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Introduction: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI., Methods: A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN., Results: Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81)., Conclusion: The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452257, identifier CRD42023452257., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Liu, Huang, Wu, Tsai, Hung, Chen and Feng.)

Objective: To investigate the role and mechanism of trimethylamine N-oxide (TMAO), a uremic toxin, in renal fibrosis., Methods: A total of 20 male BALB/c mice were randomly and evenly assigned to a Control group and a TMAO group. Mice in the Control group received intraperitoneal injection of normal saline, while mice in the TMAO group received intraperitoneal injection of TMAO (20 mg/[kg·d]). The injection was given once a day for 8 weeks. Histopathology and fibrosis of kidney were observed by H&E staining and Masson staining. Immunohistochemistry was performed to determine the levels of alpha smooth muscle actin (α-SMA), recombinant human fibronectin fragment (Fibronectin), and sterol-regulatory element binding protein 1 (SREBP1). Western blot was performed to determine α-SMA, SREBP1, phosphatidylinositol 3 kinase (PI3K), phospho-phosphatidylinositol 3 kinase (p-PI3K), protein kinase B (PKB, also known as AKT), and phospho-AKT (p-AKT) protein levels. HK2 cells were treated with SREBP 1 small interfering RNA (siRNA) and PI3K/AKT inhibitor, respectively, and the reversal of the effects of TMAO was examined., Results: Animal experiments showed that, compared with the Control group, the mice treated with TMAO experienced pathological damage and fibrosis of the kidney tissue and the expression levels of fibrosis markers, α-SMA and Fibronectin, in the kidney were increased (all P <0.05). According to the findings from further investigation, the TMAO-treatment group showed increased expression of SREBP1 and an up-regulation of PI3K phosphorylation ratio and AKT phosphorylation ratio compared with those of the Control group (all P <0.05). Cell experiments produced results similar to those of the animal experiment. After siRNA interference with SREBP1 expression, the expression levels of fibrosis marker proteins decreased ( P <0.05). Besides, the high expression of SREBP1 caused by TMAO was inhibited after HK2 cells were incubated with LY294002, a PI3K-AKT pathway inhibitor ( P <0.05)., Conclusion: TMAO may induce renal fibrosis by promoting the PI3K/AKT/SREBP1 pathway., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2023《四川大学学报（医学版）》编辑部 版权所有Copyright ©2023 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Adriamycin (ADR) nephropathy is the most widely used nephropathy model to study the pathophysiological mechanisms of chronic kidney disease (CKD) in mice. However, its application is limited to a few mouse strains such as the BALB/c strain; the standard strain, C57BL/6J (B6J), does not develop ADR nephropathy. Nevertheless, Arif et al. reported that C57BL/6N (B6N), another standard strain, is ADR-susceptible. Since then, no follow-up reports or other studies have been published on ADR nephropathy in B6N mice. Therefore, the goal of this study was to determine whether B6N mice are indeed susceptible to ADR nephropathy and whether there are differences in ADR susceptibility among the substrains of C57BL/6NCrl (NCrl) and C57BL/6NJcl (NJcl). NCrl mice showed marked albuminuria and mesangial cell proliferation, which are associated with mild ADR nephropathy, confirming that NCrl mice were susceptible to ADR nephropathy. On the other hand, NJcl mice did not exhibit these symptoms. ADR nephropathy models are usually generated by administering ADR through the tail vein, but Arif et al. administered ADR through the orbital vein. Therefore, we investigated the effect of the route of administration on ADR nephropathy. The degree of ADR nephropathy was found to vary based on the route of administration: more severe nephropathy was observed upon administration through the tail vein than through the orbital vein. Therefore, we conclude that NCrl mice are susceptible to ADR nephropathy, and the severity of ADR-induced nephropathy through orbital vein administration is relatively lower than that through the tail vein.

Podocyte injury is the common initiating event in focal segmental glomerulosclerosis (FSGS). Oxidative stress and inflammation mediate podocyte injury in FSGS. NRF2 pathway regulates the constitutive and inducible transcription of various genes that encode antioxidant proteins and anti-inflammatory proteins and have pivotal roles in the defense against cellular oxidative stress. In this study, we used adriamycin-induced nephropathy (ADR) in mice as a model of FSGS to confirm that CDDO-Me treatment ameliorated adriamycin-induced kidney damage by improving renal function and kidney histology. CDDO-Me inhibited the level of oxidative stress, inflammation, and apoptosis in adriamycin-induced podocyte injury by activating NRF2 pathway in vivo and in vitro. Furthermore, CDDO-Me stabled the cytoskeleton by regulating NRF2/srGAP2a pathway. Together, these findings show that by activating NRF2 pathway, CDDO-Me could be a therapeutic strategy to prevent the adverse effects of adriamycin-induced podocyte injury., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: We aimed to investigate the risk factors of colistin-associated nephrotoxicity in patients older than 65 years treated in the palliative care unit., Methods: 119 palliative care patients who received intravenous colistimethate for at least 7 days were included in the study. The estimated glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Data were obtained from the hospital information system., Results: The mean age of the participants was 76.7 ± 9.9 years and 49.4% were female. Of the 119 patients, 57 had colistin-induced nephropathy (CIN) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The rate of CIN was higher in women than in men. The baseline phosphate level was higher in the CIN (+) group than in the CIN (-) group. The lower GFR values in patients with pneumonia persisted at days 14 and 30, whereas the lower GFR in patients without pneumonia did not. According to multivariate logistic regression, female gender and baseline phosphate level ≥ 4.5 mg/dl were found as independent variables for the development of nephropathy., Conclusions: The creatinine levels of the patients with pneumonia and CIN did not improve after nephrotoxicity, whereas the creatinine levels of the other patients without pneumonia and CIN did. Female gender and baseline phosphate were independent risk factors for CIN. Prolonged kidney failure may lead to a more difficult clinical follow-up process for clinicians. Therefore, clinicians should be aware of persistent renal insufficiency in older patients with pneumonia receiving colistimethate.

Cadmium (Cd) exposure induces kidney damage by mediating oxidative stress and inflammation. In this study, the role of Crassocephalum rubens -gold nanoparticles ( C. rubens -AuNPs) in down-regulating kidney injury molecules-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) genes and inhibiting oxidative stress in Cd-induced kidney damage in rats was investigated. Thirty male Wistar rats were distributed randomly into six groups ( n  = 5). Group I served as control, while groups II, III, IV, and V rats were administered with 20 mg/kg b.w. cadmium chloride (CdCl 2 ) for five consecutive days. Groups III, IV, and V rats were treated, 24 h after the last dose of CdCl 2 , with silymarin, 5 mg/kg and 10 mg/kg C. rubens -AuNPs, respectively, for 14 days. Group VI rats received 10 mg/kg C. rubens -AuNPs only for 14 days. Animals were sacrificed 24 h after the last dose of the treatment. Biochemical parameters such as kidney function markers, biomarkers of nephrotoxicity, and oxidative stress markers were assayed. Results indicated that 20 mg/kg b.w. CdCl 2 caused kidney damage, as evidenced by significant ( p  < 0.05) increase in the levels of serum urea and creatinine, malondialdehyde, reduced level of superoxide dismutase (SOD), and increased mRNA expression of the kidney injury biomarkers (KIM-1 and NGAL genes), when compared with the control. However, these changes were attenuated by both doses of C. rubens -AuNPs when compared with Cd-induced nephrotoxic rats. It can be suggested that C. rubens -AuNPs have the potential to ameliorate kidney damage induced by Cd via oxidative stress inhibition and down-regulation of KIM-1/NGAL genes.

Background: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) has been shown to improve renal outcomes in both diabetic and non-diabetic kidney disease. However, the effect of SGLT2i on renal outcomes in patients with non-diabetic obesity is still not established., Materials and Methods: In this double-blind, randomized controlled trial, we assigned non-diabetic patients with body mass index (BMI) ≥ 25 kg/m 2 , persistent 24-hour urine albumin-creatinine ratio (UACR) ≥ 10 mg/gCr, and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 , who had been treated with renin-angiotensin system blockade, to canagliflozin 100 mg daily or placebo for 24 weeks. The reduction in UACR and eGFR at 12 and 24 weeks were explored. (Thai Clinical Trials Registry 20190203003)., Results: Of 247 non-diabetic obese patients screened, 32 patients met inclusion criteria and underwent randomization. The median baseline of UACR was 69.1 mg/gCr. There were no statistically significant differences in albuminuria reduction between the groups at 12 weeks and 24 weeks. The estimated GFR in the canagliflozin group decreased significantly from baseline at 12 weeks (-5.39 mL/min/1.73m 2 ; 95% CI -9.81 to -0.97; p = 0.017) but not at 24 weeks (-1.16 mL/min/1.73m 2 ; 95% CI -5.58 to 3.26; p = 0.66), and there was no significant change from baseline in the placebo group at both 12 and 24 weeks., Conclusion: Canagliflozin 100 mg daily was well tolerated but did not significantly reduce UACR in non-diabetic obese patients with microalbuminuria. However, a significant temporary decline in eGFR might reflect a subtle reduction in glomerular hyperfiltration.

Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment., Competing Interests: Declaration of competing interest The authors declare no relationships with industry and no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lead is one of the cursed substances that threaten all human life. Lead poisoning can occur through food or water contaminations and it is hard to be detected. This incognito metal accumulates over time and resides in the liver, kidneys, and brain tissues leading to serious medical conditions, affecting organ functions, causing failure, kidney tubule degeneration, and destroying neuronal development. However, known metal chelators have bad negative effects. Asparagus officinalis (AO) is a promising herb; its root extract exhibited antioxidant, antiapoptotic, protective, and immunomodulatory activities. Inspired by those reasons, this study investigated to which extent Asparagus extract affected male mice's renal toxicity caused by lead acetate (LA) and antioxidant defense system. This work screened for its nephroprotective activity in four mouse groups: negative and positive control, LA group with renal injury, and diseased but pretreated mice with AO extract (AOE). Kidney index and kidney function biomarkers were evaluated. Antioxidant activities, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), nitric oxide (NO), and reduced glutathione (GSH) were also tested. Furthermore, inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)), inducible nitric oxide synthase (iNOS), renal pro-apoptotic protein (Bax), antiapoptotic protein (Bcl-2), and caspase-3 levels were evaluated. The results showed that LA administration induced oxidative stress, renal inflammation, apoptosis, and renal histopathological alteration. However, due to its antioxidant activities, AOE was found to restrain oxidative stress, therefore preventing inflammation and apoptosis. Collectively, AOE perfectly clogged lead poisoning sneaking, stopped the bad deterioration, and succeeded to protect kidney tissues from toxicity, inflammation, and apoptosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Contrast Induced Nephropathy (CIN) is a major complication of angiographic procedures. Primary percutaneous coronary intervention (pPCI) is the preferred treatment for ST-segment elevation myocardial infarction (STEMI) but is associated with a risk of CIN. Oxidative stress and free radical damage play a role in the pathogenesis of CIN. Bilirubin has anti-inflammatory and antioxidant activity and has been shown to have a protective effect on endothelial cells. The present study aimed to assess the association between serum bilirubin level and development of CIN after pPCI. Sequential STEMI patients (n = 595) who underwent pPCI between January 2021 and December 2022 were enrolled. Among the participants, 116 (19.5%) developed CIN. Serum total bilirubin level was significantly lower in the CIN group ( P = .001). In multivariate logistic regression analysis, serum bilirubin level was found as an independent predictor of CIN. Age, gender, contrast volume, and white blood cell count were other independent predictors of CIN. A higher serum bilirubin level is associated with a lower risk of CIN in the present study. In STEMI patients undergoing pPCI, serum bilirubin level may be helpful to predict the risk of CIN and may help ensure early initiation of preventive treatment and careful follow-up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are well-known to promote hepatotoxicity and nephrotoxicity in vivo, which may be counteracted by natural compounds like fermented whey (FW). Carbamoyl phosphate synthetase 1 (CPS1) and kidney injury molecule 1 (KIM-1) are typical biomarkers used to detect liver and kidney damage, respectively. Thus, RT-qPCR and droplet digital PCR (ddPCR) analysis were performed to assess the potential beneficial effect of FW against AFB1 and OTA hepatotoxicity and nephrotoxicity in male and female Wistar rats by analyzing the altered gene expression of hepatic CPS1 and renal KIM-1 after 28 days of oral exposure. In male livers, the most damaging treatment was AFB1 by reducing CPS1 expression, which was totally reversed by FW-administration. This bioactive compound also improved gene expression changes induced by OTA and mycotoxins mixture. In female livers, a significant CPS1 overexpression was observed for each exposure performed, in which FW-supplementation reported no remarkable differences compared with mycotoxins exposure. Conversely, in the kidneys of male and female rats, exposure to mycotoxins promoted renal damage by altering KIM-1 gene expression, being OTA-exposure the most harmful condition. In both sexes, ddPCR analysis demonstrated that FW-addition modulated mycotoxins induced KIM-1 gene expression changes, thus reducing kidney damage. In this organ, sex-related responses were not clearly observed. Therefore, these findings confirmed that AFB1 and OTA-promoted hepatotoxicity and nephrotoxicity in vivo , which could be modulated by dietary FW supplementation.

Ethnopharmacological Relevance: The nephrotoxicity and carcinogenicity induced by traditional Chinese medicines (TCMs) containing aristolochic acids (AAs) and related compound preparations have greatly limited their clinical application. While the toxicity of AA-I and AA-II is relatively clear, there are marked differences in the toxic effects of different types of aristolochic acid analogues (AAAs). Thus, the toxicity of TCMs containing AAAs cannot be evaluated based on the toxicity of a single compound., Aim of the Study: To systematically investigate the toxicity induced by Zhushalian (ZSL), Madouling (MDL) and Tianxianteng (TXT) as representative TCMs derived from Aristolochia., Materials and Methods: AAA contents in ZSL, MDL and TXT were determined using HPLC. Subsequently, mice were treated for 2 weeks with high (H) and low (L) dosages of TCMs containing total AAA contents of 3 mg/kg and 1.5 mg/kg, respectively. Toxicity was evaluated using biochemical and pathological examination and was based on organ indices. Correlations between AAA contents and induced toxicity were analysed using multiple methods., Results: Of the total AAA content, ZSL contained mainly AA-I and AA-II (>90%, of which AA-I accounted for 49.55%). AA-I accounted for 35.45% in MDL. TXT mainly contained AA-IVa (76.84%) and other AAAs accounted for <10%. Short-term toxicity tests indicated that ZSL and high-dose MDL induced obvious renal interstitial fibrosis and gastric injury, whereas TXT (high and low dosages) caused only slight toxicity. Correlation analysis suggested that AA-I might be the critical hazard factor for toxicity., Conclusions: The toxicity of TCMs containing AAAs cannot be generalised. The toxicity of TXT is relatively low compared with those of ZSL and MDL. The toxicity of Aristolochia depends mainly on the AA-I content; therefore, control of AA-I levels in TCMs and related compound preparations is required to reduce the risk of toxicity associated with the use of Aristolochia herbs in clinical settings., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest, (Copyright © 2023 Elsevier B.V. All rights reserved.)

The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients. Patients with thoracic cancer requiring DM pharmacotherapy, who received CDDP (≥ 60 mg/m 2 )-containing regimens using the short hydration method (n = 140), were enrolled in this retrospective multicenter observational study. The primary endpoint of the present study was the elucidation of risk factors (patient factors, DM medication influence, and treatment-related factors) associated with CIN development in patients with DM. Cisplatin-induced nephrotoxicity occurred in 22.1% of patients with DM. The median worst variation of serum creatinine levels and creatinine clearance (worst level - baseline level) was 0.16 mg/dL (range: - 0.12-1.41 mg/dL) and - 15.9 mL/min (- 85.5-24.3 mL/min), respectively. Multivariate logistic regression analyses identified female sex as the singular risk factor for CIN development in the DM population (adjusted odds ratio; 2.87, 95% confidence interval; 1.08-7.67, P = 0.04). Diabetes mellitus medication and treatment-related factors did not affect CIN development. In conclusion, our study revealed that female sex is significantly associated with CIN development in patients with DM and thoracic cancer., (© 2023. Springer Nature Limited.)

Background: The contrast-induced nephropathy (CIN) is a common complication of primary percutaneous coronary intervention (PCI) it has been reported to be associated with an increased risk of mortality. The study reported the in-hospital mortality among patients who developed CIN after primary PCI., Methods: This descriptive cross-sectional study was conducted on a sample of consecutive who developed CIN after primary PCI at a tertiary care cardiac hospital in Karachi, Pakistan. The CIN was defined as either a relative increase of 25% or an absolute increase of 0.5 mg/dL in post -procedure serum creatinine within 72 hours. The in-hospital mortality status was recorded and clinical and demographic predictors of in-hospital mortality were identified with the help of binary logistic regression analysis., Results: In the study sample of 402 patients, 74.1% (298) were male and the mean age of the study sample was 59.4±11.5 years. The in-hospital mortality rate was 9.7% (39). On multivar iable analysis, an increased risk of mortality was found to be independently associated with inferior wall myocardial infarction (IWMI) with right ventricular (RV) infarction, intra-procedure arrhythmias, and pump failure with an adjusted odds ratio of 3.63 [95% CI: 1.31-10.08; p=0.013], 5.53 [95% CI: 1.39-22.06; p=0.015], and 8.94 [95% CI: 3.99-20.02; p<0.001], respectively., Conclusions: In conclusion, there is a high rate of mortality for patients who develop CIN after primary PCI, and the risk of mortality is further aggravated by the presence of IWMI with RV infarction, intra-procedure arrhythmias, and pump failure.

Background: Contrast induced nephropathy (CIN) is one of the feared complications of contrast medium-using procedures. Present study was conducted in order to evaluate the value of systemic inflammatory-response index (SIRI) for development of CIN among patients who underwent primary percutaneous intervention., Methods: Six hundred seventy-six patients with the diagnosis of ST elevation myocardial infarction were included. The patients were divided into two groups according to the presence of CIN. Patients without ( n  = 530) and with ( n  = 146) CIN constituted group 0 and group 1, respectively. Clinical and biochemical features of the patients were recorded. Calculation of SIRI was made for each patient., Result: CIN patients were older, had higher prevalence of hyperlipidaemia, higher values of pre- and post-procedural creatinine levels, neutrophil and monocyte counts, neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) and SIRI. They had lower values of left ventricular ejection fraction (LVEF), haemoglobin and high-density lipoprotein-cholesterol levels. SIRI had the highest area under the curve (AUC) for prediction of CIN. Pairwise analyses of the AUC's demonstrated that SIRI had statistically significantly higher AUC compared to NLR and MLR. Multivariate logistic regression analysis showed that besides from LVEF and pre-procedural creatinine, NLR and SIRI were the independent predictors of CIN. SIRI had a higher odds ratio compared to NLR., Conclusion: SIRI had greater diagnostic power than NLR and MLR and it can easily be used by physicians for the identification of high-risk patients for the occurrence of CIN.

Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients with coronary artery disease undergoing elective percutaneous coronary intervention(PCI). We developed a machine learning-based risk stratification model to predict contrast-induced nephropathy after PCI. A study retrospectively enrolling 240 patients eligible for PCI from December 2017 to May 2020 was performed. CIN was defined as a rise in serum creatinine levels ≥0.5 mg/dL or ≥25% from baseline within 72 h after surgery. Eight machine learning methods were performed based on clinical variables. Shapley Additive exPlanation values were also used to interpret the best-performing prediction models. Development of CIN was found in 37 patients(16.5%) after PCI. There were 11 significant predictors of CIN, including uric acid, peripheral vascular disease, cystatin C, creatine kinase-MB, haemoglobin, N-terminal pro-brain natriuretic peptide, age, diabetes, systemic immune-inflammatory index, total protein, and low-density lipoprotein. Regarding the efficacy of the machine learning model that accurately predicted CIN, SVM exhibited the most outstanding AUC value of 0.784. The SHAP and radar plots were used to illustrate the positive and negative effects of the 11 features attributed to the SVM. Machine learning models have the potential to identify the risk of CIN for elective PCI patients.

Purpose: Tumors can be visualized using 5-Aminolevulinic acid hydrochloride (5-ALA) during transurethral resection of bladder tumors (TURBT). Hypotension is an adverse effect of 5-ALA; however, its incidence and morbidity rates are unknown. This study aimed to describe the incidence of perioperative hypotension and identify risk factors for hypotension among patients after 5-ALA administration in TURBT., Methods: This retrospective multicenter cohort study was conducted at three general hospitals in Japan. Adult patients who underwent elective TURBT after 5-ALA administration between April 2018 and August 2020 were included. The primary outcome was the incidence of perioperative hypotension (mean blood pressure < 65 mmHg). The secondary outcomes were the use of vasoactive agents and adverse events, including urgent intensive care unit (ICU) admission. Multivariate logistic regression analysis was performed to investigate risk factors of the incidence of intraoperative hypotension., Results: The median age of 261 patients was 73 years. General anesthesia was induced in 252 patients. The intraoperative hypotension was observed in 246 (94.3%) patients. Three patients (1.1%) were urgently admitted to the ICU for continued vasoactive agent use after surgery. All three patients had renal dysfunction. Multivariate logistic regression analysis revealed that general anesthesia was significantly associated with intraoperative hypotension (adjusted odds ratio, 17.94; 95% confidence interval, 3.21-100.81)., Conclusion: The incidence of hypotension in patients undergoing TURBT after 5-ALA administration was 94.3%. The incidence of urgent ICU admission with prolonged hypotension was 1.1% in all patients with renal dysfunction. General anesthesia was significantly associated with intraoperative hypotension., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Epithelial-mesenchymal transition (EMT) plays a critical role in hypertension-induced renal fibrosis, a final pathway that leads to end-stage renal failure. C-Atrial natriuretic peptide (ANP) 4-23 , a specific agonist of natriuretic peptide receptor-C (NPR-C), has been reported to have protective effects against hypertension. However, the role of C-ANP 4-23 in hypertension-associated renal fibrosis has not yet been elucidated. In this study, mice were randomly divided into SHAM group, DOCA-salt group and DOCA-salt + C-ANP 4-23 group. Renal morphology changes, renal function and fibrosis were detected. Human proximal tubular epithelial cells (HK2) stimulated by aldosterone were used for cell function and mechanism study. The DOCA-salt treated mice exhibited hypertension, kidney fibrosis and renal dysfunction, which were attenuated by C-ANP 4-23 . Moreover, C-ANP 4-23 inhibited DOCA-salt treatment-induced renal EMT as evidenced by decrease of the mesenchymal marker alpha-smooth muscle actin (ACTA2) and vimentin and increase of epithelial cell marker E-cadherin. In HK2 cells, aldosterone induced EMT response, which was also suppressed by C-ANP 4-23 . The key transcription factors (twist, snail, slug and ZEB1) involved in EMT were increased in the kidney of DOCA-salt-treated mice, which were also suppressed by C-ANP 4-23 . Mechanistically, C-ANP 4-23 inhibited the aldosterone-induced translocation of MR from cytosol to nucleus without change of MR expression. Furthermore, C-ANP 4-23 rescued the enhanced expression of NADPH oxidase (NOX) 4 and oxidative stress after aldosterone stimulation. Aldosterone-induced Akt and Erk1/2 activation was also suppressed by C-ANP 4-23 . Our data suggest that C-ANP 4-23 attenuates renal fibrosis, likely through inhibition of MR activation, enhanced oxidative stress and Akt and Erk1/2 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Promising results with the CHA 2 DS 2 -VASc risk score (CVRS) have been reported for the prediction of contrast-induced nephropathy (CIN). The aim of this study is to consolidate all the data available and examine the association between elevated CVRS and the incidence of CIN in patients undergoing percutaneous coronary intervention (PCI)., Methods: We systematically searched PubMed, Embase, and Scopus for abstracts and full-text articles from inception to May 2022. Studies were included if they evaluated the association between a high CVRS and the incidence of CIN in patients undergoing PCI. Data were integrated using the random-effects, generic inverse variance method of DerSimonian and Laird. Prospero registration: CRD42022334065., Results: Seven studies from 2016 to 2021 with a total of 7,401 patients were included. In patients undergoing PCI, a high CVRS (≥2: Odds ratio [OR]:2.98, 95% confidence interval [95% CI] 2.25-3.94, p  < .01, I 2 = 1%, ≥3: OR 4.46, 95% CI 2.27-8.78, p  < .01, I 2 =56% and ≥4: OR:2.75, 95% CI 1.76-4.30, p  < .01, I 2 = 11%) was significantly associated with an increase incidence for CIN. Subgroup analyses were done in patients with acute coronary syndrome, and association with CIN remained statistically significant (≥2: OR 2.93, 95% CI 2.11-4.07, p  < .01, I 2 =22%and ≥4: OR:2.24, 95% CI 1.36-3.69, p  < .01, I 2 = 0%,)., Conclusion: In patients undergoing PCI, an elevated CVRS is associated with an increased risk for CIN. More rigorous studies are needed to clarify this association and to identify strategies to reduce CIN.

Elevated systemic immune-inflammation index (SII) has associated with coronary heart disease and poor clinical outcomes. However, the relationship between SII and contrast-induced nephropathy (CIN) in patients who underwent elective percutaneous coronary intervention (PCI) is still unclear. We aimed to investigate the association of SII with the development of CIN in elective PCI patients. A retrospective study with 241 participants was performed from March 2018 to July 2020. CIN was defined as any of the following: increase in serum creatinine (SCr) level by ≥0.5 mg/dl (≥44.2 mol/L) or increase in SCr to ≥25% over the baseline value within 48-72 h after PCI. The SII levels in patients with CIN ( n  = 40) were significantly higher than those without. In correlation analysis, SII positively correlated to uric acid but negatively with the estimated glomerular filtration rate. Increased log2(SII) levels were independent risk factors for patients with CIN [odds ratio (OR) = 2.686; 95% confidence interval (CI), 1.457-4.953]. In the subgroup analysis, increased log2(SII) was strongly associated with the presence of CIN in male participants (OR = 3.669; 95% CI, 1.925-6.992; P  < 0.05), whereas no association was found in females (OR = 1.552; 95% CI, 0.533-4.515; P  > 0.05). Receiver operating characteristic analysis demonstrated that in a cutoff of 586.19, SII showed 75% sensitivity and 54.2% specificity for predicting CIN in patients undergoing elective PCI, respectively. In conclusion, elevated SII was an independent risk factor of CIN development in patients undergoing elective PCI, particularly in male people., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Anthurium schlechtendalii Kunth is used by the Zoque group in southeastern Mexico for kidney and urinary diseases, but its safety and effectiveness are unproven, therefore a model of adenine-induced renal failure in rats was performed. The rats were fed with solid and aqueous plant extracts for 4 weeks to study its effects on kidney histological morphology. Kidneys were examined, and statistical analysis was performed. The adenine-containing diet caused renal failure, characterized by crystal deposits, cystic dilatation of tubules, and micro-abscesses. Both extracts caused tubular damage and collagen increase without inflammation. However, when combined with adenine, the extracts showed some protective effects, although cystic dilatation and granulomatous inflammation were observed. The extracts at the tested doses resulted in glomerular and tubular damage, aggravating cystic degeneration, therefore, its indiscriminate use in Humans is not safe. Additionally, the extracts can serve as a model for studying renal damage without crystal deposits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The contrast-induced nephropathy (CIN) rate is increasing globally and can increase the rate of mortality and long-term problems. This study aims to determine the effect of Nicorandil on preventing CIN among patients undergoing cardiac catheterization., Methods: In a controlled randomized open-labeled clinical trial, all included patients undergoing cardiac catheterization due to coronary problems and possessing at least two risk factors of contrast nephropathy were divided into two groups of intervention and control. The intervention group received oral Nicorandil and normal saline, while the control group was treated with intravenous normal saline. Serum creatinine was measured before and 48 h after the procedure, and patients were assessed regarding CIN., Results: In this study, 172 patients entered each group; 41.86% and 45.34% were male in the control and Nicorandil groups. We showed that the incidence of CIN was meaningfully lower in the Nicorandil group (12, 7%) than in the control group (34, 19.8%, P = 0.001). Additionally, the incidence of CIN was notably lower in the female patients in the Nicorandil (85.7%) than in the control group (14.3%, P = 0.001); however, these numbers were not significantly different among men (64.0% and 36.0%, respectively, P = 0.850). After the injection of the contrast agent, the serum levels of blood urea nitrogen (P = 0.248), creatinine (P = 0.081), and glomerular filtration rate (P = 0.386) showed no significant differences between the control and Nicorandil groups. Multivariate regression analysis showed that Nicorandil significantly lowered the odds of CIN [odds ratio (OR) = 0.299, 95% confidence interval (CI) 0.149-0.602; P = 0.001] after adjustment for baseline creatinine (OR = 1.404, 95% CI 0.431-4.572; P = 0.574)., Conclusion: Our results indicate that pre-procedural treatment with Nicorandil may be effective against CIN in contrast to agent-exposed patients., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

This study evaluated the effectiveness of prognostic nutritional index (PNI) in predicting contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS). This study included 925 ACS patients (mean age 62.5 ± 12.4 years, 73.5% male); 604 were diagnosed as unstable angina pectoris/non-ST-elevation myocardial infarction (USAP/NSTEMI) and 321 as ST-elevation myocardial infarction (STEMI). The PNI formula was: 10 × serum albumin (g/dL) + .005 × total lymphocyte count (/mm 3 ). The patients were divided into two groups: CIN (n = 232) and non-CIN (n = 693). Patients without CIN had a significantly lower PNI than patients with CIN (44.3 ± 6.9 vs 54.7 ± 7.4; P < .001). In the receiver operating characteristic (ROC) curve analysis, the cut-off value for PNI of 48.6 has 80% specificity and 81% sensitivity in predicting CIN (area under the ROC curve (AUC): .87, 95% CI [.84-.89]). PNI <48.6 (odds ratio (OR): 6.765, P < .001), pre-procedural creatinine levels (OR: 6.223, P < .001), left ventricular ejection fraction (LVEF) (OR: .960, P < .001), age (OR: 1.025, P = .005), diabetes mellitus (DM) (0R: 1.768, P = .006), contrast amount (OR: 1.003, P = .038), and having STEMI (OR: .594, P = .029) were found independently associated with CIN. PNI is a strong independent predictor of CIN in ACS patients.

Background: Renal dysfunction is one of the adverse effects observed in methamphetamine (MET) or tramadol abusers. In this study, we aimed to review articles involving intoxication with MET or tramadol to assess the occurrence of renal dysfunction., Methods: Two researchers systematically searched PubMed, Scopus, Web of Sciences, and Google Scholar databases from 2000 to 2022. All articles that assessed renal function indexes including creatine, Blood Urea Nitrogen (BUN), and Creatine phosphokinase (CPK) in MET and tramadol intoxication at the time of admission in hospitals were included. We applied random effect model with Knapp-Hartung adjustment for meta-analysis using STATA.16 software and reported outcomes with pooled Weighted Mean (WM)., Results: Pooled WM for BUN was 29.85 (95% CI, 21.25-38.46) in tramadol intoxication and 31.64(95% CI, 12.71-50.57) in MET intoxication. Pooled WM for creatinine in tramadol and MET intoxication was respectively 1.04 (95% CI, 0.84-1.25) and 1.35 (95% CI, 1.13-1.56). Also, pooled WM for CPK was 397.68(376.42-418.94) in tramadol and 909.87(549.98-1269.76) in MET intoxication. No significance was observed in publication bias and heterogeneity tests., Conclusion: Our findings showed that tramadol or MET intoxication is associated with a considerably increased risk of renal dysfunction that may result in organ failure., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In aging kidneys, a decline of function resulting from extracellular matrix (ECM) deposition and organ fibrosis is regarded as "physiological." Whether a direct link between high salt intake and fibrosis in aging kidney exists autonomously from arterial hypertension is unclear. This study explores kidney intrinsic changes (inflammation, ECM derangement) induced by a high-salt diet (HSD) in a murine model lacking arterial hypertension. The contribution of cold shock Y-box binding protein (YB-1) as a key orchestrator of organ fibrosis to the observed differences is determined by comparison with a knockout strain ( Ybx1 ΔRosaERT+TX ). Comparisons of tissue from mice fed with normal-salt diet (NSD, standard chow) or high-salt diet (HSD, 4% NaCl in chow; 1% NaCl in water) for up to 16 mo revealed that with HSD tubular cell numbers decrease and tubulointerstitial scarring [periodic acid-Schiff (PAS), Masson's trichrome, Sirius red staining] prevails. In Ybx1 ΔRosaERT+TX animals tubular cell damage, a loss of cell contacts with profound tubulointerstitial alterations, and tubular cell senescence was seen. A distinct tubulointerstitial distribution of fibrinogen, collagen type VI, and tenascin-C was detected under HSD, transcriptome analyses determined patterns of matrisome regulation. Temporal increase of immune cell infiltration was seen under HSD of wild type, but not Ybx1 ΔRosaERT+TX animals. In vitro Ybx1 ΔRosaERT+TX bone marrow-derived macrophages exhibited a defect in polarization (IL-4/IL-13) and abrogated response to sodium chloride. Taken together, HSD promotes progressive kidney fibrosis with premature cell aging, ECM deposition, and immune cell recruitment that is exacerbated in Ybx1 ΔRosaERT+TX animals. NEW & NOTEWORTHY Short-term experimental studies link excessive sodium ingestion with extracellular matrix accumulation and inflammatory cell recruitment, yet long-term data are scarce. Our findings with a high-salt diet over 16 mo in aging mice pinpoints to a decisive tipping point after 12 mo with tubular stress response, skewed matrisome transcriptome, and immune cell infiltration. Cell senescence was aggravated in knockout animals for cold shock Y-box binding protein (YB-1), suggesting a novel protective protein function.

Methamphetamine (MA) is a widely abused drug that can cause kidney damage. However, the molecular mechanism remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates resistance to oxidative and proteotoxic stress. In this study, we investigated the role of Nrf2 in MA-induced renal injury in mice. Nrf2 was pharmacologically activated and genetically knocked-out in mice. The animal model of MA-induced nephrotoxicity was established by injecting MA (2 mg/kg) intraperitoneally twice a day for 5 days. Histopathological alterations were shown in the MA-exposed kidneys. MA significantly increased renal function biomarkers and kidney injury molecule-1 (KIM-1) levels. MA decreased superoxide dismutase activity and increased malondialdehyde levels. Autophagy-related factors (LC3 and Beclin 1) were elevated in MA-treated mice. Furthermore, Nrf2 increased in the MA-exposed kidneys. Activation of Nrf2 may attenuate histopathological changes in the kidneys of MA-treated mice. Pre-administration of Nrf2 agonist significantly decreased KIM-1 expression, oxidative stress, and autophagy in the kidneys after MA toxicity. In contrast, Nrf2 knockout mice treated with MA lost renal tubular morphology. Nrf2 deficiency increased KIM-1 expression, oxidative stress, and autophagy in the MA-exposed kidneys. Our results demonstrate that Nrf2 may protect against MA-induced nephrotoxicity by mitigating oxidative stress and autophagy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Environmental cadmium (Cd) exposure is a serious public health concern, as the kidney is the primary target for Cd exposure. The present study aimed to investigate the role and underlying mechanisms of nuclear factor erythroid-derived 2-like 2 (Nrf2) in renal fibrosis induced by chronic Cd exposure. Nrf2 knockout (Nrf2-KO) mice and their wild-type littermates (Nrf2-WT) were exposed to 100 or 200 ppm Cd in drinking water for up to 16 or 24 weeks. Following the Cd exposures, Nrf2-KO mice showed elevated urinary neutrophil gelatinase-associated lipocalin (NGAL) and BUN levels compared to Nrf2-WT mice. Masson's trichrome staining and expression of fibrosis-associated proteins revealed that more severe renal fibrosis occurred in Nrf2-KO than that in Nrf2-WT mice. Renal Cd content in the Nrf2-KO mice exposed to 200 ppm Cd was lower than that in Nrf2-WT mice, which might be a consequence of the severe renal fibrosis in the Nrf2-KO mice. Mechanistic studies showed that Nrf2-KO mice exhibited higher levels of oxidative damage, lower antioxidant levels, and more regulated cell death, apoptosis in particular, than those in Nrf2-WT mice caused by Cd exposure. In conclusion, Nrf2-KO mice were more prone to develop renal fibrosis induced by chronic Cd exposure, partially due to a weakened antioxidant, detoxification capacity and increased oxidative damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cadmium (Cd) is a toxic heavy metal that targets the kidney directly in the body. Chrysin (CHR) is a natural flavonoid with many properties such as antioxidant, anti-inflammatory and anti-apoptotic. The current study discloses new evidence as regards of the curative effects of CHR on Cd-induced nephrotoxicity by regulating oxidative stress, apoptosis, autophagy, and inflammation. Cd was administered orally at a dose of 25 mg/kg body weight alone or in combination with orally administered CHR (25 and 50 mg/kg body weight) for 7 days. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in renal tissue. Renal function tests were also evaluated. Cd caused an increase in serum toxicity markers, lipid peroxidation and a decrease in the activities of antioxidant enzymes. Nrf-2 triggered inflammatory responses by suppressing HO-1 and NQO1 mRNA transcripts and increasing NF-κB, TNF-α, IL-1β and iNOS mRNA transcripts. Cd caused inflammasome by increasing RAGE and NLRP3 mRNA transcripts. In addition, Cd application caused apoptosis by increasing Bax, Apaf-1 and Caspase-3 mRNA transcripts and decreasing Bcl-2 mRNA transcript level. It caused autophagy by increasing the activity of Beclin-1 level. CHR treatment had the opposite effect on all these values and reduced the damage caused by all these signal pathways. Overall, the data of this study indicate that renal damage associated with Cd toxicity could be ameliorated by CHR administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-β1 (TGF-β1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.

The impact of cadmium (Cd) on the function and structure of the kidney and the potential protective effect of an extract from Aronia melanocarpa L. berries were investigated in a rat model of low- and moderate-level environmental exposure to this heavy metal (1 and 5 mg Cd/kg feed for up to 24 months). The sensitive biomarkers of Cd-induced damage to the kidney tubules (N-acetyl-β-D-glucosaminidase (NAG), alkaline phosphatase (ALP), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) in the urine), clinically relevant early markers of glomerular damage (albumin in the urine and creatinine clearance), and other markers of the general functional status of this organ (urea, uric acid, and total protein in the serum and/or urine) and Cd concentration in the urine, were evaluated. The morphological structure of the kidney and inflammatory markers (chemerin, macrophage inflammatory protein 1 alpha (MIP1a), and Bcl2-associated X protein (Bax)) were also estimated. Low-level and moderate exposure to Cd led to damage to the function and structure of the kidney tubules and glomeruli. The co-administration of A. melanocarpa berry extract significantly protected against the injurious impact of this toxic element. In conclusion, even low-level, long-term exposure to Cd poses a risk of kidney damage, whereas an intake of Aronia berry products may effectively protect from this outcome.

Adriamycin (ADR) is an effective chemotherapy drug for various cancers but has serious side effects. ADR-induced liver damage is a common problem during therapy, but the underlying mechanism remains to be fully understood. In contrast, ADR-induced glomerular damage is well studied in rodents, and sensitivity to ADR-induced nephropathy is because of the R2140C polymorphism of Prkdc gene. To investigate whether strain differences or sensitivity to ADR-induced liver damage are related to Prkdc polymorphism, this study compared the sensitivity to ADR-induced liver damage among C57BL/6J (B6J), B6-Prkdc R2140C , and BALB/c mice. Although B6J exhibits resistance to ADR-induced liver injury, BALB/c and B6-Prkdc R2140C are more susceptible to liver injury, which is exacerbated by the presence of R2140C mutation in PRKDC.

Epidemiologic evidence on the relationship between air pollution and kidney disease remains inconclusive. We evaluated associations between short-term exposure to PM 2.5 , NO 2 and O 3 and unplanned hospital visits for seven kidney-related conditions (acute kidney failure [AKF], urolithiasis, glomerular diseases [GD], renal tubulo-interstitial diseases, chronic kidney disease, dysnatremia, and volume depletion; n = 1,209,934) in New York State (2007-2016). We applied a case-crossover design with conditional logistic regression, controlling for temperature, dew point temperature, wind speed, and solar radiation. We used a three-pollutant model at lag 0-5 days of exposure as our main model. We also assessed the influence of model adjustment using different specifications of temperature by comparing seven temperature metrics (e.g., dry-bulb temperature, heat index) and five intraday temperature measures (e.g., daily mean, daily minimum, nighttime mean), according to model performance and association magnitudes between air pollutants and kidney-related conditions. In our main models, we adjusted for daytime mean outdoor wet-bulb globe temperature, which showed good model performance across all kidney-related conditions. We observed the odds ratios (ORs) for 5 μg/m 3 increase in daily mean PM 2.5 to be 1.013 (95% confidence interval [CI]: 1.001, 1.025) for AKF, 1.107 (95% CI: 1.018, 1.203) for GD, and 1.027 (95% CI: 1.015, 1.038) for volume depletion; and the OR for 5 ppb increase in daily 1-hour maximum NO 2 to be 1.014 (95% CI; 1.008, 1.021) for AKF. We observed no associations with daily 8-hour maximum O 3 exposure. Association estimates varied by adjustment for different intraday temperature measures: estimates adjusted for measures with poorer model performance resulted in the greatest deviation from estimates adjusted for daytime mean, especially for AKF and volume depletion. Our findings indicate that short-term exposure to PM 2.5 and NO 2 is a risk factor for specific kidney-related conditions and underscore the need for careful adjustment of temperature in air pollution epidemiologic studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The studies investigated the predictive value of the contrast media volume to creatinine clearance ratio (V/CrCl) for contrast-induced nephropathy (CIN) after a percutaneous coronary intervention (PCI) showed conflicting results and different cut-off values. The objective is to evaluate V/CrCl in the prediction of CIN after PCI. PubMed, Embase, and the Cochrane library were searched for eligible studies published from inception to November 2020. The optimal cut-off points of V/CrCl for predicting CIN were examined using odds ratios (ORs) and 95% confidence intervals (CIs). The random-effect model was used for analyses. Six studies (8 datasets, 16 899 patients) were included. V/CrCl was associated with CIN (OR = 2.67, 95% CI: 1.88-3.78, P < .001; I 2 = 79.3%, P heterogeneity < .001). V/CrCl was associated with CIN in Asians (OR = 2.13, 95% CI: 1.52-2.98, P = .022; I 2 = 68.8%, P heterogeneity < .001) and Europeans (OR = 3.87, 95% CI: 1.77-8.45, P < .001; I 2 = 85.1%, P heterogeneity = .001). The association between V/CrCl and CIN was observed in the prospective cohort studies (OR = 2.16, 95% CI: 1.42-3.29, P = .009; I 2 = 78.9%, P heterogeneity < .001) and retrospective cohort studies (OR = 3.31, 95% CI: 1.82-6.02, P < .001; I 2 = 80.6%, P heterogeneity < .001). The sensitivity analysis showed the results were robust. V/CrCl is independently associated with an increased risk of CIN. V/CrCl could be considered a reliable predictor for the development of CIN in patients undergoing PCI.

More and more clinical evidence shows that occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) patients often present immune kidney damage. However, the exact mechanisms of cell-to-cell transmission in TCE-induced immune kidney damage remain poorly understood. The present study aimed to explore the role of high mobility group box-1 (HMGB 1) in glomerular endothelial cell-podocyte transmission. 17 OMDT patients and 34 controls were enrolled in this study. We observed that OMDT patients had renal function injury, endothelial cell activation and podocyte injury, and these indicators were associated with serum HMGB 1. To gain mechanistic insight, a TCE-sensitized BALB/c mouse model was established under the interventions of sirtuin 1 (SIRT 1) activator SRT 1720 (0.1 ml, 5 mg/kg) and receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM 1 (0.1 ml, 1.5 mg/kg). We identified HMGB 1 acetylation and its endothelial cytoplasmic translocation following TCE sensitization, but SRT 1720 abolished the process. RAGE was located on podocytes and co-precipitated with extracellular acetylated HMGB 1, promoting podocyte injury, while SRT 1720 and FPS-ZM 1 both alleviated podocyte injury. The results demonstrate that interventions to upstream and downstream pathways of HMGB 1 may weaken glomerular endothelial cell-podocyte transmission, thereby alleviating TCE-induced immune renal injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Hemodynamic instability plays an important role in the development of contrast-induced nephropathy (CIN), which is an important complication of coronary angiography. Left ventricular (LV) end-diastolic pressure (LVEDP) accurately reflects hemodynamic changes. In clinical practice, measuring LVEDP invasively presents some challenges and is not always accessible. This study aimed to investigate the relationship between tissue Doppler-derived early diastolic conduction velocity (E)/[early mitral annular diastolic velocity (Ea), × peak systolic annular velocity (Sa)] index, an important surrogate for LVEDP, and CIN in patients undergoing elective coronary angiography (ECA)., Patients and Methods: This retrospective study included 388 consecutive patients undergoing ECA. CIN was defined as a 25% or 0.5 mg/dL increase in serum creatinine compared to baseline values within 72 hours after ECA. Mehran score was calculated in all patients and systolic and diastolic functions were evaluated with Doppler echocardiography., Results: The incidence of CIN was 9.7%. There was a positive correlation between LV EDP levels and LV E/(Ea × Sa) index (r = 0.691, p < 0.001). Higher LV E/(Ea × Sa) index (OR = 1.03, p < 0.001) and Mehran score (OR = 1.41, p < 0.001) were independent predictors of CIN. The threshold value of LV E/(Ea × Sa) index in predicting CIN was > 1.71 with 75.7% sensitivity and 84.3% specificity (AUC = 0.825)., Conclusions: In patients undergoing ECA, the non-invasively measured E/(Ea × Sa) index can be used as a risk indicator for CIN.

Background: Activation of renal fibroblasts into myofibroblasts plays an important role in promoting renal interstitial fibrosis (RIF). Ginkgo biloba extract (EGb) can alleviate RIF induced by cisplatin (CDDP)., Purpose: To elucidate the effect of EGb treatment on cisplatin-induced RIF and reveal its potential mechanism., Methods: The two main active components in EGb were determined by high-performance liquid chromatography (HPLC) analysis. Rats were induced by CDDP and then treated with EGb, 2ME2 (HIF-1α inhibitor) or amifostine. After HK-2 cells and HIF-1α siRNA HK-2 cells were treated with CDDP, EGb or amifostine, the conditioned medium from each group was cultured with NRK-49F cells. The renal function of rats was detected. The renal damage and fibrosis were evaluated by H&E and Masson trichrome staining. The IL-6 content in the cell medium was detected by ELISA. The expression levels of indicators related to renal fibrosis and signaling pathway were examined by western blotting and qRT-PCR., Results: HPLC analysis showed that the contents of quercetin and kaempferol in EGb were 36.0 μg/ml and 45.7 μg/ml, respectively. In vivo, EGb and 2ME2 alleviated renal damage and fibrosis, as well as significantly decreased the levels of α-SMA, HIF-1α, STAT3 and IL-6 in rat tissues induced by CDDP. In vitro, the levels of HIF-1α, STAT3 and IL-6 were significantly increased in HK-2 cells and HIF-1α siRNA HK-2 cells induced by CDDP. Notably, HIF-1α siRNA significantly decreased the levels of HIF-1α, STAT3 and IL-6 in HK-2 cells, as well as the IL-6 level in medium from HK-2 cells. Additionally, the α-SMA level in NRK-49F cells was significantly increased after being cultured with conditioned medium from HK-2 cells or HIF-1α siRNA HK-2 cells exposed to CDDP. Furthermore, exogenous IL-6 increased the α-SMA level in NRK-49F cells. Importantly, the expression levels of the above-mentioned indicators were significantly decreased after the HK-2 cells and HIF-1α siRNA HK-2 cells were treated with EGb., Conclusion: This study revealed that EGb improves CDDP-induced RIF, and the mechanism may be related to its inhibition of the renal fibroblast activation by down-regulating the HIF-1α/STAT3/IL-6 pathway in renal tubular epithelial cells., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to disclose., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Hydration is currently the main measure to prevent contrast-induced nephropathy (CIN). We aimed to compare the preventive effect of preprocedure and postprocedure hydration on CIN in patients with coronary heart disease undergoing elective percutaneous coronary intervention (PCI)., Methods: A retrospective study included 198 cases of postprocedure hydration and 396 cases of preprocedure hydration using propensity score matching. The incidence of CIN 48 h after PCI and adverse events within 30 days after contrast media exposure were compared between the two groups. Logistic regression analysis was used to analyse the risk factors for CIN., Results: The incidence of CIN in the postprocedure hydration group was 3.54%, while that in the preprocedure hydration group was 4.8%. There was no significant difference between the two groups (p = 0.478). Multivariate logistic regression analysis showed that diabetes mellitus, baseline BNP and cystatin C levels, and contrast agent dosage were independent risk factors for CIN. There was no significant difference in the incidence of major adverse events between the two groups (3.03% vs. 2.02%, p = 0.830)., Conclusions: Postprocedure hydration is equally effective compared to preoperative hydration in the prevention of CIN in patients with coronary heart disease undergoing elective PCI., (© 2023. The Author(s).)

Previous studies have reported that microcystin-LR (MC-LR) levels are highly correlated with abnormal renal function indicators, suggesting that MC-LR is an independent risk factor for kidney damage. However, the evidence for the exact regulation mechanism of MC-LR on kidney damage is still limited, and further in-depth exploration is needed. In addition, the mitochondria-related mechanism of MC-LR leading to kidney damage has not been elucidated. To this end, the present study aimed to further explore the mechanism of mitophagy related to kidney damage induced by MC-LR through in vitro and in vivo experiments. Male C57BL/6 mice were fed with a standard rodent pellet and exposed daily to MC-LR (20 μg/kg·bw) via intraperitoneal injections for 7 days. Moreover, HEK 293 cells were treated with MC-LR (20 μM) for 24 h. The histopathological results exhibited kidney damage after MC-LR exposure, characterized by structurally damaged nephrotomies, with inflammatory cell infiltration. Similarly, a significant increase in renal interstitial fibrosis was observed in the kidneys of MC-LR-treated mice compared with those of the control group (CT) mice. MC-LR exposure caused impaired kidney function, with markedly increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in mice. Ultrastructural analysis exhibited obviously swollen, broken, and disappearing mitochondrial crests, and partial mitochondrial vacuoles in the MC-LR-treated HEK 293 cells. The Western blotting results demonstrated that exposure to MC-LR significantly increased the protein expressions of MKK6, p-p38, and p62, while the expression of mitophagy-related proteins was significantly inhibited in the kidneys of mice and HEK293 cells, including parkin, TOM20, and LC3-II, indicating the inhibition of mitophagy. Therefore, our data suggest that the inhibition of MKK6-mediated mitophagy might be the toxicological mechanism of kidney toxicity in mice with acute exposure to MC-LR.

The clinical use of cyclosporin A (CsA) has led to significant advances and achievements in the field of transplantation and immune diseases. However, the nephrotoxicity of CsA is a major concern in current immunosuppression regimens. CsA causes abnormal kidney function while treating kidney disease, causing problems for clinicians and patients. Evidence of CsA nephrotoxicity is almost always present in transplant recipients after long-term CsA administration (up to 10 years), and similar phenomena occur with other calcineurin inhibitors. In this review, we summarize the mechanisms and influencing factors of CsA for the treatment of primary nephrotic syndrome. The mechanisms of CsA nephrotoxicity, clinical-pathological features, diagnosis, prevention strategies, and risk factors are summarized. We discuss the correlates and mechanisms of the switch between kidney disease prevention and nephrotoxicity of CsA to better understand the function of CsA in the kidney and to provide a basis for the prevention and treatment of CsA nephrotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance. Although animal models have enhanced knowledge of disease mechanisms, human (patho-)physiology may not be adequately represented in animals. Developments in microfluidics and renal cell biology have enabled the development of dynamic models to study renal (patho-)physiology in vitro. Allowing inclusion of human cells and combining different organ models, such as kidney-on-a-chip (KoC) models, enable the refinement and reduction of animal experiments. We systematically reviewed the methodological quality, applicability and effectiveness of kidney-based (multi-)organ-on-a-chip models, and describe the state-of-the-art, strengths and limitations, and opportunities regarding basic research and implementation of these models. We conclude that KoC models have evolved to complex models capable of mimicking systemic (patho-)physiological processes. Commercial chips and human induced pluripotent stem cells and organoids are important for KoC models to study disease mechanisms and assess drug effects, even in a personalized manner. This contributes to the Reduction, Refinement and Replacement of animal models for kidney research. A lack of reporting of intra- and inter-laboratory reproducibility and translational capacity currently hampers implementation of these models., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background: Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE)., Aims: We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients., Methods: This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs. iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration., Results: A total of 2,268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs. low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P =.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs. 29 (2.6%) in the low-osmolarity group (P =.4)., Conclusion: Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.

This study investigated the role of atherogenic index of plasma (AIP) in predicting contrast induced nephropathy (CIN) in patients who underwent percutaneous coronary intervention due to non-ST elevated myocardial infarction. Of these, 1644 patients were included in the study. Retrospective data of patients were obtained from hospital records. For the diagnosis of CIN, peri-procedural patient records were scanned. There was a significant difference between age, diabetes mellitus, hyperlipidemia, albumin, high density lipoprotein cholesterol, triglycerides, number of stenotic vessels, creatinine increase rate, baseline creatinine, hemoglobin, hematocrit, AIP, and two groups (CIN- and CIN+) (P < .05, for all). In multivariate logistic regression analysis, AIP was an independent predictor of CIN (odds ratio: 20.352, 95% CI: 12.696-32.624, P < .001). Receiver operating characteristic analysis showed that AIP values of ≥.62 could predict CIN with a sensitivity of 70% and specificity of 58% for predicting CIN (area under curve = .710, P < .001). Atherogenic index of plasma may be helpful as a biomarker to predict CIN.

Background: Rostellularia procumbens (L) Nees. is an effective traditional Chinese herbal medicine for the treatment of patients with chronic glomerulonephritis (CGN) in the clinic. However, the underlying molecular mechanisms need further elucidation., Purpose: This study aims to investigate the renoprotective mechanisms of n-butanol extract from Rostellularia procumbens (L) Nees. (J-NE) in vivo and in vitro., Methods: The components of J-NE were analyzed by UPLC-MS/MS. In vivo, the nephropathy model was induced in mice by tail vein injection with adriamycin (10 mg·kg -1 ), and mice were treated with vehicle or J-NE or benazepril by daily gavage. In vitro, MPC5 cells exposed to adriamycin (0.3 μg/ml) were treated with J-NE. The effects of J-NE inhibit podocyte apoptosis and protect against adriamycin-induced nephropathy were determined by Network pharmacology, RNA-seq, qPCR, ELISA, immunoblotting, flow cytometry, and TUNEL assay, according to the experimental protocols., Result: The results showed that treatment significantly improved ADR-induced renal pathological changes, and the therapeutic mechanism of J-NE was related to the inhibition of podocyte apoptosis. Further molecular mechanism studies found that J-NE inhibited inflammation, increase the proteins expression levels of Nephrin and Podocin, reduce TRPC6 and Desmin expression levels and calcium ion levels in podocytes, and decrease the proteins expression levels of PI3K, p-PI3K, Akt and p-Akt to attenuated apoptosis. Furthermore, 38 compounds of J-NE were identified., Conclusion: J-NE exerted the renoprotective effects by inhibiting podocyte apoptosis, which provides effective evidence for the treatment of J-NE targeting renal injury in CGN., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published by other journals. All authors declare that there are not any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Epoetin has been used to treat patients with renal anemia since 1988. -Anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) has been associated with epoetin usage, and a PRCA incidence of 4.5 per 10,000 patient-years was observed for epoetin-α (Eprex) in 2002. The PASCO II study (post-authorization safety cohort observation of Retacrit and Silapo (epoetin-ζ) administered subcutaneously for the treatment of renal anemia) followed 6,346 patients (4,501 Retacrit (group R); 1,845 Silapo (group S)) for up to 3 years of subcutaneous treatment with the biosimilar epoetin-ζ. One PRCA in 1 (0.02%) patient in group R who tested positive for neutralizing antibodies was reported. Overall, 527 adverse events of special interest (AESI) including PRCA occurred in 418 (6.60%) patients, lack of efficacy occurred in 34 (0.54%), and thromboembolic events in 389 (6.14%) patients. 41 adverse drug reactions other than AESIs were reported in 28 (0.44%) patients. The exposure-adjusted incident rate of PRCA was 0.84 per 10,000 patient-years. This real-world study showed that among patients with renal anemia receiving subcutaneous administration of the biosimilar product epoetin-ζ, the incidence rate of PRCA was substantially below the risk observed in 2002 for Eprex and that there was no immunogenicity concern or other new safety concern.

Anticancer drug therapy for cancer is developing rapidly, including molecular-targeted drugs and immune checkpoint inhibitors that are used in clinical settings in addition to conventional cytotoxic drugs. In daily clinical practice, clinicians sometimes encounter situations in which the effects of these chemotherapeutic agents are considered unacceptable in high-risk patients with liver or renal dysfunction, those undergoing dialysis and older adults. There is no clear evidence regarding anticancer drugs administration to patients with renal dysfunction. However, there are indications for dose setting based on the theory of the renal function responsible for drug excretion and past administration experience. This review outlines anticancer drugs' administration in patients with renal dysfunction., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)