Neutrophil gelatinase-associated lipocalin worsens ischemia/reperfusion damage of kidney cells by autophagy

This study aimed to explore the influence of neutrophil gelatinase-associated lipocalin on autophagy and its role in ischemia/reperfusion injury in human kidney-2 (HK-2) cells during acute kidney injury (AKI). HK-2 cells were given hypoxia/reoxygenation treatment for different times to simulate ischemia/reperfusion injury. Autophagy was evaluated by western blot and immunofluorescence of GFP-LC3. Cell viability was tested to reflect the degree of cell damage. The autophagy inhibitor 3-MA was used to inhibit autophagy and determine the role of autophagy in ischemia/reperfusion injury. HK-2 cells were hypoxia for 1?h, followed by reoxygenation treatment for 24?h. These cells were then exposed to human recombinant protein neutrophil gelatinase-associated lipocalin (NGAL) (50, 100, 200, 400, or 1000?ng/mL) with or without 3-MA. Our results showed that autophagy was induced by hypoxia treatment and was further enhanced by reoxygenation after hypoxia treatment. Cell viability was decreased with the inhibition of autophagy in the process. Autophagic flux was further induced with NGAL (>200?ng/mL), while cell viability declined in this condition. Cell viability was recovered when autophagy was inhibited. These results indicate that autophagy plays, in part, a protective role in renal ischemia/reperfusion injury. Furthermore, the data suggest that NGAL strengthens the level of autophagy in this process. Overall, a large quantity of NGAL produced by renal proximal tubular epithelial cells may induce excessive autophagy and increase renal ischemia/reperfusion injury in acute kidney injury.     

Critically ill,tubular injury,delayed early recovery: characteristics of acute kidney disease with renal oxalosis

ObjectsThis study aimed to analyze the clinicopathological features of acute kidney disease (AKD) with renal oxalosis.MethodsData for biopsy-proven AKD with oxalosis diagnosed from Jan 2011 to Oct 2018 was collected. The underlying diseases, dietary habits, clinical and pathological characteristics of newly emerging kidney disease were analyzed. The long-term renal prognosis was observed.ResultsA total of 23 patients were included, comprised of 18 men and 5 women with a mean age of 51.6 ± 15.9 years. The peak Scr was 669.9 ± 299.8 μmol/L, and 95.7% of patients had stage 3 acute kidney injury (AKI). Drug-induced tubulointerstitial nephritis (TIN) was the most common cause (65.2%) of AKD, followed by severe nephrotic syndrome (17.4%). All patients had pathological changes indicating TIN, and 11 patients were complicated with the newly emerging glomerular disease (GD). The risk of oxalosis caused by increased enterogenous oxalate absorption accounted for only 26.1%, and others came from new kidney diseases. The majority (75%) of abundant (medium to severe) oxalosis occurred in patients without GD. There were no significant differences in the score for tubular injury (T-IS) and interstitial inflammation with different severities of oxalosis. Rate of Scr decrease (ΔScr%) at 2 weeks was negatively correlated with the severity of oxalosis (R = −0.542, p = 0.037), score for T-IS (R = −0.553, p = 0.033), and age (R = −0.736, p = 0.002). The decrease in Scr at 4 weeks was correlated with T-IS (R = −0.433), but had no correlation with oxalosis.ConclusionsThe present findings revealed that 95.7% of AKD with secondary renal oxalosis occurred in critically ill patients. AKD from tubular injury was the prominent cause. Severe oxalosis contributed to delayed early recovery of AKD.     

Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury

Ischemia is the most frequent cause of acute kidney injury (AKI), which is characterized by apoptosis of renal tubular cell. A common result of ischemia in AKI is dysfunction of endoplasmic reticulum (ER), which causes the protein-folding capacity to lag behind the protein-folding load. The abundance of misfolded proteins stressed the ER and results in induction of the unfolded protein response (UPR). While the UPR is an adaptive response, over time it can result in apoptosis when cells are unable to recover quickly. Recent research suggests that ER stress is a major factor in renal tubular cell apoptosis resulting from ischemic AKI. Thus, ER stress may be an important new progression factor in the pathology of ischemic AKI. In this article, we review UPR signaling, describe pathology and pathophysiology mechanisms of ischemic AKI, and highlight the dual function of ER stress on renal tubular cell apoptosis.     

Role of serotonin in the regulation of renal proximal tubular epithelial cells

In various renal injuries, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as serotonin, are released into microenvironment upon platelet activation following renal injury. In the present study, we aimed to investigate whether platelets and platelet-released serotonin are involved in the functional regulation of renal proximal tubular epithelial cells (PTECs). PTECs were obtained by primary cell culture and treated with platelet lysate (PL) (2?×?10⁶/mL, 4?×?10⁶/mL, 8?×?10⁶/mL) or serotonin (1?μM or 5?μM) for 12 or 24?h. Phenotypic transdifferentiation of epithelial cells into myofibroblasts were demonstrated under light microscope and confirmed by the determination of α-smooth muscle actin gene expression. Serotonin and PL were shown to induce epithelial–mesenchymal transdifferentiation of PTECs. After stimulation of PTECs with serotonin or PL, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and collagen-α1 gene expressions, which were reported to be elevated in renal injury, were determined by real-time PCR and found to be upregulated. Expressions of some inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and transforming growth factor-β1 were found to be increased in both protein and gene levels. Recently there is no published report on the effect of serotonin on renal PTECs. Results obtained in this study have lightened the role of serotonin and platelet-mediated effects of serotonin on fibrotic and inflammatory processes in PTECs.     

Stem cells improve right ventricular functional recovery after acute pressure overload and ischemia reperfusion injury

BACKGROUND: In many clinical scenarios, a relatively untrained right ventricle may be subjected to acute elevations in pulmonary artery and right ventricular pressures. The right and left heart are distinctly different in this regard and there is currently no in vivo model to study right ventricular ischemia in the setting of acute pressure overload. In acute injury, cardiomyocytes produce tumor necrosis factor, which mediates a proinflammatory pathway, eventually leading to myocardial dysfunction. Stem cells have been shown to reduce the production of proinflammatory mediators by the ischemic myocardium and protect the myocardium. Pretreatment with stem cells has been shown to protect the left ventricle. The effect of acute pressure overload to the untrained right ventricle is still not well understood. Furthermore, it is unclear whether pretreatment with stem cells would protect the right ventricle when it is subjected to acute pressure overload and concomitant ischemia reperfusion injury. The purpose of this study was (1) to create a simple model of acute pressure overload for the study of concomitant right ventricular ischemia and reperfusion, and (2) to evaluate the effect of pretreatment with stem cells prior to ischemia reperfusion injury. MATERIALS AND METHODS: Isolated rat hearts were perfused with the modified Langendorff technique with the latex balloon in the right ventricle instead of the left, with a pressure-transduced balloon being used to create an acute elevation in right ventricular pressure before ischemia. In the first of a two-series experiment, there were two experimental groups (N = 8 per group): one with right ventricular balloon end-diastolic pressure (EDP) of 5 mmHg (physiological), and the other with an EDP of 40 mmHg (pathologic). In the second series, the hearts with the higher balloon pressure (EDP 40 mmHg) were divided into two experimental groups (N = 5 per group). The control group was not pretreated. One group was pretreated with human mesenchymal stem cells 5 min immediately prior to ischemia reperfusion injury. Right ventricular developed pressure (RVDP), contractility (+dP/dt), and compliance (-dP/dt) were continuously assessed. Additionally, mesenchymal stem cells (MSCs) in culture were stressed by hypoxia and activation was determined by measuring vascular endothelial growth factor-A (VEGF) and hepatocyte growth factor (HGF) production by enzyme-linked immunosorbent assay. RESULTS: Recovery of RVDP, +dP/dt, and -dP/dt was significantly higher (P < 0.001) in the group with lower EDP compared to the group with the higher EDP [RVDP: 79.53 +/- 6.34 versus 54.28 +/- 10.76%; +dP/dt: 76.54 +/- 8.79 versus 38.75 +/- 19.74%; -dP/dt: 72.29 +/- 7.02 versus 30.54 +/- 12.44%]. In the higher EDP groups, pretreatment with human mesenchymal stem cells significantly improved myocardial function recovery (P < 0.01) when compared to controls [RVDP: 75.76 +/- 7.97 versus 59.10 +/- 11.18%; +dP/dt: 71.78 +/- 10.36 versus 54.93 +/- 12.64%; -dP/dt: 77.38 +/- 11.09 versus 59.30 +/- 15.20%]. Further, hypoxic MSCs demonstrated significantly greater VEGF and HGF release than controls. CONCLUSION: This compounded injury model allowed the study of right ventricular dysfunction in the setting of acute pressure overload and ischemia. Additionally, we have also demonstrated that pretreatment with stem cells of an acutely pressure overloaded right ventricle prior to ischemia reperfusion injury improves functional recovery. This is the first report of a modified Langendorff technique to study right ventricular function in the setting of acute pressure overload and ischemia and the effect of pretreatment with stem cells.     

亚致死性过氧化氢损伤致肾小管上皮细胞整合素受体分布的改变

目的探讨急性肾功能衰竭（ＡＲＦ）时活性肾小管上皮细胞脱落现象及管型阻塞的机制。方法用猪肾小管上皮细胞株（ＬＬＣＰＫ１）观察亚致死性Ｈ２Ｏ２损伤致细胞与基质粘附性及整合素受体α３分布的改变。结果细胞与基质间粘附力显著降低（Ｐ＜００５），细胞表面整合素受体α３由原先基侧部分布变为半随机分布（Ｐ＜００５）。结论细胞受亚致死性Ｈ２Ｏ２损伤后，可使整合素受体α３分布改变，细胞基质粘附力降低，致使活性细胞脱落和管腔阻塞。     

Sclerosing Encapsulating Peritonitis in an Anti-HCV-Positive Patient on Chronic Ambulatory Peritoneal Dialysis

We investigated the role of neutrophil gelatinase-associated lipocalin (NGAL) on renal tubular epithelial cell in the renal ischemia/reperfusion injury (IRI) rats. Male Sprague–Dawley rats were randomly assigned to three groups. The control group (n = 5) underwent left nephrectomy. The ischemia/reperfusion (I/R) + normal saline (NS) (n = 5) and I/R + NGAL groups (n = 5) were subjected to 45 min right renal ischemia followed by 48 h of reperfusion after left nephrectomy. The pathological changes of kidney tissues were investigated using hematoxylin–eosin staining; renal tubular epithelial cell apoptosis was detected using terminal dUTP nick-labeling method; expression of apoptosis-regulating protein Fas and Bcl-2 was measured using real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Compared with I/R + NS group, kidney tissues from I/R + NGAL group revealed reduced histological damage and a decreased number of renal tubular epithelial cell apoptosis (9.2 ± 2.53 nuclei or 4.0 ± 0.7 per high-power field vs. 20.3 ± 3.7 nuclei or 8.1 ± 0.3 per high-power field); rats with NGAL showed downregulated fas mRNA (2.34 ± 0.51 vs. 6.84 ± 2.34), fas protein (0.65 ± 0.05 vs. 0.95 ± 0.08), and upregulated bcl-2 protein (0.33 ± 0.05 vs. 0.24 ± 0.03). The results had statistical significance (p < 0.05). We think NGAL could protect against renal IRI and might be related to decreasing tubular epithelial cell apoptosis via adjusting the expression of apoptosis-regulating proteins.     

Sonic hedgehog signaling is involved in aristolochic acid-induced renal tubular epithelial cells injury in vitro

Objective To investigate the molecular mechanism of aristolochic acid (AA)-induced renal tubular epithelial cells (NRK-52E) injury, and to elucidate possible role of sonic hedgehog (Shh) signaling in this process. Methods The proliferation inhibition rate was measured by WST-1 assay in vitro after NRK-52E cells were treated with AA (1, 10, 100 mg/L) for 12, 24, and 48 h, respectively. Cell apoptosis was determined by Hoechst 33258 staining. mRNA expressions of Smo, Ptch1, α-SMA, E-cadherin, TGF-β1, and type III collagen were detected by real-time PCR. The levels of Shh and TGF-β1 were detected by ELISA assay. The expressions of bcl-2, bax, α-SMA, and E-cadherin were examined by Western blotting. Results WST-1 assay showed that AA significantly inhibited the proliferation of NRK-52E cells after 24 h, which was in a dose-dependent pattern (r＝0.817, P＝0.047). Evidence from Hoechst 33258 staining revealed that lower concentration (1, 10 mg/L) AA induced cell apoptosis, but higher concentration (100 mg/L) AA induced cell necrosis. In AA-treated cells (10 mg/L), apoptosis was induced, which was partly mediated by the mitochondrial pathway with decreased bcl-2 and enhanced bax expression. The over-expression of Shh protein and Smo mRNA, and down-regulation of Ptch1 mRNA expression were found, indicating that Shh signaling was activated. In addition, the expressions of α-SMA, TGF-β1, and type Ⅲ collagen were significantly increased, but E-cadherin expression was decreased, suggesting that epithelial-to-mesenchymal transition and fibrosis occurred. Conclusions AA can significantly inhibit proliferation, and induce apoptosis and necrosis in NRK-52E cells. In this process, Shh signaling is activated, which promotes epithelial-to-mesenchymal transition and fibrosis.     

Mannan-binding lectin mediates renal ischemia/reperfusion injury independent of complement activation

Ischemia/reperfusion injury (IRI) remains a major problem in renal transplantation. Clinical studies have identified that high serum levels of Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, are associated with inferior renal allograft survival. Using a rat model, we identified an entirely novel role for MBL in mediating renal IRI. Therapeutic inhibition of MBL was protective against kidney dysfunction, tubular damage, neutrophil and macrophage accumulation, and expression of proinflammatory cytokines and chemokines. Following reperfusion, exposure of tubular epithelial cells to circulation-derived MBL resulted in internalization of MBL followed by the rapid induction of tubular epithelial cell death. Interestingly, this MBL-mediated tubular injury was completely independent of complement activation since attenuation of complement activation was not protective against renal IRI. Our identification that MBL-mediated cell death precedes complement activation strongly suggests that exposure of epithelial cells to MBL immediately following reperfusion is the primary culprit of tubular injury. In addition, also human tubular epithelial cells in vitro were shown to be susceptible to the cytotoxic effect of human MBL. Taken together, these data reveal a crucial role for MBL in the early pathophysiology of renal IRI and identify MBL as a novel therapeutic target in kidney transplantation.     

中性粒细胞明胶酶相关脂质运载蛋白对大鼠肾脏缺血再灌注损伤肾小管上皮细胞的保护作用

目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对大鼠缺血再灌注损伤肾脏肾小管上皮细胞凋亡的保护作用及机制.方法 建立大鼠肾脏缺血再灌注模型,雄性SD大鼠随机分为对照组、缺血再灌注模型组、NGAL组 ;HE染色观察3组大鼠肾组织病理变化 ;TUNEL法检测肾小管上皮细胞凋亡 ;实时定量PCR、Western印迹法检测凋亡蛋白fas、bcl-2的表达变化.结果 与缺血再灌注模型组比较,NGAL组肾小管上皮细胞凋亡数量显著减少[(8.6±3.4)/HP比(20.8±3.7)/HP,P＜0.05] ;NGAL组肾组织fas mRNA(2.34±0.51比6.84±2.34,P＜0.05)、fas蛋白(0.65±0.05比0.95±0.08,P＜0.05)表达显著下调,bcl-2蛋白(0.33±0.05比0.24±0.03,P＜0.05)表达显著上调,但bcl-2 mRNA表达无明显改变.结论 NGAL对大鼠缺血再灌注损伤肾小管上皮细胞有保护作用,其作用可能与减少细胞凋亡、改变凋亡蛋白的表达有关.     

Is patchy tubular injury a histopathological marker of acute rejection?

Abstract:  Renal allograft specimens often show patchy tubular injury (PTI), or patches of injured tubular sections. PTI reflects damage to the proximal tubules, and the histologic findings consist of tubular cell necrosis and tubular regeneration without tubulitis. Unlike acute tubular necrosis (ATN) in cadaveric donors, PTI can be observed in kidneys from living donors when there is no history of acute renal failure after transplantation. In this study, we examined the clinicopathological importance of PTI in acute rejection. Between April 2000 and May 2007, 2252 biopsies of living kidney grafts were performed at least one d after the transplant operation. Acute rejection was observed in 877 biopsies. Of these cases, 78 (8.9%) biopsies from 43 patients showed PTI. The severity of the PTI was graded semiquantitatively as follows: grade 1 cases had three or four damaged tubular sections, grade 2 cases had >5 sections, and grade 3 cases had >10 sections. The incidence of PTI was significantly higher in vascular rejection (VR) and antibody-mediated rejection (AMR) patients than in those experiencing tubulointerstitial rejection (TIR). The mean PTI score was significantly higher (2.00 ± 0.12) in VR than in TIR (1.39 ± 0.10) and AMR (1.68 ± 0.08) patients. The mean serum creatinine (sCr) at the time of biopsy was higher in VR patients than in AMR and TIR patients. Moreover, in VR patients, those with severer PTI developed higher sCr levels. These data suggest that PTI has a strong relationship with local ischemic damage delegated by VR, and the severity of PTI could be a practical histological marker in acute vascular rejection.     

Hepatic ischemia reperfusion injury is associated with acute kidney injury following donation after brain death liver transplantation

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury (AKI). This suggests that hepatic ischemia‐reperfusion injury may play a critical role in the pathogenesis of AKI after liver transplantation. The aim of this single‐center study was to determine if hepatic ischemia‐reperfusion injury, estimated by peak peri‐operative serum amino‐transferase (AST), is associated with AKI following donation after brain death (DBD) liver transplantation. A total of 296 patients received 298 DBD liver transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI was a risk factor for chronic kidney disease (P = 0.037) and mortality (P = 0.002). On univariate analysis, peak AST correlated with peak creatinine (P < 0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak AST of <1500, 1500–2999 and ≥3000 U/l was 26.1%, 39.8% and 71.2%, respectively (P < 0.001). On multiple logistic regression analysis, peak AST was independently associated with the development of AKI (P < 0.001). In conclusion, hepatic ischemia‐reperfusion injury demonstrates a strong relationship with peri‐operative AKI in DBD liver transplant recipients.     

Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats

Purpose: Acute kidney injury (AKI) induces acute lung injury (ALI) through releasing injurious mediators or impairing clearance of systemic factors. To determine the links between AKI and ALI, pulmonary and blood variables were evaluated following induction of AKI via different experimental models of bilateral renal ischemia/reperfusion (BIR: renal ischemia with uremia), unilateral renal ischemia/reperfusion (UIR: renal ischemia without uremia), bilateral nephrectomy (BNX: uremia without renal ischemia), and unilateral nephrectomy (UNX: without uremia and renal ischemia).

Methods: Ninety male Sprague–Dawley rats were divided into six groups. Animals had 1-h bilateral or 2-h unilateral renal ischemia followed by 24-h reperfusion in the BIR and UIR groups, respectively, and 24-h period following bilateral or unilateral nephrectomy in the BNX and UNX groups, respectively. There were also sham and control groups with and without sham-operation, respectively.

Results: Plasma malondialdehyde and nitric oxide were elevated by BIR more than UIR, but not changed by UNX and BNX. UIR slightly increased plasma creatinine, whereas BIR and BNX largely increased plasma creatinine, urea, K^+?and osmolality and decreased arterial HCO₃^?, pH, and CO₂. UNX and UIR did not affect lung, but BIR and BNX induced ALI with equal capillary leak and macrophages infiltration. However, there were more prominent lung edema and vascular congestion following BNX and more severe neutrophils infiltration and P_aO₂/F_iO₂ reduction following BIR.

Conclusion: Acutely accumulated systemic mediators following renal failure in the absence of kidneys vary from those due to combined renal failure with ischemic-reperfused kidneys and consequently they induce ALI with distinct characteristics.     

Effect of erythropoietin on the oriented chemotaxis of bone-marrow mesenchymal stem cells under acute kidney injury microenvironment

Objective To investigate the migration of bone-marrow mesenchymal stem cells (BMSCs) under acute kidney injury (AKI) microenvironment in vitro and the effect of erythropoietin (EPO) intervention, and to explore its underlying mechanism. Methods Renal tubular epithelial cells (RTECs) were cultured in hypoxia/ re-oxygenation (HR) condition for 12 h, respectively, in order to establish HR-RTEC. BMSCs and RTECs were co-cultured by Transwell system and were divided into 7 groups: control group (group①, only BMSC cultured), BMSC-RTEC co-culturing group (group②), BMSC-HR-RTEC co-culturing ＋EPO intervention groups (group③to group⑦, EPO concentration: 0, 1, 5, 10, 50 IU/ml). All the groups were cultured for 48 h and the number of migrating BMSCs was detected. Western blotting was applied for the detection of SDF-1 expression in RTECs and p-MAPK and MAPK levels in BMSCs. SDF-1 concentration in the RTECs culture supernatant was tested by ELISA. Results The number of BMSCs migrating to the low chamber where HR-RTECs were cultured was increased, and EPO intervention further enhanced this migration which reached the peak at the concentration of 10 IU/ml [Compared with group③, (46.67±7.37) cells vs (19.00±2.37) cells, P＜0.05]. Intracellular expression level and the secreated level of SDF-1 in HR-RTECs in group③ were higher than those in RTECs of group② [0.37±0.01 vs 0.19±0.01, P＜0.05; (61.64±4.88) μg/L vs (35.26±8.78) μg/L, P＜0.05]. EPO intervention increased above SDF-1 levels and reached the peak at the concentration of 10 IU/ml [group⑥ vs group③：(173.53±14.66) μg/L vs (61.64±4.88) μg/L, P＜0.05], accompanied with enhanced phosphorylation of MAPK in BMSCs. Conclusions AKI microenvironment has obvious chemotaxis effect on BMSCs, and EPO intervention can strengthen this effect. The increased SDF-1 level and enhanced phosphorylation of MAPK, the downstream signal protein of SDF-1/CXCR4 axis, are the possible mechanism for EPO performance.     

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m(2) ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.     

急性肾损伤的体外细胞治疗

急性肾损伤是临床常见病,其发病率有逐年升高趋势。伴有急性肾损伤的危重症患者往往具有高死亡率的特点。近年来,开展了众多不同于传统疗法的治疗研究,以期改变急性肾损伤患者预后不佳的现状。其中,细胞疗法逐渐发展为一种用于治疗大量临床疾病的新方法。出于安全考虑,体外细胞疗法可能会是一种更好的选择,因为其不仅替代了受损细胞的功能或调整了病理生理过程,而且提供了免疫绝缘屏障。本文就肾小管上皮细胞、粒细胞及血管内皮细胞的不同体外细胞疗法做出阐述。相比于传统的连续性肾脏替代治疗,肾小管上皮细胞、粒细胞的体外细胞疗法对于急性肾损伤患者的存活有着重大且积极的影响。上海交通大学医学院附属第九人民医院肾脏科构建了一种血管内皮体外细胞治疗系统,可明显改善脓毒症动物的血流动力学稳定性及多种脏器功能,并提高存活率。这些研究对于改善急性肾损伤患者的预后具有积极意义。     

Characteristics and risk factors for renal recovery after acute kidney injury in critically ill patients in cohorts of elderly and non-elderly: a multicenter retrospective cohort study

BackgroundThe purpose of this study was to explore the risk factors for renal nonrecovery among elderly and nonelderly patients with acute kidney injury (AKI) in critically ill patients.MethodsA multicenter retrospective cohort of 583 critically ill patients with AKI was examined. We found the best cutoff value for predicting renal recovery by age was 63 years old through logistic regression. All patients were divided into two cohorts, age <63 and age ≥63-years old; on the basis of renal recovery at 30 days after AKI, the two patient cohorts were further divided into a renal recovery group and a renal nonrecovery group. Multivariate logistic regression was used to analyze the risk factors affecting renal recovery in the two cohorts.ResultsThe 30-day renal recovery rate of patients aged <63 years was 70.0% (198/283), multivariate analysis showed that the independent risk factors affecting renal nonrecovery in age <63 years old included AKI stage, blood lactate level and hemoglobin level. The 30-day renal recovery rate of patients aged ≥63 years was 28.7% (86/300), multivariate analysis showed that the independent risk factors for renal nonrecovery in age ≥63-years old included diabetes mellitus, surgery with general anesthesia, AKI stage, APACHE II score, eGFR, and hemoglobin level.ConclusionsThe renal nonrecovery after AKI in critically ill patients in patients aged ≥63 years was more strongly affected by multiple risk factors, such as diabetes mellitus, surgery with general anesthesia, eGFR, and APACHE II score, in addition to hemoglobin and AKI stage.