Urinary urea excretion index to guide weaning from renal replacement therapy in patients with acute kidney injury: Still haven’t found what i’m weaning for

Abstract

To the Editor,

We acknowledge the effort by Bodot et al. to explore the under-addressed topic of renal replacement therapy (RRT) discontinuation in critically ill patients with acute kidney injury (AKI) [1]. The study addresses a relevant issue and, in its introduction, rightly refers to the hypothesis that RRT itself may contribute to ongoing kidney injury through hemodynamic instability and other mechanisms. However, we believe that certain methodological and conceptual aspects, beginning with the underlying rationale, could benefit from further refinement, which may enhance the robustness of the conclusions and support broader applicability of the proposed approach in routine practice.

While the authors do not explicitly frame their study in these terms, their approach reflects an increasingly common tendency to define RRT discontinuation through structured protocols and fixed variable thresholds, in a manner reminiscent of mechanical ventilation (MV) weaning [2]. However, the process of MV weaning is critical because premature extubation can result in emergency reintubation, and increased mortality [3]. By contrast, stopping RRT too early typically leads only to the resumption of RRT (with need for catheter reinsertion in some instances) which is rarely associated with significant harm. The authors suggest that stopping RRT too early could result in fluid accumulation, delayed MV weaning, prolonged ICU stays, and increased mortality. This contention is not convincingly supported by the existing literature. In fact, emerging data, suggest that an overly aggressive approach to fluid removal in the early phase of AKI might actually worsen outcomes [4]. Then, the potential harms of RRT continuation, including hemodynamic instability and catheter-related complications, may outweigh the speculative risks of early cessation. The emphasis should therefore shift from the fear of stopping too soon to a more nuanced assessment of when further sessions are truly beneficial. From this perspective, the risk associated with early discontinuation of RRT is modest. It is therefore debatable whether the search for strict RRT weaning criteria is justified. In other words, the more relevant clinical question may not be “when to stop RRT” based on a predefined threshold, but rather “whether to continue” on a given day, depending on the patient’s evolving condition and ongoing indication for RRT. In this view, the focus shifts from a binary decision based on fixed criteria to a continuous clinical judgement aiming not only to avoid premature discontinuation, but also to recognize when further RRT sessions are no longer necessary [5].

Beyond this, the methodological framework chosen by the authors raises additional concerns. The primary endpoint, catheter-free days at day 28, relies on a clinician-driven decision and, while it captures a relevant process of care, it remains a surrogate outcome that does not directly measure total RRT duration, renal recovery, or any patient-centered benefit. Since the authors explicitly aim to define objective criteria for RRT discontinuation, one would have expected a primary outcome more directly linked to renal function or clinical recovery, rather than an indirect and operator-dependent measure. Moreover, in a before–after design, one cannot exclude that the observed differences stemmed in part from increased awareness and procedural vigilance regarding catheter removal in the second period, a form of behavioral shift that commonly arises when a protocol is introduced on a topic perceived as a “hot issue” by the clinical team. The introduction of a formal urinary biomarker–based strategy may have reinforced a shared perception that catheter removal should be actively pursued, thus increasing protocol adherence and shortening time to discontinuation, even independently of the urinary urea excretion index (UUEI) itself. Without objective data on overall RRT use, timing to renal recovery, or complications avoided, it remains uncertain whether the intervention truly impacted patient outcomes or primarily altered procedural momentum.

The physiological appeal of using urinary urea excretion as a marker of renal recovery is understandable since the ability to concentrate urea reflects tubular function and medullary integrity. However, the evidence supporting the urinary UUEI is thin. The threshold of 1.35 mmol/kg/24 h originates from a small, single-center, retrospective study conducted over a decade ago and involving only 67 patients [6]. This study has not been prospectively validated or replicated. Its findings, while intriguing, cannot serve as a foundation for practice-changing recommendations. While a meta-analysis reports a high AUROC in favor of UUEI (0.96 versus 0.86 for urine output [UO]), this result stems entirely from the original study [2]. This apparent superiority may be misleading: UUEI is calculated by simply multiplying two existing variables: UO and urinary urea concentration. As such, it is not an independent marker, but rather a composite of values already used in clinical practice. Because UO is both a component of UUEI and the main comparator, this mathematical overlap artificially boosts the correlation between the two, making the index seem more predictive than it may actually be. Without external validation, it is unclear whether UUEI truly adds useful clinical information beyond what is already provided by its two individual components. This uncertainty extends to its practical value at the bedside. Indeed, if intensivists observe a UO exceeding 8.5 mL/kg over 24 h (as reported in the initial study [6]), they already have a strong signal of potential renal recovery. Measuring urinary urea, calculating a product, and comparing it to a rigid threshold adds layers of complexity and delay without demonstrable benefit. Urine output, although imperfect, remains an accessible, reproducible, and widely accepted surrogate for renal function recovery which is already used in numerous protocols [7, 8]. If we accept that UO is an acceptable benchmark, and that avoiding unnecessary sessions is a worthwhile goal, then the focus should be on identifying even earlier predictors than UO itself. The goal should not be to confirm recovery that is already evident, but to avoid prolonging RRT when it is no longer useful. The problem is not the absence of strict thresholds but the continuation of RRT by default in patients who may not need it. In this light, indices like UUEI do not solve the problem, they shift it into a different form, with added complexity.

Finally, the use of a before–after methodology in the field of RRT is debatable. Clinical practice around RRT has changed over the past decade, especially with the publication of major trials advocating for delayed RRT initiation [9]. These changes influence not only when RRT is started, but also which patients are selected, what modalities are used, and how clinicians approach weaning. It is therefore difficult to isolate the effect of a new protocol from these background shifts. The authors acknowledge that in at least one center, catheter withdrawal occurred earlier in the period due to different initiation practices.

In conclusion, determining the optimal timing for RRT discontinuation and catheter removal is a relevant and practical question for intensivists. However, the methodological limitations of the present study including its before–after design, reliance on an unvalidated index threshold, and the lack of patient-centered outcomes weaken the strength of its conclusions. While the authors contribute to an important discussion, these limitations argue against adopting such a protocol beyond its original context. Until more robust evidence is available, the discontinuation of RRT should remain a flexible, patient-specific decision, grounded in clinical judgment.

No datasets were generated or analysed during the current study.

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9. 44th International Symposium on Intensive Care & Emergency Medicine. Critical Care. From evidence to practice: declining use of renal replacement therapy in critically ill patients with acute kidney injury Critical Care 2025, 29(S1):P058.

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Authors and Affiliations

1. Département de réanimation médico-chirurgicale, APHP Hôpital Avicenne, Bobigny, France

   Khalil Chaïbi & Stéphane Gaudry

2. Common and Rare Kidney Diseases, Sorbonne Université, INSERM, UMR-S 1155, Paris, France

   Khalil Chaïbi & Stéphane Gaudry

3. Investigation Network Initiative–Cardiovascular and Renal Clinical Trialists, Bobigny, France

   Khalil Chaïbi & Stéphane Gaudry

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1. Khalil ChaïbiView author publications

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2. Stéphane GaudryView author publications

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KC and SG wrote the manuscript.

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Correspondence to Khalil Chaïbi.

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Chaïbi, K., Gaudry, S. Urinary urea excretion index to guide weaning from renal replacement therapy in patients with acute kidney injury: Still haven’t found what i’m weaning for. Crit Care 29, 326 (2025). https://doi.org/10.1186/s13054-025-05581-7

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• Received: 18 July 2025

• Accepted: 22 July 2025

• Published: 26 July 2025

• DOI: https://doi.org/10.1186/s13054-025-05581-7

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