = 0.17). The mean duration of extracorporeal life support after therapeutic plasma exchange according to timing of therapeutic plasma exchange was not statistically different among all patients or among survivors. CONCLUSIONS: The use of therapeutic plasma exchange in children on extracorporeal life support with sepsis-induced multiple organ dysfunction syndrome is associated with organ failure recovery and improved hemodynamic status. Initiating therapeutic plasma exchange early in the hospital course was associated with greater improvement in organ dysfunction and decreased requirement for vasoactive and/or inotropic agents.