Kidney Injury Research Articles

Cancer drugs and acute kidney injury: new therapies and new challenges.

Cancer therapies continue to evolve at a rapid pace and although novel treatments, including immunotherapies and targeted therapies have allowed for substantial improvements in cancer survival, they carry associated risks of acute kidney injury (AKI). We aim to summarize the existing literature on AKI associated with the spectrum of systemic cancer treatments, including conventional chemotherapies, newer immunotherapies, and the growing number of targeted cancer therapies, which may be associated with both AKI and 'pseudo-AKI'. Conventional cytotoxic chemotherapies (e.g. cisplatin and other platinum-based agents, methotrexate, pemetrexed, ifosfamide, etc.) with well recognized nephrotoxicities (predominantly tubulointerstitial injury) remain in widespread use. Immunotherapies (e.g., immune checkpoint inhibitors and CAR-T therapies) may be associated with kidney immune-related adverse events, most often acute interstitial nephritis, and rarely, glomerular disease. Recently, multiple targeted cancer therapies have been associated with reduced renal tubular secretion of creatinine, causing elevations in serum creatinine and apparent 'pseudo-AKI'. To complicate matters further, these agents have had biopsy-proven, 'true' kidney injury attributed to them in numerous case reports. Clinicians in nephrology and oncology must be aware of the various potential kidney risks with these agents and recognize those with clinically meaningful impact on both cancer and kidney outcomes.

Comparative evaluation of postoperative outcomes and expenditure between robotic and conventional single-level lumbar fusion surgery: a comprehensive analysis of nationwide inpatient sample data.

In this study, we investigate the evolution of lumbar fusion surgery with robotic assistance, specifically focusing on the impact of robotic technology on pedicle screw placement and fixation. Utilizing data from the Nationwide Inpatient Sample (NIS) covering 2016 to 2019, we conduct a comprehensive analysis of postoperative outcomes and costs for single-level lumbar fusion surgery. Traditionally, freehand techniques for pedicle screw placement posed risks, leading to the development of robotic-assisted techniques with advantages such as reduced misplacement, increased precision, smaller incisions, and decreased surgeon fatigue. However, conflicting study results regarding the efficacy of robotic assistance in comparison to conventional techniques have prompted the need for a thorough evaluation. With a dataset of 461,965 patients, our aim is to provide insights into the impact of robotic assistance on patient care and healthcare resource utilization. Our primary goal is to contribute to the ongoing discourse on the efficacy of robotic technology in lumbar fusion procedures, offering meaningful insights for optimizing patient-centered care and healthcare resource allocation. This study employed data from the Nationwide Inpatient Sample (NIS) spanning the years 2016 to 2019 from USA, 461,965 patients underwent one-level lumbar fusion surgery, with 5770 of them having the surgery with the assistance of robotic technology. The study focused primarily on one-level lumbar fusion surgery and excluded non-elective cases and those with prior surgeries. The analysis encompassed the identification of comorbidities, surgical etiologies, and complications using specific ICD-10 codes. Throughout the study, a constant comparison was made between robotic and non-robotic lumbar fusion procedures. Various statistical methods were applied, with a p value threshold of < 0.05, to determine statistical significance. Robotic-assisted lumbar fusion surgeries demonstrated a significant increase from 2016 to 2019, comprising 1.25% of cases. Both groups exhibited similar patient demographics, with minor differences in payment methods, favoring Medicare in non-robotic surgery and more private payer usage in robotic surgery. A comparison of comorbid conditions revealed differences in the prevalence of hypertension, dyslipidemia, and sleep apnea diagnoses-In terms of hospitalization outcomes and costs, there was a slight shorter hospital stay of 3.06days, compared to 3.13days in non-robotic surgery, showcasing a statistically significant difference (p = 0.042). Robotic surgery has higher charges, with a mean charge of $154,673, whereas non-robotic surgery had a mean charge of $125,467 (p < 0.0001). Robotic surgery demonstrated lower rates of heart failure, acute coronary artery disease, pulmonary edema, venous thromboembolism, and traumatic spinal injury compared to non-robotic surgery, with statistically significant differences (p < 0.05). Conversely, robotic surgery demonstrated increased post-surgery anemia and blood transfusion requirements compared to non-robotic patients (p < 0.0001). Renal disease prevalence was similar before surgery, but acute kidney injury was slightly higher in the robotic group post-surgery (p = 0.038). This is the first big data study on this matter, our study showed that Robotic-assisted lumbar fusion surgery has fewer post-operative complications such as heart failure, acute coronary artery disease, pulmonary edema, venous thromboembolism, and traumatic spinal injury in comparison to conventional methods. Conversely, robotic surgery demonstrated increased post-surgery anemia, blood transfusion and acute kidney injury. Robotic surgery has higher charges compared to non-robotic surgery.

Diuretic response after neonatal cardiac surgery: a report from the NEPHRON collaborative.

Multicenter early diuretic response (DR) analysis of single furosemide dosing following neonatal cardiac surgery is lacking to inform whether early DR predicts adverse clinical outcomes. We performed a retrospective cohort study utilizing data from the NEPHRON registry. Random forest machine learning generated receiver operating characteristic-area under the curve (ROC-AUC) and odds ratios for mechanical ventilation (MV) and respiratory support (RS). Prolonged MV and RS were defined using ≥ 90th percentile of observed/expected ratios. Secondary outcomes were prolonged CICU and hospital length of stay (LOS) and kidney failure (stage III acute kidney injury (AKI), peritoneal dialysis, and/or continuous kidney replacement therapy on postoperative day three) assessed using covariate-adjusted ROC-AUC curves. A total of 782 children were included. Cumulative urine output (UOP) metrics were lower in prolonged MV and RS patients, but DR poorly predicted prolonged MV (highest AUC 0.611, OR 0.98, sensitivity 0.67, specificity 0.53, p = 0.006, 95% OR CI 0.96-0.99 for cumulative 6-h UOP) and RS (highest AUC 0.674, OR 0.94, sensitivity 0.75, specificity 0.54, p < 0.001, 95% CI 0.91-0.97 UOP between 3 and 6h). Secondary outcome results were similar. DR had fair discrimination for kidney failure (AUC 0.703, OR 0.94, sensitivity 0.63, specificity 0.71, 95% OR CI 0.91-0.98, p < 0.001, cumulative 6-h UOP). Early DR poorly discriminated patients with prolonged MV, RS, and LOS in this cohort, though it may identify severe postoperative AKI phenotype. Future work is warranted to determine if early DR or late postoperative DR later, in combination with other AKI metrics, may identify a higher-risk phenotype.

Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function with chronic kidney disease.

Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function. An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate. In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study. This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.

HIF-1α participates in the regulation of S100A16-HRD1-GSK3β/CK1α pathway in renal hypoxia injury

S100 calcium-binding protein 16 (S100A16) is implicated in both chronic kidney disease (CKD) and acute kidney injury (AKI). Previous research has shown that S100A16 contributes to AKI by facilitating the ubiquitylation and degradation of glycogen synthase kinase 3β (GSK3β) and casein kinase 1α (CK1α) through the activation of HMG-CoA reductase degradation protein 1 (HRD1). However, the mechanisms governing S100A16-induced HRD1 activation and the upregulation of S100A16 expression in renal injury are not fully understood. In this study, we observed elevated expression of Hypoxia-inducible Factor 1-alpha (HIF-1α) in the kidneys of mice subjected to ischemia-reperfusion injury (IRI). S100A16 deletion attenuated the increased HIF-1α expression induced by IRI. Using a S100A16 knockout rat renal tubular epithelial cell line (NRK-52E cells), we found that S100A16 knockout effectively mitigated apoptosis during hypoxic reoxygenation (H/R) and cell injury induced by TGF-β1. Our results revealed that H/R injuries increased both protein and mRNA levels of HIF-1α and HRD1 in renal tubular cells. S100A16 knockout reversed the expressions of HIF-1α and HRD1 under H/R conditions. Conversely, S100A16 overexpression in NRK-52E cells elevated HIF-1α and HRD1 levels. HIF-1α overexpression increased HRD1 and β-catenin while decreasing GSK-3β. HIF-1α inhibition restored HRD1 and β-catenin upregulation and GSK-3β downregulation by cellular H/R injury. Notably, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated HIF-1α binding signals on the HRD1 promoter, and luciferase reporter gene assays confirmed HIF-1α‘s transcriptional regulation of HRD1. Additionally, we identified Transcription Factor AP-2 Beta (TFAP2B) as the upregulator of S100A16. ChIP and luciferase reporter assays confirmed TFAP2B as a transcription factor for S100A16. In summary, this study identifies TFAP2B as the transcription factor for S100A16 and demonstrates HIF-1α regulation of HRD1 transcription within the S100A16-HRD1-GSK3β/CK1α pathway during renal hypoxia injury. These findings provide crucial insights into the molecular mechanisms of kidney injury, offering potential avenues for therapeutic intervention.

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery

Cytomegalovirus infection and disease in systemic lupus erythematosus patients at a high-complexity hospital in southwestern Colombia.

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

Prognostic Assessment of Histopathologic Lesions in Patients with Community-Acquired Acute Kidney Injury with Biopsy-Proven Acute Tubular Necrosis.

Community-acquired acute kidney injury (CA-AKI) was more likely to be comorbid with underlying kidney histopathological lesions in addition to acute tubular necrosis (ATN). Thus, we tried to clarify the histological determinants that could influence the prognosis and recovery of CA-AKI patients with biopsy-proven ATN. Adult patients with CA-AKI with biopsy-proven ATN who underwent renal biopsy at Shanghai Changzheng Hospital from January 1, 2010, to December 31, 2018, were included and followed up for 5 years. The impacts of histopathological lesions on short-term and long-term renal dysfunction were also analysed. Multivariate analysis revealed that ATNs, crescents, and decrease of arteriole lumens increased short-term dialysis requirements. The severity of ATN was closely associated with renal survival. According to the Kaplan-Meier analysis, the severity of ATN was significantly associated with short-term dialysis needs and long-term development of end-stage kidney disease (ESKD) during follow-up. Crescent and decrease of arteriole lumens are significantly associated with progression to ESKD and exert synergistic effects with ATN. For patients who did not progress to dialysis, tubular atrophic/interstitial fibrosis and endocapillary lesions were more relevant to partial recovery of renal function after CA-AKI at the three-month follow-up and increased the risk of chronic kidney disease (CKD) stage 3-5 at the five-year follow-up. According to our correlation analysis, endocapillary lesions and crescents were positively correlated with ATN. Histopathologic lesions, apart from tubular necrosis, contributed to the detrimental short-term and long-term renal prognosis of CA-AKI patients with ATN; concomitant histopathologic lesions exerted a combined impact on renal survival together with ATN in CA-AKI patients.

Beneficial effect of Alhagi maurorum on rats submitted to sulfadimidine-induced kidney injury

Beneficial effect of Alhagi maurorum on rats submitted to sulfadimidine-induced kidney injury

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

BackgroundTacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.Methods and resultsThirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.ConclusionLina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

Diagnosis, management, and outcomes of immune checkpoint inhibitor induced acute interstitial nephritis: A single-center experience.

Immune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (AIN) is a recognized complication of immunotherapy (IO), but literature on its management and outcomes is limited. We retrospectively reviewed patients who received ICIs and developed biopsy-proven or clinically-suspected ICI-associated AIN at the University of Virginia Comprehensive Cancer Center from 2012-2023. We analyzed baseline characteristics and clinical outcomes, including treatment interruption and rechallenge rates. Acute kidney injury (AKI) was defined as a ≥ 1.5-fold increase in baseline creatinine under seven days, a two-fold increase above the upper limit of normal, or an increase by ≥0.3 mg/dL. Kidney function returning to within 0.3 mg/dL or less than twice baseline was considered complete (CRc) and partial (PRc) recovery, respectively. We identified 12 cases of ICI-AIN: four by biopsy (33%) and eight (67%) by clinical suspicion. Two patients received anti-CTLA-4 and anti-PD1, six received anti-PD1 alone, and four received chemo-immunotherapy. The majority (58%) of patients developed AIN within the first 5 cycles. Eight patients developed ≥ Grade 3 AKI, and six developed multiple irAEs. ICI was permanently discontinued in seven patients (58%) and temporarily interrupted in four (30%). The CRc and PRc rates were 67% and 8%, respectively. Upon AIN onset, the best disease response was stable disease in five patients, partial response in three, and progressive disease in three. Median overall survival was 4.87 years, and progression-free survival was 1.5 years. Rechallenge with IO after kidney irAE may be possible in some patients but requires careful evaluation on an individual basis.

Intrarenal pH-Responsive Self-Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury.

Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated β-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10 min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.

Intrarenal pH‐Responsive Self‐Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury

Metabolic acidosis‐induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end‐stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH‐responsive luminescent gold nanoparticles (p‐AuNPs) in the second near‐infrared emission co‐coated with 2,3‐dimethylaleic anhydride conjugated β‐mercaptoethylamine and cationic 2‐diethylaminoethanethiol hydrochloride, which showed sensitive pH‐induced charge reversal and intrarenal self‐assembly for highly sensitive and long‐time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH‐induced intrarenal self‐assembly and enhanced interactions between pH‐triggered positively charged p‐AuNPs and renal tubular cells, the early‐ and late‐stage MAKI could be differentiated rapidly within 10 min post‐injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p‐AuNPs were demonstrated to effectively real‐time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH‐responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early‐stage diagnosis of pH‐related diseases.

Comparators in Pharmacovigilance: A Quasi-Quantification Bias Analysis.

It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance. We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury. We assessed the directionality of three disproportionality analysis estimates (reporting odds ratio, proportional reporting ratio, information component) using one unrestricted comparator (full data) and two restricted comparators (active comparator, active comparator with class exclusion). Analyses were conducted within two calendar time periods, defined based on external events (approval of direct oral anticoagulants, Food and Drug Administration safety warning on acute kidney injury with sodium-glucose cotransporter 2 inhibitors) hypothesized to alter reporting rates. There were no false-positive signals for rivaroxaban and hepatotoxicity irrespective of the comparator. Restricting to the initial post-approval period led to false-positive signals, with restricted comparators performing worse. There were false-positive signals for canagliflozin and acute kidney injury, with restricted comparators performing better. Restricting to the period before the Food and Drug Administration warning weakened the false-positive signal for canagliflozin and acute kidney injury across comparators. We could not identify a consistent and predictable pattern to the directionality of disproportionality analysis estimates with specific comparators. Calendar time-based restrictions anchored on relevant external events had a considerable impact.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

The mechanisms of ferroptosis in the pathogenesis of kidney diseases.

The pathological features of acute and chronic kidney diseases are closely associated with cell death in glomeruli and tubules. Ferroptosis is a form of programmed cell death characterized by iron overload-induced oxidative stress. Ferroptosis has recentlygained increasing attention as a pathogenic mechanism of kidney damage. Specifically, the ferroptosis signaling pathway has been found to be involved in the pathological process of acute and chronic kidney injury, potentially contributing to the development of both acute and chronic kidney diseases. This paper aims to elucidate the underlying mechanisms of ferroptosis and its role in the pathogenesis of kidney disease, highlighting its significance and proposing novel directions for its treatment.

Source Tracing of Kidney Injury via the Multispectral Fingerprint Identified by Machine Learning-Driven Surface-Enhanced Raman Spectroscopic Analysis.

Early diagnosis of drug-induced kidney injury (DIKI) is essential for clinical treatment and intervention. However, developing a reliable method to trace kidney injury origins through retrospective studies remains a challenge. In this study, we designed ordered fried-bun-shaped Au nanocone arrays (FBS NCAs) to create microarray chips as a surface-enhanced Raman scattering (SERS) analysis platform. Subsequently, the principal component analysis (PCA)-two-layer nearest neighbor (TLNN) model was constructed to identify and analyze the SERS spectra of exosomes from renal injury induced by cisplatin and gentamycin. The established PCA-TLNN model successfully differentiated the SERS spectra of exosomes from renal injury at different stages and causes, capturing the most significant spectral features for distinguishing these variations. For the SERS spectra of exosomes from renal injury at different induction times, the accuracy of PCA-TLNN reached 97.8% (cisplatin) and 93.3% (gentamicin). For the SERS spectra of exosomes from renal injury caused by different agents, the accuracy of PCA-TLNN reached 100% (7 days) and 96.7% (14 days). This study demonstrates that the combination of label-free exosome SERS and machine learning could serve as an innovative strategy for medical diagnosis and therapeutic intervention.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Experimental animal model. The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.