Renal Failure Research Articles

Tumor characteristics in immunosuppressed and renal dysfunction populations

PurposeRenal transplantation and end-stage renal disease are increasingly common. Renal dysfunction and immunosuppression are two risk factors in the development of renal cell carcinoma. Carcinomas in these patients are thought to be more indolent, however data are limited and mixed. Our objective was to describe the histology of resected tumors from the transplant and renal dysfunction population and compare them to a control population. Materials and MethodsThis was a single-center retrospective cohort study of all patients who had a nephrectomy for a renal mass from 2009 to 2019. All transplant status and end-stage renal disease diagnoses were identified by diagnostic or procedural coding and confirmed by chart review. Our primary endpoint was the pathology for each patient's tumor. Tumors were classified into aggressive or nonaggressive categories based on their histology and grade. ResultsWe identified 1,150 radical and partial nephrectomies, of which 1,057 met inclusion criteria. Of these, 68 patients (6.4%) had renal dysfunction or a kidney transplant on immunosuppression at time of nephrectomy. After pathologic review, 270 (25%) tumors were classified as aggressive, and 673 (64%) tumors were pT1a or pT1b. On multivariable logistic regression controlling for age and gender, renal dysfunction was not associated with having an aggressive tumor (OR 1.24, 95%CI 0.72–2.15; P = 0.44). ConclusionsWe did not observe a relationship between renal dysfunction status and aggressive pathology. These data suggest that renal dysfunction and transplant patients are at similar risk for aggressive pathology as the general population and should be managed according to the same clinical guidelines.

Jia Wei Qingxin Lotus Seed Drink ameliorates epithelial mesenchymal transition injury in diabetic kidney disease via inhibition of JMJD1C/SP1/ZEB1 signaling pathway

BackgroundDiabetic kidney disease (DKD) is one of the most common microvascular complications in patients with diabetes mellitus. In this condition, renal tubular epithelial mesenchymal transition (EMT) is an important factor accelerating the progression of DKD and a major cause of renal fibrosis and end-stage renal disease. However, the therapeutic effect is unsatisfactory because of the lack of effective drugs. Jia Wei Qingxin Lotus Seed Drink (QISD) is a traditional Chinese medicine compound formula that has shown to be effective in the clinical treatment of DKD. However, the potential of QISD in DKD-EMT treatment has yet to be fully explored. PurposeThis study aimed to investigate the role of QISD in ameliorating DKD-EMT injury and its mechanism. MethodsThe active ingredients of QISD were identified via ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). A DKD mouse model was constructed by high-fat diet feeding and intraperitoneal injection of STZ (60 mg/kg), and QISD (14.46, 28.92, and 57.84 g/kg/day) was administered by gavage for 12 consecutive weeks. Dapagliflozin (1 mg/kg/d) was used as a positive control. Renal pathological damage was observed by HE, PAS, and Masson staining. The expression levels of EMT-related proteins and pathway proteins were detected via immunohistochemistry, RT-qPCR, and western blot. In in vitro experiments, EMT injury was induced in human kidney tubular epithelial cells (HK-2) by using lipopolysaccharide (LPS). A combination of CCK8 assay, wound healing assay, small-molecule inhibitor intervention, and overexpression lentiviral transfection was used to investigate the effects of QISD on cell migration ability, adhesion ability, fibrotic factor formation, and mesenchymal properties. ResultsAnimal experiments showed that QISD improved blood glucose, body weight, symptoms of excessive drinking and eating, and renal pathological injury in mice, reduced extracellular matrix deposition, delayed renal EMT injury, and inhibited the activation of the histone demethylase JMJD1C. UHPLC-MS/MS and molecular docking indicated that baicalin, wogonoside, oroxylin A-7-O-β-D-glucuronide, and glulisine A found in QISD could bind to JMJD1C. The ameliorating effect of QISD on DKD-EMT injury might be related to JMJD1C. The improvement of DKD-EMT injury by QISD was accompanied by the reduction of SP1 and ZEB1 expression. The SP1 overexpression not only reversed the therapeutic effect of JIB-04, an inhibitor of JMJD1C, on DKD-EMT but also exacerbated the expression of ZEB1 and downstream EMT-related factors. Thus, QISD might affect the expression of the epithelial marker E-cadherin by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway, consequently preventing the transformation of epithelial cells to mesenchymal cells and ameliorating DKD-EMT injury. ConclusionThis study was the first to demonstrate that QISD might ameliorate DKD-EMT injury by inhibiting the JMJD1C/SP1/ZEB1 signaling pathway. These findings provide strong pharmacologic evidence for the clinical use of QISD in the treatment of DKD.

Management of Venoarterial Extracorporeal Membrane Oxygenation Cannulation-Associated Groin Wound Complications With Muscle Flaps at a High-Acuity Cardiac Referral Center.

The insertion of large bore cannulas into the femoral vessels for venous-arterial extracorporeal membrane oxygenation (VA-ECMO) administration has been associated with significant acute and chronic wound complications in patients with significant medical and surgical comorbidities, including vessel exposure and lymphocele development. In this series, we report our experience using muscle flap reconstruction in the management of post-ECMO groin wounds, with particular emphasis on groin lymphocele. VA-ECMO patients at a high-acuity cardiac referral center who developed groin cannulation site complications requiring muscle flap closure were included for retrospective review. Preoperative, perioperative, and postoperative factors were analyzed. Fifteen patients were included. The most common comorbidities were hypertension (66.7%), diabetes (46.7%), and renal failure (60.0%). Eight (53.3%) patients were immunosuppressed. The most frequent indications for surgery were groin lymphocele (n = 8, 53.3%) and exposed femoral vessels (n = 7, 46.7%). Median time from ECMO decannulation to reconstruction was 49.0 days. Most reconstructions were performed using a rectus femoris flap (n = 13, 86.7%). Two (13.3%) shallow wounds were covered with a sartorius muscle flap. Intraoperative cultures were positive in 9 (60.0%) patients. Seven (46.7%) patients experienced complications, including hematoma (n = 5), dehiscence (n = 1), recipient site infection (n = 1), and donor site infection (n = 1). In both groups, there were no cases involving lymphocele recurrence following reconstruction. There were no flap-specific complications and no cases of amputation. Four patients died within 1 year from septic shock (n = 3) and heart failure (n = 1). We report successful reconstruction in the majority of patients. In particular, muscle flap reconstruction is a useful technique for addressing ECMO-associated lymphocele development and recurrence. Future studies are needed to determine ideal timing of reconstruction and if early plastic surgeon involvement can reduce morbidity and mortality of these difficult to treat infections.

Does mannitol prime help patients with renal dysfunction during cardiac surgery? A randomized trial.

Does mannitol prime help patients with renal dysfunction during cardiac surgery? A randomized trial.

Collagen peptide and taurine synergistically improve hypertensive kidney injury induced by high salt diet through gut-kidney axis

Hypertensive kidney injury is significantly associated with oxidative stress, inflammation and gut microbiota. Collagen peptide and taurine (Tau) are key natural compounds known for their antioxidant, anti-inflammatory, and intestinal flora improvement. However, the potential synergistic actions of combining collagen peptides with Tau on hypertensive kidney damage remain unclear. Therefore, our study investigated the effects of collagen peptide LALFVPR (LR-7) derived from Harpadon nehereus in conjunction with Tau on renal injury in high salt (HS)-induced hypertension. The results showed that combination of LR-7 and Tau significantly alleviated renal fibrosis, glomerular atrophy, and impaired renal function in hypertensive mice. Furthermore, this combination outperformed individual treatments with either LR-7 or Tau alone in enhancing antioxidant enzyme activity while decreasing inflammatory factors and adhesion molecules levels in the kidneys. Moreover, LR-7 and Tau synergistically ameliorated HS-induced intestinal flora disturbance by promoting microbial diversity and adjusting the ratio of beneficial and harmful bacteria. Our research is pioneering in demonstrating that LR-7 combined with Tau may exert a synergistic effect on mitigating kidney damage in HS-induced hypertension through the gut-renal axis. This investigation provides a new strategy for utilizing combinations of food-derived functional compounds to effectively address complications arising from hypertension.

Chronic central nervous system leptin administration attenuates kidney dysfunction and injury in a model of ischemia/reperfusion-induced acute kidney injury.

In the present study, we examined whether chronic intracerebroventricular (ICV) leptin administration protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Twelve-week-old male rats were implanted with an ICV cannula into the right lateral ventricle, and 8-10 days after surgery, leptin (0.021 µg/h, n = 8) or saline vehicle (0.5 µL/h, n = 8) was infused via osmotic minipump connected to the ICV cannula for 12 days. On day 8 of leptin or vehicle infusion, rats were submitted to unilateral ischemia/reperfusion (UIR) by clamping the left pedicle for 30 min. To control for leptin-induced reductions in food intake, the vehicle-treated group was pair-fed (UIR-PF) to match the same amount of food consumed by leptin-treated (UIR-Leptin) rats. On the 12th day of leptin or vehicle infusion (fourth day after AKI), single-left kidney glomerular filtration rate (GFR) was measured, blood samples were collected to quantify white blood cells, and kidneys were collected for histological assessment of injury. UIR-Leptin-treated rats showed reduced right and left kidney weights (right: 1,040 ± 24 vs. 1,281 ± 36 mg; left: 1,127 ± 71 vs. 1,707 ± 45 mg, for UIR-Leptin and UIR-PF, respectively). ICV leptin infusion improved GFR (0.50 ± 0.06 vs. 0.13 ± 0.03 mL/min/g kidney wt) and reduced kidney injury scores. ICV leptin treatment also attenuated the reduction in circulating adiponectin levels that was observed in UIR-PF rats and increased the circulating white blood cells count compared with UIR-PF rats (16.3 ± 1.3 vs. 9.8 ± 0.6 k/µL). Therefore, we show that leptin, via its actions on the central nervous system, confers significant protection against major kidney dysfunction and injury in a model of ischemia/reperfusion-induced AKI.NEW & NOTEWORTHY A major new finding of this study is that chronic activation of leptin receptors in the CNS markedly attenuates acute kidney injury and protects against severe renal dysfunction after ischemia/reperfusion, independently of leptin's anorexic effects.

Artificial Intelligence-Based Classification of CT Images Using a Hybrid SpinalZFNet.

The kidney is an abdominal organ in the human body that supports filtering excess water and waste from the blood. Kidney diseases generally occur due to changes in certain supplements, medical conditions, obesity, and diet, which causes kidney function and ultimately leads to complications such as chronic kidney disease, kidney failure, and other renal disorders. Combining patient metadata with computed tomography (CT) images is essential to accurately and timely diagnosing such complications. Deep Neural Networks (DNNs) have transformed medical fields by providing high accuracy in complex tasks. However, the high computational cost of these models is a significant challenge, particularly in real-time applications. This paper proposed SpinalZFNet, a hybrid deep learning approach that integrates the architectural strengths of Spinal Network (SpinalNet) with the feature extraction capabilities of Zeiler and Fergus Network (ZFNet) to classify kidney disease accurately using CT images. This unique combination enhanced feature analysis, significantly improving classification accuracy while reducing the computational overhead. At first, the acquired CT images are pre-processed using a median filter, and the pre-processed image is segmented using Efficient Neural Network (ENet). Later, the images are augmented, and different features are extracted from the augmented CT images. The extracted features finally classify the kidney disease into normal, tumor, cyst, and stone using the proposed SpinalZFNet model. The SpinalZFNet outperformed other models, with 99.9% sensitivity, 99.5% specificity, precision 99.6%, 99.8% accuracy, and 99.7% F1-Score in classifying kidney disease.

Engineering of phosphatidylserine-targeting ROS-responsive polymeric prodrug for the repair of ischemia-reperfusion-induced acute kidney injury

Ischemia-reperfusion-induced acute kidney injury (IR-AKI) commonly occurs in situations such as hemorrhagic shock, kidney transplantation, and cardiovascular surgery. As one of the significant causes of AKI, IR-AKI is characterized by its high incidence and mortality rates. Currently, effective inflammation control is the key for the treatment of IR-AKI. In this study, we developed an ROS-responsive polymeric prodrugs (Zn-D/DTH) which could target the externalized PS of apoptotic cells, and then responsively released HDM (anti-inflammatory peptides) in the presence of intracellular ROS. Zn-D/DTH effectively ameliorated renal function and mitigated pathological alterations such as the loss of the brush border, tubular dilation, and accumulation of cellular debris within the tubular lumens. Furthermore, Zn-D/DTH greatly reduced the generation of pro-inflammatory factors like IL-6, COX-2, and iNOS in renal tissues, suggesting its protective role largely stems from suppression of the inflammatory response. Additional mechanism exploration revealed that Zn-D/DTH markedly decreased the expression levels of TLR4 and MyD88, as well as the phosphorylation of NF-κB in the damaged kidneys. This, in turn, reduced the number of apoptotic tubular cells and the activity of Caspase 9 and Caspase 3 caused by ischemia-reperfusion. Additionally, Zn-D/DTH treatment showed improvement in the long-term renal damage and fibrosis induced by ischemia-reperfusion. The experimental outcomes indicated that Zn-D/DTH attenuated renal ischemia-reperfusion injury and delayed the transition from acute kidney injury to chronic kidney disease by downregulating the TLR4/MyD88/NF-κB signaling pathway and reducing the expression of apoptotic caspases, thereby inhibiting inflammation and reducing cell apoptosis.

Molecular mechanisms and potential targets of lycopene for alleviating renal ischemia-reperfusion injury revealed by network pharmacology and animal experiments

ObjectiveRenal IRI is one of the leading causes of AKI. How to effectively mitigate renal IRI is important for the recovery of renal function. The regulatory mechanism of lycopene, a natural antioxidant, in renal IRI is currently unknown. Therefore, we utilized network pharmacology and animal experiments to explore the possible mechanisms and potential targets of lycopene for alleviating renal IRI. MethodsWe obtained lycopene-regulated genes and renal IRI-related genes from the CTD database and GeneCards database, respectively. Subsequently, the two were intersected and the intersecting genes we defined as lycopene-regulated genes in renal IRI. Next, we explored their potential biological functions and mechanisms through enrichment analysis. Meanwhile, we constructed a rat renal IRI model and validated the protective effects of lycopene and related mechanisms. To further explore the Hub genes regulated by lycopene, we constructed a PPI protein interactions network and characterized the Hub genes using Cytoscape software. We also verified the expression of Hub genes using animal experiments and molecular docking techniques. Finally, we constructed TF-Hub gene and miRNA-Hub gene regulatory networks. ResultsWe obtained a total of 255 lycopene-regulated genes and 327 renal IRI-related genes. The enrichment analysis revealed that they were closely related to the regulation of oxidative stress as well as the regulation of inflammatory factors. At the same time, the MAPK signaling pathway was significantly enriched. Next, we found in animal experiments that lycopene significantly alleviated the level of oxidative stress and inflammation during renal IRI, and had a protective effect on kidney damage. Also, we found that this protective effect may be achieved by inhibiting the MAPK signaling pathway. Next, we identified a total of five Hub genes using Cytoscape software: TNF, AKT1, MAPK3, IL6 and CASP3. Both animal experiments and molecular docking techniques demonstrated that lycopene can effectively regulate the expression of Hub genes. Finally, our constructed TF-Hub gene and miRNA-Hub gene regulatory network provide a theoretical basis for further regulation of Hub genes in follow-up. ConclusionsThis study suggests that lycopene is a promising option in mitigating renal IRI. Lycopene may exert protective effects by inhibiting the MAPK signaling pathway.

Automatic kidney disease prediction using deep learning techniques

The kidneys play an energetic role in eliminating excess products and fluids from the body, by a complex mechanism which is crucial for upholding a stable balance of body chemicals. Chronic kidney disease (CKD) is considered by an unhurried weakening in renal function that may eventually result in kidney injury or failure. The difficulty of diagnosing the illness rises as it worsens. However, using data from normal medical visits to evaluate the various phases of CKD could help with early detection and prompt care. Researchers suggest a classification strategy for CKD along with optimization strategies used in the learning process. The incorporation of artificial intelligence offers promise because it may often astonish with its skills and enable seemingly difficult undertakings. Modern machine learning techniques have been developed to detect renal illness in light of this. In the current study, a new deep learning model for CKD initial recognition and prediction is introduced. The main objective of the project is to build a strong deep neural network (DNN) and estimate its result outcomes in comparison to other leading-edge machine learning techniques. The outcomes demonstrate that the proposed strategy outperforms current approaches and has promise as a useful tool for CKD detection.

Fenofibrate attenuates renal lipotoxicity in uninephrectomized mice with high-fat diet-induced obesity.

The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy. C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers. High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21. Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors.

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study

This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide. The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5mg (0.35mg, moderate renal impairment) and enzalutamide 160mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment. In the all-comers (n=398) and HRR-deficient populations (n=198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9% and 66.2% of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7% and 40.9%, respectively), neutropenia (18.3% and 18.7%), and thrombocytopenia (7.3% and 7.1%). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8% and 10.1% of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1% and 57.6%), reduction (52.8% and 52.0%), hematologic supportive care (13.1% and 10.6%), and packed red blood cell transfusions (39.2% and 35.9%). Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations. NCT03395197.

Omega-3 polyunsaturated fatty acids protect against cisplatin-induced nephrotoxicity by activating the Nrf2 signaling pathway

Nephrotoxicity is a prevalent side effect observed in patients undergoing chemotherapy. The pathogenesis of chemotherapy-induced nephrotoxicity involves various factors such as oxidative stress, DNA damage, inflammation, and apoptosis. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess anti-inflammatory and antioxidant properties. This study investigated the effects of EPA and DHA, either alone or in combination, on cisplatin-induced nephrotoxicity in mice, as well as their underlying mechanisms of action. The combined administration of EPA and DHA demonstrated superior efficacy in mitigating cisplatin-induced nephrotoxicity compared to administration alone, including the reduction of oxidative damage, inflammation, and apoptosis. Moreover, the combination of EPA and DHA suppressed inflammation and prevented the development of chronic kidney fibrosis during prolonged observations following repeated cisplatin administration. Mechanistically, ω-3 PUFAs enhance the expression of antioxidant genes by activating the p62-Keap1-Nrf2 signaling pathway. Furthermore, Nrf2 activation can inhibit the cisplatin-induced p53 apoptosis signal by upregulating the expression of MDM2 in renal tubular epithelial cells. Consequently, ω-3 PUFAs exert a protective effect against cisplatin-induced renal injury through activating the Nrf2 signaling pathway, suggesting that ω-3 PUFAs intake holds promise as a therapeutic strategy for combating cisplatin-induced nephrotoxicity.

Disruption of local circadian clocks in aristolochic acid-induced nephropathy in mice

BackgroundAristolochic acid I (AAI), an emerging biogenic contaminant widely present in Aristolochic plants, has been implicated in the progression of tubulointerstitial disease, known as aristolochic acid nephropathy (AAN). The circadian clock, a vital regulator of organ homeostasis, is susceptible to external chemical cues, including toxins. However, the reciprocal interactions between AAI and the circadian clock remain unexplored. MethodsWe initially assessed sex- and time-dependent nephropathy and behavioral responses in C57BL/6J mice exposed to AAI. Subsequently, we evaluated changes in the expression of circadian clock genes following treatment with AAI or its bioactive metabolite, aristolactam I, using real-time quantitative PCR and immunoblotting in renal tissues and cells. Additionally, real-time reporter assays were conducted on kidney explants from PER2::Luc knock-in reporter mice and Per2-dLuc/Bmal1-dLuc reporter cell lines. To further elucidate the regulatory role of circadian clocks in AAI-induced nephropathy, mice with global or kidney-specific knockout of Bmal1, as well as mice subjected to experimental jetlag, were utilized. ResultsOur findings revealed a sex-dependent nephrotoxicity of AAI, with males exhibiting greater vulnerability. AAI-induced nephropathy was accompanied by impaired spatial cognitive function, disruptions in free-running locomotor activity, altered renal expression of multiple core clock genes, and disturbances in the circadian rhythm of renal PER2::Luc activity. Notably, kidney-specific ablation of the core clock gene Bmal1 significantly exacerbated renal injury and inflammation, whereas disruptions to the central clock, either genetically (through conventional knockout of Bmal1) or environmentally (mimicking jetlag), had minimal effects on AAI nephrotoxicity. Furthermore, both AAI and its bioactive metabolite aristolactam I demonstrated the ability to disrupt circadian clocks in human osteosarcoma cells (U2OS) and mouse renal tubular epithelial cells (mRTEC). ConclusionCollectively, these findings highlight the detrimental impact of aristolochic acids on local renal circadian clocks, ultimately exacerbating kidney damage. This study provides novel insights into the molecular mechanisms underlying AAI nephrotoxicity, potentially opening avenues for therapeutic interventions aimed at modulating the renal circadian clock to treat AAN.

Single Nucleus RNA Sequencing Reveals Cellular and Molecular Responses to Vanadium Exposure in Duck Kidneys

Vanadium (V) exposure is known to induce renal toxicity, yet its specific effects on renal cell types and molecular mechanisms remain incompletely understood. We used single nucleus RNA sequencing (snRNA-seq) to characterize the impact of V on duck kidney cells at a cellular resolution. Following a 44-day exposure, immunofluorescence analysis revealed a significant increase in α-SMC expression in the renal interstitium, indicative of fibrotic response. SnRNA-seq identified 12 major cell types organized into 19 clusters within the kidney. Significant changes in cell composition were observed, notably an increase in proximal tubule cells (PT2 subtype), glomerular endothelial cells, principal cells, and alterations in immune cell proportions, while collecting duct intercalated cells (CD-IC) and thick ascending limb showed decreased percentages. Differential gene expression analysis highlighted pathways implicated in V toxicity across different cell types. Changes in drug metabolism-cytochrome P450, butanoate metabolism, and actin cytoskeleton regulation were exhibited by PT cells. Alterations in collecting duct secretion, oxidative phosphorylation, and bicarbonate reclamation pathways were shown in CD-IC cells. Furthermore, immune cells displayed changes in T cell receptor and chemokine signaling pathways, indicative of altered immune responses. Taken together, these findings contribute to a better shedding light on the pathogenic mechanisms of V induced renal injury.

Total alkaloids of Aconitum carmichaelii Debx alleviate cisplatin-induced acute renal injury by inhibiting inflammation and oxidative stress related to gut microbiota metabolism

BackgroundCisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of Aconitum carmichaelii Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear. PurposeThis study aimed to elucidate the effect of Aconitum carmichaelii Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms. MethodsThe major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting. ResultsFour main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of Escherichia-Shigella, Clostridium, and Ruminococcus, as well as increasing Ligilactobacillus, Anaerotruncus, Bacteroides and Desulfovibrio levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1β, IL-6, and TNF-α), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-κB pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression. ConclusionACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.

Improvement in Kidney damage resulting from stanozolol intramuscular injections in rats by Natural Cocoa Powder (NCP) Administration.

BackgroundStanozolol, an anabolic steroid, has been shown to induce kidney damage through mechanisms involving oxidative stress and inflammation. Natural Cocoa Powder (NCP), known for its high antioxidant content, may offer protective effects against such damage. AimThis study aimed to evaluate the potential of Natural Cocoa Powder (NCP) in ameliorating kidney damage caused by stanozolol intramuscular injections in rats. MethodsThirty rats were randomly assigned into five groups (G1–G5) and fed with standard rat chow. G1 and G3 received 2 mg/kg stanozolol intramuscularly twice weekly, G2 and G4 received 5 mg/kg stanozolol twice weekly, while G5 served as the control with no stanozolol. G1, G2, and G5 had 24-hour access to water, while G3 and G4 had water replaced with 2% NCP from 6 am to 6 pm daily. After 8 weeks, kidneys were perfusion-fixed and analyzed histomorphometrically for proximal/distal tubules, Bowman's space, glomerular tuft, and renal corpuscle composition.Before and after treatments, renal function was measured by serum creatinine and blood urea nitrogen, whilst systemic inflammation was monitored by erythrocyte sedimentation rate and serum C-reactive protein tests. Results & DiscussionStanozolol administration significantly increased kidney damage in a dose-dependent manner, with marked rises in the volume densities of the proximal convoluted tubule (PCT), distal convoluted tubule (DCT), glomerular tuft, and renal corpuscle. At higher doses, PCT and DCT volume densities increased by 143% and 223%, respectively, compared to controls. Natural cocoa powder (NCP) mitigated these effects, reducing PCT, DCT, and glomerular tuft volume densities by 92%, 77%, and 86%, respectively. Stanozolol also elevated serum markers of kidney dysfunction and inflammation, such as blood urea nitrogen (BUN), serum creatinine (SCr), and C-reactive protein (CRP). While NCP significantly lowered BUN and SCr levels, it did not fully normalize CRP, which remained elevated in stanozolol-treated rats. ConclusionIncreased volume density of kidney components indicated hypertrophy, which was associated with elevated serum creatinine, blood urea nitrogen (BUN), and C-reactive protein (CRP) levels, reflecting impaired renal function and heightened systemic inflammation. The reduction in these markers with NCP ingestion suggests its potential to mitigate stanozolol-induced renal damage. It is proposed that the antioxidant properties of NCP may have reduced inflammation by counteracting oxidative stress, thereby contributing to the observed improvement in kidney function and structure.

Reliability of neutrophil gelatinase-associated lipocalin in detecting acute tubular necrosis in decompensated cirrhosis: Systematic review and meta-analysis

BACKGROUND Acute kidney injury (AKI) in cirrhosis is common. The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine. However, urine biomarkers could also be used to assess the type of AKI and the severity of the disease. We performed a systematic review with meta-analysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin (NGAL) marker in identifying acute tubular necrosis (ATN) in patients with cirrhosis. AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis. METHODS We systematically searched MEDLINE and PubMed using keywords including “urine biomarkers”, “NGAL”, “kidney dysfunction”, and “cirrhosis” to identify relevant studies. Data was screened and extracted. Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker. We synthesized the data using diagnostic odds ratio (DOR), comparative and descriptive analyses, and Cochran Mantel-Haenszel (CMH) statistics to evaluate heterogeneity. RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies. The DOR of 14 of those studies [pooled DOR: 22.150, (95%CI: 17.58-27.89), P < 0.0001] demonstrated a significant association between urine NGAL levels and its identification of ATN. Following stratification by cirrhosis status, heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI (CMH statistic = 702.19, P < 0.0001). CONCLUSION In patients with cirrhosis, the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.

Development of homemade oral nutrition supplements for individuals with kidney failure on hemodialysis: physicochemical properties, nutrient composition, and sensory evaluation

Purpose Protein-energy wasting is a common complication among patients with kidney failure undergoing dialysis. This study aims to develop a homemade oral nutrition supplement (ONS) to fulfill the energy and protein requirements of these patients. Design/methodology/approach Three formulations of homemade ONS were developed using soybean milk, whey protein isolates and canola oil. Two of these formulations were flavored with pineapple and honeydew juices, respectively. The energy and macronutrient contents were determined using proximate analyses, and mineral contents were determined using inductively coupled plasma optical emission spectroscopy. The acceptance of homemade ONS for five attributes, namely color, taste, odor, consistency and overall acceptability, was assessed using the nine-point hedonic scale. Findings The homemade ONS provided 198–212 kcal and 8.4–9.6 g protein per 100 mL, which were comparable to commercial products. Similarly, the sodium (45–65 mg/100 mL) and phosphorus (56–66 mg/100 mL) contents were on par with commercial products. However, the potassium content of homemade ONS was higher, ranging from 141 to 155 mg per 100 mL. The sensory evaluation indicated that the formulation added with honeydew juice had a similar degree of acceptance as the commercial ONS, while formulations containing pineapple juice and without added fruit juice were less favored. Originality/value A few studies have investigated the development of food products for individuals with kidney failure on dialysis. However, to the best of the authors’ knowledge, this is the first study to focus on developing a homemade ONS specifically tailored to meet the unique nutritional needs of hemodialysis patients. In addition, this research included a comprehensive assessment of the beverage’s nutritional content and sensory attributes.

Incremental hemodialysis transition in veterans and nonveterans with kidney failure

Purpose of review Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients’ residual kidney function (RKF), comorbidities, and preferences. Recent findings Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD. Summary Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.