Association Between Red Cell Distribution Width-to-Albumin Ratio and Sepsis-Associated Acute Kidney Injury

Association Between Red Cell Distribution Width-to-Albumin Ratio and Sepsis-Associated Acute Kidney Injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association Between Red Cell Distribution Width-to-Albumin Ratio and Sepsis-Associated Acute Kidney Injury Mengqi Mi, jinyu Li, junjie liu, jianjun Wang, yuan liu, Hao Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7135515/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2026 Read the published version in BMC Nephrology → Version 1 posted 10 You are reading this latest preprint version Abstract Background Sepsis constitutes a critical syndrome frequently observed in ICUs, posing a major worldwide health challenge.Recent data indicate that roughly one fifth of non-critical sepsis patients develop AKI, with its frequency continuing to rise.Although the erythrocyte distribution width–albumin ratio (RA) has emerged as a new indicator, its role in forecasting SA-AKI is still poorly characterized.Accordingly, we sought to determine whether RA independently predicts the onset of SA-AKI. Methods A retrospective cohort of 133 sepsis patients admitted to our ICU between September 2019 and September 2021 was analyzed.Using KDIGO 2012 guidelines, participants were classified into AKI and non-AKI cohorts based on the emergence of AKI within 28 days of ICU entry. The predictive value of RA for SA-AKI was assessed by univariate and multivariate logistic regression analysis.Subgroup analyses stratified by sex, age, APACHE II score, comorbidities, mechanical ventilation, and whether vasoactive drugs were applied. Results Of the 133 included sepsis cases, 56 (42.1%) experienced AKI during ICU stay.Intergroup comparisons revealed marked discrepancies in RA, PCT, Lac, RDW, MPV, APACHE II scores, and rates of mechanical ventilation or vasopressor use (all P < 0.05). After multivariable adjustment, RA remained independently associated with AKI (OR 1.53; 95% CI 1.06–2.21; P = 0.023). Subgroup analyses confirmed the robustness of this association across diverse clinical strata. Conclusion Elevated RA independently forecasts SA-AKI, underscoring its utility as a readily available early warning index in septic individuals. Intensive care unit erythrocyte distribution width to albumin ratio sepsis acute kidney injury Figures Figure 1 1. INTRODUCTION Sepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. It remains a major global health concern and is a common cause of multiple organ failure [ 1 ] . When sepsis leads to acute renal dysfunction, it is referred to as sepsis-associated acute kidney injury (SA-AKI). A retrospective cohort study reported that 47.1% of sepsis patients developed concurrent AKI, which was significantly associated with prolonged ICU stay and poor short- and long-term outcomes [ 2 ] . The high prevalence and substantial economic burden of SA-AKI have prompted researchers to identify its risk factors.While both RDW and albumin individually predict AKI [3、4] , their combined predictive utility for SA-AKI remains unestablished. Erythrocyte distribution width is a parameter that reflects the heterogeneity of erythrocyte volume and reflects the heterogeneity of erythrocyte size. It is closely associated with the development of many diseases and is also an important predictor of disease occurrence [ 5 ] . Serum albumin is an important protein for the maintenance of osmotic pressure in the body, with anti-inflammatory and antioxidant effects, and is closely related to the prediction and prognosis of kidney injury [ 6 ] . The predictive value of erythrocyte distribution width to albumin ratio as a relatively new index in SA-AKI has not been adequately demonstrated. Therefore, we hypothesized that the erythrocyte distribution width to albumin ratio has a predictive value for the occurrence of AKI in patients with sepsis, with the aim of providing clinicians with a useful reference for the early recognition and prevention of SA-AKI. 2. Methods 2.1 Study design and RA definition We retrospectively leveraged anonymized electronic health records stored at the Affiliated Hospital of North China University of Science and Technology.Between September 2020 and September 2021, 133 consecutive adults who fulfilled the Sepsis-3 definitions were enrolled from our critical care department [ 1 ] . Using KDIGO 2012 guidelines, participants were dichotomized into AKI and non-AKI cohorts according to AKI onset within 28 days of ICU stay [ 7 ] .Baseline demographics, comorbidities, vital parameters, and laboratory indices were extracted for each subject.The RA was calculated by dividing the red cell distribution width (RDW, %) by the serum albumin level (g/dL )[ 8 ] , both measured from blood samples collected upon ICU admission. The study protocol adhered to the ethical principles of the Declaration of Helsinki and received formal approval from the Ethics Committee at North China University of Science and Technology Affiliated Hospital (Approval No. SQ2024029).Given the retrospective nature and use of anonymized data, informed consent was waived by the Ethics Committee. 2.2 Inclusion criteria Eligible individuals were adults (> 18 y) with newly diagnosed sepsis and complete clinical-laboratory datasets who developed AKI within 28 days. We excluded patients with chronic kidney disease, prior renal transplantation, active malignancy, or immune-mediated disorders. 2.3 Collection of variables All variables were retrieved from the hospital’s integrated electronic health platform. Laboratory panels comprised PCT, WBC, neutrophil ratio, MPV, RDW, electrolytes, albumin, lactate, D-dimer, and serial creatinine values.Supplementary variables encompassed demographics, comorbidities, APACHE II scores, and therapeutic interventions (CRRT, ventilation, vasopressors). Baseline indices were captured within 24 h of ICU arrival.The primary endpoint was incident SA-AKI within 28 days. 2.4 Quality control. To curtail selection and information bias, we applied rigorous eligibility filters and systematic data abstraction, with regular audits to exclude ineligible cases.These measures bolstered internal validity and data integrity. Potential confounding was addressed by harmonized data collection and multivariable modelling.Standardized abstraction protocols and multivariable adjustment minimized residual confounding. 2.5 Statistical methods All statistical analyses were performed using R software (version 4.2.0; R Foundation for Statistical Computing, Vienna, Austria) and Free Statistics software version 2.2.All tests were two-sided, and a p-value < 0.05 was considered statistically significant. Continuous data are shown as mean ± SD or median [IQR]; categorical data as n (%). Intergroup differences were assessed with t-tests, χ², or Mann–Whitney U tests as appropriate. Multivariable logistic and stratified analyses explored RA–SA-AKI relations. Sequential models adjusted for demographics (Model 2) and comprehensive covariates (Model 3). 3. Results 3.1 Baseline data characteristics A total of 133 patients diagnosed with sepsis according to Sepsis-3 criteria were included. Based on the KDIGO criteria, patients were divided into the non-AKI group (n = 77) and the AKI group (n = 56) according to the KDIGO criteria. The mean age of the participants was 70.5±11.1 years, with 85 (63.9%) being male. The average baseline RA was 4.6±1.5. Statistical analysis showed that patients in the AKI group had significantly higher RA levels than those in the non-AKI group. Additionally, the need for mechanical ventilation, vasoactive medications, and continuous renal replacement therapy (CRRT) was significantly greater in the AKI group.Disease severity was greater in the AKI group, as indicated by elevated APACHE II scores, procalcitonin (PCT), Red Cell Distribution Width (RDW)，Mean Platelet Volume (MPV)and lactate levels.Renal function indicators, including serum creatinine (Cr) and peak creatinine (Crmax), were significantly elevated in the AKI group. No significant differences were observed between the two groups in terms of sex distribution, age, blood pressure at admission, prevalence of hypertension, coronary artery disease, diabetes mellitus, leukocyte count, neutrophil percentage, estimated glomerular filtration rate (eGFR), serum sodium, albumin, or D-dimer levels(Refer to Table 1). 3.2 Unifactorial and multifactorial Logistic regression analysis for the occurrence of AKI in patients with sepsis Univariate logistic regression analysis revealed that RA, mechanical ventilation, use of vasoactive drugs, CRRT, APACHE II score, procalcitonin (PCT), mean platelet volume (MPV), red cell distribution width (RDW), lactate (Lac), serum creatinine (Cr), and peak creatinine (Crmax) were all significantly associated with AKI in sepsis patients (Refer to Table 2). The association between RA and SA-AKI was further assessed using multivariate logistic regression across three analytical models.In Model 1 (unadjusted), elevated RA was significantly associated with an increased risk of AKI (OR = 1.51, 95% CI: 1.13–2.03, P = 0.006).In Model 2, after adjusting for age and sex, RA remained significantly associated with AKI (OR = 1.51, 95% CI: 1.13–2.03, P = 0.015).In Model 3, which was adjusted for comorbidities, mechanical ventilation, and relevant biochemical parameters, RA remained an independent predictor of AKI in sepsis patients (OR = 1.53, 95% CI: 1.06–2.21, P = 0.023; Refer to Table 3). 3.3 Subgroup analysis To evaluate the impact of RA on SA-AKI across different patient subgroups, subgroup analyses were conducted (see Table 4).The results indicated that the association between RA and SA-AKI remained consistent across subgroups. Significant associations were observed in male patients (OR = 1.49, 95% CI: 1.03–2.14), patients without hypertension (OR = 1.90, 95% CI: 1.11–3.26), those requiring mechanical ventilation (OR = 1.77, 95% CI: 1.17–2.66), those receiving vasoactive medications (OR = 1.91, 95% CI: 1.18–3.09), and those not undergoing CRRT (OR = 2.24, 95% CI: 1.23–4.08). Notably, formal interaction tests (P for interaction) showed no statistically significant differences in the association between RA and SA-AKI across subgroups stratified by sex (P = 0.898), hypertension (P = 0.220), coronary artery disease (P = 0.928), diabetes mellitus (P = 0.847), mechanical ventilation (P = 0.055), use of vasoactive drugs (P = 0.141), CRRT (P = 0.087), age group (P = 0.882), or APACHE II score group (P = 0.681).Although point estimates varied slightly among subgroups (e.g., higher ORs in patients without hypertension and those not receiving CRRT), none of these interactions were statistically significant, indicating that the association between RA and SA-AKI was robust across populations.（Refer to Figure 1） 4. Discussion Despite extensive adjustment, RA retained independent predictive capacity for SA-AKI. An elevated RA was associated with a higher risk of AKI development in sepsis patients.This association was consistent across various subgroups stratified by sex, age, APACHE II score, comorbidities, and the use of CRRT, vasoactive drugs, or mechanical ventilation. Sepsis stems from a maladaptive host reaction to pathogens and frequently evolves into multiorgan dysfunction. Prompt biomarker-guided intervention is thus essential to enhance survival.Emerging evidence indicates that biomarkers like NGAL and cystatin C facilitate prompt identification, stratification, and outcome prediction in SA-AKI [ 9 ] .Red cell distribution width (RDW), traditionally used to classify types of anemia, has recently emerged as a predictor of systemic inflammatory, cardiovascular, and renal conditions [ 10 ] .Yi-Hsiang Pan et al [ 11 ] . reported that RDW, when combined with other markers, can improve the predictive accuracy for sepsis.The study by Honghao et al. demonstrated that RDW is a prognostic marker for SA-AKI, with elevated RDW values significantly associated with increased 28-day mortality [ 12 ] .In sepsis patients, RDW is a useful predictor of disease occurrence and prognosis, as systemic inflammation alters erythrocyte morphology and increases heterogeneity, thereby elevating RDW. Serum albumin mirrors nutritional reserves and modulates inflammatory cascades while serving as a gauge of renal integrity; in septic patients, reduced levels independently forecast acute and chronic organ failure and heightened mortality.In sepsis, increased vascular permeability causes albumin to leak into interstitial tissues, resulting in hypoalbuminemia. [ 13 ] Consequently, low albumin levels serve as an independent risk factor for sepsis progression and poor long-term prognosis. [ 13 ] Hypoalbuminemia and sepsis reinforce each other in a vicious cycle, amplifying the detrimental impact of low albumin on patient outcomes. [ 14 ] The red cell distribution width-to-albumin ratio (RA) is a relatively novel biomarker that is readily obtainable in clinical practice and more cost-effective than many emerging indicators.Previous studies have demonstrated the predictive value of RA in various diseases.Jie Liu et al. [ 15 ] found that RA was a stronger predictor than RDW for diabetes prevalence and long-term prognosis. Moreover, higher RA levels were associated with shorter survival among diabetic patients under 60 years old.Liang Ruan et al. [ 16 ] demonstrated that RA is a key predictor of renal and cardiorenal function in patients with acute myocardial infarction (AMI).RA was an independent predictor of type 1 cardiorenal syndrome (CRS-1) in patients with AMI, with elevated RA levels linked to a higher incidence of CRS-1. RA may therefore serve as a useful marker for risk stratification in these patients.Although RA has shown predictive value in various diseases, its role in predicting SA-AKI remains largely unexplored, and no prior studies have specifically investigated its association with SA-AKI development.Nevertheless, previous studies have suggested that RA may serve as an independent prognostic indicator in critically ill elderly patients with AKI, with higher RA levels associated with increased mortality and a higher incidence of septic shock.These findings align with our results, which identified RA as an independent risk factor for SA-AKI. [ 17 ] The pathophysiological mechanisms underlying SA-AKI have been well studied in previous research.During sepsis, a cytokine storm and excessive activation of complement and antibodies trigger apoptosis of renal vascular endothelial cells. [18、19] This results in increased protein leakage, impaired renal perfusion due to systemic neuroendocrine dysregulation, and abnormal renal hemodynamics. Consequently, renal ischemia, tubular necrosis, epithelial shedding, and glomerular capillary fibrin thrombosis occur, ultimately leading to acute kidney injury [ 20 ] .Sepsis-induced inflammation activates intracellular signaling pathways, promotes the release of cytokines such as IL-6, and suppresses erythropoietin production, resulting in increased release of immature erythrocytes [ 21 ] .In addition, inflammatory factors stimulate the production of reactive oxygen species (ROS), which damage erythrocyte membranes, alter cell morphology, and reduce erythrocyte deformability. These impaired erythrocytes may obstruct renal tubules, leading to localized renal ischemia, hypoxia, tubular necrosis, and impaired filtration function.Reduced serum albumin compromises the integrity of the endothelial glycocalyx, weakening its protective function against inflammatory mediators and nephrotoxic insults, thereby contributing to AKI development.The RA, as a composite marker, amplifies the effects of subtle systemic changes on renal function.Sepsis-induced inflammation and oxidative stress elevate RDW and decrease serum albumin levels, both of which synergistically impair renal microcirculation and damage the endothelial glycocalyx, ultimately promoting kidney injury. [ 22 ] Evidence suggests that RA levels increase 6–12 hours earlier than serum creatinine, indicating its potential utility as an early biomarker for SA-AKI [ 23 ] .Future research aimed at elucidating the underlying mechanisms may establish RA not only as an early warning biomarker for SA-AKI, but also as a potential therapeutic target. Our study has some limitations. The chief limitation is the single-center retrospective framework, susceptible to selection bias.Residual confounding from unmeasured factors cannot be entirely excluded. Multicenter prospective validation is warranted to corroborate these results. 5. Conclusion In conclusion,RA is an independent risk factor for AKI in sepsis patients. Elevated RA levels are significantly associated with increased AKI risk, and this association remains robust across subgroups. Declarations Acknowledgements The authors extend sincere gratitude to all patients, physicians, and technical staff at our center for their invaluable contributions to this study. The research protocol, including study design, ethical compliance, and data collection procedures, was supervised and approved by the Institutional Ethics Committee of North China University of Science and Technology Affiliated Hospital Authors’ contributions MQM and JJL: Contributed equally to study design and data interpretation; Performed primary data analysis.JYL, JJW, JJL, ABC: Contributed to the conception/design of the study and data interpretation; Critically revised the manuscript.MQM,JYL,JJL,JJW,YL,HW,ABC: Conducted the research.All authors: Contributed to data acquisition and statistical analysis; Drafted the manuscript; Read and approved the final manuscript. All authors agree to be fully accountable for ensuring the integrity and accuracy of the work. Funding The authors Jinyu Li, Jianjun Wang, and Aibin Cheng are currently funded by the Health Commission of Hebei Province (#20250928). Ethics approval and consent to participate The study protocol adhered to the ethical principles of the Declaration of Helsinki and received formal approval from the Ethics Committee at North China University of Science and Technology Affiliated Hospital (Approval No. SQ2024029).Given the retrospective nature and use of anonymized data, informed consent was waived by the Ethics Committee. Consent for publication Not applicable. No individual personal data is included in the study. Availability of data and materials The cohorts generated and/or analyzed during this study are not publicly available, due to currently ongoing research studies, but the data are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. References SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)[J]. JAMA. 2016;315(8):801–10. Zarbock A et al. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.Nature reviews. Nephrology 19,6 (2023): 401–17. Zheng B et al. Combined effect of anion gap and red cell distribution width on the risk of acute kidney injury after cardiac surgery. J Cardiothorac Surg 19,1 612. 23 Oct. 2024. Schnabel K, et al. Urinary albumin-to-creatinine ratio and serum albumin are predictors of acute kidney injury in non-ventilated COVID-19 patients: a single-center prospective cohort study. Int Urol Nephrol vol. 2023;55(3):711–20. Cai S et al. Jun. Red blood cell distribution width combined with age as a predictor of acute ischemic stroke in stable COPD patients. Frontiers in neurology vol. 14 1165181. 5 2023. Michelis R et al. Unexpected Normal Colloid Osmotic Pressure in Clinical States with Low Serum Albumin. PloS one vol. 11,7 e0159839. 25 Jul. 2016. Lameire NH et al. Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.Kidney international vol. 100,3 (2021): 516–526. Ertekin B, Tarık. Acar.The Relationship Between Prognosis and Red Cell Distribution Width (RDW) and RDW-Albumin Ratio (RAR) in Patients with Severe COVID-19 Disease. Int J Gen Med. 2022;15:8637–45. 16 Dec. Dai X et al. Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury. Crit Care (London England) 19,1 223. 6 May. 2015. Lu X, et al. Prognostic significance of increased preoperative red cell distribution width (RDW) and changes in RDW for colorectal cancer. Cancer Med vol. 2023;12(12):13361–73. Pan Y-H et al. Early Identification of Sepsis-Induced Acute Kidney Injury by Using Monocyte Distribution Width, Red-Blood-Cell Distribution, and Neutrophil-to-Lymphocyte Ratio. Diagnostics (Basel Switzerland) 14,9 918. 28 Apr. 2024. Lai H, et al. Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching. J intensive Med vol. 2023;3(3):275–82. 20 Apr. Wang T-H. and Yin-Chou Hsu. Red Cell Distribution Width as a Prognostic Factor and Its Comparison with Lactate in Patients with Sepsis. Diagnostics (Basel Switzerland) 11,8 1474. 14 Aug. 2021. Wiedermann CJ. Hypoalbuminemia as Surrogate and Culprit of Infections. Int J Mol Sci. 2021;22:4496. Liu J et al. Jul. Red blood cell distribution width to albumin ratio associates with prevalence and long-term diabetes mellitus prognosis: an overview of NHANES 1999–2020 data. Frontiers in endocrinology vol. 15 1362077. 24 2024. Ruan L, et al. Red Blood Cell Distribution Width to Albumin Ratio for Predicting Type I Cardiorenal Syndrome in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study. J Inflamm Res. 2024;17:3771–84. 12 Jun. Jing R et al. Association between redMar. cell distribution width-to-albumin ratio and prognostic outcomes in pediatric intensive care unit patients: a retrospective cohort study. Frontiers in pediatrics vol. 12 1352195. 6 2024. Zhong Y, et al. LIGHT aggravates sepsis-associated acute kidney injury via TLR4-MyD88-NF-κB pathway. J Cell Mol Med vol. 2020;24(20):11936–48. Kounatidis D et al. Mar. Sepsis-Associated Acute Kidney Injury: Where Are We Now? Medicina (Kaunas, Lithuania) vol. 60,3 434. 6 2024. Yuan N et al. Comparison of sepsis-associated acute kidney injury with different degrees and causes reveals patterns in mitochondrial metabolism and immune infiltration changes. Sci Rep 15,1 22738. 2 Jul. 2025. Lam LK, Metthew, et al. Red blood cells capture and deliver bacterial DNA to drive host responses during polymicrobial sepsis. J Clin Invest vol. 2024;135(4):e182127. 12 Dec. Hu Z et al. Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.Circulation research 136,1 (2025): 59–74. Wu W et al. Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives. Crit Care (London England) 29,1 168. 23 Apr. 2025. Tables Tables 1 to 3 are available in the Supplementary Files section. Tables 4 not included with this version. Additional Declarations No competing interests reported. Supplementary Files Table.doc Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2026 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 03 Dec, 2025 Reviews received at journal 02 Dec, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviews received at journal 13 Sep, 2025 Reviewers agreed at journal 29 Aug, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviewers invited by journal 29 Jul, 2025 Editor assigned by journal 21 Jul, 2025 Submission checks completed at journal 21 Jul, 2025 First submitted to journal 15 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7135515","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":494164042,"identity":"2b08431c-4cb2-4e5b-a3f6-788bac7b5e77","order_by":0,"name":"Mengqi Mi","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Mengqi","middleName":"","lastName":"Mi","suffix":""},{"id":494164043,"identity":"d4bb3d3e-7af2-4e88-8c6e-2b789af569bb","order_by":1,"name":"jinyu Li","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"jinyu","middleName":"","lastName":"Li","suffix":""},{"id":494164044,"identity":"27889245-0932-4dab-9422-8834f4e8124b","order_by":2,"name":"junjie liu","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"junjie","middleName":"","lastName":"liu","suffix":""},{"id":494164045,"identity":"e5aec7ff-3b58-4418-844c-e28d33a010dc","order_by":3,"name":"jianjun Wang","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"jianjun","middleName":"","lastName":"Wang","suffix":""},{"id":494164046,"identity":"84c07150-689f-411e-ac01-1141b0bde98b","order_by":4,"name":"yuan liu","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"yuan","middleName":"","lastName":"liu","suffix":""},{"id":494164047,"identity":"acb93b12-93ab-43b6-8ca0-a8a48285aac4","order_by":5,"name":"Hao Wang","email":"","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Wang","suffix":""},{"id":494164048,"identity":"bf4fc99e-2f92-4f8e-99d2-7211249d4bbf","order_by":6,"name":"Aibin Cheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFAC5oOP//yQkGNjbz9ArBa2ZAPeHgtjPp4zCcRq4TGT4GGrSJwn4WBAnAbd9hxjAwkeifQ2CYYEhh8V2whrMTvzrPCBgYVEbpt04wHGnjO3idByI3mzQQIPUIvMgQRmxjaitCSYSRxgk0hnk0gwIFZLiplkA1A9CVrOPEs2ZuyRMGwDBvJB4vxyPPngY4YfdfLy7e0HH/yoIEILAzBo4eAAMepRtYyCUTAKRsEowAoAu747hCDxFA4AAAAASUVORK5CYII=","orcid":"","institution":"North China University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Aibin","middleName":"","lastName":"Cheng","suffix":""}],"badges":[],"createdAt":"2025-07-16 04:08:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7135515/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7135515/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12882-026-04755-x","type":"published","date":"2026-02-07T15:58:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88489798,"identity":"27389333-b767-42db-b222-fa0041b97588","added_by":"auto","created_at":"2025-08-07 04:09:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":549770,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plot of subgroup analysis for RA and SA-AKI\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Forestplot.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7135515/v1/e41e0fc02288c69430ff1c3a.jpg"},{"id":102234241,"identity":"96dab0e8-4dc4-4971-b6ff-5fa284e91a01","added_by":"auto","created_at":"2026-02-09 16:08:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1106780,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7135515/v1/3dfe54f2-5a90-4a69-9bc4-cc4fca5c4705.pdf"},{"id":88491084,"identity":"ca977f5d-ff76-4d62-9898-0e1d6ec5ecea","added_by":"auto","created_at":"2025-08-07 04:17:22","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":110080,"visible":true,"origin":"","legend":"","description":"","filename":"Table.doc","url":"https://assets-eu.researchsquare.com/files/rs-7135515/v1/b69e2ea6b24465108c6ae6de.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Red Cell Distribution Width-to-Albumin Ratio and Sepsis-Associated Acute Kidney Injury","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eSepsis is defined as a life-threatening organ dysfunction resulting from a dysregulated host response to infection. It remains a major global health concern and is a common cause of multiple organ failure\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. When sepsis leads to acute renal dysfunction, it is referred to as sepsis-associated acute kidney injury (SA-AKI). A retrospective cohort study reported that 47.1% of sepsis patients developed concurrent AKI, which was significantly associated with prolonged ICU stay and poor short- and long-term outcomes\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The high prevalence and substantial economic burden of SA-AKI have prompted researchers to identify its risk factors.While both RDW and albumin individually predict AKI\u003csup\u003e[3、4]\u003c/sup\u003e, their combined predictive utility for SA-AKI remains unestablished.\u003c/p\u003e\u003cp\u003eErythrocyte distribution width is a parameter that reflects the heterogeneity of erythrocyte volume and reflects the heterogeneity of erythrocyte size. It is closely associated with the development of many diseases and is also an important predictor of disease occurrence\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Serum albumin is an important protein for the maintenance of osmotic pressure in the body, with anti-inflammatory and antioxidant effects, and is closely related to the prediction and prognosis of kidney injury\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The predictive value of erythrocyte distribution width to albumin ratio as a relatively new index in SA-AKI has not been adequately demonstrated. Therefore, we hypothesized that the erythrocyte distribution width to albumin ratio has a predictive value for the occurrence of AKI in patients with sepsis, with the aim of providing clinicians with a useful reference for the early recognition and prevention of SA-AKI.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study design and RA definition\u003c/h2\u003e\u003cp\u003eWe retrospectively leveraged anonymized electronic health records stored at the Affiliated Hospital of North China University of Science and Technology.Between September 2020 and September 2021, 133 consecutive adults who fulfilled the Sepsis-3 definitions were enrolled from our critical care department\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Using KDIGO 2012 guidelines, participants were dichotomized into AKI and non-AKI cohorts according to AKI onset within 28 days of ICU stay\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.Baseline demographics, comorbidities, vital parameters, and laboratory indices were extracted for each subject.The RA was calculated by dividing the red cell distribution width (RDW, %) by the serum albumin level (g/dL\u003csup\u003e)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, both measured from blood samples collected upon ICU admission. The study protocol adhered to the ethical principles of the Declaration of Helsinki and received formal approval from the Ethics Committee at North China University of Science and Technology Affiliated Hospital (Approval No. SQ2024029).Given the retrospective nature and use of anonymized data, informed consent was waived by the Ethics Committee.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Inclusion criteria\u003c/h2\u003e\u003cp\u003eEligible individuals were adults (\u0026gt;\u0026thinsp;18 y) with newly diagnosed sepsis and complete clinical-laboratory datasets who developed AKI within 28 days.\u003c/p\u003e\u003cp\u003eWe excluded patients with chronic kidney disease, prior renal transplantation, active malignancy, or immune-mediated disorders.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Collection of variables\u003c/h2\u003e\u003cp\u003eAll variables were retrieved from the hospital\u0026rsquo;s integrated electronic health platform. Laboratory panels comprised PCT, WBC, neutrophil ratio, MPV, RDW, electrolytes, albumin, lactate, D-dimer, and serial creatinine values.Supplementary variables encompassed demographics, comorbidities, APACHE II scores, and therapeutic interventions (CRRT, ventilation, vasopressors). Baseline indices were captured within 24 h of ICU arrival.The primary endpoint was incident SA-AKI within 28 days.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Quality control.\u003c/h2\u003e\u003cp\u003eTo curtail selection and information bias, we applied rigorous eligibility filters and systematic data abstraction, with regular audits to exclude ineligible cases.These measures bolstered internal validity and data integrity.\u003c/p\u003e\u003cp\u003ePotential confounding was addressed by harmonized data collection and multivariable modelling.Standardized abstraction protocols and multivariable adjustment minimized residual confounding.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical methods\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using R software (version 4.2.0; R Foundation for Statistical Computing, Vienna, Austria) and Free Statistics software version 2.2.All tests were two-sided, and a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003cp\u003eContinuous data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median [IQR]; categorical data as n (%). Intergroup differences were assessed with t-tests, χ\u0026sup2;, or Mann\u0026ndash;Whitney U tests as appropriate. Multivariable logistic and stratified analyses explored RA\u0026ndash;SA-AKI relations. Sequential models adjusted for demographics (Model 2) and comprehensive covariates (Model 3).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e\u0026nbsp;3.1 Baseline data characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;A total of 133 patients diagnosed with sepsis according to Sepsis-3 criteria were included. Based on the KDIGO criteria, patients were divided into the non-AKI group (n = 77) and the AKI group (n = 56) according to the KDIGO criteria. The mean age of the participants was 70.5±11.1 years, with 85 (63.9%) being male. The average baseline RA was 4.6±1.5. Statistical analysis showed that patients in the AKI group had significantly higher RA levels than those in the non-AKI group. Additionally, the need for mechanical ventilation, vasoactive medications, and continuous renal replacement therapy (CRRT) was significantly greater in the AKI group.Disease severity was greater in the AKI group, as indicated by elevated APACHE II scores, procalcitonin (PCT), Red Cell Distribution Width (RDW)，Mean Platelet Volume (MPV)and lactate levels.Renal function indicators, including serum creatinine (Cr) and peak creatinine (Crmax), were significantly elevated in the AKI group. No significant differences were observed between the two groups in terms of sex distribution, age, blood pressure at admission, prevalence of hypertension, coronary artery disease, diabetes mellitus, leukocyte count, neutrophil percentage, estimated glomerular filtration rate (eGFR), serum sodium, albumin, or D-dimer levels(Refer to Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;3.2 Unifactorial and multifactorial Logistic regression analysis for the occurrence of AKI in patients with sepsis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Univariate logistic regression analysis revealed that RA, mechanical ventilation, use of vasoactive drugs, CRRT, APACHE II score, procalcitonin (PCT), mean platelet volume (MPV), red cell distribution width (RDW), lactate (Lac), serum creatinine (Cr), and peak creatinine (Crmax) were all significantly associated with AKI in sepsis patients (Refer to Table 2).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The association between RA and SA-AKI was further assessed using multivariate logistic regression across three analytical models.In Model 1 (unadjusted), elevated RA was significantly associated with an increased risk of AKI (OR = 1.51, 95% CI: 1.13–2.03, P = 0.006).In Model 2, after adjusting for age and sex, RA remained significantly associated with AKI (OR = 1.51, 95% CI: 1.13–2.03, P = 0.015).In Model 3, which was adjusted for comorbidities, mechanical ventilation, and relevant biochemical parameters, RA remained an independent predictor of AKI in sepsis patients (OR = 1.53, 95% CI: 1.06–2.21, P = 0.023; Refer to Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;3.3 Subgroup analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;To evaluate the impact of RA on SA-AKI across different patient subgroups, subgroup analyses were conducted (see Table 4).The results indicated that the association between RA and SA-AKI remained consistent across subgroups. Significant associations were observed in male patients (OR = 1.49, 95% CI: 1.03–2.14), patients without hypertension (OR = 1.90, 95% CI: 1.11–3.26), those requiring mechanical ventilation (OR = 1.77, 95% CI: 1.17–2.66), those receiving vasoactive medications (OR = 1.91, 95% CI: 1.18–3.09), and those not undergoing CRRT (OR = 2.24, 95% CI: 1.23–4.08).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Notably, formal interaction tests (P for interaction) showed no statistically significant differences in the association between RA and SA-AKI across subgroups stratified by sex (P = 0.898), hypertension (P = 0.220), coronary artery disease (P = 0.928), diabetes mellitus (P = 0.847), mechanical ventilation (P = 0.055), use of vasoactive drugs (P = 0.141), CRRT (P = 0.087), age group (P = 0.882), or APACHE II score group (P = 0.681).Although point estimates varied slightly among subgroups (e.g., higher ORs in patients without hypertension and those not receiving CRRT), none of these interactions were statistically significant, indicating that the association between RA and SA-AKI was robust across populations.（Refer to Figure 1）\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eDespite extensive adjustment, RA retained independent predictive capacity for SA-AKI. An elevated RA was associated with a higher risk of AKI development in sepsis patients.This association was consistent across various subgroups stratified by sex, age, APACHE II score, comorbidities, and the use of CRRT, vasoactive drugs, or mechanical ventilation.\u003c/p\u003e\u003cp\u003eSepsis stems from a maladaptive host reaction to pathogens and frequently evolves into multiorgan dysfunction. Prompt biomarker-guided intervention is thus essential to enhance survival.Emerging evidence indicates that biomarkers like NGAL and cystatin C facilitate prompt identification, stratification, and outcome prediction in SA-AKI\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.Red cell distribution width (RDW), traditionally used to classify types of anemia, has recently emerged as a predictor of systemic inflammatory, cardiovascular, and renal conditions\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.Yi-Hsiang Pan et al\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. reported that RDW, when combined with other markers, can improve the predictive accuracy for sepsis.The study by Honghao et al. demonstrated that RDW is a prognostic marker for SA-AKI, with elevated RDW values significantly associated with increased 28-day mortality\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.In sepsis patients, RDW is a useful predictor of disease occurrence and prognosis, as systemic inflammation alters erythrocyte morphology and increases heterogeneity, thereby elevating RDW. Serum albumin mirrors nutritional reserves and modulates inflammatory cascades while serving as a gauge of renal integrity; in septic patients, reduced levels independently forecast acute and chronic organ failure and heightened mortality.In sepsis, increased vascular permeability causes albumin to leak into interstitial tissues, resulting in hypoalbuminemia.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e Consequently, low albumin levels serve as an independent risk factor for sepsis progression and poor long-term prognosis.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003eHypoalbuminemia and sepsis reinforce each other in a vicious cycle, amplifying the detrimental impact of low albumin on patient outcomes.\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003eThe red cell distribution width-to-albumin ratio (RA) is a relatively novel biomarker that is readily obtainable in clinical practice and more cost-effective than many emerging indicators.Previous studies have demonstrated the predictive value of RA in various diseases.Jie Liu et al.\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e found that RA was a stronger predictor than RDW for diabetes prevalence and long-term prognosis. Moreover, higher RA levels were associated with shorter survival among diabetic patients under 60 years old.Liang Ruan et al.\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e demonstrated that RA is a key predictor of renal and cardiorenal function in patients with acute myocardial infarction (AMI).RA was an independent predictor of type 1 cardiorenal syndrome (CRS-1) in patients with AMI, with elevated RA levels linked to a higher incidence of CRS-1. RA may therefore serve as a useful marker for risk stratification in these patients.Although RA has shown predictive value in various diseases, its role in predicting SA-AKI remains largely unexplored, and no prior studies have specifically investigated its association with SA-AKI development.Nevertheless, previous studies have suggested that RA may serve as an independent prognostic indicator in critically ill elderly patients with AKI, with higher RA levels associated with increased mortality and a higher incidence of septic shock.These findings align with our results, which identified RA as an independent risk factor for SA-AKI.\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe pathophysiological mechanisms underlying SA-AKI have been well studied in previous research.During sepsis, a cytokine storm and excessive activation of complement and antibodies trigger apoptosis of renal vascular endothelial cells.\u003csup\u003e[18、19]\u003c/sup\u003e This results in increased protein leakage, impaired renal perfusion due to systemic neuroendocrine dysregulation, and abnormal renal hemodynamics. Consequently, renal ischemia, tubular necrosis, epithelial shedding, and glomerular capillary fibrin thrombosis occur, ultimately leading to acute kidney injury\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.Sepsis-induced inflammation activates intracellular signaling pathways, promotes the release of cytokines such as IL-6, and suppresses erythropoietin production, resulting in increased release of immature erythrocytes\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.In addition, inflammatory factors stimulate the production of reactive oxygen species (ROS), which damage erythrocyte membranes, alter cell morphology, and reduce erythrocyte deformability. These impaired erythrocytes may obstruct renal tubules, leading to localized renal ischemia, hypoxia, tubular necrosis, and impaired filtration function.Reduced serum albumin compromises the integrity of the endothelial glycocalyx, weakening its protective function against inflammatory mediators and nephrotoxic insults, thereby contributing to AKI development.The RA, as a composite marker, amplifies the effects of subtle systemic changes on renal function.Sepsis-induced inflammation and oxidative stress elevate RDW and decrease serum albumin levels, both of which synergistically impair renal microcirculation and damage the endothelial glycocalyx, ultimately promoting kidney injury.\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003eEvidence suggests that RA levels increase 6\u0026ndash;12 hours earlier than serum creatinine, indicating its potential utility as an early biomarker for SA-AKI\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.Future research aimed at elucidating the underlying mechanisms may establish RA not only as an early warning biomarker for SA-AKI, but also as a potential therapeutic target.\u003c/p\u003e\u003cp\u003eOur study has some limitations. The chief limitation is the single-center retrospective framework, susceptible to selection bias.Residual confounding from unmeasured factors cannot be entirely excluded. Multicenter prospective validation is warranted to corroborate these results.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion,RA is an independent risk factor for AKI in sepsis patients. Elevated RA levels are significantly associated with increased AKI risk, and this association remains robust across subgroups.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe authors extend sincere gratitude to all patients, physicians, and technical staff at our center for their invaluable contributions to this study. The research protocol, including study design, ethical compliance, and data collection procedures, was supervised and approved by the Institutional Ethics Committee of North China University of Science and Technology Affiliated Hospital\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eMQM and JJL: Contributed equally to study design and data interpretation; Performed primary data analysis.JYL, JJW, JJL, ABC: Contributed to the conception/design of the study and data interpretation; Critically revised the manuscript.MQM,JYL,JJL,JJW,YL,HW,ABC: Conducted the research.All authors: Contributed to data acquisition and statistical analysis; Drafted the manuscript; Read and approved the final manuscript. All authors agree to be fully accountable for ensuring the integrity and accuracy of the work.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe authors Jinyu Li, Jianjun Wang, and Aibin Cheng are currently funded by the Health Commission of Hebei Province (#20250928).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol adhered to the ethical principles of the Declaration of Helsinki and received formal approval from the Ethics Committee at North China University of Science and Technology Affiliated Hospital (Approval No. SQ2024029).Given the retrospective nature and use of anonymized data, informed consent was waived by the Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. No individual personal data is included in the study.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe cohorts generated and/or analyzed during this study are not publicly available, due to currently ongoing research studies, but the data are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)[J]. JAMA. 2016;315(8):801\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZarbock A et al. Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.Nature reviews. Nephrology 19,6 (2023): 401\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng B et al. Combined effect of anion gap and red cell distribution width on the risk of acute kidney injury after cardiac surgery. J Cardiothorac Surg 19,1 612. 23 Oct. 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchnabel K, et al. Urinary albumin-to-creatinine ratio and serum albumin are predictors of acute kidney injury in non-ventilated COVID-19 patients: a single-center prospective cohort study. Int Urol Nephrol vol. 2023;55(3):711\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCai S et al. Jun. Red blood cell distribution width combined with age as a predictor of acute ischemic stroke in stable COPD patients. Frontiers in neurology vol. 14 1165181. 5 2023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMichelis R et al. Unexpected Normal Colloid Osmotic Pressure in Clinical States with Low Serum Albumin. PloS one vol. 11,7 e0159839. 25 Jul. 2016.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLameire NH et al. Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.Kidney international vol. 100,3 (2021): 516\u0026ndash;526.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eErtekin B, Tarık. Acar.The Relationship Between Prognosis and Red Cell Distribution Width (RDW) and RDW-Albumin Ratio (RAR) in Patients with Severe COVID-19 Disease. Int J Gen Med. 2022;15:8637\u0026ndash;45. 16 Dec.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDai X et al. Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury. Crit Care (London England) 19,1 223. 6 May. 2015.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu X, et al. Prognostic significance of increased preoperative red cell distribution width (RDW) and changes in RDW for colorectal cancer. Cancer Med vol. 2023;12(12):13361\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePan Y-H et al. Early Identification of Sepsis-Induced Acute Kidney Injury by Using Monocyte Distribution Width, Red-Blood-Cell Distribution, and Neutrophil-to-Lymphocyte Ratio. Diagnostics (Basel Switzerland) 14,9 918. 28 Apr. 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLai H, et al. Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching. J intensive Med vol. 2023;3(3):275\u0026ndash;82. 20 Apr.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang T-H. and Yin-Chou Hsu. Red Cell Distribution Width as a Prognostic Factor and Its Comparison with Lactate in Patients with Sepsis. Diagnostics (Basel Switzerland) 11,8 1474. 14 Aug. 2021.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWiedermann CJ. Hypoalbuminemia as Surrogate and Culprit of Infections. Int J Mol Sci. 2021;22:4496.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J et al. Jul. Red blood cell distribution width to albumin ratio associates with prevalence and long-term diabetes mellitus prognosis: an overview of NHANES 1999\u0026ndash;2020 data. Frontiers in endocrinology vol. 15 1362077. 24 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRuan L, et al. Red Blood Cell Distribution Width to Albumin Ratio for Predicting Type I Cardiorenal Syndrome in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study. J Inflamm Res. 2024;17:3771\u0026ndash;84. 12 Jun.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJing R et al. Association between redMar. cell distribution width-to-albumin ratio and prognostic outcomes in pediatric intensive care unit patients: a retrospective cohort study. Frontiers in pediatrics vol. 12 1352195. 6 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhong Y, et al. LIGHT aggravates sepsis-associated acute kidney injury via TLR4-MyD88-NF-κB pathway. J Cell Mol Med vol. 2020;24(20):11936\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKounatidis D et al. Mar. Sepsis-Associated Acute Kidney Injury: Where Are We Now? Medicina (Kaunas, Lithuania) vol. 60,3 434. 6 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYuan N et al. Comparison of sepsis-associated acute kidney injury with different degrees and causes reveals patterns in mitochondrial metabolism and immune infiltration changes. Sci Rep 15,1 22738. 2 Jul. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLam LK, Metthew, et al. Red blood cells capture and deliver bacterial DNA to drive host responses during polymicrobial sepsis. J Clin Invest vol. 2024;135(4):e182127. 12 Dec.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu Z et al. Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.Circulation research 136,1 (2025): 59\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu W et al. Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives. Crit Care (London England) 29,1 168. 23 Apr. 2025.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e\n\u003cp\u003eTables 4 not included with this version.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Intensive care unit, erythrocyte distribution width to albumin ratio, sepsis, acute kidney injury","lastPublishedDoi":"10.21203/rs.3.rs-7135515/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7135515/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSepsis constitutes a critical syndrome frequently observed in ICUs, posing a major worldwide health challenge.Recent data indicate that roughly one fifth of non-critical sepsis patients develop AKI, with its frequency continuing to rise.Although the erythrocyte distribution width\u0026ndash;albumin ratio (RA) has emerged as a new indicator, its role in forecasting SA-AKI is still poorly characterized.Accordingly, we sought to determine whether RA independently predicts the onset of SA-AKI.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e A retrospective cohort of 133 sepsis patients admitted to our ICU between September 2019 and September 2021 was analyzed.Using KDIGO 2012 guidelines, participants were classified into AKI and non-AKI cohorts based on the emergence of AKI within 28 days of ICU entry. The predictive value of RA for SA-AKI was assessed by univariate and multivariate logistic regression analysis.Subgroup analyses stratified by sex, age, APACHE II score, comorbidities, mechanical ventilation, and whether vasoactive drugs were applied.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf the 133 included sepsis cases, 56 (42.1%) experienced AKI during ICU stay.Intergroup comparisons revealed marked discrepancies in RA, PCT, Lac, RDW, MPV, APACHE II scores, and rates of mechanical ventilation or vasopressor use (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). After multivariable adjustment, RA remained independently associated with AKI (OR 1.53; 95% CI 1.06\u0026ndash;2.21; P\u0026thinsp;=\u0026thinsp;0.023). Subgroup analyses confirmed the robustness of this association across diverse clinical strata.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eElevated RA independently forecasts SA-AKI, underscoring its utility as a readily available early warning index in septic individuals.\u003c/p\u003e","manuscriptTitle":"Association Between Red Cell Distribution Width-to-Albumin Ratio and Sepsis-Associated Acute Kidney Injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-07 04:01:18","doi":"10.21203/rs.3.rs-7135515/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-03T09:06:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-02T21:41:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"25277049410911141693230440878306160690","date":"2025-11-25T11:42:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-14T01:14:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306613666223251658022996238005619924268","date":"2025-08-29T16:14:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330463463245148996838837806199278315455","date":"2025-08-18T05:59:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-30T03:19:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-21T12:11:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-21T12:09:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-07-16T03:56:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fc83517f-4ae6-4a95-90bb-a742348ca1af","owner":[],"postedDate":"August 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:04:13+00:00","versionOfRecord":{"articleIdentity":"rs-7135515","link":"https://doi.org/10.1186/s12882-026-04755-x","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2026-02-07 15:58:53","publishedOnDateReadable":"February 7th, 2026"},"versionCreatedAt":"2025-08-07 04:01:18","video":"","vorDoi":"10.1186/s12882-026-04755-x","vorDoiUrl":"https://doi.org/10.1186/s12882-026-04755-x","workflowStages":[]},"version":"v1","identity":"rs-7135515","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7135515","identity":"rs-7135515","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}