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Introduction: Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms., Methods: We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin., Results: In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments., Conclusion: Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Furosemide, a frequently prescribed diuretic for managing congestive heart failure and edema, remains a topic of debate regarding its potential risk of inducing acute kidney injury (AKI) in patients. Consequently, this study aims to examine the occurrence of hospital-acquired AKI (HA-AKI) in hospitalized patients who are administered furosemide and to investigate potential risk factors associated with this outcome., Methods: This study encompassed a cohort of 22374 hospitalized patients who either received furosemide treatment or not from June 1, 2012, to December 31, 2017. Propensity score matching was employed to establish comparability between the two groups regarding covariates. Subsequently, a nomogram was constructed to predict the probability of AKI occurrence among patients who underwent furosemide treatment., Results: The regression analysis identified the single-day total dose of furosemide as the most significant factor for AKI, followed by ICU administration, estimated glomerular filtration rate, antibiotic, statin, NSAIDs, β-blockers, proton pump inhibitor, chronic kidney disease, and 7 other indicators. Subgroup analysis revealed a synergistic effect of furosemide with surgical operation, previous treatment with β-blockers, ACEI/ARB and antibiotics, leading to an increased risk of AKI when used in combination. Subsequently, a visually represented prognostic nomogram was developed to predict AKI occurrence in furosemide users. The predictive accuracy of the nomogram was assessed through calibration analyses, demonstrating an excellent agreement between the nomogram predictions and the actual likelihood of AKI, with a probability of 77.40%., Conclusions: Careful consideration of factors such as dosage, concurrent medication use, and renal function of the patient is necessary for clinical practice when using furosemide. Our practical prognostic model for HA-AKI associated with furosemide use can be utilized to assist clinicians in making informed decisions about patient care and treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.

Background: Acute kidney injury (AKI) is a common and serious complication of sepsis. MicroRNA-22-3p (miR-22-3p) has been found to be involved in septic AKI progression. The purpose of this study was to analyze both the serum and urinary expression of miR-22-3p in septic AKI patients, and evaluated the clinical value of miR-22-3p in the diagnosis and prognosis of sepsis-induced AKI., Methods: Serum and urinary expression of miR-22-3p was examined using qRT-PCR. The risk factors related with septic AKI onset were assessed using logistic analysis. A receiver-operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of miR-22-3p, and the Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the predictive value of miR-22-3p for the 28-day survival of septic AKI patients., Results: Both serum and urinary miR-22-3p expression was decreased and negatively correlated with kidney injury biomarkers in septic AKI patients. MiR-22-3p expression was a risk factor for AKI onset and had diagnostic accuracy in septic AKI patients. The expression of both serum and urinary miR-22-3p was lower in patients who died, and served as a prognostic biomarker to predict 28-day survival in septic AKI patients., Conclusion: Serum and urinary miR-22-3p was reduced in sepsis-induced AKI patients, and served as a biomarker to predict AKI occurrence and 28-day survival in sepsis patients., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Objective: Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI)., Methods: AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI., Results: Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively., Conclusion: SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

Objective: The aim of the study was to establish a predictive postoperative nomogram for acute kidney injury (AKI) after intracranial aneurysm clipping surgery, in order to early identify patients with high postoperative AKI risk., Methods: This is a retrospective study, which included patients who underwent intracranial aneurysm clipping surgery. Multivariate logistic regression was employed to select confound factors that associated with AKI, then incorporated into the nomogram. The predictive accuracy of the model was assessed by concordance index (C-Index)., Results: A total of 365 patients after intracranial aneurysm clipping surgery were enrolled in the study eventually, of which 68 (18.63%) suffered postoperative AKI, and the incidence of stage 1, stage 2 and stage 3 were 92.65% (63/68), 5.88% (4/68), and 1.47% (1/68), respectively. Univariate logistic regression revealed that high density lipoprotein (HDL), prothrombin time (PT), estimated glomerular filtration rate (eGFR), size of aneurysm ≥10 mm, and aneurysm ruptured before surgery were associated with AKI after surgery, while multivariate logistic regression showed same results as the size of aneurysm ≥10 mm and aneurysm ruptured were independent AKI risk factors. In addition, the nomogram demonstrated a good accuracy in estimating intracranial aneurysm clipping associated AKI, as a C-Index and a bootstrap-corrected one of 0.772 and 0.737, respectively. Moreover, calibration plots showed consistency with the actual presence of AKI., Conclusion: The novel nomogram model can serve as a promising predictive tool to improve the identification of AKI among those who underwent intracranial aneurysm clipping surgery.

Background: We aimed to develop a nomogram based on preprocedural features for early prediction of acute kidney injury (AKI) and to assess the prognosis in patients after radical and partial nephrectomy., Methods: The study included a development cohort of 1111 patients who were treated between June 2012 and June 2017 and an additional validation cohort of 356 patients who were treated between July 2017 and June 2018. Stepwise regression and logistic regression analyses were used to evaluate the association between predictors and AKI. Incorporating all independent predictors, a nomogram for postoperative AKI was developed and externally validated. Patients were followed up for 5 years to assess renal function, acute kidney disease (AKD), chronic kidney disease (CKD), hospital readmission and mortality were key prognosis we focused on., Results: After multivariate logistic regression, radical nephrectomy (odds ratio (OR) = 3.57, p < 0.001), aspirin (OR = 1.79, p = 0.008), systolic blood pressure (OR = 1.41, p = 0.004), triglyceride (OR = 1.26, p = 0.024), and alkaline phosphatase (OR = 1.75, p = 0.034) were independent risk factors for postoperative AKI, while albumin (OR = 0.72, p = 0.031) was a protective factor for postoperative AKI. Patients with a higher estimated glomerular filtration rate (eGFR) (60-90 ml/min/1.73 m 2 , OR = 0.41, p = 0.004; ≥ 90 ml/min/1.73 m 2 , OR = 0.37, p < 0.001) were less prone to AKI than those with a lower eGFR (< 15 ml/min/1.73 m 2 ). These predictors were all included in the final nomogram. The area under the receiver operating characteristics curve for the model were 0.77 (p < 0.001) in the development cohort and 0.72 (p < 0.001) in the validation cohort. The incidence of AKD and CKD were 27.12 and 18.64% in AKI group, which were much higher than those in no AKI group (p < 0.001)., Conclusions: The nomogram had excellent predictive ability and might have significant clinical implications for the early detection of AKI in patients undergoing nephrectomy.

Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.

Objective: Cardiac surgery-associated acute kidney injury (CSA-AKI), one of the most severe complications in patients with cardiac surgery, is associated with considerable morbidity, mortality and high costs thus placing a heavy burden to society. Therefore, we aimed to build a predictive model based on preoperative features in order to early recognize and intervene for patients with high risk of CSA-AKI., Methods: In this retrospective cohort study, baseline perioperative hospitalization information of patients who underwent cardiac surgery from October 2012 to October 2017 were screened. After multivariate logistic regression, identified independent predictive factors associated with CSA-AKI were incorporated into the nomogram and the discriminative ability and predictive accuracy of the model was assessed by concordance index (C-Index). Additionally, internal validation was performed by using bootstrapping technology with 1000 resamples to reduce the over-fit bias., Results: In all 4395 patients with cardiac surgery October 2012-October 2017, no patients were excluded for the continuous renal replacement therapy (CRRT) before surgery while 2495 patients were excluded due to only one or less than one Scr assay post-surgery. In the end, a total of 1900 patients were enrolled in the study, of which 698 patients (74.89%) developed AKI stage 1, 158 (16.96%) AKI stage 2 and 76 (8.15%) AKI stage 3. After multivariate logistic regression, age, perioperative estimated glomerular filtration rate (eGFR), lactate dehydrogenase (LDH), prothrombin time (PT), with a history of surgery, transfusion, cardiac arrhythmia, coronary heart disease (CHD), or chronic kidney disease (CKD), using calcium channel blocker (CCB), proton pump inhibitors (PPI), non-steroidal anti-inflammatory drugs (NSAID), antibiotic or statin before surgery were predictive factors of CSA-AKI. In addition, the nomogram demonstrated a good accuracy in estimating CSA-AKI, with an C-Index and a bootstrap-corrected one of 0.796 (SD = 0.018, 95% CI 0.795-0.797) and 0.789 (SD = 0.015, 95% CI 0.788-0.790), respectively. Moreover, calibration plots showed an optimal consistency with the actual presence of CSA-AKI., Conclusion: The novel predictive nomogram achieved a good preoperative prediction of CSA-AKI within the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Though the model, the risk of an individual patient with "subclinical AKI" undergoing cardiac surgery could be determined earlier and such application was helpful for timely intervention in order to improve patient's prognosis.

Introduction: Nicotiflorin is the main characteristic component of Nymphaea candida, which is a natural product that reportedly ameliorates acute injury of the liver and cerebral cortex, but the effect of nicotiflorin on acute kidney injury (AKI) remains unknown. This study aimed to investigate the effects of nicotiflorin on ischaemia/reperfusion (I/R) AKI and the associated mechanisms. Methods: We performed both (a) in vivo experiments with C57BL/6 mice with bilateral renal pedicles clamped for 45 minutes and (b) in vitro experiments with human kidney epithelial cells (HK‐2) exposed to hypoxia/reoxygenation to mimic I/R injury to study the role of nicotiflorin in AKI. Results: In vivo, nicotiflorin administration exerted protective effects on renal injury, as demonstrated by reductions in the levels of caspase3 and Bad (P <.05), the upregulation of Bcl‐2 expression (P <.05) and improved renal histologic changes, which suggested that nicotiflorin can alleviate I/R injury and cell apoptosis. In vitro, nicotiflorin at a concentration of 75 μg/mL protected cells from hypoxia, which further confirmed that nicotiflorin exerts beneficial effects on hypoxia/reoxygenation. Through computational molecular docking, we found that activating transcription factor 3 (ATF3) exhibits a robust interaction with nicotiflorin with a simulated binding energy of −9.2°. We verified the interaction of nicotiflorin with ATF3 in HK‐2 cells, and found that nicotiflorin reduced the apoptosis of HK‐2 through ATF3. Conclusion: Based on the above‐described results, nicotiflorin appears to have a beneficial impact on deteriorated renal function, as demonstrated using an experimental I/R model. The underlying mechanisms of nicotiflorin might inhibit HK‐2 cell apoptosis through ATF3. SUMMARY AT A GLANCE: The study suggests that nicotiflorin, the component from a Chinese herb, has protective effect in a mouse model of renal ischaemia/reperfusion injury. By using computational molecular docking analysis and RNA silencing, the authors identified that nicotiflorin ameliorates renal cell apoptosis via activation of transcription factor 3 (ATF3). [ABSTRACT FROM AUTHOR]

Aim: Studies have shown that cysteine‐rich protein 61 (Cyr61) increased in the post‐ischemic human kidney tissue. However, it is still unknown whether Cyr61 can be used as a biomarker in kidney ischemia/reperfusion (I/R) injury. Methods: Microarray data were collected from GSE58438 and GSE52004. The rat I/R model was established to evaluate the messenger RNA and protein expression of Cyr61, localization of Cyr61 by immunohistochemical and immunofluorescence staining, and changes in serum creatinine (Scr) at the same time. Results: Bioinformatics result showed that Cyr61 was significantly increased at 3 h after I/R in rat kidney, and involved in angiogene, positive regulation of locomotion and single organism cell adhesion. The rat I/R model results showed that Cyr61 was mainly expressed in renal tubular epithelial cells with I/R injury and the expression of Cyr61 was up‐regulated at I/R 1 h, peaked at 4–8 h and began to decay at 12 h. The area under curve of receiver operating characteristics of kidney tissue Cyr61 messenger RNA and urine Cyr61 were 90.2% and 86.1%, which all better than Scr 67.1% (P < 0.05). Conclusion: We made a preliminary investigation of the relationship between Cyr61 and AKI, which identifies that Cyr61 may replace Scr as an ultra‐early new biomarker in AKI. SUMMARY AT A GLANCE: Although Cystatin C (CysC) was recommended by some authors to be measured in addition to creatinine in glomerular filtration rate estimation, it has found its place in early detection of acute kidney injury after ischaemia/reperfusion injury in rat kidney. [ABSTRACT FROM AUTHOR]