Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India.
Aliment Pharmacol Ther. 2023 Sep;58(6):593-610. doi: 10.1111/apt.17639. Epub 2023 Jul 16.
Renal tubular epithelial cells (RTECs) cause maladaptive repair and perpetuate renal fibrosis.
To evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and RTEC as risk factors for non-resolution of acute kidney injury (AKI-NR) at day seven and chronic kidney disease (CKD) in critically ill patients with cirrhosis.
We performed urinary NGAL and microscopy at enrolment and day 7 in all patients. We assessed 17 renal injury, endothelial injury and repair markers, genes for mitochondrial biogenesis by qRT-PCR in RTEC, and post-mortem renal biopsies for understanding mechanisms of AKI non-resolution (n = 30).
We enrolled 310 patients, aged 48.1 ± 11.6 years, 87% male, 90% alcoholic. Of these, 36% had RTEC at enrolment, and 53% had AKI-NR on day 7. On mean follow-up of 136 days (range 43-365), 150 (48.3%) developed CKD. The presence of RTEC or granular casts, NGAL and AKI-NR were independent predictors of CKD development on competing risk analysis. Higher MCP-1, renal endothelial injury, decrease in tubular repair markers and failure of mitochondrial biogenesis in RTEC were seen in patients with AKI-NR compared with AKI-R (p < 0.05). Renal biopsies showed infiltration with monocyte-macrophage, increased α-SMA, and tubulointerstitial fibrosis.
Almost two-thirds of critically ill patients with cirrhosis have AKI, which resolves in only one-half at day seven and predicts the development of CKD. Higher NGAL, RTEC, or granular casts were independent predictors of AKI-NR and CKD development. Enhanced tubular and endothelial injury, decreased repair, monocyte-macrophage infiltration and mitochondrial dysfunction in RTEC are associated with AKI non-resolution and risk of renal fibrosis.
肾小管上皮细胞（RTEC）引起适应性修复并使肾纤维化持续存在。
评估尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和 RTEC 是否为肝硬化危重症患者第 7 天急性肾损伤（AKI-NR）和慢性肾脏病（CKD）无法缓解的危险因素。
我们对所有患者在入组时和第 7 天进行尿 NGAL 和显微镜检查。我们评估了 17 种肾损伤、内皮损伤和修复标志物、RTEC 中线粒体生物发生的 qRT-PCR 基因，并进行了死后肾活检以了解 AKI 无法缓解的机制（n=30）。
我们共纳入 310 名患者，年龄 48.1±11.6 岁，男性占 87%，90%为酒精性。其中，36%在入组时存在 RTEC，53%在第 7 天发生 AKI-NR。在平均随访 136 天（范围 43-365 天）后，150 例（48.3%）发生 CKD。在竞争风险分析中，存在 RTEC 或颗粒状管型、NGAL 和 AKI-NR 是 CKD 发展的独立预测因子。与 AKI-R 相比，AKI-NR 患者的 MCP-1 更高，肾内皮损伤更严重，管状修复标志物减少，RTEC 中线粒体生物发生失败（p<0.05）。肾活检显示单核细胞-巨噬细胞浸润、α-SMA 增加和肾小管间质纤维化。
近三分之二的肝硬化危重症患者存在 AKI，其中只有一半在第 7 天得到缓解，并且预测了 CKD 的发生。更高的 NGAL、RTEC 或颗粒状管型是 AKI-NR 和 CKD 发展的独立预测因子。RTEC 中增强的管状和内皮损伤、减少的修复、单核细胞-巨噬细胞浸润和线粒体功能障碍与 AKI 无法缓解和肾纤维化风险相关。
