---
title: "Metolazone as Adjunct Therapy for Furosemide-Refractory Fluid Overload in Critically Ill Children"
id: "pubmed-42717003"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42717003"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42717003/"
doi: "10.1007/s00467-026-07544-8"
published_at: "2026-09-10T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Metolazone as Adjunct Therapy for Furosemide-Refractory Fluid Overload in Critically Ill Children
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42717003
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42717003/)
- **DOI:** [10.1007/s00467-026-07544-8](https://doi.org/10.1007%2Fs00467-026-07544-8)
- **Published At:** 2026-09-10T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This retrospective pediatric ICU cohort examined **metolazone** use in children with KDIGO stage 2–3 **acute kidney injury (AKI)** who remained oliguric despite continuous **furosemide** infusion and were not on chronic dialysis. - Inclusion required moderate-to-severe AKI (KDIGO stage 2/3), ongoing continuous furosemide infusion, metolazone initiation for inadequate urine output, and no chronic dialysis history. - Of 196 metolazone-treated children screened, 62 met inclusion criteria; median age 40.5 months; 61% had stage 3 AKI; 90% were intubated; median vasoactive-inotropic score was 10. - Urine output rose significantly after metolazone initiation: median from 0.8 mL/kg/h pre-treatment to 1.49, 1.37, 2.5, and 2.68 mL/kg/h across 0–6, 6–12, 12–24, and 24–48 h intervals, respectively (all p < 0.01). - Median number of metolazone doses over 48 h was 3. - Twenty patients (32%) progressed to **kidney replacement therapy (KRT)**. Greater urine-output increase during 12–24 h after metolazone was associated with lower odds of requiring KRT (OR 0.59 per unit increase; 95% CI 0.36–0.96; p = 0.034). - Receiver operating characteristic (ROC) analysis showed an AUC of 0.708 for 12–24-h urine-output change (optimal cutoff ≥ 0.85 mL/kg/h). A 24-h landmark analysis gave an AUC of 0.683 with the same cutoff. - Authors conclude metolazone initiation was followed by increased **urine output** and that early response was associated with reduced likelihood of KRT; they note findings are exploratory and call for prospective validation. - Conflict of interest: none declared. Details on adverse events, long-term outcomes, and specific dosing strategies beyond median doses were not reported in the abstract.
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Online ahead of print. # Adjunctive metolazone in critically ill children with moderate-to-severe acute kidney injury and furosemide-refractory fluid overload [Avichai Weissbach](https://pubmed.ncbi.nlm.nih.gov/?term=Weissbach+A&cauthor_id=42717003)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-1 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. weissbac@gmail.com.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-2 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. weissbac@gmail.com."), [Liron Sadovski](https://pubmed.ncbi.nlm.nih.gov/?term=Sadovski+L&cauthor_id=42717003)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Victoria Finkel](https://pubmed.ncbi.nlm.nih.gov/?term=Finkel+V&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel."), [Gili Kadmon](https://pubmed.ncbi.nlm.nih.gov/?term=Kadmon+G&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Elhanan Nahum](https://pubmed.ncbi.nlm.nih.gov/?term=Nahum+E&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Rotem Davidovich](https://pubmed.ncbi.nlm.nih.gov/?term=Davidovich+R&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Gal Benshalom](https://pubmed.ncbi.nlm.nih.gov/?term=Benshalom+G&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Eytan Kaplan](https://pubmed.ncbi.nlm.nih.gov/?term=Kaplan+E&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#full-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.") Affiliations Expand ### Affiliations * 1 Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. weissbac@gmail.com. * 2 Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. weissbac@gmail.com. * 3 Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. * 4 Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. * PMID: **42717003** * DOI: [ 10.1007/s00467-026-07544-8 ](https://doi.org/10.1007/s00467-026-07544-8) Item in Clipboard # Adjunctive metolazone in critically ill children with moderate-to-severe acute kidney injury and furosemide-refractory fluid overload Avichai Weissbach et al. Pediatr Nephrol. 2026. Show details Display options Display options Format Abstract PubMed PMID Pediatr Nephrol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Pediatr+Nephrol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Pediatr+Nephrol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42717003/) . 2026 Sep 10. doi: 10.1007/s00467-026-07544-8. Online ahead of print. ### Authors [Avichai Weissbach](https://pubmed.ncbi.nlm.nih.gov/?term=Weissbach+A&cauthor_id=42717003)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-1 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. weissbac@gmail.com.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-2 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. weissbac@gmail.com."), [Liron Sadovski](https://pubmed.ncbi.nlm.nih.gov/?term=Sadovski+L&cauthor_id=42717003)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Victoria Finkel](https://pubmed.ncbi.nlm.nih.gov/?term=Finkel+V&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel."), [Gili Kadmon](https://pubmed.ncbi.nlm.nih.gov/?term=Kadmon+G&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Elhanan Nahum](https://pubmed.ncbi.nlm.nih.gov/?term=Nahum+E&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Rotem Davidovich](https://pubmed.ncbi.nlm.nih.gov/?term=Davidovich+R&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Gal Benshalom](https://pubmed.ncbi.nlm.nih.gov/?term=Benshalom+G&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel."), [Eytan Kaplan](https://pubmed.ncbi.nlm.nih.gov/?term=Kaplan+E&cauthor_id=42717003)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-4 "Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42717003/#short-view-affiliation-3 "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.") ### Affiliations * 1 Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. weissbac@gmail.com. * 2 Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. weissbac@gmail.com. * 3 Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. * 4 Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel. * PMID: **42717003** * DOI: [ 10.1007/s00467-026-07544-8 ](https://doi.org/10.1007/s00467-026-07544-8) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Data on metolazone in children with fluid overload and moderate-to-severe acute kidney injury (AKI) inadequately responsive to continuous furosemide infusion are limited. We describe its use and factors associated with kidney replacement therapy (KRT). **Methods:** This retrospective cohort study in a pediatric intensive care unit included patients with KDIGO stage 2/3 AKI, continuous furosemide infusion, metolazone for inadequate urine output, and no chronic dialysis. Urine output was compared between the 6 h before metolazone and predefined 48-h intervals. Multivariable logistic regression and receiver operating characteristic (ROC) analysis evaluated associations with KRT. **Results:** Of 196 metolazone-treated children, 62 met inclusion criteria. Median age was 40.5 months (IQR 11-144.5); 61% had stage 3 AKI, 90% were invasively ventilated, and median vasoactive-inotropic score was 10 (IQR 0-26). Median urine output increased from 0.8 mL/kg/h before metolazone to 1.49, 1.37, 2.5, and 2.68 mL/kg/h during 0-6, 6-12, 12-24, and 24-48 h, respectively (all p < 0.01). Children received a median of 3 doses over 48 h. Twenty children (32%) required KRT. Greater 12-24-h urine-output increase was associated with lower KRT odds (odds ratio 0.59, 95% CI 0.36-0.96; p = 0.034). AUC was 0.708 (95% CI 0.568-0.849; p = 0.010), with optimal cutoff ≥ 0.85 mL/kg/h; in 24-h landmark analysis, AUC was 0.683 (95% CI 0.527-0.838; p = 0.021), with the same cutoff. **Conclusions:** Metolazone initiation was followed by increased urine output. Response was associated with lower KRT likelihood. These exploratory findings require prospective validation. **Keywords:** Acute kidney injury; Fluid overload; Kidney replacement therapy; Metolazone; Pediatric intensive care. © 2026. The Author(s), under exclusive licence to International Pediatric Nephrology Association. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of Interest and Source of Funding: None declared. ## References 1. 1. Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138 2. 1. Selewski DT, Cornell TT, Heung M et al (2014) Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med 40:1481–1488 - [DOI](https://doi.org/10.1007/s00134-014-3391-8) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/25079008/) 3. 1. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators AWARE (2017) Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 376:11–20 - [DOI](https://doi.org/10.1056/nejmoa1611391) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/27959707/) 4. 1. Kuai Y, Li M, Chen J et al (2022) Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study. Crit Care 26:207 - [DOI](https://doi.org/10.1186/s13054-022-04083-0) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35799300/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/9264539/) 5. 1. Tai CW, Gibbons K, Schlapbach LJ, Raman S (2022) Acute kidney injury: epidemiology and course in critically ill children. J Nephrol 35:559–565 - [DOI](https://doi.org/10.1007/s40620-021-01071-5) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34076880/) Show all 27 references [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM **Send To** * [Clipboard](https://pubmed.ncbi.nlm.nih.gov/42717003/) * [Email](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42717003%2F%23open-email-panel) * [Save](https://pubmed.ncbi.nlm.nih.gov/42717003/) * [My Bibliography](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42717003%2F%23open-bibliography-panel) * [Collections](https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F42717003%2F%23open-collections-panel) * [Citation Manager](https://pubmed.ncbi.nlm.nih.gov/42717003/) [x] NCBI Literature Resources [MeSH](https://www.ncbi.nlm.nih.gov/mesh/) [PMC](https://www.ncbi.nlm.nih.gov/pmc/) [Bookshelf](https://www.ncbi.nlm.nih.gov/books) [Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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