基于脓毒症相关急性肾损伤病理生理机制的液体管理策略研究进展
Advances in Fluid Management Strategies for Sepsis-Associated Acute Kidney Injury Based on Pathophysiological Mechanisms
DOI: 10.12677/jcpm.2026.53177, PDF,   
作者: 谢冰卿：重庆医科大学第一临床医学院，重庆；陈雪梅*：重庆医科大学附属第一医院重症医学科，重庆
关键词: 脓毒症；急性肾损伤；病理生理机制；液体管理；Sepsis； Acute Kidney Injury； Pathophysiological Mechanisms； Liquid Management
摘要: 脓毒症相关急性肾损伤(Sepsis-associated Acute Kidney Injury, SA-AKI)是脓毒症最常见的严重并发症之一，与高死亡率与不良预后密切相关。液体管理是SA-AKI治疗的核心环节，早期液体复苏有助于改善组织灌注、避免缺血性损伤；但过量输液可能导致液体外渗和间质性水肿，加重微循环障碍，加剧肾脏甚至多器官损伤。本文系统综述了SA-AKI液体管理策略的演进，分析了当前临床争议，并展望未来研究方向，旨在为临床制定个体化、循证的液体管理方案提供参考。
Abstract: Sepsis-associated acute kidney injury (SA-AKI) is one of the most common severe complications of sepsis and is closely associated with high mortality and poor prognosis. Fluid management constitutes a core component in the treatment of SA-AKI. Early fluid resuscitation contributes to improved tissue perfusion and prevention of ischemic injury; however, excessive fluid infusion may lead to extravascular fluid extravasation and interstitial edema, exacerbate microcirculatory dysfunction, and aggravate renal and even multiple organ damage. This article systematically reviews the evolution of fluid management strategies for SA-AKI, analyzes current clinical controversies, and prospects future research directions, with the aim of providing references for the formulation of individualized and evidence-based fluid management regimens in clinical practice.
文章引用：谢冰卿, 陈雪梅. 基于脓毒症相关急性肾损伤病理生理机制的液体管理策略研究进展[J]. 临床个性化医学, 2026, 5(3): 1-12. https://doi.org/10.12677/jcpm.2026.53177

参考文献

[1] Zarbock, A., Koyner, J.L., Gomez, H., Pickkers, P., Forni, L., Nadim, M.K., et al. (2023) Sepsis-Associated Acute Kidney Injury—Treatment Standard. Nephrology Dialysis Transplantation, 39, 26-35. [Google Scholar] [CrossRef] [PubMed]
[2] Peerapornratana, S., Manrique-Caballero, C.L., Gómez, H. and Kellum, J.A. (2019) Acute Kidney Injury from Sepsis: Current Concepts, Epidemiology, Pathophysiology, Prevention and Treatment. Kidney International, 96, 1083-1099. [Google Scholar] [CrossRef] [PubMed]
[3] Chang, L., Chao, Y., Chiu, C., Chen, P. and Lin, H.Y. (2024) Mitochondrial Signaling, the Mechanisms of AKI-To-CKD Transition and Potential Treatment Targets. International Journal of Molecular Sciences, 25, Article 1518. [Google Scholar] [CrossRef] [PubMed]
[4] Kim, J., Kim, Y., Ryoo, S., Sohn, C., Seo, D., Ahn, S., et al. (2018) One-Year Progression and Risk Factors for the Development of Chronic Kidney Disease in Septic Shock Patients with Acute Kidney Injury: A Single-Centre Retrospective Cohort Study. Journal of Clinical Medicine, 7, Article 554. [Google Scholar] [CrossRef] [PubMed]
[5] Byrne, L., Obonyo, N.G., Diab, S.D., Dunster, K.R., Passmore, M.R., Boon, A., et al. (2018) Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia. American Journal of Respiratory and Critical Care Medicine, 198, 1043-1054. [Google Scholar] [CrossRef] [PubMed]
[6] Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C.M., French, C., et al. (2021) Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Medicine, 47, 1181-1247. [Google Scholar] [CrossRef] [PubMed]
[7] Prescott, H.C., Antonelli, M., Alhazzani, W., Møller, M.H., Alshamsi, F., Azevedo, L.C.P., et al. (2026) Executive Summary: Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Critical Care Medicine, 54, 715-724. [Google Scholar] [CrossRef] 
[8] Kounatidis, D., Vallianou, N.G., Psallida, S., Panagopoulos, F., Margellou, E., Tsilingiris, D., et al. (2024) Sepsis-Associated Acute Kidney Injury: Where Are We Now? Medicina, 60, Article 434. [Google Scholar] [CrossRef] [PubMed]
[9] Srdić, T., Đurašević, S., Lakić, I., Ružičić, A., Vujović, P., Jevđović, T., et al. (2024) From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction. International Journal of Molecular Sciences, 25, Article 7770. [Google Scholar] [CrossRef] [PubMed]
[10] Zampieri, F.G., Bagshaw, S.M. and Semler, M.W. (2023) Fluid Therapy for Critically Ill Adults with Sepsis. JAMA, 329, 1967-1980. [Google Scholar] [CrossRef] [PubMed]
[11] An, S., Yao, Y., Hu, H., Wu, J., Li, J., Li, L., et al. (2023) PDHA1 Hyperacetylation-Mediated Lactate Overproduction Promotes Sepsis-Induced Acute Kidney Injury via Fis1 Lactylation. Cell Death & Disease, 14, Article No. 457. [Google Scholar] [CrossRef] [PubMed]
[12] Molema, G., Zijlstra, J.G., van Meurs, M. and Kamps, J.A.A.M. (2022) Renal Microvascular Endothelial Cell Responses in Sepsis-Induced Acute Kidney Injury. Nature Reviews Nephrology, 18, 95-112. [Google Scholar] [CrossRef] [PubMed]
[13] Chen, X., Wang, X., Honore, P.M., Spapen, H.D. and Liu, D. (2018) Renal Failure in Critically Ill Patients, Beware of Applying (Central Venous) Pressure on the Kidney. Annals of Intensive Care, 8, 91. [Google Scholar] [CrossRef] [PubMed]
[14] Russell, P.S., Hong, J., Windsor, J.A., Itkin, M. and Phillips, A.R.J. (2019) Renal Lymphatics: Anatomy, Physiology, and Clinical Implications. Frontiers in Physiology, 10, Article 251. [Google Scholar] [CrossRef] [PubMed]
[15] Zarbock, A., Nadim, M.K., Pickkers, P., Gomez, H., Bell, S., Joannidis, M., et al. (2023) Sepsis-Associated Acute Kidney Injury: Consensus Report of the 28th Acute Disease Quality Initiative Workgroup. Nature Reviews Nephrology, 19, 401-417. [Google Scholar] [CrossRef] [PubMed]
[16] Torres, J.S.S., Tamayo-Giraldo, F.J., Bejarano-Zuleta, A., Nati-Castillo, H.A., Quintero, D.A., Ospina-Mejía, M.J., et al. (2025) Sepsis and Post-Sepsis Syndrome: A Multisystem Challenge Requiring Comprehensive Care and Management—A Review. Frontiers in Medicine, 12, Article 1560737. [Google Scholar] [CrossRef] [PubMed]
[17] Nakazawa, D., Kumar, S.V., Marschner, J., Desai, J., Holderied, A., Rath, L., et al. (2017) Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. Journal of the American Society of Nephrology, 28, 1753-1768. [Google Scholar] [CrossRef] [PubMed]
[18] Sullivan, R.C., Rockstrom, M.D., Schmidt, E.P. and Hippensteel, J.A. (2021) Endothelial Glycocalyx Degradation during Sepsis: Causes and Consequences. Matrix Biology Plus, 12, Article ID: 100094. [Google Scholar] [CrossRef] [PubMed]
[19] Uchimido, R., Schmidt, E.P. and Shapiro, N.I. (2019) The Glycocalyx: A Novel Diagnostic and Therapeutic Target in Sepsis. Critical Care, 23, Article No. 16. [Google Scholar] [CrossRef] [PubMed]
[20] Poudel, N., Zheng, S., Schinderle, C.M., Sun, N., Hu, S. and Okusa, M.D. (2020) Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy. Nephron, 144, 621-625. [Google Scholar] [CrossRef] [PubMed]
[21] Aguilar, M.G., AlHussen, H.A., Gandhi, P.D., Kaur, P., Pothacamuri, M.A., Talikoti, M.A.H., et al. (2024) Sepsis-associated Acute Kidney Injury: Pathophysiology and Treatment Modalities. Cureus, 16, e75992. [Google Scholar] [CrossRef] [PubMed]
[22] Toro, J., Manrique-Caballero, C.L. and Gómez, H. (2021) Metabolic Reprogramming and Host Tolerance: A Novel Concept to Understand Sepsis-Associated AKI. Journal of Clinical Medicine, 10, Article 4184. [Google Scholar] [CrossRef] [PubMed]
[23] Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., et al. (2001) Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. New England Journal of Medicine, 345, 1368-1377. [Google Scholar] [CrossRef] [PubMed]
[24] Dellinger, R.P., Levy, M.M., Rhodes, A., Annane, D., Gerlach, H., Opal, S.M., et al. (2013) Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Medicine, 39, 165-228. [Google Scholar] [CrossRef] [PubMed]
[25] Hernández, G., Ospina-Tascón, G.A., Damiani, L.P., Estenssoro, E., Dubin, A., Hurtado, J., et al. (2019) Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality among Patients with Septic Shock. JAMA, 321, 654-664. [Google Scholar] [CrossRef] [PubMed]
[26] Kim, I.Y., Kim, S., Ye, B.M., Kim, M.J., Kim, S.R., Lee, D.W., et al. (2023) Effect of Fluid Overload on Survival in Patients with Sepsis-Induced Acute Kidney Injury Receiving Continuous Renal Replacement Therapy. Scientific Reports, 13, Article No. 2796. [Google Scholar] [CrossRef] [PubMed]
[27] Wiedemann, H.P., Wheeler, A.P., Bernard, G.R., Thompson, B.T., Hayden, D., deBoisblanc, B., et al. (2006) Comparison of Two Fluid-Management Strategies in Acute Lung Injury. The New England Journal of Medicine, 354, 2564-2575.
[28] Marik, P.E., Byrne, L. and van Haren, F. (2020) Fluid Resuscitation in Sepsis: The Great 30 mL per Kg Hoax. Journal of Thoracic Disease, 12, S37-S47. [Google Scholar] [CrossRef] [PubMed]
[29] The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network (2023) Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. New England Journal of Medicine, 388, 499-510. [Google Scholar] [CrossRef] [PubMed]
[30] Meyhoff, T.S., Hjortrup, P.B., Wetterslev, J., Sivapalan, P., Laake, J.H., Cronhjort, M., et al. (2022) Restriction of Intravenous Fluid in ICU Patients with Septic Shock. New England Journal of Medicine, 386, 2459-2470. [Google Scholar] [CrossRef] [PubMed]
[31] Yu, J., Che, L., Zhu, A., Xu, L. and Huang, Y. (2022) Goal-Directed Intraoperative Fluid Therapy Benefits Patients Undergoing Major Gynecologic Oncology Surgery: A Controlled Before-And-After Study. Frontiers in Oncology, 12, Article 833273. [Google Scholar] [CrossRef] [PubMed]
[32] Dellinger, R.P., Rhodes, A., Evans, L., Alhazzani, W., Beale, R., Jaeschke, R., et al. (2023) Surviving Sepsis Campaign. Critical Care Medicine, 51, 431-444. [Google Scholar] [CrossRef] [PubMed]
[33] 中华医学会肾脏病学分会专家组. 连续性肾替代治疗容量评估与管理专家共识[J]. 中华肾脏病杂志, 2024, 40(1): 74-81.
[34] De Backer, D., Deutschman, C.S., Hellman, J., Myatra, S.N., Ostermann, M., Prescott, H.C., et al. (2024) Surviving Sepsis Campaign Research Priorities 2023. Critical Care Medicine, 52, 268-296. [Google Scholar] [CrossRef] [PubMed]
[35] Monnet, X., Lai, C. and Teboul, J. (2023) How I Personalize Fluid Therapy in Septic Shock? Critical Care, 27, Article No. 123. [Google Scholar] [CrossRef] [PubMed]
[36] Kiernan, E., Zelnick, L.R., Khader, A., Coston, T.D., Bailey, Z.A., Speckmaier, S., et al. (2025) Molecular Phenotyping of Sepsis and Differential Response to Fluid Resuscitation. American Journal of Respiratory and Critical Care Medicine, 211, 1681-1688. [Google Scholar] [CrossRef] [PubMed]
[37] Douglas, I.S., Alapat, P.M., Corl, K.A., Exline, M.C., Forni, L.G., Holder, A.L., et al. (2020) Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest, 158, 1431-1445. [Google Scholar] [CrossRef] [PubMed]
[38] White, K.C., Serpa-Neto, A., Hurford, R., Clement, P., Laupland, K.B., See, E., et al. (2023) Sepsis-associated Acute Kidney Injury in the Intensive Care Unit: Incidence, Patient Characteristics, Timing, Trajectory, Treatment, and Associated Outcomes. a Multicenter, Observational Study. Intensive Care Medicine, 49, 1079-1089. [Google Scholar] [CrossRef] [PubMed]
[39] Huo, Y., Wang, X., Li, B., Rello, J., Kim, W.Y., Wang, X., et al. (2022) Impact of Central Venous Pressure on the Mortality of Patients with Sepsis-Related Acute Kidney Injury: A Propensity Score-Matched Analysis Based on the MIMIC IV Database. Annals of Translational Medicine, 10, 199-199. [Google Scholar] [CrossRef] [PubMed]
[40] Arabi, Y.M., Belley-Cote, E., Carsetti, A., De Backer, D., Donadello, K., Juffermans, N.P., et al. (2024) European Society of Intensive Care Medicine Clinical Practice Guideline on Fluid Therapy in Adult Critically Ill Patients. Part 1: The Choice of Resuscitation Fluids. Intensive Care Medicine, 50, 813-831. [Google Scholar] [CrossRef] [PubMed]
[41] (2025) Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: Research Summary. JAMA, 334, e2520962.
[42] Yunos, N.M., Bellomo, R., Glassford, N., Sutcliffe, H., Lam, Q. and Bailey, M. (2015) Chloride-Liberal vs. Chloride-Restrictive Intravenous Fluid Administration and Acute Kidney Injury: An Extended Analysis. Intensive Care Medicine, 41, 257-264. [Google Scholar] [CrossRef] [PubMed]
[43] Semler, M.W., Self, W.H., Wanderer, J.P., Ehrenfeld, J.M., Wang, L., Byrne, D.W., et al. (2018) Balanced Crystalloids versus Saline in Critically Ill Adults. New England Journal of Medicine, 378, 829-839. [Google Scholar] [CrossRef] [PubMed]
[44] Sankar, J., Muralidharan, J., Lalitha, A.V., Rameshkumar, R., Pathak, M., Das, R.R., et al. (2023) Multiple Electrolytes Solution versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial*. Critical Care Medicine, 51, 1449-1460. [Google Scholar] [CrossRef] [PubMed]
[45] Smart, L., Boyd, C., Litton, E., Pavey, W., Vlaskovsky, P., Ali, U., et al. (2021) A Randomised Controlled Trial of Succinylated Gelatin (4%) Fluid on Urinary Acute Kidney Injury Biomarkers in Cardiac Surgical Patients. Intensive Care Medicine Experimental, 9, Article No. 48. [Google Scholar] [CrossRef] [PubMed]
[46] Caironi, P., Tognoni, G., Masson, S., Fumagalli, R., Pesenti, A., Romero, M., et al. (2014) Albumin Replacement in Patients with Severe Sepsis or Septic Shock. New England Journal of Medicine, 370, 1412-1421. [Google Scholar] [CrossRef] [PubMed]
[47] Holst, L.B., Haase, N., Wetterslev, J., Wernerman, J., Guttormsen, A.B., Karlsson, S., et al. (2014) Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock. New England Journal of Medicine, 371, 1381-1391. [Google Scholar] [CrossRef] [PubMed]
[48] Titeca-Beauport, D., Diouf, M., Daubin, D., Vong, L.V., Belliard, G., Bruel, C., et al. (2024) The Combination of Kidney Function Variables with Cell Cycle Arrest Biomarkers Identifies Distinct Subphenotypes of Sepsis-Associated Acute Kidney Injury: A POST-HOC Analysis (the PHENAKI Study). Renal Failure, 46, Article ID: 2325640. [Google Scholar] [CrossRef] [PubMed]
[49] Wiersema, R., Jukarainen, S., Vaara, S.T., Poukkanen, M., Lakkisto, P., Wong, H., et al. (2020) Two Subphenotypes of Septic Acute Kidney Injury Are Associated with Different 90-Day Mortality and Renal Recovery. Critical Care, 24, Article No. 150. [Google Scholar] [CrossRef] [PubMed]
[50] Jiang, W., Zhang, Y., Weng, J., Song, L., Liu, S., Li, X., et al. (2025) Explainable Machine Learning Model for Predicting Persistent Sepsis-Associated Acute Kidney Injury: Development and Validation Study. Journal of Medical Internet Research, 27, e62932. [Google Scholar] [CrossRef] [PubMed]
[51] Yue, S., Li, S., Huang, X., Liu, J., Hou, X., Zhao, Y., et al. (2022) Machine Learning for the Prediction of Acute Kidney Injury in Patients with Sepsis. Journal of Translational Medicine, 20, Article No. 215. [Google Scholar] [CrossRef] [PubMed]
[52] Tseng, C., Chen, T., Wu, M., Chan, M., Shih, M. and Tu, Y. (2020) Resuscitation Fluid Types in Sepsis, Surgical, and Trauma Patients: A Systematic Review and Sequential Network Meta-Analyses. Critical Care, 24, Article No. 693. [Google Scholar] [CrossRef] [PubMed]
[53] Fang, Y., Wang, X., Xu, C., Zhu, Q., Zang, X., Liu, J., et al. (2025) Preclinical Evaluation of STSA-1002, a Novel Human and Rhesus Monkeys Cross-Reactive Monoclonal Antibody Targeting C5a, in Acute Respiratory Distress Syndrome Models. International Immunopharmacology, 164, Article ID: 115338. [Google Scholar] [CrossRef] [PubMed]