Kidney Disease Research Articles

Correlation Between Renal Dimensions and Anthropometric Indices Using Computed Tomography in Adults Without Known Renal Disease: A Cross-Sectional Prospective Study

Background: Assessing renal volume as a potential indicator of renal function and related disorders is valuable for clinical decision-making. Computed tomography (CT) can accurately estimate actual kidney size. Objectives: This study aimed to evaluate the relationship between anthropometric parameters and renal dimensions measured by CT. Methods: Renal CT scan evaluations were performed on 634 individuals (308 males and 326 females) who had undergone abdominopelvic CT scans for indications unrelated to renal disease. Renal parameters, including length, width, depth, volume, and cortex length, were measured. Results: The mean age of participants was 53.5 ± 13.7 years (range: 18 - 86 years). Renal dimensions in males were larger than those in females. Additionally, the left kidney showed larger dimensions than the right kidney in both genders. Renal dimensions increased with age initially, but began to decrease after the sixth decade of life. A significant negative correlation was found between age and renal length, cortex, and left renal volume. In contrast, a significant positive correlation was observed between weight and both renal depth, length, volume, and left renal cortex, as well as between height and both renal length and volume on both sides. All dimensions except renal length were greater with increasing Body Mass Index (BMI). Conclusions: The results indicate a significant correlation between kidney dimensions and various anthropometric factors such as age, weight, height, and BMI. These findings provide valuable insights into kidney dimensions measured on CT scans, potentially aiding in the diagnosis and treatment of kidney diseases.

Histone deacetylase 9 promotes osteogenic trans-differentiation of vascular smooth muscle cells via ferroptosis in chronic kidney disease vascular calcification.

Vascular calcification, a common complication of chronic kidney disease (CKD), remains an unmet therapeutic challenge. The trans-differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells is crucial in the pathogenesis of vascular calcification in CKD. Despite ferroptosis promotes vascular calcification in CKD, the upstream or downstream regulatory mechanisms involved remains unclear. In this study, we aimed to investigate the regulatory mechanism involved in ferroptosis in CKD vascular calcification. Transcriptome sequencing revealed a potential relationship between HDAC9 and ferroptosis in CKD vascular calcification. Subsequently, we observed increased expression of HDAC9 in calcified arteries of patients undergoing hemodialysis and in a rat model of CKD. We further demonstrated that knockout of HDAC9 attenuates osteogenic trans-differentiation and ferroptosis in VSMCs stimulated by high calcium and phosphorus. In addition, RSL3 exacerbated ferroptosis and osteogenic trans-differentiation of VSMCs exposed to high levels of calcium and phosphorus, and these effects were suppressed to some extent by HDAC9 knockout. In summary, our findings suggest that HDAC9 promotes VSMCs osteogenic trans-differentiation involving ferroptosis, providing new insights for the therapy of CKD vascular calcification.

Osmotic demyelination syndrome: revisiting the diagnostic criteria through two fatal cases

BackgroundOsmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS.Case presentationCase #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient’s condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient’s condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission.ConclusionODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia.

Black Garlic Supplementation and Glomerular Protection in Hyperuricemic Rats: A Study on Kidney Health Prevention

Introduction: Hyperuricemia is a significant risk factor for the development of chronic kidney disease. Excessive uric acid can deposit in the kidneys, triggering inflammatory reactions and oxidative stress, leading to structural damage in the glomeruli. Black garlic, with its antioxidant and bioactive compounds, has the potential to protect the kidneys from hyperuricemia-induced damage. Our objective is to evaluate the effect of black garlic supplementation on the histopathological features of glomeruli in a hyperuricemic rat model. Methods: This study was an analytical observational study using Biological Remnant Materials (BRM) from a previous study. The sample consisted of 30 male Sprague-Dawley rats divided into 5 groups: disease control, drug control (allopurinol), and 3 black garlic dose groups (240 mg/day, 480 mg/day, and 960 mg/day). Data were collected through histopathological examination of kidney tissue using the glomerular damage scoring method (0-3). Data analysis was performed using one-way ANOVA and post hoc LSD tests. Results: Black garlic demonstrated protective effects on the histopathological features of glomeruli in hyperuricemic rats. The 240 mg/day dose showed the most significant improvement in kidney health, reducing glomerular damage scores compared to the disease control group (p < 0.05). These findings suggest that black garlic can serve as a preventive agent against kidney complications caused by hyperuricemia. Conclusion: Black garlic provides protective effects on glomerular histopathology in hyperuricemic rats, with the 240 mg/day dose being the most effective. These results suggest potential use for black garlic in preventing kidney complications in hyperuricemia.

Acute Pancreatitis with Pancreatic Pseudocyst in a Chronic Kidney Disease Patient: A Case Study

Acute Pancreatitis with Pancreatic Pseudocyst in a Chronic Kidney Disease Patient: A Case Study

Elevated risk of end-stage kidney disease in stroke patients: A population-based observational study.

Estimating the incidence of end-stage kidney disease (ESKD) in stroke survivors is important to assess and predict clinical course, improve post-stroke quality of life, and ultimately reduce health burden. Our objective was to assess the risk of ESKD in patients compared to a matched stroke-free control cohort. A nationwide retrospective cohort study was conducted in 315,326 stroke subjects and 390,781 matched stroke-free control subjects. Health examination results and claims data were collected from the Korean National Health Insurance Service during 2010-2018. Cox proportional hazard models were used to assess the risk of ESKD in the stroke cohort. During a mean follow-up period of 4.3 years, the incidence of ESKD was 1.83 per 100,000 person-years in the stroke cohort versus 0.57 per 100,000 person-years in the control cohort. The stroke cohort exhibited a significantly higher risk of developing ESKD compared to the matched control, with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval (CI) = 1.67-1.93). Stroke survivors were associated with a higher risk of developing ESKD, regardless of the severity of disability (aHRs of 1.93, 95% CI = 1.69-2.21 for severe disability; 1.71, 95% CI = 1.41-2.07 for mild disability; and 1.78, 95% CI = 1.65-1.92 for no disability), compared to the matching control cohort. The elevated risk was observed in both hemorrhagic stroke (aHR = 1.96, 95% CI = 1.73-2.23) and ischemic stroke (aHR = 1.75, 95% CI = 1.62-1.89). This study demonstrates that stroke patients have a significantly higher risk of incident ESKD. This highlights the need for heightened clinical awareness and improved monitoring of kidney function in this population.

Optimizing anemia management using artificial intelligence for patients undergoing hemodialysis

Patients with end-stage kidney disease (ESKD) frequently experience anemia, and maintaining hemoglobin (Hb) levels within a targeted range using erythropoiesis-stimulating agents (ESAs) is challenging. This study introduces a gated recurrent unit-attention-based module (GAM) for efficient anemia management among patients undergoing chronic dialysis and proposes a novel alert system for anticipating the need for red blood cell transfusions. Data on demographic characteristics, dialysis metrics, drug administration, laboratory tests, and transfusion history were retrospectively collected from patients undergoing hemodialysis at Kangwon National University Hospital between 2017 and 2022. After preprocessing, a final dataset of 252 patients was used for model training. Our model functions in two major phases: (1) Hb level prediction and ESA dose recommendation and (2) transfusion alert framework. The GAM model outperformed traditional machine learning algorithms, including linear regression, XGBoost, and multilayer perceptron, in predicting Hb levels (R-squared value = 0.60). The model also demonstrated a recommendation accuracy of 0.78 compared to that of clinical experts, indicating a high degree of concordance with the ESA dosing recommendations. Additionally, the model exhibited considerably high accuracy (0.99) for transfusion alarms. Thus, the GAM model holds promise for improving anemia management in patients with ESKD by optimizing ESA dosages and providing timely transfusion alerts.

Psychological distress in adults after pediatric kidney replacement therapy.

There is limited information about psychological distress in adults who underwent kidney replacement therapy (KRT) during childhood. This study aimed to describe psychological distress in adults after KRT during childhood in comparison to the Swiss general population and to evaluate associations with sociodemographic and clinical characteristics. We sent a questionnaire to 143 people from the Swiss Pediatric Renal Registry (SPRR), who were alive, over 18years old, started KRT before the age of 18years, and were German speakers. We measured psychological distress using the Brief Symptom Inventory 18 (BSI-18) and evaluated the Global Severity Index 18 (GSI-18), reflecting the overall level of distress, and the three subscales: depression, somatization, and anxiety. We compared levels of psychological distress to normal data from the Swiss general population and used regression models to identify associations with sociodemographic and clinical characteristics. Eighty persons with a mean age of 39years (SD 10.1) responded to the questionnaire (response rate 56%). Overall, the GSI-18 and all subscales of the BSI-18 were similar. Unemployed participants (25%) reported higher levels of somatization and were more likely to experience psychological distress. Participants using psychotropic drugs (14%) reported higher levels of overall psychological distress (10%), depression (13%) and somatization (9%). Adults after KRT during childhood showed good long-term psychological well-being. These results are encouraging and underline the favorable outcome of these patients. So besides the excellent somatic outcome, these patients can achieve a psychological healthy life after diagnosis of chronic kidney disease.

Association between blood heavy metals and diabetic kidney disease among type 2 diabetic patients: a cross-sectional study.

Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.

Our previous work established a role for actin associated myosin motor proteins MYH9 and MYH10 in the trafficking of thick ascending limb (TAL) specific cargoes, uromodulin (UMOD) and Na+K+2Cl- cotransporter (NKCC2). Here, we have generated a TAL-specific Myh9&10 conditional knockout (Myh9&10 TAL-cKO) mouse model to determine the cell autonomous roles for MYH9&10 proteins in TAL cargo transport and to understand the consequence of TAL dysfunction in the adult kidney. Myh9&10 TAL-cKO mice develop progressive kidney disease with pathological tubular injury confirmed by histological changes, tubular injury markers, upregulation of ER stress/unfolded protein response pathway, and higher blood urea nitrogen and serum creatinine. However, male mice survive twice as long as female mice. We determined that the sexual dimorphism in morbidity is due to adaptation of the distal nephron and the collecting ducts in response to TAL dysfunction and significantly lower NKCC2 expression. We demonstrate that this triggers a compensatory mechanism involving sex-specific cellular adaptation within the distal tubules and collecting ducts to boost sodium reabsorption. While both sexes overcompensate by activating ENaC expression in the medullary collecting ducts resulting in hypernatremia, this is subdued in male Myh9&10 TAL-cKO mice as they initially promote higher sodium chloride cotransporter (NCC) expression within the distal nephron. Our results indicate that compromised TAL function results in maladaptation of medullary collecting duct cells, which acquire cortical-like properties, including ENaC expression. This work further confirms a cell autonomous role for myosin motor proteins MYH9&10 in the maintenance of NKCC2 expression in the TAL and uncover adaptive mechanisms of the distal nephron and the collecting duct segments in response to TAL dysfunction.

Unraveling Uncertainty: The Impact of Biological and Analytical Variation on the Prediction Uncertainty of Categorical Prediction Models.

Interest in prediction models, including machine learning (ML) models, based on laboratory data has increased tremendously. Uncertainty in laboratory measurements and predictions based on such data are inherently intertwined. This study developed a framework for assessing the impact of biological and analytical variation on the prediction uncertainty of categorical prediction models. Practical application was demonstrated for the prediction of renal function loss (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) and 31-day mortality (advanced ML model) in 6360 emergency department patients. Model outcome was calculated in 100 000 simulations of variation in laboratory parameters. Subsequently, the percentage of discordant predictions was calculated with the original prediction as reference. Simulations were repeated assuming increasing levels of analytical variation. For the ML model, area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity were 0.90, 0.44, and 0.96, respectively. At base analytical variation, the median [2.5th-97.5th percentiles] percentage of discordant predictions was 0% [0%-28.8%]. In addition, 7.2% of patients had >5% discordant predictions. At 6× base analytical variation, the median [2.5th-97.5th percentiles] percentage of discordant predictions was 0% [0%-38.8%]. In addition, 11.7% of patients had >5% discordant predictions. However, the impact of analytical variation was limited compared with biological variation. AUROC, sensitivity, and specificity were not affected by variation in laboratory parameters. The impact of biological and analytical variation on the prediction uncertainty of categorical prediction models, including ML models, can be estimated by the occurrence of discordant predictions in a simulation model. Nevertheless, discordant predictions at the individual level do not necessarily affect model performance at the population level.

Practicing health equity in kidney care by establishing improved access to timely disease management and kidney replacement therapy options: from providers to patients.

The aim of this article is to review the current understanding of disparities in healthcare experienced by people living with kidney disease and emerging approaches to address root causes. Health equity for any disease state is an aspirational goal commonly sought out by the medical community, but all too often lacking the understanding and support required to improve the outcomes of people with complex conditions such as chronic kidney disease (CKD). The main themes of the literature covered in this article include a review of the structural drivers of healthcare outcomes, a description of research in the fields of health literacy and patient activation for patients with CKD, and an analysis of the examples of healthcare disparities in CKD patients that include involuntary discharges from dialysis facilities as well as the toll taken from dialysis populations during natural disasters. The National Forum of the ESRD Networks is a coalition of 18 congressionally mandated ESRD network organizations committed to equitable access to home and in-center dialysis modalities and preemptive kidney transplantation. We conclude with the patient-centered story of a patient living with end-stage kidney disease for over 40 years and how her journey has helped shape her view on what she believes should encompass a 'call to action' to provide more equitable healthcare to people living with kidney disease. The overarching implications of this article focus on improving the understanding of present-day healthcare inequality within the community of people living with kidney disease and providing a roadmap of resources and ideas that will help achieve more equitable outcomes. The National Forum of the ESRD Networks is committed to the effective implementation of 'Practicing Health Equity in Kidney Care' and improving access to dialysis modalities including home dialysis as well as kidney transplantation including preemptive transplant options.

Random Oversampling-Based Diabetes Classification via Machine Learning Algorithms

Diabetes mellitus is considered one of the main causes of death worldwide. If diabetes fails to be treated and diagnosed earlier, it can cause several other health problems, such as kidney disease, nerve disease, vision problems, and brain issues. Early detection of diabetes reduces healthcare costs and minimizes the chance of serious complications. In this work, we propose an e-diagnostic model for diabetes classification via a machine learning algorithm that can be executed on the Internet of Medical Things (IoMT). The study uses and analyses two benchmarking datasets, the PIMA Indian Diabetes Dataset (PIDD) and the Behavioral Risk Factor Surveillance System (BRFSS) diabetes dataset, to classify diabetes. The proposed model consists of the random oversampling method to balance the range of classes, the interquartile range technique-based outlier detection to eliminate outlier data, and the Boruta algorithm for selecting the optimal features from the datasets. The proposed approach considers ML algorithms such as random forest, gradient boosting models, light gradient boosting classifiers, and decision trees, as they are widely used classification algorithms for diabetes prediction. We evaluated all four ML algorithms via performance indicators such as accuracy, F1 score, recall, precision, and AUC-ROC. Comparative analysis of this model suggests that the random forest algorithm outperforms all the remaining classifiers, with the greatest accuracy of 92% on the BRFSS diabetes dataset and 94% accuracy on the PIDD dataset, which is greater than the 3% accuracy reported in existing research. This research is helpful for assisting diabetologists in developing accurate treatment regimens for patients who are diabetic.

092. Overview of the Prevalence of Chronic Kidney Disease (CKD) in Kidney and Ureter Stones at Zainoel Abidin Hospital Banda Aceh, 2021

Background: Kidney stones are a predictor and risk factor for CKD and the prevalence rate is 5-10% with comorbid factors which can increase the risk of CKD events. Chronic Kidney Disease (CKD) is a serious complication of urinary tract stones. Chronic kidney disease can occur as a result of urological procedures, obstruction or due to causes inherent in stone formation. Methods: This type of research is descriptive research using secondary data in the form of medical record data. The design of this research is cross sectional with data collection carried out retrospectively. The samples in this study were patients diagnosed with CKD in patients with ureteral stones or kidney stones at Zainoel Abidin Hospital, Banda Aceh. Samples were taken using the total sampling method. Results: In this study, 70 samples were taken and the results of this study based on gender are majority were found to be men 48 samples (68.6%), the most common age category was 41 - 50 years with 28 samples (40.0% ), the most common comorbid factor causing CKD was hypertension in 30 samples (42.5%), the type of urinary tract stones most often found was ureter stones, namely 34 samples (49.0%), and the most common location or urinary tract was ureter stones. bilateral, namely 22 samples (31.4%). Conclusion: The male gender most often experiences CKD due to complications from urinary tract stones, where the age range of 41 - 50 years is the age that experiences the most complications. The most common type of urinary tract stone is ureteral stone with a bilateral location.

Noncanonical microglial IL-1β maturation in chronic kidney disease.

Organ transplantation reverses cognitive impairment in chronic kidney disease (CKD), indicating that cognitive impairment driven by CKD is therapeutically amendable. We recently demonstrated that impaired cognition in CKD is linked to IL-1β-release from microglia and IL-1R1-signaling in neuronal cells, thereby identifying a signaling pathway that can be exploited therapeutically. However, the mechanism of IL-1β-maturation in microglia in CKD remains unknown. We hypothesized that microglia cells require caspase-1 for CKD-driven cognitive impairment. We used a combination of single cell analyses, in situ analyses, genetically modified mouse models (including newly generated Cre-LoxP mouse models) and in vitro models. The current study builds on a recently identified intercellular crosstalk between microglia and neurons that impairs cognition in chronic kidney disease (CKD). Here, we show that despite NLRP3 inflammasome activation in the brain and protection of mice with constitutive NLRP3 deficiency from CKD-induced cognitive impairment, (i) caspase-1 is not required for IL-1β maturation in microglia and (ii) targeted caspase-1 deficiency in microglia does not improve cognition in CKD mice. These data indicate that IL-1β maturation in microglia is independent of the NLRP3-caspase-1 interaction in CKD. Indeed, microglia activation in CKD induces noncanonical, cathepsin C-caspase-8 mediated IL-1β maturation. Depletion of cathepsin C or caspase-8 blocks IL-1β maturation in microglia. Preliminary analyses suggest that noncanonical microglia IL-1β maturation occurs also in diabetes mellitus. These results identify a noncanonical IL-1β-maturation pathway as a potential therapeutic target to combat microglia-induced neuronal dysfunction in CKD and possible other peripheral diseases.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Association of serum uric acid with all-cause and cardiovascular mortality in cardiovascular disease patients

The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005–2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34–110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16–1.64) and the risk of CVM (HR 1.39, 95% CI 1.04–1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p < 0.001 for all nonlinearities) between SUA, ACM, and CVM in the overall population and in men. Subgroup analysis showed a nonlinear association between ACM and CVM with SUA in patients with CVD combined with chronic kidney disease (CKD), with thresholds of 5.49 and 5.64, respectively. Time-dependent ROC curves indicated areas under the curve of 0.61, 0.60, 0.58, and 0.55 for 1-, 3-, 5-, and 10-year survival for ACM and 0.69, 0.61, 0.59, and 0.56 for CVM, respectively. We demonstrate that SUA is an independent prognostic factor for the risk of ACM and CVM in patients with CVD, supporting a U-shaped association between SUA and mortality, with thresholds of 5.49 and 5.64, respectively. In patients with CVD combined with CKD, the association of the ACM and the CVM with SUA remains nonlinear.

Comparative Analysis of Comorbidities and Outcomes in Endoscopic versus Open Treatment of Carpal Tunnel Release in Patients with Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a known risk factor for carpal tunnel syndrome, possibly because the inflammation causes compression of the median nerve. Endoscopic and open carpal tunnel release (ECTR and OCTR) have been studied extensively in the general population but less so in patients with RA. The purpose of our study was to analyze outcomes and patient-specific comorbidities associated with ECTR and OCTR in patients with RA. Methods: We conducted a retrospective cohort study using the PearlDiver database to identify patients with RA who underwent either ECTR or OCTR between 2010 and 2014. Demographic data, comorbidities, and complication rates were analyzed. We used univariate and multivariable analysis to assess differences between the treatment methods. Results: Comparing 4,234 patients who underwent OCTR to 683 patients who underwent ECTR, we found no significant differences in medical comorbidities such as hypertension, obesity, chronic kidney disease, hypothyroidism, and diabetes mellitus. Patients who underwent ECTR were significantly more likely to require a repeat procedure within 90 days of the initial procedure. However, this difference was not consistent in multivariate analysis controlling for comorbidities. Conclusion: Our study found that RA and ECTR were identified as independent risk factors for revision release, with ECTR showing a higher likelihood of repeat procedures within 90 days compared with OCTR. Despite similar demographics and comorbidities in the two study cohorts, use of OCTR outpaced ECTR use in the study period. Future research should explore further characterization of repeat procedures in this higher risk patient subset.

Tolvaptan Safety in Autosomal Dominant Polycystic Kidney Disease; Focus on Idiosyncratic Drug Induced Liver Injury Liabilities.

Tolvaptan is a vasopressin V2 receptor antagonist which has proven to be an effective and mostly well-tolerated agent for the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, its administration is associated with rare but serious idiosyncratic liver injury, which has warranted a black box warning on the drug labels and frequent monitoring of liver blood tests in the clinic. This review outlines mechanistic investigations that have been conducted to date and constructs a working narrative as explanation for the IDILI events that have occurred thus far. Potential risk factors which may contribute to individual susceptibility to DILI reactions are addressed, and key areas for future investigative/clinical development are highlighted.

Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy.

Aims: The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. Results: Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. Innovation and Conclusion: This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. Antioxid. Redox Signal. 00, 000-000.