Shashaty Michael G S, Reilly John P, Sims Carrie A, Holena Daniel N, Qing Danielle, Forker Caitlin M, Hotz Meghan J, Meyer Nuala J, Lanken Paul N, Feldman Harold I, Christie Jason D, Mangalmurti Nilam S
*Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania †Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania ‡Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania §Division of Traumatology, Surgical Critical Care, and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania ||Center for Resuscitation Science, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania ¶Renal, Electrolyte, and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Shock. 2016 Aug;46(2):139-43. doi: 10.1097/SHK.0000000000000596.
Receptor interacting protein kinase-3 (RIP3) is a key mediator of necroptosis, a form of regulated cell death recently implicated in murine models of renal ischemia-reperfusion injury and transfusion-associated endothelial injury. The importance of necroptosis in human AKI is unknown. We hypothesized that plasma RIP3 concentrations would be associated with acute kidney injury (AKI) after severe trauma.
We performed a case-control study nested in a prospective cohort of critically ill trauma patients. AKI was defined by AKI Network creatinine criteria within 6 days of presentation. Of 158 cohort subjects, we selected 13 who developed AKI stage 2 or 3, 27 with AKI stage 1, and 40 without AKI. We compared plasma RIP3 concentrations across these groups at presentation and 48 h. Since red blood cell (RBC) transfusion is an AKI risk factor, we also tested the association of RBCs transfused during resuscitation with RIP3 levels.
Median plasma RIP3 concentration rose more than 10-fold from presentation (15.6 (interquartile range 15.6-41.3) pg/mL) to 48 h (164.7 (66.9-300.6) pg/mL; P <0.001). RIP3 concentrations at 48 h were associated with AKI stage (no AKI: 144.8 (58.6-234.9) pg/mL; AKI stage 1: 165.8 (43.0-310.9) pg/mL; AKI stage 2-3: 365.5 (155.1-727.5) pg/mL; P = 0.010) whereas this association was not seen at presentation (P = 0.324). RBC transfusions were also associated with 48-h plasma RIP3 (no RBCs: 99.4 (15.6-166.1) pg/mL; 1-5 units: 182.6 (98.5-274.1) pg/mL; >5 units: 341.8 (150.1-423.8) pg/mL; P <0.001).
In critically ill trauma patients, plasma levels of the necroptosis mediator RIP3 at 48 h were associated with AKI stage and RBC transfusions.
受体相互作用蛋白激酶3（RIP3）是坏死性凋亡的关键介质，坏死性凋亡是一种受调控的细胞死亡形式，最近在肾缺血再灌注损伤和输血相关内皮损伤的小鼠模型中被发现。坏死性凋亡在人类急性肾损伤（AKI）中的重要性尚不清楚。我们假设血浆RIP3浓度与严重创伤后的急性肾损伤（AKI）相关。
我们在一个重症创伤患者的前瞻性队列中进行了一项病例对照研究。AKI根据急性肾损伤网络肌酐标准在就诊后6天内定义。在158名队列受试者中，我们选择了13名发生2期或3期AKI的患者、27名1期AKI患者和40名无AKI的患者。我们比较了这些组在就诊时和48小时时的血浆RIP3浓度。由于红细胞（RBC）输血是AKI的一个危险因素，我们还测试了复苏期间输注的RBC与RIP3水平之间的关联。
血浆RIP3浓度中位数从就诊时的15.6（四分位间距15.6 - 41.3）pg/mL上升至48小时时的164.7（66.9 - 300.6）pg/mL，升高超过10倍（P < 0.001）。48小时时的RIP3浓度与AKI分期相关（无AKI：144.8（58.6 - 234.9）pg/mL；AKI 1期：165.8（43.0 - 310.9）pg/mL；AKI 2 - 3期：365.5（155.1 - 727.5）pg/mL；P = 0.010），而在就诊时未观察到这种关联（P = 0.324）。RBC输血也与48小时时的血浆RIP3相关（未输血：99.4（15.6 - 166.1）pg/mL；1 - 5单位：182.6（98.5 - 274.1）pg/mL；>5单位：341.8（150.1 - 423.8）pg/mL；P < 0.001）。
在重症创伤患者中，48小时时坏死性凋亡介质RIP3的血浆水平与AKI分期和RBC输血相关。
