Treatment preference and quality of life impact: ravulizumab vs eculizumab for atypical hemolytic uremic syndrome.

Aim: Ravulizumab and eculizumab are complement C5 inhibitors approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Ravulizumab requires less frequent infusions than eculizumab, which may reduce treatment burden. This study investigated patients' treatment preferences and the impact of both treatments on patient and caregiver quality of life. Materials & methods: Two surveys were conducted (one for adult patients with aHUS and one for caregivers of pediatric patients with aHUS) to quantitatively assess treatment preference and the patient- and caregiver-reported impact of ravulizumab and eculizumab on quality of life. Patients were required to have a diagnosis of aHUS, to be currently receiving treatment with ravulizumab and to have received prior treatment with eculizumab. Participants were recruited via various sources: the Alexion OneSource™ patient support program, the Rare Patient Voice recruitment agency, the aHUS Foundation and directly via a clinician involved in the study. Results: In total, 50 adult patients (mean age: 46.5 years) and 16 caregivers of pediatric patients (mean age: 10.1 years) completed the surveys. Most adult patients (94.0%) and all caregivers reported an overall preference for ravulizumab over eculizumab; infusion frequency was one of the main factors for patients when selecting their preferred treatment. Fewer patients reported disruption to daily life and the ability to go to work/school due to ravulizumab infusion frequency (4.0% and 5.7%, respectively) than eculizumab infusion frequency (72.0% and 60.0%), with similar results for caregivers. Conclusion: Adult patients and caregivers of pediatric patients indicated an overall preference for ravulizumab than eculizumab for the treatment of aHUS, driven primarily by infusion frequency. This study contributes to the emerging real-world evidence on the treatment impact and preference in patients with aHUS.

Ethical Concerns for Amnioinfusions to Treat Early-Onset Anhydramnios.

This Viewpoint discusses the long-term medical, emotional, and financial implications of using amnioinfusion to treat anhydramnios; outlines the ongoing Renal Anhydramnios Fetal Therapy (RAFT) trial, which aims to document outcomes and survival in infants after amnioinfusion; and suggests that amnioinfusions be withheld in early anhydramnios, pending the findings of the RAFT trial.

Variants in AQP11 may result in autosomal recessive bilateral cystic renal dysgenesis.

Congenital renal cystic dysplasia is a rare disease that occurs in approximately 1 in 4000 children and is often discovered in the antenatal period by ultrasound. It is commonly associated with oligohydramnios in utero and/or renal insufficiency or failure in the postnatal period. Aquaporins are membrane proteins that serve as transport channels in the transfer of water or small solutes across cell membranes. They play a role in the development of renal cysts. Aquaporin 11 (AQP11) deficient mice develop polycystic kidney disease in utero due to disruption of polycystin-1. Here we describe a case of bilateral cystic kidney disease in a patient with novel compound heterozygous variants in AQP11: c.780G>T (p. Trp260Cys) and c.472C>T (p.Pro158Ser) (NM_173039.2) identified by whole genome sequencing. These findings suggest, for the first time, the potential role of AQP11 in congenital renal cystic dysplasia.

Enteral Sodium Chloride Supplementation and Fluid Balance in Children Receiving Diuretics.

The use of sodium chloride (NaCl) supplementation in children being prescribed diuretics is controversial due to concerns that supplementation could lead to fluid retention. This is a single-center retrospective study in which fluid balance and diuretic dosing was examined in children prescribed enteral NaCl supplements for hyponatremia while receiving loop diuretics. The aim of this study was to determine whether significant fluid retention occurred with the addition of NaCl. Fifty-five patients with 68 events were studied. The median age was 5.2 months, and 82% were hospitalized for cardiac disease. Daily fluid balance the seven days prior to NaCl supplementation was lower than the seven days after, with measurement of: median 17 mL/kg/day (7-26) vs. 22 mL/kg/day (13-35) (p = 0.0003). There was no change in patient weight after supplementation (p = 0.63). There was no difference in the median loop diuretic dose before and after supplementation, with the diuretic dose in furosemide equivalents of 3.2 mL/kg/day (2.3-4.4) vs. 3.2 mL/kg/day (2.2-4.7) (p = 0.50). There was no difference in the proportion of patients receiving thiazide diuretics after supplementation (56% before vs. 50% after (p = 0.10)). NaCl supplementation in children receiving loop diuretics increased calculated fluid balance, but weight was unchanged, and this was not associated with an increase in diuretic needs, suggesting clinicians did not consider the increase in fluid balance to be clinically significant.

Diagnostic performance of 2D-shear wave elastography and serum fibrosis markers for evaluation of hepatic graft fibrosis in pediatric liver-inclusive transplant recipients: A prospective pilot study.

BACKGROUND: Liver biopsy is the gold standard for hepatic fibrosis staging, but it is invasive and has potential severe complications. We aimed to determine the diagnostic performance of 2D-SWE and serum markers to predict significant hepatic graft fibrosis (≥F2) in pediatric liver-inclusive transplant recipients. METHODS: This prospective, cross-sectional pilot study included children younger than 19 years who had received a LT or LSBT and underwent a liver biopsy performed for clinical indications. LS was measured using 2D-SWE. The AUROC was calculated to evaluate the diagnostic performance of 2D-SWE and biomarkers (AST/ALT ratio, APRI, FIB4) for predicting significant fibrosis. RESULTS: Twenty-two children (13 males, 8 LSBT) were included. Eighteen (81.8%) children received a whole liver graft. Thirteen (59.1%) patients had hepatic fibrosis (≥F1) and four (18.2%) had significant fibrosis. The AUROCs of AST/ALT ratio, APRI, and FIB4 for predicting significant hepatic graft fibrosis were 0.71 (p = .29), 0.85 (p = .0001), and 0.76 (p = .03), respectively. When FIB4 was calculated using the hepatic graft's age, its AUROC improved to 0.85 (p < .0001). The AUROC of 2D-SWE for predicting significant hepatic graft fibrosis was 0.80 (p = .046). When 2D-SWE was combined with APRI or FIB4, its AUROC improved to 0.82 (p = .08) and 0.87 (p = .002), respectively. CONCLUSIONS: APRI and FIB4 can accurately predict significant hepatic graft fibrosis. 2D-SWE may serve as a valuable adjunct tool to detect significant graft fibrosis, especially when combined with these serum markers.

Post-transplant hepatic fibrosis in pediatric liver-small bowel transplant recipients: A single-center, retrospective, observational study.

BACKGROUND: Little is known about the prevalence of hepatic graft fibrosis in combined LSBT children. We aimed to determine the prevalence of and identify potential predictors for hepatic graft fibrosis in LSBT children and to compare them with those in LT children. METHODS: We retrospectively included children younger than 19 years who had received a primary LT/LSBT between 2000 and 2018 and had a liver biopsy performed at least 6 months post-transplant. A Cox proportional hazards regression model was used to determine predictors associated with significant hepatic graft fibrosis (≥F2) in LSBT vs LT children. RESULTS: Ninety-six children (47 LSBT, 54 females) were included. The median post-transplant follow-up (years) was 12.8 in LT vs 10.5 in LSBT patients (P = .06). Hepatic graft fibrosis was found in 81.6% of LT vs 70.2% of LSBT children (P = .19), after a median time of 2.5 years and 2.6 years, respectively. On multivariate analyses, having post-transplant biliary complications was found to be associated with significant graft fibrosis in LT children, whereas AST/ALT ratio was found to predict significant hepatic graft fibrosis in LSBT children. The use of parenteral nutrition after transplant was not associated with significant hepatic graft fibrosis. CONCLUSIONS: The prevalence of hepatic graft fibrosis in LSBT children did not significantly differ from that in LT children, but the predictors may differ. Future studies should investigate the role of post-transplant autoimmune antibodies and donor-specific antibodies in the development and progression of hepatic graft fibrosis in LSBT children.

Diagnostic performance of non-invasive tests for evaluation of hepatic graft fibrosis in pediatric liver transplantation: A scoping review.

BACKGROUND: Hepatic graft fibrosis is a common histologic finding of pediatric liver transplant (LT) that might affect long-term graft outcome. However, its diagnosis and staging require an invasive liver biopsy. AIM: To review the published literature on the diagnostic accuracy of elastography and serum-based fibrosis markers for assessing hepatic graft fibrosis in pediatric LT recipients. METHODS: A scoping review was conducted using a systematic search of published literature in PubMed (MEDLINE), EMBASE, SCOPUS, and Cochrane Library between 2002 and 2019. We included all English conference abstracts or full-text articles that examined the diagnostic accuracy of the non-invasive test(s) to assess hepatic fibrosis in LT children, using liver biopsy as the reference test. RESULTS: Eight studies were included, of which 6 examined transient elastography (TE), one investigated acoustic radiation force impulse elastography, and 5 examined serum-based fibrosis markers (AST/ALT ratio, AST-to-platelet ratio index, FibroTest, enhanced liver fibrosis test). TE reportedly had a good AUROC (range: 0.82-0.92) to distinguish children with hepatic graft fibrosis (≥F1) from those with no fibrosis. However, there was considerable overlap of liver stiffness cutoffs in the mild to significant fibrosis groups (≥F1 and ≥F2). Current serum-based fibrosis markers reportedly had an unsatisfactory diagnostic accuracy. CONCLUSIONS: TE in LT children has similar diagnostic value and limitations as in the non-transplant setting. Prospective studies are warranted to validate an optimal liver stiffness cutoff for predicting significant hepatic graft fibrosis (≥F2) and to determine if a meaningful change in liver stiffness from baseline could identify patients at risk for fibrosis progression.