Fluid overload is common and clinically important in critically ill children with moderate-to-severe acute kidney injury (AKI). Evidence on treatment options when continuous furosemide infusion fails to achieve adequate diuresis is limited in pediatrics. This retrospective cohort study describes use of metolazone as an adjunct diuretic in children with KDIGO stage 2 or 3 AKI and fluid overload who remained inadequately responsive to continuous furosemide, and evaluates factors associated with subsequent need for kidney replacement therapy (KRT).
The authors performed a retrospective cohort analysis in a pediatric intensive care unit. Eligible patients met these criteria: KDIGO stage 2 or 3 AKI; were receiving continuous furosemide infusion; received metolazone for inadequate urine output; and had no history of chronic dialysis. Urine output before metolazone and during predefined 48-hour intervals after initiation were compared. Multivariable logistic regression assessed associations between urine-output response and KRT. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance for KRT and to identify an optimal urine-output change cutoff.
From 196 children who received metolazone, 62 met the study inclusion criteria. Median age was 40.5 months (interquartile range 11–144.5 months). Sixty-one percent of the cohort had KDIGO stage 3 AKI. Ninety percent were invasively ventilated at baseline, and the median vasoactive-inotropic score was 10 (IQR 0–26). These data indicate a severely ill pediatric population with substantial organ support requirements.
Median urine output prior to metolazone was 0.8 mL/kg/h. Following metolazone initiation, median urine output increased across all predefined intervals: to 1.49 mL/kg/h during 0–6 h, 1.37 mL/kg/h during 6–12 h, 2.5 mL/kg/h during 12–24 h, and 2.68 mL/kg/h during 24–48 h after the first dose. All increases were statistically significant (p < 0.01). These findings indicate an early and progressive diuretic response when metolazone was added to existing continuous furosemide therapy.
In this cohort, children received a median of 3 doses of metolazone over the first 48 hours after initiation. The abstract does not report additional granular dosing details (dose per kilogram, timing of individual doses) or protocols for coadministration with other diuretics beyond the continuous furosemide infusion.
Twenty of the 62 included children (32%) required subsequent KRT. In multivariable analysis, a greater increase in urine output during the 12–24-hour interval after metolazone initiation was associated with lower odds of progressing to KRT (odds ratio 0.59; 95% CI 0.36–0.96; p = 0.034). This suggests that an early diuretic response to adjunctive metolazone may identify patients less likely to need KRT.
ROC analysis evaluated the predictive value of urine-output change for KRT. The area under the curve (AUC) for the 12–24-hour urine-output change was 0.708 (95% CI 0.568–0.849; p = 0.010), with an optimal cutoff identified as an increase of ≥ 0.85 mL/kg/h. In a 24-hour landmark analysis the AUC was 0.683 (95% CI 0.527–0.838; p = 0.021) using the same cutoff. These AUC values indicate modest discriminative performance in this exploratory dataset.
In this retrospective cohort of critically ill children with moderate-to-severe AKI and fluid overload refractory to continuous furosemide, initiation of adjunctive metolazone was followed by a significant increase in urine output. An early urine-output response—particularly during 12–24 hours—was associated with a lower likelihood of progression to KRT. The authors characterize these results as exploratory and recommend prospective validation before changes to practice can be endorsed.
The abstract reports that the study is retrospective and exploratory. Specific limitations such as potential confounding, selection bias, and lack of a comparator group are inherent to the design but are not detailed in the abstract. Adverse events, electrolyte disturbances, or longer-term renal and clinical outcomes were not reported in the abstract. Detailed dosing regimens beyond the median number of doses and protocolized criteria for KRT initiation were also not provided in the abstract. These gaps highlight the need for prospective studies to determine safety, optimal dosing, and whether metolazone reduces the need for KRT or improves other patient-centered outcomes.
Conflict of interest: none declared. The authors note that findings require prospective validation before broader clinical application.