Beyond Overhydration: Considering the J‐Curve of Fluid Status in Hemodialysis Outcomes

We read with great interest the recent retrospective study by Jeon et al. [1] which investigated the association between body composition and hospitalization among patients undergoing hemodialysis (HD). Using multifrequency bioelectrical impedance analysis (BIA), the authors demonstrated that a higher baseline extracellular water to total body water ratio (ECW/TBW) is independently associated with an increased risk of hospitalization in HD patients. Furthermore, hospitalization was associated with a decrease in body mass index and percent body fat, as well as an increase in ECW/TBW. This finding underscores the critical clinical relevance of fluid status assessment in this vulnerable population. The study also highlights the practical utility of serial BIA measurements for predicting hospitalization risk in HD cohorts. The results of Jeon et al.'s study are consistent with a substantial body of evidence identifying chronic fluid overload, quantified by the ECW/TBW, as an independent predictor of adverse outcomes in HD patients. Nevertheless, the endpoint of most previous studies was mortality, a more solid endpoint than hospitalization. A multicenter, prospective, observational study by Pérez-Morales et al. [2] found that a higher ECW/TBW was associated with increased risks of all-cause and cardiovascular mortality in HD patients. Similarly, the retrospective study by Yajima and Yajima [3] demonstrated that the post-dialysis ECW/TBW (measured approximately 30 min after HD sessions) was independently associated with protein-energy wasting (PEW), cardiothoracic ratio, and C-reactive protein levels. Both a higher ECW/TBW (> 0.40) and the presence of PEW independently predicted all-cause mortality in HD patients. Moreover, a meta-analysis by Wang and Gu [4] which included 55 studies with 104 758 dialysis patients, confirmed that an ECW/TBW > 0.40 was associated with higher all-cause mortality and cardiovascular events, supporting the independent prognostic role of BIA-defined overhydration. However, a more nuanced interpretation of the relationship between fluid status and outcomes is warranted, one that moves beyond the simple linear notion that “less fluid is better.” Recently, Wang et al. [5] reported a J-shaped association between ECW/TBW and all-cause mortality, with an inflection point at an ECW/TBW of 0.42, in a large-scale, population-based cohort of 6338 adults who were not limited to hemodialysis patients. Historically, most dialysis studies have focused on high ECW/TBW (right arm of the J-shaped curve, clinically interpreted as overhydration) and its cardiovascular consequences compared to “not high” ECW/TBW; in contrast, the implications of an extremely low ECW/TBW (e.g., the left-sided peak of the J-shaped curve) have been less frequently examined and remain poorly characterized. Potential mechanisms underlying a low ECW/TBW include: (1) true hypovolemia resulting from excessive ultrafiltration or inadequate interdialytic fluid intake, reducing ECW relative to TBW; [6] (2) obesity-related expansion of intracellular water, which lowers the ECW/TBW [7]; and (3) malnutrition, which alters body water distribution and complicates the interpretation of BIA indices. Clarifying the potential adverse implications of a low ECW/TBW, representing the left arm of the J-shaped curve, is crucial for HD management, particularly in determining dry weight and refining fluid management strategies. Persistent hypovolemia may lead to recurrent intradialytic or chronic hypotension, organ stunning (especially renal and myocardial), and eventual chronic volume depletion, all of which are independently associated with poor outcomes. In light of this emerging concept, we would like to raise two specific comments: First, we encourage the authors to explore the association between ECW/TBW and mortality in addition to hospitalization risks, a more definitive clinical endpoint than hospitalization, given the robust data likely available in their cohort. Second, as the relationship between ECW/TBW and outcomes may follow a J- or U-shaped pattern, we suggest that the authors examine the outcomes of patients with extremely low ECW/TBW. Elucidating such a non-linear relationship in the HD population would not only provide a more comprehensive physiological understanding but also inform fluid management targets, supporting a precision medicine approach that minimizes the risks of both chronic overhydration and iatrogenic volume depletion. Conceptualization: Chih-Chung Shiao. Writing – original draft preparation: Shu-Ming Chen, Rong-Na Jhen, Yu-Ming Chang, Jsun-Liang Kao, Chih-Hsien Wang, Chih-Chung Shiao. Writing – review, and editing: Chih-Hsien Wang, Chih-Chung Shiao. Supervision: Chih-Chung Shiao. All authors have read and agreed to the published version of the manuscript. During the preparation of this work, the authors used Grammarly to improve readability. After using this tool/service, the authors reviewed and edited the content as needed and took full responsibility for the publication's content. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.