Jou-Valencia Daniela, Koeze Jacqueline, Popa Eliane R, Aslan Adnan, Zwiers Peter J, Molema Grietje, Zijlstra Jan G, van Meurs Matijs, Moser Jill
Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, Medical Biology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Crit Care Explor. 2019 Oct 14;1(10):e0047. doi: 10.1097/CCE.0000000000000047. eCollection 2019 Oct.
To identify mechanisms associated with sepsis-acute kidney injury based on the expression levels of renal injury biomarkers, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 in renal biopsies which may allow the identification of sepsis-acute kidney injury patient subtypes.
Prospective, clinical laboratory study using "warm" human postmortem sepsis-acute kidney injury kidney biopsies.
Research laboratory at university teaching hospital.
Adult patients who died of sepsis in the ICU and control patients undergoing tumor nephrectomy.
Reverse transcription quantitative polymerase chain reaction and immunohistochemical staining were used to quantify messenger RNA and protein expression levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in the kidney of sepsis-acute kidney injury patients and control subjects. Morphometric analysis was used to quantify renal and glomerular neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 protein levels. Neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 messenger RNA and protein levels were increased in kidneys of sepsis-acute kidney injury patients compared with control kidney tissue. Neutrophil gelatinase-associated lipocalin was localized in the distal tubules, collecting ducts, the adventitia of the renal arterioles, and in the glomerular tufts of renal biopsies from sepsis-acute kidney injury patients. In contrast, kidney injury molecule-1 was localized at the brush border of the proximal tubules. There was no correlation between neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels. Furthermore, renal neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels were not associated with the extent of renal injury, the severity of critical illness, or serum creatinine levels at either ICU admission or day of expiration. By laser microdissecting glomeruli, followed by reverse transcription quantitative polymerase chain reaction, we identified heterogenous glomerular neutrophil gelatinase-associated lipocalin production in the kidney of sepsis-acute kidney injury patients.
We found differences in the expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in patients with the same syndrome "sepsis-acute kidney injury" meaning there is no single pathway leading to sepsis-acute kidney injury. This underscores the beliefs that there are many/different pathophysiological pathways that can cause sepsis-acute kidney injury. Hence, patients with criteria that meet the definitions of both acute kidney injury and sepsis can be divided into subtypes based on pathophysiological features.
基于肾活检中肾损伤生物标志物、中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1的表达水平，确定与脓毒症相关性急性肾损伤相关的机制，这可能有助于识别脓毒症相关性急性肾损伤患者的亚型。
使用“温热”的人类脓毒症相关性急性肾损伤死后肾活检进行前瞻性临床实验室研究。
大学教学医院的研究实验室。
在重症监护病房死于脓毒症的成年患者和接受肿瘤肾切除术的对照患者。
采用逆转录定量聚合酶链反应和免疫组织化学染色法，对脓毒症相关性急性肾损伤患者和对照受试者肾脏中中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1的信使核糖核酸和蛋白表达水平进行定量。形态计量分析用于量化肾脏和肾小球中中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1的蛋白水平。与对照肾组织相比，脓毒症相关性急性肾损伤患者肾脏中中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1的信使核糖核酸和蛋白水平升高。中性粒细胞明胶酶相关脂质运载蛋白定位于脓毒症相关性急性肾损伤患者肾活检的远端小管、集合管、肾小动脉外膜和肾小球丛中。相比之下，肾损伤分子-1定位于近端小管的刷状缘。中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1水平之间无相关性。此外，肾脏中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1水平与肾损伤程度、危重病严重程度或重症监护病房入院时或死亡当天的血清肌酐水平均无关。通过激光显微切割肾小球，随后进行逆转录定量聚合酶链反应，我们在脓毒症相关性急性肾损伤患者的肾脏中发现了异质性的肾小球中性粒细胞明胶酶相关脂质运载蛋白产生。
我们发现在患有同一综合征“脓毒症相关性急性肾损伤”的患者中，中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1的表达存在差异，这意味着不存在导致脓毒症相关性急性肾损伤的单一途径。这强调了存在许多/不同的病理生理途径可导致脓毒症相关性急性肾损伤的观点。因此，符合急性肾损伤和脓毒症定义标准的患者可根据病理生理特征分为不同亚型。
