Acute Kidney Injury Therapy Research Articles

The role of LncRNA-regulated autophagy in AKI.

Acute kidney injury (AKI) is a complex clinical syndrome involving a series of pathophysiological processes regulated by multiple pathways at the molecular and cellular level. Long noncoding RNAs (lncRNAs) play an important role in the regulation of epigenetics, and their regulation of autophagy-related genes in AKI has attracted increasing attention. However, the role of lncRNA-regulated autophagy in AKI has not been fully elucidated. Evidence indicated that lncRNAs play regulatory roles in most factors that induce AKI. LncRNAs can regulate autophagy in AKI via a complex network of regulatory pathways to affect the development and prognosis of AKI. This article reviewed and analyzed the pathways of lncRNA regulation of autophagy in AKI in recent years. The results provide new ideas for further study of the pathophysiological process and targeted therapy for AKI.

Renal Tubular CD24 Upregulation Aggravates Folic Acid Induced Acute Kidney Injury: A Possible Role for T Regulatory Cells Inhibition in Mice.

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24-/- FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI.

Peroxynitrite activated near-infrared fluorescent probe for evaluating ferroptosis-mediated acute kidney injury

Ferroptosis is a form of programmed cell death mostly characterized by a serious misadjustment in the production and degradation of lipid reactive oxygen species (ROS). Meanwhile, numerous studies have indicated that ferroptosis is crucial to the progression and pathophysiology of acute kidney injury (AKI). ROS have been implicated as a pivotal causative factor in cell damage, peroxynitrite (ONOO−) is one of the most prominent ROS which is intimately correlated to ferroptosis-mediated AKI. Therefore, monitoring ONOO− levels in ferroptosis-mediated AKI is important for exploring its physiological and pathological roles. Nevertheless, no probes for detecting ONOO− in ferroptosis-mediated AKI have been reported. Meanwhile, resveratrol (Res) is a bioactive component and has been used to the treatment of AKI. However, the effect of Res on ferroptosis during AKI progression remains elusive. Herein, we evaluated the fluctuation of ONOO− during ferroptosis-mediated AKI using the near-infrared (NIR) fluorescence probe (NFP-ONOO) for the first time. The probe NFP-ONOO showed excellent specificity and sensitivity for the detection of ONOO−. Furthermore, utilizing this probe, we demonstrated Res effectively mitigates AKI induced by folic acid (FA) and cisplatin (CP) by inhibitingferroptosis. Collectively, this work will provide a powerful guidance for the prophylaxis, diagnosis, and therapy of ferroptosis-mediated AKI.

Bioinspired Multiantioxidant‐Cooperative Nanotheranostic Platform for Realizing Time‐Sensitive Management of Acute Kidney Injury

AbstractTargeting the pivotal pathological processes of acute kidney injury (AKI) and parallelly monitoring the treatment process has emerged as an intriguing strategy for the timely tailored treatment of AKI, especially in the acute phase. Unfortunately, current clinical treatment approaches are restricted to supportive care, which shows limited efficiency. Herein, a multiantioxidant‐cooperative polydopamine‐based nanotheranostic platform (mc‐PDATP) is reported to achieve imaging‐assisted time‐sensitive therapy of AKI. Benefiting from the decoration of atomic Cu, mc‐PDATP comprehensively mimics the complicated antioxidant defense system as in natural environment, thus displaying improved catalytic activity to multiple toxic reactive oxygen species (ROS). Consequently, both in vitro and in vivo experiments confirm mc‐PDATP can efficiently protect the kidney from ROS attack and rescue the kidney function via targeting the inflammatory network of AKI. In addition, the coordinated atomic Gd contributes to a desired magnetic resonance (MR) T1‐weighted contrast effect of mc‐PDATP, which can be used to construct the sensitive MR histogram imaging signatures for pinpointing treatment effects in a timely manner. The study represents an innovative strategy for anti‐AKI therapy, which will facilitate the development of next‐generation theranostic nano‐antioxidants.

Study of plasma neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury following contrast agents

Introduction: Acute kidney injury (AKI) is a common illness among hospitalized patients, which increases mortality and morbidity rate. Creatinine and neutrophil gelatinase-associated lipocalin (NGAL) are the most commonly conducted biomarkers of AKI. Objectives: The aim of current study was to assess NGAL as an early biomarker for AKI diagnosis following contrast agents. Patients and Methods: To follow the aim of the present case-control research, 165 individuals were entered the study; 80 patients were selected from Valiasr hospital of Zanjan city, and 85 healthy individuals were enrolled voluntarily. There were not any significant differences in sex distribution among healthy subjects. Plasma NGAL and creatinine were measured immediately before and at 12 and 72 hours post-contrast agents’ exposure. Results: There were 89 males and 76 females in the study groups. The mean age was 61.3 ± 18.2 years and 62.1 ± 17.2 years in the intervention and healthy groups, respectively. The mean of serum creatinine and NGAL level were 1.0± 0.2 mg/dL and 63.6 ±23.6 ng/mL in the control and 0.92 ± 0.23 mg/dL and 110 ± 82.3 ng/mL in the case group, respectively. There were remarkable different between serum NGAL and creatinine in the both groups. The NGAL level in the healthy and the patient group were 63.6 ± 23.6 ng/mL and 100.1 ± 121.7 ng/mL, respectively, which was considerably different between the case and control groups (P=0.01). The highest level of specificity and sensitivity were 86 and 55.5; they could be the main appropriate options for defining cut off. Conclusion: The findings showed, that NGAL level is an extremely specific and sensitive indicator for AKI diagnosis after 72 hours. Hence, this approach can open a novel insight into the AKI therapies.

Kidney targeting peptide-modified biomimetic nanoplatforms for treatment of acute kidney injury.

The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery (KMZ@FGF21) for AKI treatment. KMZ@FGF21 could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of KMZ@FGF21. The results showed that injected KMZ@FGF21 specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.

A single administration of FGF2 after renal ischemia-reperfusion injury alleviates post-injury interstitial fibrosis.

Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At an early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by ischemia-reperfusion (I/R) injury. Unilateral renal I/R with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined. Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with the I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1)-mediated inflammatory response, the inhibition of transforming growth factor beta (TGF-β1)/Smads signaling-induced epithelial-mesenchymal transition and the maintenance of peritubular capillary structure. A single dose of exogenous FGF2 administration 1 h or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI-to-CKD progression and underscored the potential of FGF-based therapy for this devastating disease.

Inhibition of sepsis-induced acute kidney injury via the circITCH-miR-579-3p-ZEB2 axis.

Circular RNAs (circRNAs) are linked to the regulation of sepsis-induced acute kidney injury (AKI). However, the function of circITCH in the development of sepsis-induced AKI is still unclear. The levels of circITCH, miR-579-3p and ZEB2 were examined by real-time PCR and immunoblotting. Then, the roles of circITCH in cell viability, apoptosis, and inflammation in lipopolysaccharide (LPS)-treated HK-2 cells were evaluated. The further mechanism was investigated using rescue assays. CircITCH was downregulated in septic AKI patients and LPS-triggered HK-2 cells. CircITCH overexpression restored cell viability in LPS-treated HK-2 cells and restrained apoptosis and inflammatory cytokine production. CircITCH negatively regulated miR-579-3p, thereby upregulating ZEB2 expression. Taken together, circITCH alleviates LPS-induced HK-2 cell injury by regulating miR-579-3p/ZEB2 signal axis, which provides a theoretical basis for AKI therapy.

Simultaneous Elimination of Reactive Oxygen Species and Activation of Nrf2 by Ultrasmall Nanoparticles to Relieve Acute Kidney Injury.

Excess reactive oxygen species (ROS) can induce serious acute kidney injury (AKI) to result in numerous deaths annually in clinical practice. Elimination of excess ROS by advanced nanotechnology is a very promising AKI therapy. In this Article, we report that PVP-stabilized and quercetin-functionalized ultrasmall Cu2-xSe nanoparticles (abbreviated as CSPQ NPs) can efficiently scavenge ROS and increase the expression of intracellular antioxidative enzymes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein, which drastically alleviates the cellular oxidative stress. Our ultrasmall nanoparticles exhibit excellent biocompatibility. They can be rapidly accumulated into the injured kidney to simultaneously eliminate ROS and activate Nrf2 to improve the renal function. This work demonstrates the great potential of simultaneous elimination of ROS and activation of intracellular Nrf2 in treatment of AKI. It also highlights the potential of CSPQ NPs in protection and prevention of AKI.

Mesenchymal Stem Cells in the Treatment of Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD) and the AKI-to-CKD Transition

ABSTRACT Acute kidney injury (AKI) and chronic kidney disease (CKD) are global health burdens that result in high economic costs to healthcare systems. AKI is a known risk factor for progression to CKD. The global absolute CKD prevalence increased by 28.2% from 2007–2017 among females and 25.4% among males. Current best clinical practice only slows the progress of renal fibrosis, the final pathological consequence of renal injury, in CKD. Kidney transplantation and dialysis are the only options for the management of kidney failure, which results in a significant burden on the health system. Hence innovative strategies are urgently needed to both prevent and treat CKD. Many studies have demonstrated that mesenchymal stem cells (MSCs) exert a therapeutic role through regenerating/repairing damaged tissues primarily through cargo secreted in extracellular vesicles. In recent years, the therapeutic effect of stem cells in the treatment of acute and chronic kidney disease have been primarily assessed in preclinical studies. This review outlines the safety and efficacy of MSCs in AKI, CKD and the AKI-to-CKD transition based on recent animal studies and clinical trials. It elucidates the antifibrotic mechanisms of MSCs and provides novel insights into MSC therapy in AKI, CKD and the transition from AKI to CKD.

CIRC_0008882 STIMULATES PDE7A TO SUPPRESS SEPTIC ACUTE KIDNEY INJURY PROGRESSION BY SPONGING MIR-155-5P.

Background: The importance of circular RNA (circRNA) in the progression of septic acute kidney injury (AKI) was gradually recognized. It has been confirmed that circ_0008882 expression was decreased in the blood of patients with AKI. However, the role of circ_0008882 in septic AKI progression remains unclear. Methods: Human kidney-2 (HK2) cells were stimulated with lipopolysaccharide (LPS) to establish a septic AKI cell model. The RNA and protein expression of circ_0008882, miR-155-5p, phosphodiesterase 7A (PDE7A), PCNA, Bax, and Bcl-2 were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability was investigated by cell counting kit-8 assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of inflammatory factors (TNF-α, IL-1β, and IL-6). Flow cytometry was implemented to evaluate cell cycle and cell apoptosis. The Caspase3 activity was examined using Caspase3 Assay Kit. Dual-luciferase reporter assay and RNA immunoprecipitation assay were applied to verify the molecular target relations. Results: Septic AKI serum samples and LPS-induced HK2 cells displayed low expression of circ_0008882 and PDE7A, and high expression of miR-155-5p when compared with the controls. Overexpression of circ_0008882 relieved LPS-induced HK2 cell injury. MiR-155-5p was a target of circ_0008882, and miR-155-5p mimic restored circ_0008882 overexpression-mediated effects on LPS-treated HK2 cells. PDE7A was identified as a target gene of miR-155-5p, and PDE7A downregulation almost reverted the improvement impacts induced by the miR-155-5p inhibitor. Conclusions: Overexpression of circ_0008882 impeded LPS-induced HK2 cell injury by modulating miR-155-5p/PDE7A pathway, implying that circ_0008882 might be a possible circRNA-targeted therapy for septic AKI.

Consulting to nephrologist when starting continuous renal replacement therapy for acute kidney injury is associated with a survival benefit.

Several studies suggest improved outcomes for patients with kidney disease who consult a nephrologist. However, it remains undetermined whether a consultation with a nephrologist is related to a survival benefit after starting continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI). Data from 2,397 patients who started CRRT due to severe AKI at Seoul National University Hospital, Korea between 2010 and 2020 were retrospectively collected. The patients were divided into two groups according to whether they underwent a nephrology consultation regarding the initiation and maintenance of CRRT. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of mortality during admission to the intensive care unit after adjusting for multiple variables. A total of 2,153 patients (89.8%) were referred to nephrologists when starting CRRT. The patients who underwent a nephrology consultation had a lower mortality rate than those who did not have a consultation (HR = 0.47 [0.40-0.56]; P < 0.001). Subsequently, patients who had nephrology consultations were divided into two groups (i.e., early and late) according to the timing of the consultation. Both patients with early and late consultation had lower mortality rates than patients without consultations, with HRs of 0.45 (0.37-0.54) and 0.51 (0.42-0.61), respectively. Consultation with a nephrologist may contribute to a survival benefit after starting CRRT for AKI.

Nanosystems for oxidative stress regulation in the anti-inflammatory therapy of acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome that results from a rapid decline in renal structure or renal functional impairment with the main pathological feature of sublethal and lethal damage to renal tubular cells. However, many potential therapeutic agents cannot achieve the desired therapeutic effect because of their poor pharmacokinetics and short retention time in the kidneys. With the recent emergence and progress of nanotechnology, nanodrugs with unique physicochemical properties could prolong circulation time, enhance efficient targeted delivery, and elevate the accumulation of therapeutics that can cross the glomerular filtration barrier and indicate comprehensive application prospects in the prevention and treatment of AKI. In this review, various types of nanosystems (such as liposomes, polymeric nanosystems, inorganic nanoparticles and cell-derived extracellular vesicles) are designed and applied to improve the pharmacokinetics of drug formation, which could further relieve the burden on the kidneys caused by the final cumulative dose of drugs in conventional treatments. Moreover, the passive or active targeting effect of nanosystems can also reduce the total therapeutic dose and off-target adverse effects on other organs. Nanodelivery systems for treating AKI that alleviate oxidative stress-induced renal cell damage and regulate the inflammatory kidney microenvironment are summarized.

Neutrophil-to-Lymphocyte ratio as a prognostic marker of mortality and disease severity in septic Acute kidney injury Patients: A retrospective study

BackgroundAcute kidney injury (AKI) is a frequent complication of sepsis associated with increased mortality and morbidity. The neutrophil-to-lymphocyte ratio (NLR) has been shown as a risk factor for septic AKI. In this study, we aimed to further evaluate NLR’s prediction value on the prognosis of septic AKI patients. MethodsSeptic AKI patients at a tertiary university-affiliated medical center were retrospectively enrolled from August 2015 to August 2021. The primary outcomes were 30-day and 90-day mortality, and secondary outcomes were disease severity, length of stay, and rehospitalization in survivors. Kaplan–Meier curves, Cox proportional hazards, cubic spline and logistics regression analyses were performed for adverse outcomes basing on NLR. The predictive value of NLR on morality was also estimated by the area under the receiver operating characteristic curve (AUROC). ResultsA total of 309 septic AKI patients were included with a mean age of 57.8 ± 18.1 years and 92 (29.8 %) being female. The 30-day mortality was 43.4 % and 90-day morality was 61.8 %. When divided by the median of NLR at hospital admission, patients in the high NLR group were associated with an increased 30-day/90-day mortality. After adjusting for multiple covariates, the predictive value of NLR remained significant for 30-day mortality (HR: 2.96, 95 % CI: 1.48–5.92, p = 0.002) and 90-day mortality (HR: 1.88, 95 % CI: 1.11–3.16, p = 0.018).NLR at admission had the highest AUROC (0.618) for 30-day mortality compared with other parameters such as white blood cell (0.573), neutrophil (0.579), lymphocyte (0.567), platelet (0.546), BUN (0.580), albumin (0.545), C-reactive protein (0.571) and procalcitonin (0.534). A similar predictive value on mortality was also observed for NLR measured at septic AKI diagnosis. For secondary outcomes, high NLR was associated with increased risk of transfer to ICU, mechanical ventilation, stage-3 AKI and renal replacement therapy, but not with length of hospital/ICU stay or long-term rehospitalization. ConclusionHigh NLR is independently associated with 30-day/90-day mortality and disease severity in septic AKI patients. NLR may serve as an economic and widely available biomarker of septic AKI prognosis.

Validation of Various Prediction Scores for Cardiac Surgery-Associated Acute Kidney Injury.

Following cardiac surgery, acute kidney injury (AKI) is a well-known complication that increases morbidity and mortality. This study was carried out to determine the factors associated with acute kidney injury and to assess the predictive value of three predictive scores for the development of AKI post-cardiac surgery in the Saudi community. In this retrospective study, the medical records of patients aged 18 years and above who underwent cardiac surgery on cardiopulmonary bypass (CPB) at Saud Albabtin Cardiac Center between January 2018 and March 2021 were reviewed. The first stage of both Kidney Disease Improving Global Outcomes (KDIGO) criteria and the risk, injury, failure, loss, end-stage (RIFLE) criteria were used to define AKI. The predicting value for acute kidney injury following cardiac surgery (AKICS score) and Renal replacement therapy for acute kidney injury (RRT-AKI) (Cleveland score, and SRI) were evaluated by area under receiver operating characteristic curve (AUROC) for the discrimination and Hosmer-Lemeshow test for the calibration. Among the 329 patients evaluated, the total postoperative incidence of acute kidney injury was 26.4%. Moreover, the incidence of RRT-AKI was 2.1%. Using multivariate logistic analysis, the factors independently associated with AKI were CABG on pump-beating heart, presence of chronic kidney disease, pre-operative anemia, prolonged bypass time, and post-operative exposure to inotropes or vasopressors. For the prediction of CSA-AKI, the discrimination of AKICS (AUROC = 0.689) was poor, while the calibration (x2 = 9.380, P = 0.311) was fair. For RRT-AKI prediction, the discrimination of Cleveland score (AUROC = 0.717) was fair while the discrimination of SRI (AUROC = 0. 681) was poor. On the other hand, the calibration for both of them was fair (Cleveland score x2 = 3.339, P = 0.342; SRI x2 = 7.326, P = 0.120). In this single-center study, SRI score demonstrated a reasonably good prediction of RRT-AKI incidence. However, further researches are required to investigate the perioperative factors in order to create a unique risk score model that may be used in a population with widespread comorbidities.

Hyperlactatemia is a predictor of mortality in patients undergoing continuous renal replacement therapy for acute kidney injury

BackgroundHyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury.MethodsA total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models.ResultsA total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22–2.20) and 4.18 (2.99–5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score).ConclusionsHyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

Mesenchymal stem cells ameliorate cisplatin-induced acute kidney injury via let-7b-5p.

Acute kidney injury (AKI) is a clinically common kidney disease. Age is an important factor that contributes to the susceptibility to AKI. Mesenchymal stem cells (MSCs) are a promising therapy for AKI, and miRNAs in exosomes (Exos) derived from MSCs are an important aspect of MSC treatment. However, the therapeutic effect of miRNA from MSC-derived Exos on AKI and the related mechanism have not been fully clarified. Whether there is a relationship between the mechanisms of senescence for AKI susceptibility and the therapeutic effect of MSCs has not been studied. We compared the degree of cisplatin-induced AKI injury in young and elderly mice and investigated changes in the expression of p53 and markers of DNA damage and apoptosis, which are important in both senescence and AKI. Ageing mice exhibited increased expression of p53 and pro-apoptosis markers. Upregulation of the senescence-associated DNA damage/p53 pathway may be an important susceptibility factor for cisplatin-induced AKI. Treatment with MSCs can reduce the degree of DNA damage and suppress p53 expression and apoptosis. Upon screening for differentially expressed miRNAs, let-7b-5p levels were found to be lower in aged mice than in young mice, and MSC treatment increased let-7b-5p levels. The presence of let-7b-5p in MSC-derived Exos alleviates tubular epithelial cell apoptosis by inhibiting p53, which reduces DNA damage and apoptosis pathway activity. Let-7b-5p downregulation may lead to increased renal AKI susceptibility, thus indicating that this miRNA is a potential driver of the MSC treatment response in AKI.

NIR-II Photoacoustic-Active DNA Origami Nanoantenna for Early Diagnosis and Smart Therapy of Acute Kidney Injury.

Herein, we designed and synthesized a novel microRNA (miR)-responsive nanoantenna capable of early diagnosis and smart treatment of acute kidney injury (AKI). The nanoantenna was made of two miniature gold nanorods (AuNRs) (e.g., length: ∼48 nm; width: ∼9 nm) linked together by a rectangular DNA origami nanostructure (rDONs) scaffold (e.g., length: ∼90 nm; width: ∼60 nm) (rDONs@AuNR dimer). The surface plasmon resonance peak of the constructed nanoantenna is located within the NIR-II window (e.g., ∼1060 nm), thus guaranteeing photoacoustic (PA) imaging of the nanoantenna in deep tissues. Intriguingly, the nanoantenna displayed exclusive kidney retention in both healthy mice and ischemia reperfusion-induced AKI mice by leveraging the kidney-targeting ability of rDONs. Distinguished from the stable signals in the healthy mice, the PA signals of the nanoantenna would turn down in the AKI mice due to the AuNR detached from rDONs upon interaction with miR-21, which were up-expressed in AKI mice. The limit of detection toward miR-21 was down to 2.8 nM, enabling diagnosis of AKI as early as 10 min post-treatment with ischemia reperfusion, around 2 orders of magnitude earlier than most established probes. Moreover, the naked rDON scaffold generated by AKI could capture more reactive oxygen species (e.g., 1.5-fold more than rDONs@AuNR dimer), alleviating ischemic AKI. This strategy provided a new avenue for early diagnosis and smart treatment of AKI.

Association of Baseline Renal Function with Mortality in Patients with Sepsis Requiring Continuous Renal Replacement Therapy for Acute Kidney Injury: A Single-Center Retrospective Study

Introduction: To date, the prognosis of patients with sepsis and underlying chronic kidney disease (CKD) had been poor. However, the impact of preseptic renal function on the short-term prognosis of patients with extremely severe septic shock with acute kidney injury (AKI) that requires renal replacement therapy (RRT) is unclear. Methods: Of the septic shock cases treated at the intensive care unit for ≥48 h, 131 adults who were diagnosed as septic AKI and underwent continuous venovenous hemodiafiltration were retrospectively analyzed. The relationships of demographic, clinical, and laboratory data with mortality were evaluated, and the independent risk factors for death were identified. Results: The median age of the subjects was 73 (range, 63–80) years, and 76 (58%) were men. The rate of mortality was significantly higher among patients with CKD (n = 42) than in those without CKD (n = 89) (43% vs. 22%, p < 0.016). On univariate and multivariate logistic regression analyses, the associated factors and independent predictors of death were Sequential Organ Failure Assessment score (odds ratios [ORs] 1.151, 95% confidence intervals [CIs] 1.026–1.293, p = 0.017, and OR 1.129, 95% CI 1.003–1.271, respectively); baseline estimated glomerular filtration rate (OR 0.986, 95% CI 0.975–0.997, p = 0.016, and OR 0.983, 95% CI 0.970–0.996, respectively); and lactic acid (OR 1.094, 95% CI 1.005–1.190, p = 0.038, and OR 1.110 CI 1.015–1.215, respectively). Conclusion: Reduced baseline renal function may be a factor for poor short-term prognosis in severe septic AKI cases requiring RRT.

Calorie Restriction Provides Kidney Ischemic Tolerance in Senescence-Accelerated OXYS Rats

Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR.