eGFR Levels Research Articles

Therapeutic effects of Huangqi formula (Eefooton) in chronic kidney disease: clinical research and narrative literature review.

The study aimed to assess the clinical effects of employing the Huangqi formula (Eefooton; EFT) for chronic kidney disease (CKD) treatment. A narrative literature review was undertaken to elucidate the specific ingredients of EFT and their potential impact on renal health. A retrospective observational study investigated EFT treatment in outpatients with stable CKD (stages 3B to 5) from March 2019 to March 2021. Patients received 20 mL of EFT thrice daily for 6 months, along with standard treatment. Control groups were matched to the EFT cohort. Regular assessments of renal, liver functions, and lipid profiles were conducted. Serum creatinine (Cr) and eGFR levels consistently improved in stage 3B CKD patients at each follow-up visit. At 6 months, improvement in Cr and eGFR was observed for stage 4 and 5 CKD. Stage 3B CKD patients exhibited notable reductions in systolic blood pressure after 3 and 6 months of EFT treatment. Remarkably, a substantial decrease in HbA1C was noted in stage 4 CKD individuals after three months of therapy. Additionally, stage 4 CKD patients saw a significant reduction in LDL levels after both 3 and 6 months of EFT treatment. A literature review on EFT ingredients indicated that the positive effects of EFT might be associated with its anti-inflammatory, antioxidant, and anti-fibrotic properties. This research demonstrated that incorporating EFT alongside standard treatment enhanced renal function in individuals with CKD. EFT is proposed as a feasible complementary treatment for CKD patients, emphasizing the importance of early intervention.

Establishment of reference intervals for estimated glomerular filtration rate in apparently healthy adults based on the full age spectrum equation: A single-centre study.

Identifying gender and age-related eGFR trends is crucial for precise renal function assessment. This study aims to analyse eGFR distribution with the full age spectrum (FAS) equation and establish reference intervals based on gender and age in a single-centre cohort. Following the inclusion and exclusion criteria outlined in this study, a total of 24,024 reference individuals were ultimately selected. Using the approach recommended by the CLSI C28-A3 guidelines, we assessed the distribution of eGFR across different gender and age groups. The two-sided nonparametric method (P2.5-P97.5) was applied to establish the eGFR reference intervals for a healthy Chinese population. The eGFR levels in healthy adults exhibited a non-normally distributed pattern. Notably, there were significant differences in eGFR levels between males and females, with females showing a notably higher eGFR level than males. Additionally, eGFR levels demonstrated significant variations across different age groups within both male and female cohorts. As age increased, eGFR showed a significant decline, except in individuals aged 20-29 and 30-39 years. Therefore, reference intervals for eGFR were created based on both gender and age. We established the reference interval for eGFR using the FAS equation, drawing from a large sample population at a single centre. This establishes a potential framework for evaluating renal function in healthy individuals and for diagnosing and treating kidney-related diseases.

68Ga labeled Olmutinib: Design, synthesis, and evaluation of a novel PET EGFR probe.

Radiolabeled tyrosine kinase inhibitors (TKIs) offer a promising approach for molecular imaging of EGFR-positive cancers. Despite the development of various EGFR small-molecule probes, none of the 68Ga-labeled small-molecule probes based on the chelator DOTA have shown tumor-specific uptake. To address this challenge, we selected Olmutinib, a third-generation EGFR covalent inhibitor, as a PET imaging tracer for EGFR-positive tumors. We synthesized the precursor DOTA-Olmutinib through a five-step process and subsequently radiolabeled it with 68Ga to prepare 68Ga-DOTA-Olmutinib. 68Ga-DOTA-Olmutinib displayed moderate lipophilicity (log P=0.85) and exhibited high stability in vitro and in vivo. Western blot analysis was used to detect the level of EGFR in multiple tumor cells. In cell uptake experiments, 68Ga-DOTA-Olmutinib exhibited enhanced uptake specifically in tumor cells with a higher level of EGFR supporting it as an EGFR-specific tracer. Additionally, PET/CT imaging with 68Ga-DOTA-Olmutinib showed significant tumor uptake at 60min with 4% ID/g post-injection, marking a breakthrough, though the uptake is not yet ideal. Overall, our results suggest that 68Ga-labeled Olmutinib holds promise as a potential PET tracer for detecting EGFR-positive cancers.

The inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation in diabetic nephropathy by integrative approach of network pharmacology and experimental verification

BackgroundAlthough clinical strategies for diabetic nephropathy (DN) therapy include stringent blood pressure control through blockade of the renin-angiotensin system and management of hyperglycemia, the condition is still observed to progress relentlessly. PurposeTo elucidate the protective effects of rutin on podocytes in db/db mice with integrative approach of network pharmacology and experimental verification. MethodsThe study employs network pharmacology to identify common targets between rutin and DN, constructs a potential protein-protein interaction (PPI) network, and conducts Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking is utilized to evaluate the interaction between rutin and protein targets. Additionally, experimental validation is performed using db/db mice and human podocyte cell models. ResultsRutin has been found to have a significant renoprotective effect, reducing blood glucose, proteinuria, and improving renal function in db/db mice. Rutin's inhibition of Src kinase reduces the phosphorylation levels of EGFR and ERK, which may mitigate podocyte injury. Additionally, rutin exhibits antioxidant properties, capable of lowering the levels of reactive oxygen species (ROS) in kidney tissue and increasing the activity of antioxidant enzymes like superoxide dismutase (SOD). These effects help protect podocytes from oxidative stress, further supporting the potential application of rutin in the treatment of DN. ConclusionsThe inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation and protects podocyte injury in DN, indicating it might serve as a promising therapeutic agent for podocyte-targeted therapies.

Coexisting Tubulointerstitial Inflammation and Damage Is a Risk Factor for Chronic Kidney Disease in Patients With Lupus Nephritis.

This study aims to determine whether the concurrent presence of tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) predicts the progression of chronic kidney disease (CKD) in patients with lupus nephritis (LN). Data from 175 LN patients, collected at the time of renal biopsy, were analyzed. Patients were stratified into two groups based on the presence or absence of coexisting TII/TID. Uni- and multivariable Cox proportional hazard regression models were utilized to identify independent risk factors for CKD in LN patients. Of 175 patients, 110 (62.9%) exhibited coexisting TII/TID, whereas 65 (37.1%) did not. Patients with coexisting TII/TID tended to be older and presented with higher levels of ESR and 24-h proteinuria, as well as lower levels of eGFR and hemoglobin compared to those without coexisting TII/TID. Over a mean follow-up period of 89.9 months, CKD and end-stage renal disease occurred more frequently in patients with coexisting TII/TID. Notably, the presence of coexisting TII/TID was associated with a higher risk of CKD progression, with adjusted hazard ratios of 2.667 (95% CI: 1.333, 5.335, p = 0.006) for all LN patients, 3.265 (95% CI: 1.451, 7.345, p = 0.004) for those with class III, IV, and V LN, and 3.045 (95% CI: 1.289, 7.195, p = 0.011) for those with class III, IV, V LN, and eGFR ≥ 30 mL/min/1.73 m2. LN patients with coexisting TII/TID are at a heightened risk of kidney function deterioration at LN onset and subsequent development of CKD over the long term.

Relationship between IgM deposition in the mesangial region and the prognosis of IgA nephropathy: a single-centre retrospective study

ObjectiveThe aim of this study was to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of patients with immunoglobulin A nephropathy (IgAN).MethodsA retrospective analysis of clinicopathological data from 774 patients with primary IgAN at Hangzhou Hospital of Traditional Chinese Medicine between January 1, 2016, and December 31, 2018, was conducted. Patients were categorized into end-event and non-end-event groups according to whether they reached the renal composite endpoint, defined as a ≥ 50% decline in eGFR or progression to end-stage renal disease (ESRD). Risk factors for adverse renal outcomes were evaluated via univariate and multivariate Cox regression models. Patients were further divided into three groups on the basis of IgM deposition levels in the glomerular mesangial area: IgM-negative, low (IF < 2+), and high (IF ≥ 2+). Comparative analyses of clinical and histopathological characteristics, along with treatment regimens, were performed across these groups.ResultsCompared with the IgM-negative and low-deposition groups, the high-IgM deposition group exhibited significantly lower serum albumin and eGFR levels and higher cholesterol, 24-hour urine protein, and blood immunoglobulin M levels. Multivariate Cox regression analysis identified immunosuppressant use as an independent protective factor for IgAN prognosis, whereas low serum albumin, T2 lesions, and nephropathological IgM deposits were recognized as independent risk factors for the 5-year prognosis of patients with IgAN. Kaplan‒Meier survival curves revealed that patients with high IgM deposition had markedly poorer prognoses than those with negative or low IgM deposition.ConclusionIn addition to low serum albumin and T2 lesions, IgM deposition in the mesangial region has emerged as an independent risk factor for the 5-year prognosis of patients with IgAN.

Higher density of CD4+ T cell infiltration predicts severe renal lesions and renal function decline in patients with diabetic nephropathy.

More evidence have shown that the combination of immune and inflammatory mechanism was critical in diabetic nephropathy (DN). However, the relationship between CD4+ T cells and the development of DN is still unclear. Therefore, this study will focus on this issue from the perspective of clinicopathology. From September 2019 to December 2022, a total of 112 adult patients with DN were enrolled in the study. According to the density of CD4+ T cell infiltration based on immunostaining, the patients were divided into high-CD4 group (56 patients) and low-CD4 group (56 patients). Another 25 diabetic patients with minimal change disease (non-diabetic nephropathy, NDN) was reviewed as control group in clinical and molecular analysis. The clinical parameters, morphological features, and molecular characteristics were compared. The predictive value of CD4+ T cells for DN prognosis was also investigated. DN patients in the high-CD4 group suffered from higher proteinuria and lower estimated glomerular filtration rate (eGFR) level than those in the low-CD4 group and NDN patients. Renal biopsy in the high-CD4 group presented with more severe glomerular lesions, higher density of interstitial inflammation, and more severe tubular atrophy/interstitial fibrosis than in the low-CD4 group. Multivariate logistic analysis indicated that the density of CD4+ T cell infiltration could independently predict the severity of tubular atrophy/interstitial fibrosis. In addition, more severe mitochondrial damage of renal tubular epithelial cells and a more obvious expression of Bcl6, IL-6, STAT3, and TGFβ1 were observed in DN patients of the high-CD4 group, indicating the possible mechanism of CD4+ T cells involving the progression of DN. Multivariate Cox regression analysis revealed that a higher intensity of interstitial CD4+ T cell deposition remained as an independent predictor of the double endpoint with doubling of baseline serum creatinine or end-stage renal disease. The high density of CD4+ T cell infiltration was associated with renal function decline and severity of renal lesions and predicted poor renal survival for DN patients.

Effect of monoclonal gammopathy in the progression of acute kidney injury and chronic kidney disease: a retrospective observational study.

The involvement of monoclonal immunoglobulin (MIg) in renal damage in patients with haematological disorders and renal biopsy-proven monoclonal gammopathy of renal significance is well established. However, no epidemiological studies have been conducted on the effects of MIg on renal function in other patients. We aimed to evaluate the renal prognosis of MIg-positive patients and the effects of MIg on renal function. This retrospective observational study was performed using clinical data from all outpatients and inpatients who underwent MIg measurements at the time of enrolment at Kochi Medical School Hospital between 1 January 2017 and 31 December 2021. The primary outcomes were the occurrence of acute kidney injury (AKI) and a decline of > 30% in the estimated glomerular filtration rate (eGFR). Among the 1362 patients, 750 were included in our cohort. The number of MIg-positive and MIg-negative patients was 119 (15.9%) and 631 (84.1%), respectively. In addition, the MIg-positive patients were significantly older than the MIg-negative patients. The survival probability of the MIg-positive group was significantly lower than that of the MIg-negative group during the 2year observation period. The risk factors for the primary endpoint were positive MIg, female sex, lower eGFR, and lower albumin level. Our study showed that the presence of MIg was an independent risk factor for renal damage. Therefore, we suggest that MIg-positive patients require careful follow-up of their renal function, even in the absence of a clear underlying disease, such as multiple myeloma.

Comparation of two cystatin C-based eGFR equations in assessing risk of all-cause mortality and incident cardiovascular disease

BackgroundChronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 and European Kidney Function Consortium (EKFC) 2023 both recently updated the equations to estimate the glomerular filtration rate (eGFR) using cystatin C; however, little is known about the benefits of using the equations for the risk stratification of health outcomes. We conducted this longitudinal study to compare the cystatin C CKD-EPI and EKFC equations to track the risks of cardiovascular disease and all-cause mortality among Chinese adults.MethodsWe used data from China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Adjusted logistic regression models and restricted cubic spline functions were used to evaluate the relationships of cystatin C-based eGFR values with incidence of cardiovascular disease and mortality.ResultsA total of 6 496 participants were finally included in this study. The mean age of the participants was 59.6 (± 9.5) years, including 2996 (46.1%) males. There were 473 deaths and 1996 cases of cardiovascular disease observed during a maximum follow-up of 7.0 years. Using cystatin C-based CKD-EPI equation, people of eGFR < 60 mL/min/1.73 m2 had an increased risk of mortality (risk ratio [RR], 1.527; 95% CI, 1.068–2.178) and incident cardiovascular disease (RR, 1.363; 95% CI, 1.006–1.844), compared to those of eGFR ≥ 90 mL/min/1.73 m2. On the contrary, we did not observe significant associations of eGFR levels by EKFC equation with mortality nor cardiovascular disease.ConclusionsThe findings indicated that cystatin C-based eGFR using CKD-EPI equation is more closely associated with all-cause mortality and cardiovascular disease compared to EKFC equation among Chinese adults. The cystatin C-based eGFR by CKD-EPI equation should be monitored in health practice, which needs further validation in other populations.

Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease

Abstract Background We sought to comprehensively describe drug-related components associated with AKI in patients with CKD, describing the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the one-year incidences of the recurrence of drug-related AKI, kidney failure, and death. Methods CKD-REIN is a French national prospective cohort of 3,033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR &amp;lt;60 mL/min/1.73 m²). AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital reports, medical records, and patient interviews. Expert nephrologists used the KDIGO criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs). Results Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3,033 study participants. The drug-related component associated with AKI accounted for 236 cases, and 28% were judged to be preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. A history of cardiovascular events, diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥ 5 drug taken daily were associated with a greater risk of drug-related AKI. Full recovery was not attained in 64 (27%) of the 236 cases of drug-related AKI. The one-year cumulative incidences of recurrence of drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI. Conclusions Drug-related AKI is prevalent among patients with CKD. Even though a substantial proportion of these events were classified as stage 1, our findings point to a poor prognosis.

Simvastatin reduces chronic kidney disease and renal failure risk in type 2 diabetes patients: post hoc ACCORD trial analysis

ObjectiveType 2 diabetes mellitus (T2DM) poses a substantial global health concern. Statins are widely used among T2DM patients for managing dyslipidemia, preventing cardiovascular disease (CVD), and offering renal protection. However, the extent to which their renal protective effects contribute to reducing the incidence of severe renal complications, including chronic kidney disease (CKD) and renal failure, is not well-defined.MethodsThis investigation scrutinizes the impact of simvastatin versus placebo on renal outcomes among T2DM patients utilizing data from the ACCORD trial. It encompasses incidence rate comparisons, Kaplan-Meier estimates, Cox proportional hazards models, and mediation analyses.ResultsThe study consisted of 3,619 individuals diagnosed with T2DM, among which 2,753 were treated routinely with simvastatin, while 866 did not receive any statin therapy. After adjusting for baseline characteristics and time-dependent covariates, simvastatin treatment was associated with a 71% reduction in the risk of CKD (HR 0.29, 95% CI 0.27–0.31, p < 0.01) and a 47% reduction in the risk of renal failure (HR 0.53, 95% CI 0.44–0.65, p < 0.01) compared to the statin-free group. Further subgroup analysis, accounting for the initial lipid and kidney profiles, indicated variable impacts of simvastatin on CKD and renal failure outcomes. Nevertheless, a consistent reduction in CKD risk was observed across all subgroups within the statin-treated population. Additional mediation analysis revealed that the reduction in low-density lipoprotein cholesterol (LDL-C) may be a potential mediator in the association between simvastatin and CKD, with a mediation effect of 14.9%, (95% CI 0.11–0.19, p < 0.01).ConclusionAdministering statins, specifically simvastatin, to T2DM patients at elevated risk for CVD, is likely to offer augmented renal advantages, notably in lowering the occurrence of CKD and renal failure. This protective effect against CKD manifests regardless of initial lipid profiles, albuminuria, and estimated glomerular filtration rate (eGFR) levels. The association between simvastatin and CKD may be partially mediated by LDL-C reduction.

Renal tubular damage as an independent risk factor for all-cause and cardiovascular mortality in a community-based population: the Takahata study.

Renal tubular damage plays a crucial role in the development of end-stage kidney disease, a risk factor for cardiovascular events and mortality. However, the relationship between renal tubular damage and all-cause and cardiovascular mortality rates in the general population remains unclear. To address this gap, we conducted a cohort study in the general population using the urinary β2-microglobulin-creatinine ratio (UBCR) as a marker of renal tubular damage. This study included 3427 residents aged ≥ 40years in Takahata, Japan. We examined the association between the UBCR values in single-spot urine samples at enrollment and all-cause and cardiovascular mortality rates within a median follow-up of 9.2years. The participants were divided into two groups based on their UBCR levels (< 300μg/g and ≥ 300μg/g groups). Kaplan-Meier analysis showed a significantly higher incidence of all-cause and cardiovascular mortality rates in the high UBCR group (log-rank P < 0.01). Multivariable Cox proportional hazards model adjusted for age, sex, estimated glomerular filtration rate (eGFR), urine albumin level, smoking, and comorbidities showed a significantly higher hazard ratio of 1.49 (95% confidence interval (CI) 1.10-2.03, P = 0.01) for all-cause mortality and a hazard ratio of 1.73 (95% CI 1.00-2.98, P = 0.048) for cardiovascular mortality in the high-UBCR group. The net reclassification index was significantly improved by adding a high UBCR to the conventional risk factors. UBCR is an independent risk factor for all-cause and cardiovascular mortality in the general population, independent of eGFR and urinary albumin levels.

A machine learning model for predicting worsening renal function using one-year time series data in patients with type 2 diabetes.

To prevent end-stage renal disease caused by diabetic kidney disease, we created a predictive model for high-risk patients using machine learning. The reference point was the time at which each patient's estimated glomerular filtration rate (eGFR) first fell below 60 mL/min/1.73 m2. The input period spanned the reference point to 1 year prior. The primary endpoint was a 50% decrease in eGFR from the mean of the input period over the 3 year evaluation period. We created predictive models for patients' primary endpoints using time series data of various variables over the input period. Among 2,533 total patients, 1,409 had reference points, 31 had records for their input and evaluation periods and had reached their primary endpoints, and 317 patients had not. The area under the curve (AUC) of the predictive model peaked (0.81) when the minimum eGFR, the difference between maximum and minimum eGFR, and both maximum and minimum urinary protein values were included in the features. The accuracy of prognosis prediction can be improved by considering the variable components of urinary protein and eGFR levels. This model will allow us to identify patients whose renal functions are relatively preserved with eGFR of more than 60 mL/min/1.73 m2 and are likely to benefit clinically from immediate treatment intensification.

Abstract 4144585: Association of renal function with mortality and heart failure hospitalization rates after Transcatheter Mitral Valve Edge to Edge Repair

Background: Transcatheter edge to edge repair (TEER) is an established treatment for patients with symptomatic severe functional MR on optimal medical therapy or severe symptomatic primary MR and high surgical risk. Renal dysfunction is associated with adverse outcomes but the threshold at which risks rise are uncertain. Aim To determine the association of estimated glomerular filtration rate (eGFR) with adverse outcomes in patients undergoing TEER for severe symptomatic mitral regurgitation (MR) in Ontario, Canada. Methods: This was a population-based retrospective cohort study using linked administrative datasets of patients who underwent TEER in Ontario, Canada, between 2011 and 2023. The key exposure was eGFR, which was modeled using restricted cubic splines. Outcomes were 1-year mortality, cardiovascular mortality (CV) and heart failure hospitalization (HF). Cause-specific hazards regression was used to model the association between eGFR and outcomes, utilizing eGFR 30ml/min/1.73m2 as the reference value. Results: We studied 2076 patients, of whom 294 (14.2%) had eGFR &lt;30ml/min/1.73m2 and 841 (40.5%) had eGFR 30-60ml/min/1.73m2. The incidence at one year was 16.8% for all-cause mortality, 11% for CV mortality and 14.2% for HF hospitalizations. The Figure illustrates that the predicted incidence of adverse outcomes increases with lower eGFR, with subtle differences in patterns of change in risk at lower eGFR levels such that all-cause mortality and CV mortality begin to rise rapidly at eGFR values ≤30ml/min/1.73m2, while HF hospitalization increases linearly at eGFR ≤50ml/min/1.73m2. Conclusions: There was a progressive increase in all-cause, CV mortality and HF hospitalization after TEER for patients with lower eGFR, particularly those with values &lt;30 ml/min/1.73m2. This data can inform patient discussions and guide post-procedural follow-up.

Euthyroid sick syndrome predicts the risk of ischemic stroke-associated pneumonia in the acute stage of ischemic stroke: a nested case-control study.

Ischemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients. We studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group. The iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR. ESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke.

Role of metabolic dysfunction-associated steatotic liver disease and of its genetics on kidney function in childhood obesity.

Evidence linked metabolic associated steatotic liver disease (MASLD) to kidney damage with the potential contribution of the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene. We aimed at investigating the relationship of MASLD and of its genetics with kidney function in children with obesity. A comprehensive evaluation including genotyping for the I148M PNPLA3 polymorphism was performed in 1037 children with obesity. Fatty liver (FL) was assessed by liver ultrasound. According to MASLD criteria, subjects with obesity but without FL were included in group 1, while patients with obesity and FL (encompassing one MASLD criterion) were clustered into group 2. Group 3 included patients with obesity, FL, and metabolic dysregulation (encompassing >1 MASLD criterion). Alanine transaminase levels significantly increased while estimated glomerular filtration rate (eGFR) significantly reduced from group 1 to 3. Group 3 showed a higher percentage of carriers of the I148M allele of the PNPLA3 gene compared to other groups (p < 0.0001). Carriers of group 2 and of group 3 showed reduced eGFR levels than noncarriers of group 2 (p = 0.04) and of group 3 (p = 0.02), respectively. A general linear model for eGFR variance in the study population showed an inverse association of eGFR with both MASLD and PNPLA3 genotypes (p = 0.011 and p = 0.02, respectively). An inverse association of eGFR with MASLD was also confirmed only in carriers (p = 0.006). The coexistence of more than 1 MASLD criterion in children with obesity seems to adversely affect kidney function. The PNPLA3 I148M allele further impacts on this association.

Integrative bioinformatics and experimental analysis of curcumin's role in regulating ferroptosis to combat osteoporosis

This study utilized bioinformatics and data mining techniques to explore the molecular mechanism of curcumin in treating osteoporosis (OP) through the lens of ferroptosis, thereby identifying novel therapeutic targets. The datasets GSE35958, GSE35956, GSE7429, and GSE7158 were obtained from the Gene Expression Omnibus (GEO) database. GSE35958 and GSE35956 were employed as training sets for data integration, while GSE7429 and GSE7158 served as independent validation sets. Through retrieval from the FerrDb database, iron death-related genes (FRGs) were identified, and the differentially expressed genes (DEGs) were intersected to obtain differentially expressed FRGs (DEFRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, followed by the construction of a Protein-Protein Interaction (PPI) network to identify Hub genes. The DGIdb database was utilized to predict candidate drugs associated with the Hub genes, and molecular docking and in vitro experiments confirmed that curcumin targets the Hub genes EGFR and PTGS2.Through in vitro testing of curcumin on BMSC cells, researchers examined cell vitality, iron death, osteogenic differentiation, mineralization, and the impact on EGFR and PTGS2 levels. The analysis yielded 2212 DEGs, 484 FRGs, with 45 FDEGs at the intersection. GO analysis revealed involvement in regulating mitochondrial proteins, amino acid transport across plasma membranes, and protein ubiquitination. KEGG pathway analysis indicated associations with iron death, FoxO signaling, mTOR signaling, cell aging, osteoclast differentiation, and GSH metabolism. Utilizing the MCC algorithm, five Hub genes were identified: MAPK3, PTGS2, TGFB1, CYBB, and EGFR, showing diagnostic potential for iron death. Curcumin displayed affinity for EGFR and PTGS2, mitigating iron-induced effects on BMSCs such as increased reactive oxygen species, Fe3+ levels, and decreased mitochondrial membrane potential. Furthermore, curcumin reversed these effects, suggesting EGFR and PTGS2 as targets for curcumin to inhibit BMSC ferroptosis and potentially delay osteoporosis development. Maintaining iron homeostasis and targeting BMSC ferroptosis could offer therapeutic avenues for iron overload-induced osteoporosis.

Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies

Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

Relationship Between Fasting C-Peptide to Diabetes Duration Ratio (FCP/DD) and Diabetic Peripheral Neuropathy.

To explore the correlation between fasting C-peptide to diabetes duration ratio (FCP/DD) and diabetic peripheral neuropathy (DPN). The study was conducted on 816 patients with type 2 diabetes (T2DM). Subjects were classified into a diabetic peripheral neuropathy group (DPN, n=408) and a non-diabetic peripheral neuropathy group (NDPN, n=408) depending on the presence of DPN. Collected patients' baseline data, calculated the FCP/DD ratio, and analyzed the correlation between FCP/DD and DPN. A comparative analysis of general characteristics revealed that the DPN group exhibited higher values for age, DD, proportion of hypertension, proportion of DN, and proportion of DR compared to the NDPN group, Conversely, the DPN group demonstrated lower proportions of eGFR, FCP/DD, FCP, and fatty liver relative to the NDPN group, with all differences achieving statistical significance (P < 0.05). Compared to the high FCP/DD group, the low FCP/DD group exhibited higher values in age, DD, the proportion of DPN, DN, DR, and hypertension, as well as elevated levels of HDL-C and NEUT (P<0.05). Conversely, the low FCP/DD group demonstrated a lower proportion of patients who smoked and those with fatty liver, along with reduced BMI, ALB, FBG, UA, eGFR, TC, TG, and LDL-C levels (P < 0.05). In patients with T2DM, after adjusting for confounding factors, high levels of FCP/DD were found to be a protective factor for DPN (P < 0.05). The area under the curve of the FCP/DD Model predicting DPN (AUC=0.737) was higher than that of single FCP (AUC=0.587), DD (AUC=0.665). The high FCP/DD ratio was a protective factor for T2DM with DPN. Additionally, the FCP/DD ratio was found to be a better predictor for the occurrence of DPN in T2DM compared to FCP and DD alone.

Lupus nephritis: redefining the treatment goals

The course of proliferative lupus nephritis (LN) is characterized by flares of activity alternating with periods of quiescence, against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serological and histological tools to evaluate disease activity and how they may be applied to redefine the treatment goals in LN. Traditionally, treatment response is judged by the degree of proteinuria reduction and improvement of kidney function, but this fails to differentiate ongoing inflammatory disease from chronic damage. Despite intensive research, no novel biomarker has proved useful for clinical practice, and we continue to rely on anti-double-stranded DNA antibody levels (anti-dsDNA) to assess serological activity. Repeat kidney biopsies sometimes reveal persistent inflammation despite apparent clinical remission, giving credibility to the conviction that histological remission should be a treatment goal and protocol biopsies part of the decision-making process. However, the discrepancies between clinical and histological responses to therapy can be explained by persistent systemic autoimmunity with low-grade immune complex deposition or, alternatively, by delayed clearance of intrarenal inflammation once immunological remission has been achieved. Since persistent immune dysregulation is the motor of disease activity in LN, it should be the principal focus of therapy and monitoring. We propose to replace the traditional induction-remission maintenance protocol by a more dynamic and individualized approach, and aim for 3 treatment goals, concomitantly rather than sequentially: 1) Clinical remission, by attenuating renal inflammation, using microscopic hematuria, proteinuria, eGFR and complement levels as biomarkers; 2) Immunological remission, by decreasing immune complex generation, using anti-dsDNA as biomarker; 3) Preservation of kidney function, by curtailing chronic kidney damage, using eGFR slope as biomarker.