Stromal cell-derived factor-1(SDF-1) is a chemotactic and angiogenic factor that mediates the repair of various tissues. As macrophages are important contributors to ischemic kidney injury, we examine the role of SDF-1 in a rodent model of ischemia-reperfusion (I/R) injury. Male wild-type (WT) (C57BL/6) mice were subjected to bilateral I/R injury or sham operation in the presence or absence of macrophage depletion (liposomal clodronate [0.2 ml/20–25 g body weight i.p.]). Macrophage accumulation was assessed by immunohistochemistry. Tissue levels of SDF-1 (ELISA) and SDF-1 mRNA expression (real-time PCR) were measured. The cellular location of SDF-1 was assessed using immunohistochemical staining. Immunofluorescence staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. SDF-1 production was elevated in response to I/R injury and was significantly increased upon macrophage depletion. SDF-1 positive cells initially appeared initially in the cortex, and subsequently diffused to the outer medulla after I/R injury. Our study demonstrates that SDF-1 is significantly upregulated during renal I/R. We hypothesize that SDF-1 upregulation may be an important macrophage effector mechanism during I/R injury.

Purpose: Both acute respiratory failure (ARF) and acute kidney injury (AKI) are two common complications in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Moreover, both ARF and AKI are reported as increasing the risk of mortality of patients with AECOPD. However, the interaction of ARF and AKI on the mortality of patients with AECOPD remains unknown. Therefore, the aim of this study is to investigate the joint effect of ARF and AKI on in-hospital mortality in AECOPD patients. Patients and Methods: We performed a retrospective, observational cohort study of data from Nanjing First Hospital. The effect of AKI and ARF on in-hospital mortality was assessed using a multivariate logistic regression model. Additive interaction was assessed with the relative excess risk due to interaction. Results: A total of 1647 participants were enrolled. ARF and AKI occurred in 515 (31.3%) and 357 (21.7%) patients, respectively. Overall, in-hospital mortality was 5.7%. The in-hospital mortality of the neither ARF nor AKI group, the ARF only group, the AKI only group, and both the ARF and AKI group were 0.8%, 7.0%, 7.5%, and 29.9%, respectively. After multivariate logistic regression analysis, the independent factors for in-hospital death included: albumin (OR 0.88, 95% CI 0.83– 0.93, P < 0.001), ARF only (OR 8.53, 95% CI 3.64– 19.99, P < 0.001), AKI only (OR 8.99, 95% CI 3.58– 22.55, P < 0.001), and both ARF and AKI (OR 39.13, 95% CI 17.02– 89.97, P < 0.001). The relative excess risk due to interaction was 22.62 (95% CI, 0.31 to 44.93), the attributable proportion due to interaction was 0.59 (95% CI, 0.36 to 0.79), and the synergy index was 2.46 (95% CI, 1.44 to 4.20), indicating ARF and AKI had a significant synergic effect on in-hospital mortality. Conclusion: ARF and AKI had a synergistic effect on in-hospital mortality in AECOPD patients.

Background: Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear. Methods: Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively. Results: A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04–1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02–1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P < 0.001), mechanical ventilation (33.8% versus 9.3%; P < 0.001), invasive mechanical ventilation (25.9% versus 5.8%; P < 0.001), non-invasive mechanical ventilation (25.4% versus 7.1%; P < 0.001), and experienced a longer duration of hospital stay (14 days versus 10 days; P < 0.001) than those without AKI. However, no significant difference in ICU stay (11 days versus 10 days; P = 0.099) and duration of mechanical ventilation (8 days versus 8 days; P = 0.369) between AKI and non-AKI groups was found. Conclusion: AKI was common in Chinese patients with CAP. Patients with CAP who developed AKI had worse in-hospital outcomes.

Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03–2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes.

Aims. Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), and macrophages play a key role in this process. The aim of this study was to discover the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition. Main Methods. We crossed lyz2-Cre mice with IKKα-floxed mice to generate mice with IKKα ablation in macrophages (Mac IKKα-/-). A mouse renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 minutes. Treated mice were evaluated for blood biochemistry, tissue histopathology, and fibrosis markers. Macrophages were isolated from the peritoneal cavity for coculturing with tubular epithelial cells (TECs) and flow cytometry analysis. Key Findings. We found that fibrosis and kidney function loss after IRI were significantly alleviated in Mac IKKα-/- mice compared with wild-type (WT) mice. The expression of fibrosis markers and the infiltration of M2 macrophages were decreased in the kidneys of Mac IKKα-/- mice after IRI. The in vitro experiment showed that the IRI TECs cocultured with IKKα-/- macrophages (KO MΦs) downregulated the fibrosis markers accompanied by a downregulation of Wnt/β-catenin signaling. Significance. These data support the hypothesis that IKKα is involved in mediating macrophage polarization and increasing the expression of fibrosis-promoting inflammatory factors in macrophages. Therefore, knockdown of IKKα in macrophages may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.