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Background: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure. Methods: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation. Results: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2‐butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2‐butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild‐type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression. Conclusions: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is commonly managed in general practice, with established guidelines for diagnosis and management. CKD is more prevalent in the older population, and is associated with lifestyle diseases as well as social deprivation. Older patients also commonly experience multimorbidity. Current CKD guidelines do not take age into account, with the same diagnostic and management recommendations for patients regardless of their age. We sought to investigate general practitioners' (GPs') approach to older patients with CKD, and whether their assessment and management differed from guideline recommendations. We explored the reasons for variation from guideline recommendations. Methods: This was a mixed methods study of Australian GPs. An online anonymous survey about the use of CKD guidelines, and assessment and management of CKD was sent to 9500 GPs. Four hundred and sixty-nine (5%) of GPs responded, and the survey was completed by 399 GPs. Subsequently, 27 GPs were interviewed in detail about their diagnostic and management approach to older patients with declining kidney function. Results: In the survey, 48% of GPs who responded found the CKD guidelines useful for diagnosis and management. Four themes arose from our interviews: age-related decline in kidney function; whole person care; patient-centred care; and process of care that highlighted the importance of continuity of care. GPs recognised that older patients have an inherently high risk of lower kidney function. The GPs reported management of that higher risk focused on managing the whole person (not just a single disease focus) and being patient-centred. Patient-centred care expressed the importance of quality of life, shared decision making and being symptom focused. There was also a recognition that there is a difference between a sudden decline in kidney function and a stable but low kidney function and GPs would manage these situations differently. Conclusions: GPs apply guidelines in the management of CKD in older patients using a patient-centred and whole person approach to care. Older patients have a high prevalence of multimorbidity, which GPs carefully considered when applying existing CKD-specific guidelines. Future iterations of CKD Guidelines need to give due consideration to multimorbidity in older patients that can adversely impact on kidney function in addition to the expected age-related functional decline. [ABSTRACT FROM AUTHOR]

Aim Patients and Methods Results Conclusion To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity.We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low‐density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow‐up period.Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86–0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43–0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non‐users (pinteraction = 0.017, 0.033 and 0.014, respectively).The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear.We determined the causal association between IBD and CKD by performing two‐sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open‐access genome‐wide association studies (GWAS) among European ancestry. IVs–outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse‐variance‐weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta‐analysed.Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016–1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027–1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969–1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965–1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948–1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963–1.089, p = 0.447).We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD. [ABSTRACT FROM AUTHOR]

This was a retrospective study. This study investigated the occurrence of a composite endpoints (cardiovascular and cerebrovascular events, end‐stage renal disease, and death) in 153 patients (aged ≥ 18 years) with a diagnosis of in chronic kidney disease (CKD). Based on morning blood pressure surge (MBPS) defined as ≥35 mm Hg, patients were divided into two groups: with MBPS (n = 50) and without MBPS (n = 103). All patients were followed up for at least 1 year. Baseline demographic, laboratory and follow‐up data were collected. The clinical characteristics of the two groups were compared. The relationships between MBPS and endpoint events were analyzed using the Kaplan–Meier method and Cox regression model. In total, 153 patients (mean age 41.8 years; 56.86% males) were included in this study. During the follow‐up period (mean 4.3 years), 34 endpoint events occurred. After adjustment for the covariates, the risk of cardiovascular and cerebrovascular events, end‐stage renal disease and death remained significantly higher in patients with MBPS (hazard ratio [HR] and 95% confidence interval [CI] 3.124 [1.096–9.130]]) Among the other variables, systolic blood pressure, and night‐time and daytime pulse pressures remained significantly associated with outcome in patients of CKD (1.789 [1.205–2.654], 1.710 [1.200–2.437], and 1.318 [1.096–1.586], respectively]. In conclusions, MBPS was identified as an independent prognostic factor for composite endpoint events (cardiovascular and cerebrovascular events, end‐stage renal disease and death) patients with chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Importance Objective Data Sources and Study Selection Results Conclusions and Relevance The recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction‐associated fatty liver disease (MAFLD) and metabolic dysfunction‐associated steatotic liver disease (MASLD) highlights the link between hepatic steatosis and metabolic dysfunction, taking out the stigmata of alcohol.We compared the effects of NAFLD and MAFLD definitions on the risk of overall and cardiovascular (CV) mortality, liver‐related events (LRE), nonfatal CV events (CVE), chronic kidney disease (CKD), and extra‐hepatic cancers (EHC).We systematically searched four large electronic databases for cohort studies (published through August 2023) that simultaneously used NAFLD and MAFLD definitions for examining the risk of mortality and adverse CV, renal, or oncological outcomes associated with both definitions. In total, 21 eligible cohort studies were identified. Meta‐analysis was performed using random‐effects modelling.Compared with those with NAFLD, individuals with MAFLD had significantly higher rates of overall mortality (random‐effect OR 1.12, 95% CI 1.04–1.21, p = .004) and CV mortality (random‐effect OR 1.15, 95% CI 1.04–1.26, p = .004), and a marginal trend towards higher rates of developing CKD (random‐effect OR 1.06, 95% CI 1.00–1.12, p = .058) and EHC events (random‐effect OR 1.11, 95% CI 1.00–1.23, p = .052). We found no significant differences in the risk LREs and nonfatal CVE between MAFLD and NAFLD. Meta‐regression analyses identified male sex and metabolic comorbidities as the strongest risk factors related to the risk of adverse clinical outcomes in MAFLD compared to NAFLD.Individuals with MAFLD have higher rates of overall and CV mortality and higher rates of developing CKD and EHC events than those with NAFLD, possibly due to the dysmetabolic risk profile related to MAFLD. [ABSTRACT FROM AUTHOR]

Background and Purpose Approach Background and Key Results Conclusions and Impact Endothelin‐1 (ET‐1) receptor A (ETA) antagonists reduce proteinuria and prevent renal outcomes in chronic kidney disease (CKD) patients, but their utility has been limited because of associated fluid retention, resulting in increased heart failure risk. Understanding the mechanisms responsible for fluid retention could result in solutions that preserve renoprotective effects while mitigating fluid retention, but the complexity of the endothelin system has made identification of the underlying mechanisms challenging.We utilized a previously developed mathematical model of ET‐1 kinetics, ETA receptor antagonism, kidney function, haemodynamics, and sodium and water homeostasis to evaluate hypotheses for mechanisms of fluid retention with ETA antagonism. To do this, we simulated the RADAR clinical trial of atrasentan in patients with type 2 diabetes and CKD and evaluated the ability of the model to predict the observed decreases in haematocrit, urine albumin creatinine ratio (UACR), mean arterial pressure (MAP), and estimated glomerular filtration rate (eGFR).An effect of ETA antagonism on venodilation and increased venous capacitance was found to be the critical mechanism necessary to reproduce the simultaneous decrease in both MAP and haematocrit observed in RADAR.These findings indicate that fluid retention with ETA antagonism may not be caused by a direct antidiuretic effect within the kidney but is instead be an adaptive response to venodilation and increased venous capacity, which acutely tends to reduce cardiac filling pressure and cardiac output, and that fluid retention occurs in an attempt to maintain cardiac filling and cardiac output. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations, recurrent cardiovascular events, and chronic kidney disease (CKD) progression, and thus constitute a Class 1a recommendation in people with diabetes and atherosclerotic cardiovascular disease, HF, or CKD and in people with severe albuminuria or HF, regardless of diabetes status. The purpose of this study was to comprehensibly characterize the rate of SGLT2 inhibitor prescriptions among people with a Class 1a recommendation for SGLT2 inhibitor use. Among 3,189,827 adults from 28 U.S. health systems within Optum Labs Data Warehouse between April 1, 2022, and March 31, 2023, we assessed SGLT2 inhibitor prescription rates, stratified by presence of diabetes and Class 1a recommendation. Among 716,387 adults with diabetes, 63.4% had a Class 1a recommendation for SGLT2 inhibitor therapy. There was little difference by Class 1a recommendation status (present: 11.9%; 95% CI: 11.9%-12.0% vs absent: 11.4%; 95% CI: 11.3%-11.6%; standardized mean difference: 1.3%). Among 2,473,440 adults without diabetes, 6.2% had a Class 1a recommendation for SGLT2 inhibitor therapy, and 3.1% (3.0%-3.2%) of those received a prescription. Internists/family practitioners initiated SGLT2 inhibitor prescriptions most commonly among people with diabetes, whereas specialists initiated SGLT2 inhibitor prescriptions most commonly among people without diabetes. No health system had >25% SGLT2 inhibitor prescription rate among people with a Class 1a recommendation. Health systems with higher proportions of patients with commercial insurance and lower proportions with Medicare had higher SGLT2 inhibitor prescription rates. In this analysis of U.S. data from 2022 to 2023, SGLT2 inhibitor prescription among people with a Class 1a recommendation is low. Interventions are needed to increase uptake of guideline-recommended SGLT2 inhibitor use. [ABSTRACT FROM AUTHOR]

Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed. The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D. Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes. The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status. SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317) [ABSTRACT FROM AUTHOR]

Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 μg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 μg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients. [Display omitted] • Sulforaphane increases levels of nuclear factor erythroid 2-related factor 2 (NRF2). • Sulforaphane modulates oxidative stress in renal patients. • Sulforaphane increases the expression of antioxidant enzymes in renal patients. [ABSTRACT FROM AUTHOR]

Background: The relationship between epilepsy and risk of acute myocardial infarction (AMI) is not fully understood. Evidence from the Stockholm Heart Study indicates that the risk of AMI is increased in people with epilepsy. This study aims to analyze the temporal trends in prevalence, adverse clinical outcomes, and risk factors of AMI in patients with epilepsy (PWE). Methods: Patients aged 18 years or older, diagnosed with epilepsy with or without AMI and hospitalized from January 1, 2008, to December 31, 2017, were identified from the National Inpatient Sample (NIS) database. The Cochran-Armitage trend test and logistic regressions were conducted using SAS 9.4. Odds ratios (ORs) were generated for multiple variables. Results: A total of 8,456,098 inpatients were eligible for our analysis, including 181,826 comorbid with AMI (2.15%). The prevalence of AMI diagnosis in PWE significantly increased from 1,911.7 per 100,000 hospitalizations in 2008 to 2,529.5 per 100,000 hospitalizations in 2017 (Ptrend < 0.001). Inpatient mortality was significantly higher in epilepsy patients with AMI compared to those without AMI (OR = 4.61, 95% CI: 4.54 to 4.69). Factors significantly associated with AMI in PWE included age (=75 years old vs. 18 ~ 44 years old, OR = 3.54, 95% CI: 3.45 to 3.62), atherosclerosis (OR = 4.44, 95% CI: 4.40 to 4.49), conduction disorders (OR = 2.21, 95% CI: 2.17 to 2.26), cardiomyopathy (OR = 2.11, 95% CI: 2.08 to 2.15), coagulopathy (OR = 1.52, 95% CI: 1.49 to 1.54), dyslipidemia (OR = 1.26, 95% CI: 1.24 to 1.27), peptic ulcer disease (OR = 1.23, 95% CI: 1.13 to 1.33), chronic kidney disease (OR = 1.23, 95% CI: 1.22 to 1.25), smoking (OR = 1.20, 95% CI: 1.18 to 1.21), and weight loss (OR = 1.20, 95% CI: 1.18 to 1.22). Conclusion: The prevalence of AMI in PWE increased during the decade. Mortality rates were high among this population, highlighting the need for comprehensive attention to prophylaxis for risk factors and early diagnosis of AMI in PWE by physicians. [ABSTRACT FROM AUTHOR]

Purpose: To compare the dietary inflammatory index (DII), triglyceride glucose index (TyG), waist triglyceride index (WTI), and body mass index (BMI) in predicting the survival of chronic kidney disease (CKD). Methodology: Inclusion of 23,099 participants from the NHANES database who met specific criteria. Baseline was established using quartiles of DII index. The relationship between DII index, WTI index, TyG index, and BMI index with mortality rate in CKD patients was evaluated using Kaplan-Meier curves. Univariate and multivariate COX regression risk models were used to study the relationship between DII index, WTI index, and TyG index with mortality risk in CKD patients. Stratification of eGFR by age and gender was conducted to investigate the association between DII index, WTI index, and TyG index with mortality risk in CKD patients. Restricted cubic spline analysis was used to study the correlation between DII index, WTI index, and TyG index with mortality risk in CKD patients. Results: The incidence of CKD increased with the increase of DII index, WTI index and TyG index. After multivariable adjustment, the fourth quartile of DII index, TyG index and WTI index showed the highest risk for CKD [DII: hazard ratio (HR) 1.36, 95% confidential interval (CI) (1.23-1.51); TyG: HR 1.21; 95% CI (1.07-1.37); WTI: HR 1.29; 95% CI (1.13-1.46)]. There was no difference in the risk of developing CKD between the obese group (BMI ≥24 kg/m2) and the normal weight group (P>0.05). Conclusion: This study has identified a significant association between elevated DII index, WTI index, and TyG index with the risk of CKD. Furthermore, the DII index demonstrated superior prognostic capability in predicting CKD compared to other indicators. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes. Methods: We conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups. Results: The CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD. Conclusions: The dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD. [ABSTRACT FROM AUTHOR]

Dental caries and periodontal disease are typical oral diseases frequently observed in patients with renal diseases. Tooth loss is an outcome of dental caries and periodontal disease, and the number of existing teeth is an indicator of oral health status. However, the association between the number of existing teeth and end-stage kidney disease (ESKD) has not been investigated in detail. This study aimed to investigate the association between oral health status, expressed by the number of existing teeth, and ESKD. We analyzed data from the second survey of the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists, a cohort study conducted among members of the Japan Dental Association. From August 2016 to July 2017, self-administered questionnaires were mailed to 16,128 male dentists and 8,722 responded. Among them, 7,479 men with complete data on age, number of existing teeth, and ESKD were included in the analysis. Multivariate logistic regression analysis was conducted, with ESKD as the dependent variable and the number of existing teeth (≥23 teeth and <23 teeth) as the independent variable. Subgroup analysis by age (<65 years and ≥65 years) was also conducted. The <23 teeth group had a significantly higher rate of ESKD than did the ≥23 teeth group. After adjusting for age, body mass index, smoking habits, hypertension, and diabetes mellitus, there was no significant association between having <23 teeth and ESKD in all participants. However, the subgroup analysis revealed a significant association after adjustment for covariates in participants aged <65 years but not in those aged ≥65 years. In conclusion, having <23 teeth was associated with the risk of requiring maintenance dialysis therapy among Japanese men aged <65 years. Therefore, tooth loss may be associated with renal function decline. [ABSTRACT FROM AUTHOR]

End-stage kidney disease (ESKD) presents a significant public health challenge, with hemodialysis (HD) remaining one of the most prevalent kidney replacement therapies. Ensuring the longevity and functionality of arteriovenous accesses is challenging for HD patients. Blood flow sound, which contains valuable information, has often been neglected in the past. However, machine learning offers a new approach, leveraging data non-invasively and learning autonomously to match the experience of healthcare professionas. This study aimed to devise a model for detecting arteriovenous grafts (AVGs) stenosis. A smartphone stethoscope was used to record the sound of AVG blood flow at the arterial and venous sides, with each recording lasting one minute. The sound recordings were transformed into mel spectrograms, and a 14-layer convolutional neural network (CNN) was employed to detect stenosis. The CNN comprised six convolution blocks with 3x3 kernel mapping, batch normalization, and rectified linear unit activation function. We applied contrastive learning to train the pre-training audio neural networks model with unlabeled data through self-supervised learning, followed by fine-tuning. In total, 27,406 dialysis session blood flow sounds were documented, including 180 stenosis blood flow sounds. Our proposed framework demonstrated a significant improvement (p<0.05) over training from scratch and a popular pre-trained audio neural networks (PANNs) model, achieving an accuracy of 0.9279, precision of 0.8462, and recall of 0.8077, compared to previous values of 0.8649, 0.7391, and 0.6538. This study illustrates how contrastive learning with unlabeled blood flow sound data can enhance convolutional neural networks for detecting AVG stenosis in HD patients. [ABSTRACT FROM AUTHOR]

Background: Recurrent dehydration causes chronic kidney disease in humans and animal models. The dromedary camel kidney has remarkable capacity to preserve water and solute during long-term dehydration. In this study, we investigated the effects of dehydration and subsequent rehydration in the camel's kidney histology/ultrastructure and changes in aquaporin/solute carrier proteins along with gene expression. Results: In light microscopy, dehydration induced few degenerative and necrotic changes in cells of the cortical tubules with unapparent or little effect on medullary cells. The ultrastructural changes encountered in the cortex were infrequent during dehydration and included nuclear chromatin condensation, cytoplasmic vacuolization, mitochondrial swelling, endoplasmic reticulum/ lysosomal degeneration and sometimes cell death. Some mRNA gene expressions involved in cell stability were upregulated by dehydration. Lesions in endothelial capillaries, glomerular membranes and podocyte tertiary processes in dehydrated camels indicated disruption of glomerular filtration barrier which were mostly corrected by rehydration. The changes in proximal tubules brush borders after dehydration, were accompanied by down regulation of ATP1A1 mRNA involved in Na + /K + pump that were corrected by rehydration. The increased serum Na, osmolality and vasopressin were paralleled by modulation in expression level for corresponding SLC genes with net Na retention in cortex which were corrected by rehydration. Medullary collecting ducts and interstitial connective tissue were mostly unaffected during dehydration. CKD, a chronic nephropathy induced by recurrent dehydration in human and animal models and characterized by interstitial fibrosis and glomerular sclerosis, were not observed in the dehydrated/rehydrated camel kidneys. The initiating factors, endogenous fructose, AVP/AVPR2 and uric acid levels were not much affected. TGF-β1 protein and TGF-β1gene expression showed no changes by dehydration in cortex/medulla to mediate fibrosis. KCNN4 gene expression level was hardly detected in the dehydrated camel's kidney; to encode for Ca + + -gated KCa3.1 channel for Ca + + influx to instigate TGF-β1. Modulation of AQP 1, 2, 3, 4, 9 and SLC protein and/or mRNAs expression levels during dehydration/rehydration was reported. Conclusions: Long-term dehydration induces reversible or irreversible ultrastructural changes in kidney cortex with minor effects in medulla. Modulation of AQP channels, SLC and their mRNAs expression levels during dehydration/rehydration have a role in water conservation. Cortex and medulla respond differently to dehydration/rehydration. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. Methods: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. Results: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively. Conclusion: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a global public health problem with major human and economic consequences. Despite advances in clinical guidelines, classification systems and evidence-based treatments, CKD remains underdiagnosed and undertreated and is predicted to be the fifth leading cause of death globally by 2040. This review aims to identify barriers and enablers to the effective detection, diagnosis, disclosure and management of CKD since the introduction of the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in 2002, advocating for a renewed approach in response to updated Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical guidelines. The last two decades of improvements in CKD care in the UK are underpinned by international adoption of the KDIGO classification system, mixed adoption of evidence-based treatments and research informed clinical guidelines and policy. Interpretation of evidence within clinical and academic communities has stimulated significant debate of how best to implement such evidence which has frequently fuelled and frustratingly forestalled progress in CKD care. Key enablers of effective CKD care include clinical classification systems (KDIGO), evidence-based treatments, electronic health record tools, financially incentivised care, medical education and policy changes. Barriers to effective CKD care are extensive; key barriers include clinician concerns regarding overdiagnosis, a lack of financially incentivised care in primary care, complex clinical guidelines, managing CKD in the context of multimorbidity, bureaucratic burden in primary care, underutilisation of sodium-glucose co-transporter-2 inhibitor (SGLT2i) medications, insufficient medical education in CKD, and most recently – a sustained disruption to routine CKD care during and after the COVID-19 pandemic. Future CKD care in UK primary care must be informed by lessons of the last two decades. Making step change, over incremental improvements in CKD care at scale requires a renewed approach that addresses key barriers to detection, diagnosis, disclosure and management across traditional boundaries of healthcare, social care, and public health. Improved coding accuracy in primary care, increased use of SGLT2i medications, and risk-based care offer promising, cost-effective avenues to improve patient and population-level kidney health. Financial incentives generally improve achievement of care quality indicators – a review of financial and non-financial incentives in CKD care is urgently needed. [ABSTRACT FROM AUTHOR]

The article addresses the increasing recognition of genetic factors in chronic kidney disease (CKD) and the role of genetics in improving diagnosis and management. Topics include the growing importance of genetic testing for CKD, advancements in understanding the genetic basis of kidney diseases, and the evolving identification of genetic causes of CKD in both children and adults.

Aim: To describe the development of a shared decision making intervention for planning end‐of‐life care for patients with kidney failure, their relatives and health professionals in kidney services. Background: End‐of‐life care conversations within standard disease management consultations are challenging for patients with kidney failure, their relatives and health professionals. End‐of‐life care planning is about making difficult decisions in advance, which is why health professionals need shared decision making skills to be able to initiate end‐of‐life conversations. Health professionals report needing more skills to raise the issue of end‐of‐life care options within consultations and patients want to be able to discuss issues important to them about future care plans. Methods: The development design was guided by the UK Medical Research Council's framework and a user‐centred approach was applied. Four workshops were conducted with end users. The Template for Intervention Description and Replication for Population Health and Policy interventions was used to shape which questions needed to be answered through the workshops and to present the intervention. The International Patient Decision Aid Standards (IPDAS) criteria set the standards to be achieved. Results: Areas considered significant to a shared decision making intervention were training of health professionals, conversations about end‐of‐life care, planning and evaluation of the decisions, reporting decisions in health records and repetition of consultation. The development process went through 14 iterations. Conclusion: An intervention named DESIRE was developed that comprises: (1) a training programme for health professionals; (2) shared decision making conversations; and (3) a patient decision aid. The intervention met 30 out of 33 IPDAS criteria. Implications for practice: DESIRE is intended to support shared decision making about planning end‐of‐life care among patients with kidney failure, their relatives and health professionals. The study provides important tools for the stakeholders engaged that can be used within different models of care. Impact: What problem did the study address?: International guidelines recommend health professionals involve patients with kidney failure in making decisions about end‐of‐life care, but there is variation in how this is implemented within and across kidney services. Furthermore, patients, relatives and health professionals find it challenging to initiate conversations about end‐of‐life care. What were the main findings?: The study resulted in the development of a complex intervention, called DESIRE, about shared decision making and planning end‐of‐life care for patients with kidney failure, their relatives and health professionals in kidney services, including a training programme for health professionals, shared decision making conversations and a patient decision aid. Where and on whom will the research have an impact?: The research contributes a shared decision making intervention to patients in the later stage of kidney failure, their relatives and health professionals. We believe that the DESIRE intervention could be introduced during consultations with health professionals at an earlier stage of the patient's illness trajectory, as well as being applied to other chronic diseases. Reporting Method: This intervention development research is reported according to the GUIDance for the rEporting of intervention Development (GUIDED) checklist and the DEVELOPTOOLS Reporting Checklist. Patient or Public Contribution: Patients, relatives and health professionals have been involved throughout the research process as part of the research team and advisory board. For this study, the advisory board has particularly contributed to the development process of the DESIRE intervention by actively participating in the four workshops, in the iterations between the workshops and in the preparation of the manuscript. [ABSTRACT FROM AUTHOR]

Hyperkalaemia is associated with prolonged hospital admission and worse mortality. Hyperkalaemia may also necessitate clinical consults, therapies for hyperkalaemia and high-dependency bed utilisation. We evaluated the 'hidden' human and organisational resource utilisation for hyperkalaemia in hospitalised patients. This was a single-centre, observational cohort study (Jan 2017–Dec 2020) at a tertiary-care hospital. The CogStack system (data processing and analytics platform) was used to search unstructured and structured data from individual patient records. Association between potassium and death was modelled using cubic spline regression, adjusted for age, sex, and comorbidities. Cox proportional hazards estimated the hazard of death compared with normokalaemia (3.5–5.0 mmol/l). 129,172 patients had potassium measurements in the emergency department. Incidence of hyperkalaemia was 85.7 per 1000. There were 49,011 emergency admissions. Potassium > 6.5 mmol/L had 3.9-fold worse in-hospital mortality than normokalaemia. Chronic kidney disease was present in 21% with potassium 5–5.5 mmol/L and 54% with potassium > 6.5 mmol/L. For diabetes, it was 20% and 32%, respectively. Of those with potassium > 6.5 mmol/L, 29% had nephrology review, and 13% critical care review; in this group 22% transferred to renal wards and 8% to the critical care unit. Dialysis was used in 39% of those with peak potassium > 6.5 mmol/L. Admission hyperkalaemia and hypokalaemia were independently associated with reduced likelihood of hospital discharge. Hyperkalaemia is associated with greater in-hospital mortality and reduced likelihood of hospital discharge. It necessitated significant utilisation of nephrology and critical care consultations and greater likelihood of patient transfer to renal and critical care. [ABSTRACT FROM AUTHOR]

Background: Calcified amorphous tumor of the heart is a rare non-neoplastic cardiac mass composed of calcified nodules over amorphous fibrous tissue with degeneration and some chronic inflammation. Calcified amorphous tumor is often associated with mitral annular calcification in patients with end-stage renal disease on dialysis. However, the exact etiology of calcified amorphous tumors remains uncertain. Case presentation: A 77-year-old female with lung cancer showed a tumor with large mobility in the left ventricular outflow tract on transthoracic echocardiography. She had mitral annular calcification, although her renal function was normal. The tumor was excised surgically. Pathologically, the extracted specimen consisted of a calcified lesion without tumor tissue and was diagnosed as a calcified amorphous tumor. Conclusions: As the patient had no other risk factors for calcified amorphous tumor except mitral annular calcification, we considered the association of blood coagulation abnormalities due to cancer-related thrombosis. This case suggests that calcified amorphous tumors may be associated with malignant tumors. [ABSTRACT FROM AUTHOR]

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280–6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC. [ABSTRACT FROM AUTHOR]

Using a nationwide multicenter prospective registry in Japan's data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores' accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score's discrimination ability was evaluated by the receiver operating characteristic curve's area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems. [ABSTRACT FROM AUTHOR]

Background: We evaluated the prevalence of "heart stress" (HS) based on NT-proBNP cut-points proposed by the 2023 Consensus of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in asymptomatic patients with T2DM and hypertension or high-normal blood pressure (BP) eligible for SGLT2 inhibitors (SGLT2i) and/or GLP-1 receptor agonists (GLP1-RA), drugs with proven benefits on reducing the incidence of HF, hospitalizations, cardiovascular events and mortality. Methods: A cross-sectional multicentric study was conducted on 192 consecutive outpatients, aged ≥ 55 years, with hypertension or high-normal BP, referred to three diabetology units. NT-proBNP was collected before starting new anti-diabetic therapy. Patients with known HF were excluded, and participants were classified based on the age-adjusted NT-proBNP cut-points. Results: Mean age: 70.3 ± 7.8 years (67.5% males). Patients with obesity (BMI ≥ 30 Kg/m2): 63.8%. Median NT-proBNP: 96.0 (38.8–213.0) pg/mL. Prevalence of chronic kidney disease (CKD, eGFR < 60 mL/min/1.73m2): 32.1%. Mean arterial BP: 138.5/77.0 ± 15.8/9.9 mmHg. The NT-proBNP values, according to the proposed age-adjusted cut-points, classified 28.6% of patients as "HS likely" (organize elective echocardiography and specialist evaluation), 43.2% as "HS not likely" (a grey area, repeat NT-proBNP at six months) and 28.2% as "very unlikely HS" (repeat NT-proBNP at one year). The presence of CKD and the number of anti-hypertensive drugs, but not glycemic parameters, were independently associated with HS. Conclusions: According to NT-proBNP, over a quarter of T2DM patients with hypertension/high-normal BP, among those eligible for SGLT2i and/or GLP1-RA, were already at risk of cardiac damage, even subclinical. Most would receive an indication to echocardiogram and be referred to a specialist, allowing the early implementation of effective strategies to prevent or delay the progression to advanced stages of cardiac disease and overt HF. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the common outcome of practically all progressive forms of chronic kidney disease (CKD), a significant societal health concern. Glutamate dehydrogenase (GDH) 1 is one of key enzymes in glutamine metabolism to catalyze the reversible conversion of glutamate to α‐ketoglutarate and ammonia. However, its function in renal fibrosis has not yet been proven. In this study, GDH1 expression was significantly downregulated in kidney tissues of both children with kidney disease and animal models of CKD. In vivo, the use of R162 (a GDH1 inhibitor) significantly improved renal fibrosis, as indicated by Sirius red and Masson trichrome staining. These findings are consistent with the impaired expression of fibrosis indicators in kidneys from both the unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (5/6 Nx) models. In vitro, silencing GDH1 or pretreatment with R162 inhibited the induction of fibrosis indicators in tissue kidney proximal tubular cells (TKPTS) treated with Transforming growth factor Beta 1 (TGF‐β1), whereas activating GDH1 worsened TGF‐β1's induction impact. Using RNA‐sequence, luciferase reporter assays and Biacore analysis, we demonstrated that GDH1 interacts with Peroxisome proliferator‐activated receptor gamma (PPARγ) and blocks its transcriptional activity, independent of the protein's expression. Additionally, R162 treatment boosted PPARγ transcriptional activity, and blocking of this signaling pathway reversed R162's protective effect. Finally, we discovered that R162 treatment or silencing GDH1 greatly lowered reactive oxygen species (ROS) and lipid accumulation. These findings concluded that suppressing GDH1 or R162 treatment could prevent renal fibrosis by augmenting PPARγ transcriptional activity to control lipid accumulation and redox balance. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions This study aimed to explore the value of ultrasound (US) images in chronic kidney disease (CKD) screening by constructing a CKD screening model based on grey‐scale US images.According to the CKD diagnostic criteria, 1049 patients from Tongde Hospital of Zhejiang Province were retrospectively enrolled in the study. A total of 4365 renal US images were collected from these patients. Convolutional neural networks were used for feature extractions and a screening model was constructed by fusing ResNet34 and texture features to identify CKD and its stage. A comparative analysis was performed to compare the diagnosis results of the model with physicians.When diagnosing CKD or non‐CKD, the receiver operating characteristic curve (AUC) of our model was 0.918 and that of the senior physician group was 0.869 (p < .05). For the diagnosis of CKD stage, the AUC of our model for CKD G1–G3 was 0.781, 0.880, and 0.905, respectively, while the AUC of the senior physician group for CKD G1–G3 was 0.506, 0.586, and 0.796, respectively; all differences were statistically significant (p < .05). The diagnostic efficiency of our model for CKD G4 and G5 reached the level of the senior physicians group. Specifically, the AUC of our model for CKD G4‐G5 was 0.867 and 0.931, respectively, while the AUC of the senior physician group for CKD G4‐G5 was 0.838 and 0.963, respectively (all p > .05).Our deep learning radiomics model is more effective than senior physicians in the diagnosis of early CKD. [ABSTRACT FROM AUTHOR]

Introduction: There remains an unmet need to reduce kidney and cardiovascular risk in patients with chronic kidney disease (CKD). This report is therefore intended to provide real-world clinical guidance to primary care providers on sodium-glucose co-transporter-2 (SGLT2) inhibitor use in patients with CKD, focusing on practical considerations. Initially developed as glucose-lowering drugs, SGLT2 inhibitors preserve kidney function and reduce risks of cardiovascular events and mortality. Clinical benefits of SGLT2 inhibitors in CKD have been demonstrated in multiple clinical trials, yet utilization in practice remains relatively low, likely due to the complexity of labeled indications (past and present) and misconceptions about SGLT2 inhibitors as a class. Methods: A panel of 8 US-based nephrologists convened in August 2022 to develop consensus guidance for the primary care community surrounding risk assessment as well as initiation and implementation of SGLT2 inhibitors in patients with CKD. Here, we provide an adapted version of the Kidney Disease: Improving Global Outcomes (KDIGO) heatmap and a treatment-decision algorithm. Conclusions: We advocate SGLT2 inhibitors as co-first-line therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors, where RAAS inhibitor dose titration need not be completed before initiation of an SGLT2 inhibitor. In fact, SGLT2 inhibitor therapy may facilitate up-titration or maintenance of optimal RAAS inhibitor dosing. We describe potential strategies to aid implementation of an SGLT2 inhibitor in clinical practice, including improving education and awareness among care providers and patients and dispelling misconceptions about the safety of SGLT2 inhibitors. In summary, we support the use of SGLT2 inhibitors with RAAS inhibitors as co-first-line therapy in most patients with CKD. [ABSTRACT FROM AUTHOR]

Introduction: Vascular calcification is accelerated in patients with chronic kidney disease (CKD) and increases the risk of cardiovascular events. CKD is frequently associated with anemia. Daprodustat (DPD) is a prolyl hydroxylase inhibitor for the treatment of CKD-associated anemia that enhances erythropoiesis through the activation of the hypoxia-inducible factor 1 (HIF-1) pathway. Studies showed that DPD promotes osteogenic differentiation of human aortic smooth muscle cells (HAoSMCs) and increases aorta calcification in mice with CKD. HIF-1 activation has been linked with endoplasmic reticulum (ER) stress; therefore, here we investigated the potential contribution of ER stress, particularly activating transcription factor 4 (ATF4), to the pro-calcification effect of DPD. Methods: Here, we used an adenine-induced CKD mouse model and HAoSMCs as an in vitro vascular calcification model to study the effect of DPD. Results: DPD treatment (15 mg/kg/day) corrects anemia but increases the expression of hypoxia (Glut1, VEGFA), ER stress (ATF4, CHOP, and GRP78), and osteo-/chondrogenic (Runx2, Sox9, BMP2, and Msx2) markers and accelerates aorta and kidney calcification in CKD mice. DPD activates the PERK/eIF2α/ATF4/CHOP pathway and promotes high phosphate-induced osteo-/chondrogenic differentiation of HAoSMCs. Inhibition of ER stress with 4-PBA or silencing of ATF4 attenuates HAoSMC calcification. DPD-induced ATF4 expression is abolished in the absence of HIF-1α; however, knockdown of ATF4 does not affect HIF-1α expression. Conclusion: We concluded that DPD induces ER stress in vitro and in vivo, in which ATF4 serves as a downstream effector of HIF-1 activation. Targeting ATF4 could be a potential therapeutic approach to attenuate the pro-calcific effect of DPD. [ABSTRACT FROM AUTHOR]

Background: PCSK9 inhibitors are a novel class of lipid-lowering medications, and numerous clinical studies have confirmed their significant role in improving the progression of chronic kidney disease. However, recent case reports have indicated new evidence regarding their association with acute kidney injury (AKI), with some patients experiencing acute tubular injury after PCSK9 inhibitors use. Objectives: To clarify the relationship between PCSK9 inhibitors and AKI, we conducted a pharmacovigilance study. Methods: Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2015 to the fourth quarter of 2022, a disproportionality analysis was employed to identify adverse events suggestive of AKI after PCSK9 inhibitors use. The drugs of interest included evolocumab and alirocumab. Results: A total of 144,341 adverse event reports related to PCSK9 inhibitors were analyzed, among which 444 cases were suspected of AKI for evolocumab, and 172 cases for alirocumab. Evolocumab had a greater impact on AKI in males (ROR 1.4, 95% CI 1.54-1.69). The ROR and 95% CI for evolocumab and Alirocumab were 0.13 (0.12-0.14) and 0.26 (0.23-0.30) respectively. Further analysis of AKI associated with the concomitant use of PCSK9 inhibitors with cephalosporins, furosemide, torsemide, pantoprazole, omeprazole, and esomeprazole revealed ROR and 95% CI of 0.38 (0.23-0.62), 0.38 (0.31-0.48), 0.18 (0.08-0.38), 0.23 (0.17-0.29), 0.20 (0.16-0.26), and 0.14 (0.10-0.20) respectively. Conclusion: Through the FAERS database, we analyzed the clinical characteristics of AKI associated with PCSK9 inhibitors, exploring its risks. Our findings suggest that PCSK9 inhibitors might have a potential protective effect against AKI and exhibit similar effects when co-administered with other nephrotoxic drugs. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter two inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists, have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease, providing a new perspective on the clinical diagnosis and treatment of DKD. [ABSTRACT FROM AUTHOR]

Introduction: Chronic kidney disease(CKD) is a global medical problem. Serum methylmalonic acid(MMA) is a serum marker associated with many diseases. This study aimed to investigate the association between MMA and CKD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 were downloaded and analyzed. The association between MMA and CKD was confirmed by using multiple logistic regression modeling. The smooth curve fitting method was used to investigate the nonlinear relationship between them. Subgroup analyses and interaction tests were used to verify the stability of the association between different subgroups. Threshold effect analysis was used to determine the optimal control point for MMA. Results: There was a unique W-shaped nonlinear relationship between MMA and the risk of CKD, with a positive correlation between them (OR=1.66,95% CI:1.27, 2.17; P=0.0002). As the stage of CKD progressed, MMA levels increased. Age, hypertension, and serum vitamin B12 had significant influences on the association between MMA and the risk of CKD. Conclusion: Our findings revealed that serum MMA accumulation was positively associated with the risk of CKD. Serum MMA level may be a novel index to predict the development and course of CKD. This study may help in the early identification of people at risk for chronic kidney disease and provide new ideas and approaches for prevention and treatment. [ABSTRACT FROM AUTHOR]

Introduction: Data on sodium glucose co-transporter 2 inhibitors impact on lipids in patients with diabetes are available and only a handful of studies have explored this effect in individuals with both diabetes and renal impairment; lipid parameters were not the primary focus of those earlier studies. However, there is a significant research gap specifically addressing the influence of SGLT2 inhibitors on cholesterol fractions in patients exclusively with chronic kidney disease. This aim constitutes the central objective in this particular study. Methods: In this 3-month randomized controlled study, 30 patients with stage 3 chronic kidney disease and dyslipidemia were randomly assigned to receive either dapagliflozin 10 mg or placebo. Lipid profiles, renal function, and urinary albumin levels were assessed at baseline and after 3 months. Results: Compared to baseline, patients receiving dapagliflozin for 3 months showed significant improvements in serum creatinine (p <.001) and eGFR (p =.001). Total cholesterol and LDL-C levels decreased significantly (p =.010 and.006, respectively). While albumin-creatinine ratio also decreased, this change was not statistically significant. Additionally, HDL-C and TG not significantly increased. The control group without intervention experienced deterioration in serum creatinine and eGFR (p =.008, and.011, respectively), but no statistically significant lipid changes were observed. Furthermore, post-intervention total cholesterol moderately correlated with BMI (p =.032, R =.554), yet no predictors significantly influenced lipid levels in the multiple linear regression analysis. Conclusions: Dapagliflozin has a favorable effect on cholesterol fractions in stage 3 CKD patients without diabetes mellitus and this effect was different from that observed in patients with diabetes alone. [ABSTRACT FROM AUTHOR]

Background: Accurate detection of kidney damage is key to preventing renal failure, and identifying biomarkers is essential for this purpose. We aimed to assess the accuracy of miRNAs as diagnostic tools for chronic kidney disease (CKD). Methods: We thoroughly searched five databases (MEDLINE, Web of Science, Embase, Scopus, and CENTRAL) and performed a meta-analysis using R software. We assessed the overall diagnostic potential using the pooled area under the curve (pAUC), sensitivity (SEN), and specificity (SPE) values and the risk of bias by using the QUADAS-2 tool. The study protocol was registered on PROSPERO (CRD42021282785). Results: We analyzed data from 8351 CKD patients, 2989 healthy individuals, and 4331 people with chronic diseases. Among the single miRNAs, the pooled SEN was 0.82, and the SPE was 0.81 for diabetic nephropathy (DN) vs. diabetes mellitus (DM). The SEN and SPE were 0.91 and 0.89 for DN and healthy controls, respectively. miR-192 was the most frequently reported miRNA in DN patients, with a pAUC of 0.91 and SEN and SPE of 0.89 and 0.89, respectively, compared to those in healthy controls. The panel of miRNAs outperformed the single miRNAs (pAUC of 0.86 vs. 0.79, p < 0.05). The SEN and SPE of the panel miRNAs were 0.89 and 0.73, respectively, for DN vs. DM. In the lupus nephritis (LN) vs. systemic lupus erythematosus (SLE) cohorts, the SEN and SPE were 0.84 and 0.81, respectively. Urinary miRNAs tended to be more effective than blood miRNAs (p = 0.06). Conclusion: MiRNAs show promise as effective diagnostic markers for CKD. The detection of miRNAs in urine and the use of a panel of miRNAs allows more accurate diagnosis. Key Learning Points: 1. The diagnostic performance of miRNAs in chronic kidney diseases needs to be investigated, as previous systematic reviews and meta-analyses are scarce, and individual cohort studies have confirmed their importance in kidney pathophysiology. 2. Using multiple miRNAs as biomarkers can lead to more precise CKD diagnosis, as they outperform single miRNAs compared to healthy and people with chronic disease groups. The overall diagnostic accuracy of urinary miRNAs tended to be greater than that of blood samples, suggesting that they are noninvasive and readily available diagnostic markers in CKD patients. 3. Incorporating miRNAs as diagnostic markers for CKD in combination with traditional markers might improve the accuracy and efficiency of diagnosis. To optimize miRNA diagnostic performance, it is essential to consider the various biological sample types, comparison groups (control), and different kidney diseases. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A Ushaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285mmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72--7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71--4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14--0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24--4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction. [ABSTRACT FROM AUTHOR]

Introduction: Currently, kidney disease is an increasing major health problem worldwide. It is expected to be the 5th ranked cause of death by 2040. If it is early detected, further complication caused by kidney disease will be minimized. An assessment of impaired glomerular filtration rate (eGFR) has potential aids in early identification and treatment of kidney disease. However, in hospital practice instead of using eGFR, direct measurement of serum creatinine level is used for assessing renal function. Hence, this study is aimed to assess the magnitude and associated factors of impaired glomerular filtration rate among admitted patients in Wolkite University Specialized Teaching Hospital (WKUSTH). Objective: To assess the magnitude and associated factors of impaired glomerular filtration rate in WKUSTH, Ethiopia 2023. Method: Institutional based cross-sectional study with secondary data was conducted. 338 participants were selected by a convenient sampling technique. Epidata 3.1 version for data entry and SPSS version 20 for data analysis was used. Bivariate analysis was used to screen candidate variables for multivariate analysis. In the multivariate analysis a P-value < 0.05 were considered statistically significant. Results: The study enrolled 338 patients admitted to WUSTH. Seventy (20.7%) (95% CI: 16.6–25.4%) of them had impaired eGFR according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and Modification of Diet in Renal Disease (MDRD-4). older age (AOR 3.38, 95% CI; 1.31, 8.71), hypertension (AOR 17.8, 95% CI; 7.75, 41.22), anemia (AOR 2.51, 95% CI; 1.11, 5.83) DM (AOR 11.2, 95% CI; 4.11, 30.73), and high BMI (AOR 7.56, 95% CI; 3.16, 18.08), were independently associated with impaired eGFR. Conclusions: The magnitude of impaired eGFR was prevalent among adult patients admitted to WKUSTH medical ward with different medical conditions. Old age, Hypertension, Diabetes, high body mass index, and Anemia were significantly associated with impaired eGFR both in CKD-EPI and MDRD-4 equation. Estimation of GFR for all hospitalized adults with known CKD risk factors might help in early detection of CKD and prevent complications. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition, we generated a single-nucleus multiomic atlas for the full mouse AKI time course, consisting of ~280,000 single-nucleus transcriptomes and epigenomes. We reveal cell-specific dynamic alterations in gene regulatory landscapes reflecting, especially, activation of proinflammatory pathways. We further generated single-nucleus multiomic data from four human AKI samples including validation by genome-wide identification of nuclear factor κB binding sites. A regularized regression analysis identifies key regulators involved in both successful and failed repair cell fate, identifying the transcription factor CREB5 as a regulator of both successful and failed tubular repair that also drives proximal tubular cell proliferation after injury. Our interspecies multiomic approach provides a foundation to comprehensively understand cell states in AKI. [ABSTRACT FROM AUTHOR]

Increased protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) are associated with cardiovascular diseases (CVDs); however, whether retention of PBUTs causes CVD remains unclear. Previous studies assessing the impacts of PBUTs on the vasculature have relied on 2D cell cultures lacking in vivo microenvironments. Here, we investigated the impact of various PBUTs (p-cresol (PC), indoxyl sulfate (IS), and p-cresyl sulfate (PCS)) on microvascular function using an organ-on-a-chip (OOC). Human umbilical vein endothelial cells were used to develop 3D vessels. Chronic exposure to PC resulted in significant vascular leakage compared with controls, whereas IS or PCS treatment did not alter the permeability of 3D vessels. Increased permeability induced by PC was correlated with derangement of cell adherens junction complex, vascular endothelial (VE)-cadherin and filamentous (F)-actin. Additionally, PC decreased endothelial viability in a concentration-dependent manner with a lower IC50 in 3D vessels than in 2D cultures. IS slightly decreased cell viability, while PCS did not affect viability. PC induced inflammatory responses by increasing monocyte adhesion to endothelial surfaces of 3D vessels and IL-6 production. In conclusion, this study leveraged an OOC to determine the diverse effects of PBUTs, demonstrating that PC accumulation is detrimental to ECs during kidney insufficiency. [ABSTRACT FROM AUTHOR]

Ethiopia faces a significant challenge with increasing non-communicable diseases like diabetes, ranking among the top four in sub-Saharan Africa. However, there is a lack of research on how lifestyle affects chronic complications of diabetes in Ethiopia, highlighting the need for urgent exploration to develop better intervention strategies. This study aimed to evaluate the link between lifestyle factors and chronic complications of diabetes in public health hospitals in Southwest Ethiopia. A cross-sectional study involving 389 diabetes patients from Mizan-Tepi University Teaching Hospital (MTUTH) and Gebretsadik Shawo General Hospital (GSGH) in Southwest Ethiopia was conducted. Data collection methods included interviewer-administered questionnaires, patient medical record reviews, physical examination, and serum analysis. SPSS version 25 was used for data analysis, including descriptive statistics and bivariate and multivariate logistic regression analyses. Statistical significance was determined at a p-value < 0.05. The study revealed a 32.1% prevalence of chronic complications of diabetes, with 13.4% having chronic kidney disease, 8.0% experiencing visual disturbances, and 16.7% suffering from peripheral sensory pain. After adjusting for confounding variables, age (41–60 years [AOR = 1.77; 95% CI 1.01, 3.15] and > 60 years [AOR = 2.18; 95% CI 1.20, 4.33]), duration of diabetes mellitus (> 6 years [AOR = 2.90; 95% CI 1.74, 4.85]), alcohol consumption [AOR = 2.30; 95% CI 1.33, 3.98], physical inactivity [AOR = 2.43; 95% CI 1.38, 4.27], and body mass index (underweight [AOR = 7.66; 95% CI 1.68, 34.8] and obese [AOR = 3.53; 95% CI 1.84, 10.5]) were significantly associated with chronic complications of diabetes. Chronic complications of diabetes are a major problem in the study area. Lifestyle factors strongly influence chronic diabetes complications, highlighting the importance of preventive measures. Implementing health education and prevention programs focusing on modifiable lifestyle factors is crucial. [ABSTRACT FROM AUTHOR]