Association between urine microscopy and severe acute kidney injury in critically ill patients following non-cardiac surgery: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and adverse complication following non-cardiac surgery. Evidence have shown urine microscopy could help early detection, differentiating the causes and predicting the progression of AKI. However, little evidence is available on AKI after non-cardiac surgery. Thus, we investigated the association between urine microscopy and severe AKI in critically ill patients after non-cardiac surgery. METHODS: This was a single-center prospective cohort study. The primary outcome was severe AKI, defined as stage 2 or 3 according to maximal KDIGO criteria within 7 days following non-cardiac surgery. Urine microscopy immediately, 6 and 12 hours after surgical intensive care unit (SICU) admission were examined and graded by a urine microscopy score (UMS) based on the observed quantification of renal tubular cells and casts in the sediment. Then, multivariate Logistic regression models were used to analyze the associations between UMS and postoperative severe AKI. RESULTS: From May 20, 2019 to November 24, 2020, 661 patients were enrolled with 147 patients (22.2%) developing postoperative severe AKI. Multivariate Logistic regression model showed elevated UMS (≥1) 6 and 12 hours after SICU admission were independently associated with postoperative severe AKI (OR 2.200, 95% CI: 1.182-4.095, P=0.013 and OR 2.949, 95% CI: 1.657-5.248, P<0.001, respectively). Furthermore, higher UMS 6 hours after SICU admission demonstrated correlation with greater risk of severe AKI with OR 3.887 (95% CI: 1.430-10.563) for UMS ≥3 and OR 2.429 (95% CI: 1.237-4.770) for UMS =1-2. The specificity and sensitivity of UMS ≥1 for severe AKI was 93.8% (95% CI: 91.7-95.9%) and 15.6% (95% CI: 9.7-21.5%), respectively. While the negative and positive predictive value was 79.5% (95% CI: 76.3-82.7%) and 41.8% (95% CI: 28.8-54.8%), respectively. In addition, patients with higher UMS (≥3, 1-2 and 0) had significantly more postoperative complications and longer SICU stay; and they also showed a trend toward other adverse postoperative outcomes. CONCLUSIONS: Early urine microscopy was independently associated with severe AKI in critically ill patients following non-cardiac surgery with higher UMS related to greater risk. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03880110.

Human Amnion Epithelial Cells and Their Derived Exosomes Alleviate Sepsis-Associated Acute Kidney Injury via Mitigating Endothelial Dysfunction.

Background: Sepsis is characterized by organ dysfunction resulting from a patient's dysregulated response to infection. Sepsis-associated acute kidney injury (S-AKI) is the most frequent complication contributing to the morbidity and mortality of sepsis. The prevention and treatment of S-AKI remains a significant challenge worldwide. In the recent years, human amnion epithelial cells (hAECs) have drawn much attention in regenerative medicine, yet the therapeutic efficiency of hAECs in S-AKI has not been evaluated. Methods: Septic mice were induced by cecal ligation and puncture (CLP) operation. hAECs and their derived exosomes (EXOs) were injected into the mice via tail vein right after CLP surgery. The 7-day survival rate was observed. Serum creatinine level was measured and H&E staining of tissue sections were performed 16 h after CLP. Transmission electron microscopy was used to examine the renal endothelial integrity in CLP mice. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) and EXOs. Zonula occludens-1 (ZO-1) localization was observed by immunofluorescence staining. Expression of phosphor-p65 (p-p65), p65, vascular cell adhesion molecule-1 (VCAM-1), and ZO-1 in the kidney were determined by Western blot. Results: hAECs decreased the mortality of CLP mice, ameliorated septic injury in the kidney, and improved kidney function. More precisely, hAECs suppressed systemic inflammation and maintained the renal endothelial integrity in septic animals. EXOs from hAECs exhibited similar renal protective effects as their parental cells. EXOs maintained endothelial cell adhesion junction in vitro and inhibited endothelial cell hyperactivation in vivo. Mechanistically, EXOs suppressed proinflammatory nuclear factor kappa B (NF-κB) pathway activation in LPS-treated HUVECs and in CLP mice kidneys. Conclusion: Our results indicate that hAECs and their derived EXOs may ameliorate S-AKI via the prevention of endothelial dysfunction in the early stage of sepsis in mice. Stem cell or exosome-based therapy targeting endothelial disorders may be a promising alternative for treatment of S-AKI.