Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery.

BACKGROUND: The effects of anesthesia in patients undergoing thyroid cancer surgery are still not known. We investigated the relationship between the type of anesthesia and patient outcomes following elective thyroid cancer surgery. METHODS: This was a retrospective cohort study of patients who underwent elective surgical resection for papillary thyroid carcinoma between January 2009 and December 2019. Patients were grouped according to the type of anesthesia they received, desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival/recurrence curves were presented from the date of surgery to death/recurrence. Univariable and multivariable Cox regression models were used to compare hazard ratios for recurrence after propensity matching. RESULTS: A total of 621 patients (22 deaths, 3.5%) under desflurane anesthesia and 588 patients (32 deaths, 5.4%) under propofol anesthesia were included. Five hundred and eighty-eight patients remained in each group after propensity matching. Propofol anesthesia was not associated with better survival compared to desflurane anesthesia in the matched analysis (P = 0.086). However, propofol anesthesia was associated with less recurrence (hazard ratio, 0.38; 95% confidence interval, 0.25-0.56; P < 0.001) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with less recurrence, but not mortality, following surgery for papillary thyroid carcinoma than desflurane anesthesia. Further prospective investigation is needed to examine the influence of propofol anesthesia on patient outcomes following thyroid cancer surgery.

Survival benefit of a third dose of the COVID-19 vaccine among hemodialysis patients: A prospective cohort study.

BACKGROUND: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. METHODS: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. RESULTS: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17-0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. CONCLUSION: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.

A Narrative Review of Remimazolam in Procedural Sedation.

Remimazolam is a recently approved benzodiazepine for procedural sedation in Taiwan. It is a new type of short-acting γ-aminobutyric acid receptor agonist with the characteristics of non-organ-dependent metabolism, no injection pain, and inactive metabolites. Remimazolam has a mild cardiopulmonary suppressive effect, showing good effectiveness and safety in clinical applications, especially in the elderly, critically ill patients, or patients with hepatic and renal insufficiency. This review aims to provide an overview of the specific basic and clinical pharmacology of remimazolam and provide scientific support for the clinical application of this novel sedative drug in procedural sedation.

Comparison of radiographic and clinical outcomes between ALIF, OLIF, and TLIF over 2-year follow-up: a comparative study.

BACKGROUND: Regarding the increasing adoption of oblique lateral interbody fusion (OLIF) for treating degenerative lumbar disorders, we aimed to evaluate whether OLIF, one of the options for anterolateral approach lumbar interbody fusion, demonstrate clinical superiority over anterior lumbar interbody fusion (ALIF) or posterior approach, represented by transforaminal lumbar interbody fusion (TLIF). METHODS: Patients who received ALIF, OLIF, and TLIF for symptomatic degenerative lumbar disorders during the period 2017-2019 were identified. Radiographic, perioperative, and clinical outcomes were recorded and compared during 2-year follow-up. RESULTS: A total of 348 patients with 501 correction levels were enrolled in the study. Fundamental sagittal alignment profiles were substantially improved at 2-year follow-up, particularly in the anterolateral approach (A/OLIF) group. The Oswestry disability index (ODI) and EuroQol-5 dimension (EQ-5D) in the ALIF group were superior when compared to the OLIF and TLIF group 2-year following surgery. However, comparisons of VAS-Total, VAS-Back, and VAS-Leg revealed no statistically significance across all approaches. TLIF demonstrated highest subsidence rate of 16%, while OLIF had least blood loss and was suitable for high body mass index patients. CONCLUSIONS: Regarding treatment for degenerative lumbar disorders, ALIF of anterolateral approach demonstrated superb alignment correction and clinical outcome. Comparing to TLIF, OLIF possessed advantage in reducing blood loss, restoring sagittal profiles and the accessibility at all lumbar level while simultaneously achieving comparable clinical improvement. Patient selection in accordance with baseline conditions, and surgeon preference both remain crucial issues circumventing surgical approach strategy.

Prediction of the risk of developing end-stage renal diseases in newly diagnosed type 2 diabetes mellitus using artificial intelligence algorithms.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. METHODS: We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. RESULTS: The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. CONCLUSIONS: Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.

Comparison of Single Target-Controlled Infusion Pump-Delivered Mixed Propofol and Remifentanil with Two Target-Controlled Infusion Pumps-Delivered Propofol and Remifentanil in Patients Undergoing Breast Cancer Surgery-A Prospective Study.

Total intravenous anesthesia (TIVA) with remifentanil and propofol (RP) is considered to be an ideal type of general anesthesia (GA) for pediatric and adult patients undergoing medical procedures. However, delivery of an RP mixture by target-controlled infusion (TCI) for GA in surgical procedures has not been described. We investigated the merit of this approach for breast cancer surgery. Eighty-four patients (n = 42 per group) were randomly allocated to propofol and remifentanil either delivered by separate TCI pumps (S group) or in an RP mixture by a single TCI pump (M group). Dosages were adjusted based on the bispectral index (BIS) and the analgesia nociception index (ANI). The primary outcomes were adequate anesthesia (BIS 40-60 and ANI 50-70, respectively), acceptable hemodynamic fluctuations (<30% of baseline) with less frequent TCI pump adjustments, bolus injections of anesthetics, and total consumption of anesthetics during the procedure. The secondary endpoints included time of emergence from anesthesia, patient satisfaction, postoperative pain, rescue with opioids, and adverse events. The characteristics of patients, hemodynamic parameters, BIS and ANI scores, duration of surgery, anesthesia, and emergence were not significantly different between groups. The adjustment frequency of TCI was significantly higher in the S group (3 (range 0-6) vs. 2 (0-6) times; p = 0.005). The total dosage of anesthetics, pain rating, patient satisfaction, need for opioids postoperatively, and incidence of adverse events were not significantly different. We have demonstrated that this RP mixture provided adequate hypnotic and analgesic effects under BIS and ANI monitoring in patients undergoing breast cancer surgery within 1 h.

Tumor Necrosis Factor Alpha: Implications of Anesthesia on Cancers.

Cancer remains a major public health issue and a leading cause of death worldwide. Despite advancements in chemotherapy, radiation therapy, and immunotherapy, surgery is the mainstay of cancer treatment for solid tumors. However, tumor cells are known to disseminate into the vascular and lymphatic systems during surgical manipulation. Additionally, surgery-induced stress responses can produce an immunosuppressive environment that is favorable for cancer relapse. Up to 90% of cancer-related deaths are the result of metastatic disease after surgical resection. Emerging evidence shows that the interactions between tumor cells and the tumor microenvironment (TME) not only play decisive roles in tumor initiation, progression, and metastasis but also have profound effects on therapeutic efficacy. Tumor necrosis factor alpha (TNF-α), a pleiotropic cytokine contributing to both physiological and pathological processes, is one of the main mediators of inflammation-associated carcinogenesis in the TME. Because TNF-α signaling may modulate the course of cancer, it can be therapeutically targeted to ameliorate clinical outcomes. As the incidence of cancer continues to grow, approximately 80% of cancer patients require anesthesia during cancer care for diagnostic, therapeutic, or palliative procedures, and over 60% of cancer patients receive anesthesia for primary surgical resection. Numerous studies have demonstrated that perioperative management, including surgical manipulation, anesthetics/analgesics, and other supportive care, may alter the TME and cancer progression by affecting inflammatory or immune responses during cancer surgery, but the literature about the impact of anesthesia on the TNF-α production and cancer progression is limited. Therefore, this review summarizes the current knowledge of the implications of anesthesia on cancers from the insights of TNF-α release and provides future anesthetic strategies for improving oncological survival.

Plasma Galectin-9 Is a Useful Biomarker for Predicting Renal Function in Patients Undergoing Native Kidney Biopsy.

CONTEXT.­: Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear. OBJECTIVE.­: To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages. DESIGN.­: We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time polymerase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli. RESULTS.­: To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevated plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9-positive cells were macrophages, as determined by double-immunofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon-γ stimulation. CONCLUSIONS.­: Our findings suggest that plasma galectin-9 is a good biomarker for diagnosing advanced CKD.

Echocardiographic features of left ventricular dysfunction and outcomes in chronic kidney disease.

OBJECTIVE: Heart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive. METHODS: The study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratified into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes. RESULTS: In inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups. CONCLUSIONS: HF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group.

Propofol-based total intravenous anesthesia is associated with better survival than desflurane anesthesia in limb-salvage surgery for osteosarcoma: A retrospective analysis.

Previous studies have demonstrated that anesthetic techniques can affect the outcomes of cancer surgery. We investigated the association between anesthetic techniques and patient outcomes after elective limb-salvage surgery for osteosarcoma (OS). This was a retrospective cohort study of patients who underwent elective limb-salvage surgery for OS between January 2007 and December 2018. Patients were grouped according to the administration of propofol-based total intravenous anesthesia (TIVA) or desflurane (DES) anesthesia. Kaplan-Meier analysis was performed, and survival curves were constructed from the date of surgery to death. Univariate and multivariate Cox regression models were applied to compare the hazard ratios (HRs) for death after propensity matching. Subgroup analyses were done for postoperative recurrence, metastasis, and tumor-node-metastasis (TNM) staging. A total of 30 patients (17 deaths, 56.7%) who received DES anesthesia and 26 (4 deaths, 15.4%) who received TIVA were eligible for analysis. After propensity matching, 22 patients were included in each group. In the matched analysis, patients who received TIVA had better survival with a HR of 0.30 (95% confidence interval [CI], 0.11-0.81; P = .018). Subgroup analyses also showed significantly better survival in the presence of postoperative metastasis (HR, 0.24; 95% CI, 0.06-0.87; P = .030) and with TNM stage II to III (HR, 0.26; 95% CI, 0.09-0.73; P = .011) in the matched TIVA group. In addition, patients administered with TIVA had lower risks of postoperative recurrence and metastasis than those administered with DES anesthesia in the matched analyses. Propofol-based TIVA was associated with better survival in patients who underwent elective limb-salvage surgery for OS than DES anesthesia. Prospective studies are needed to assess the effects of TIVA on oncological outcomes in patients with OS.

Risk Factors Associated with Cartilage Defects after Anterior Cruciate Ligament Rupture in Military Draftees.

This study aimed to evaluate the different clinical results and factors associated with cartilage defects in military draftees who underwent different treatments after anterior cruciate ligament (ACL) rupture. Overall, 105 patients who had sustained ACL rupture were military draftees who underwent a conscription examination for physical status assessment from January 2012 to December 2020. Patients were divided into three groups: conservative treatment after ACL rupture, status post-anterior cruciate ligament reconstruction (ACLR), but graft rupture, and status post-ACLR with graft intact. Inter-group comparisons and statistical analyses were performed for age, body mass index (BMI), thigh circumference difference, side-to-side difference in anterior knee translation by KT-2000, meniscus tear, and cartilage defect. Multivariate logistic regression analysis was used to determine the factors associated with cartilage defects. The multivariable regression model showed that BMI (odds ratio OR: 1.303; 95% CI: 1.016-1.672; p = 0.037), thigh circumference difference (OR: 1.403; 95% CI: 1.003-1.084; p = 0.034), tear of lateral meniscus (LM) and medial meniscus (MM) (OR: 13.773; 95% CI: 1.354-140.09; p = 0.027), and graft rupture group (OR: 5.191; 95% CI: 1.388-19.419; p = 0.014) increased the risk of cartilage defects. There was no correlation between cartilage defects and age, KT-2000 difference, tear of LM or MM, or graft intact group. Progression of osteoarthritis was concerned after ACL rupture, and this study identified several factors of post-ACLR graft rupture, greater thigh circumference difference, BMI, and meniscus tear of both LM and MM affecting cartilage defects, which represent early degenerative osteoarthritis changes of the knee. The results of this study should be customized for rehabilitation and military training, especially in military draftees with ACL injuries.

Sepsis and the Risks of Long-Term Renal Adverse Outcomes in Patients With Chronic Kidney Disease.

Background: Sepsis is known to cause renal function fluctuations during hospitalization, but whether these patients discharged from sepsis were still at greater risks of long-term renal adverse outcomes remains unknown. Methods: From 2011 to 2018, we included 1,12,628 patients with chronic kidney disease (CKD) aged ≥ 20 years. The patients with CKD were further divided into 11,661 sepsis group and 1,00,967 non-sepsis group. The following outcome of interest was included: all-cause mortality, readmission for acute kidney injury, estimated glomerular filtration rate decline ≥50% or doubling of serum creatinine, and end-stage renal disease. Results: After propensity score matching, the sepsis group was at higher risks of all-cause mortality [hazard ratio (HR) 1.39, 95% CI, 1.31-1.47], readmission for acute kidney injury (HR 1.67, 95% CI 1.58-1.76), eGFR decline ≥ 50% or doubling of serum creatinine (HR 3.34, 95% CI 2.78-4.01), and end-stage renal disease (HR 1.43, 95% CI 1.34-1.53) than non-sepsis group. Conclusions: Our study found that patients with CKD discharged from hospitalization for sepsis have higher risks of subsequent renal adverse events.

Artificial Intelligence for Risk Prediction of End-Stage Renal Disease in Sepsis Survivors with Chronic Kidney Disease.

Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. A total of 11,661 sepsis survivors were identified from a single-center database of 112,628 CKD patients between 2010 and 2018. During a median follow-up of 3.5 years, a total of 1366 (11.7%) sepsis survivors developed ESRD after hospital discharge. We adopted the random forest, extra trees, extreme gradient boosting, light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) algorithms to predict the risk of ESRD development among these patients. GBDT yielded the highest area under the receiver operating characteristic curve of 0.879, followed by LGBM (0.868), and extra trees (0.865). The GBDT model revealed the strong effect of estimated glomerular filtration rates <25 mL/min/1.73 m2 at discharge in predicting ESRD development. In addition, hemoglobin and proteinuria were also essential predictors. Based on a large-scale dataset, we established a machine learning model computing the risk for ESRD occurrence among sepsis survivors with CKD. External validation is required to evaluate the generalizability of this model.

Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression.

Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6−510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85−7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.

Artificial Intelligence for Risk Prediction of Rehospitalization with Acute Kidney Injury in Sepsis Survivors.

Sepsis survivors have a higher risk of long-term complications. Acute kidney injury (AKI) may still be common among sepsis survivors after discharge from sepsis. Therefore, our study utilized an artificial-intelligence-based machine learning approach to predict future risks of rehospitalization with AKI between 1 January 2008 and 31 December 2018. We included a total of 23,761 patients aged ≥ 20 years who were admitted due to sepsis and survived to discharge. We adopted a machine learning method by using models based on logistic regression, random forest, extra tree classifier, gradient boosting decision tree (GBDT), extreme gradient boosting, and light gradient boosting machine (LGBM). The LGBM model exhibited the highest area under the receiver operating characteristic curves (AUCs) of 0.816 to predict rehospitalization with AKI in sepsis survivors and followed by the GBDT model with AUCs of 0.813. The top five most important features in the LGBM model were C-reactive protein, white blood cell counts, use of inotropes, blood urea nitrogen and use of diuretics. We established machine learning models for the prediction of the risk of rehospitalization with AKI in sepsis survivors, and the machine learning model may set the stage for the broader use of clinical features in healthcare.

Dose-response effects of physical activity on all-cause mortality and major cardiorenal outcomes in chronic kidney disease.

AIMS: Physical activity has a protective effect against mortality and cardiovascular events in chronic kidney disease (CKD) patients. Nonetheless, how different levels of physical activity affect the health benefits in CKD remains unclear. This study aimed to investigate the dose-response effects of physical activity on mortality and major cardiorenal events in CKD. METHODS AND RESULTS: We evaluated a longitudinal cohort of 4508 Taiwanese CKD patients between 2004 and 2017. Physical activity was assessed by the NHANES questionnaire and quantified in metabolic equivalent-hours per week (MET-hour/week). Patients were categorized into highly active (≥7.5 MET-h/week), low-active (0.1 to <7.5 MET-h/week), or inactive (0 MET-h/week) groups. Cox regression and restricted cubic spline models were utilized to explore the association between physical activity and the risks of study outcomes, including all-cause mortality, end-stage renal disease (ESRD), and major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, ischaemic stroke, and hospitalized heart failure). During a median follow-up of 686 days, 739 death, 1059 ESRD, and 521 MACE events occurred. Highly active group had the lowest chance of all study outcomes, followed by low-active and inactive groups (P < 0.001). Multivariable Cox regression showed that only highly active group was independently associated with lower risks for all-cause mortality [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.53-0.74], ESRD (HR 0.83, 95% CI 0.72-0.96), and MACE (HR 0.63, 95% CI 0.51-0.76) compared to the inactive group. The risks of MACE did not further decrease once physical activity surpassed 15 MET-h/week, indicating a U-shaped association. The results were consistent in the subgroup and sensitivity analyses. CONCLUSION: Physical activity of 7.5 to <15 MET-h/week is associated with lower risks of adverse cardiorenal outcomes and should be integrated into the care of CKD.

Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy.

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis. Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients. Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion. Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.