Evaluating the Potential of Delta Radiomics for Assessing Tyrosine Kinase Inhibitor Treatment Response in Non-Small Cell Lung Cancer Patients.

Our study aimed to harness the power of CT scans, observed over time, in predicting how lung adenocarcinoma patients might respond to a treatment known as EGFR-TKI. Analyzing scans from 322 advanced stage lung cancer patients, we identified distinct image-based patterns. By integrating these patterns with comprehensive clinical information, such as gene mutations and treatment regimens, our predictive capabilities were significantly enhanced. Interestingly, the precision of these predictions, particularly related to radiomics features, diminished when data from various centers were combined, suggesting that the approach requires standardization across facilities. This novel method offers a potential pathway to anticipate disease progression in lung adenocarcinoma patients treated with EGFR-TKI, laying the groundwork for more personalized treatments. To further validate this approach, extensive studies involving a larger cohort are pivotal.

Proteins Secreted by Lung Cancer Cells Induce the Onset of Proteinuria via Focal Adhesion Kinase Signaling in Mice.

Paraneoplastic nephrotic syndrome (PNS) is a complication seen in cancer patients. Ultrastructural examination shows the accumulation of proteins and the presence of foot process (FP) effacement in the glomeruli of PNS patients. Previously, we reported that orthotopic xenografts of Lewis lung carcinoma 1 in C57BL/6 mice caused them to develop lung cancer with albuminuria. This implies that these mice can be used as a model of human disease and suggests that Lewis lung carcinoma 1 cell-secreted proteins (LCSePs) contain nephrotoxic molecules and cause inflammation in renal cells. As podocyte effacement was present in glomeruli in this model, such podocyte injury may be attributable to either soluble LCSeP or LCSeP deposits triggering pathological progression. LCSePs in conditioned media was concentrated for nephrotoxicity testing. Integrin-focal adhesion kinase (FAK) signaling and inflammatory responses were evaluated in podocytes either exposed to soluble LCSePs or seeded onto substrates with immobilized LCSePs. FAK phosphorylation and interleukin-6 expression were higher in podocytes attached to LCSePs substrates than in those exposed to soluble LCSePs. Notably, LCSeP-based haptotaxis gave rise to altered signaling in podocytes. When podocytes were stimulated by immobilized LCSePs, FAK accumulated at focal adhesions, synaptopodin dissociated from F-actin, and disrupting the interactions between synaptopodin and α-actinin was observed. When FAK was inhibited by PF-573228 in immobilized LCSePs, the association between synaptopodin and α-actinin was observed in the podocytes. The association of synaptopodin and α-actinin with F-actin allowed FP stretching, establishing a functional glomerular filtration barrier. Therefore, in this mouse model of lung cancer, FAK signaling prompts podocyte FP effacement and proteinuria, indicative of PNS.

Coordination of LMO7 with FAK Signaling Sustains Epithelial Integrity in Renal Epithelia Exposed to Osmotic Pressure.

The kidney epithelial barrier has multifaceted functions in body fluids, electrolyte homeostasis, and urine production. The renal epithelial barrier (REB) frequently faces and challenges osmotic dynamics, which gives rise to osmotic pressure (a physical force). Osmotic pressure overloading can crack epithelial integrity and damage the REB. The endurance of REB to osmotic pressure forces remains obscure. LMO7 (LIM domain only 7) is a protein associated with the cell-cell junctional complex and cortical F-actin. Its upregulation was observed in cells cultured under hypertonic conditions. LMO7 is predominantly distributed in renal tubule epithelial cells. Hypertonic stimulation leads to LMO7 and F-actin assembly in the cortical stress fibers of renal epithelial cells. Hypertonic-isotonic alternation, as a pressure force pushing the plasma membrane inward/outward, was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. LMO7 depletion in cells resulted in junctional integrity loss in the epithelial sheet-cultured hypertonic medium or hypertonic-isotonic alternation. Conversely, FAK inhibition by PF-573228 led to failure in robust cortical F-actin assembly and LMO7 association with cortical F-actin in epithelial cells responding to hypertonic stress. Epithelial integrity against osmotic stress and LMO7 and FAK signaling are involved in assembling robust cortical F-actin and maintaining junctional integrity. LMO7 elaborately manages FAK activation in renal epithelial cells, which was demonstrated excessive FAK activation present in LMO7 depleted NRK-52E cells and epithelial integrity loss when cells with LMO7 depletion were exposed to a hypertonic environment. Our data suggests that LMO7 regulates FAK activation and is responsible for maintaining REB under osmotic disturbance.

Opportunities and Challenges of Human IPSC Technology in Kidney Disease Research.

Human induced pluripotent stem cells (iPSCs), since their discovery in 2007, open a broad array of opportunities for research and potential therapeutic uses. The substantial progress in iPSC reprogramming, maintenance, differentiation, and characterization technologies since then has supported their applications from disease modeling and preclinical experimental platforms to the initiation of cell therapies. In this review, we started with a background introduction about stem cells and the discovery of iPSCs, examined the developing technologies in reprogramming and characterization, and provided the updated list of stem cell biobanks. We highlighted several important iPSC-based research including that on autosomal dominant kidney disease and SARS-CoV-2 kidney involvement and discussed challenges and future perspectives.

Metabolic Syndrome and Obesity-Related Indices Are Associated with Rapid Renal Function Decline in a Large Taiwanese Population Follow-Up Study.

A rapid decline in renal function can cause many complications, and therefore it is important to detect associated risk factors. Few studies have evaluated the associations among obesity-related indices and metabolic syndrome (MetS) with renal function decline. This longitudinal study aimed to explore these relationships in a large cohort of Taiwanese participants. The studied obesity-related indices were waist-to-height ratio (WHtR), A body shape index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), waist-to-hip ratio (WHR), body roundness index (BRI), conicity index (CI), body mass index (BMI), body adiposity index (BAI) and abdominal volume index (AVI). We included 122,068 participants in the baseline study, of whom 27,033 were followed for a median of four years. The baseline prevalence of MetS was 17.7%. Multivariable analysis showed that the participants with MetS and high VAI, WHtR, WHR, LAP, CI, BRI, BMI, BAI, AVI, and ABSI values were significantly associated with a high baseline estimated glomerular filtration rate (eGFR) (all p < 0.001). In addition, the participants with MetS (p < 0.001), high WHtR (p = 0.007), low LAP (p < 0.001), high BRI (p = 0.002), high CI (p = 0.002), high AVI (p = 0.001), high VAI (p = 0.017), and high ABSI (p = 0.013) were significantly associated with a low △eGFR, indicating a rapid decline in renal function. These results showed associations between MetS and high values of obesity-related indices except LAP with high baseline eGFR and rapid decline in kidney function. These findings suggest that screening for MetS and obesity may help to slow the decline in renal function in high-risk populations.

Comparative Assessment of the Long-Term Effectiveness and Safety of Dapagliflozin and Empagliflozin as Add-on Therapy to Hypoglycemic Drugs in Patients with Type 2 Diabetes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce blood glucose, blood pressure, and body weight in patients with type 2 diabetes (T2D). However, the comparative long-term effectiveness and safety of SGLT2i among similar drugs, administered at different doses, have not been assessed. In this study, we compared the long-term effectiveness and safety of SGLT2i (dapagliflozin versus empagliflozin) as add-on therapy to hypoglycemic agents in T2D patients. Methods: This study was a single-center, 3-year, retrospective, observational study. For all patients in the study, drugs were evaluated for safety by documenting adverse drug reactions. The primary effectiveness was evaluated as the difference between hemoglobin A1c (HbA1c) values obtained at baseline and those obtained after 36 months of treatment. The proportion of participants with HbA1c levels <7.0% and <6.5% was also analyzed. Results: In total, 680 patients were enrolled in this study. Using propensity score matching, 234 patients each from the dapagliflozin and empagliflozin groups were selected based on patient characteristics. After 36 months of treatment, clinical parameters (including HbA1c, fasting plasma glucose, alanine aminotransferase, triglyceride levels, body weight, and systolic blood pressure) decreased significantly in these groups. The changes from the baseline for the physiological values and clinical parameters did not vary among the different dose groups of SGLT2i. The incidence of adverse drug reactions was approximately 7-8%. All patients with observed serious adverse reactions were hospitalized for urinary tract infections. Conclusion: Our study showed that the long-term continuous use of either dapagliflozin or empagliflozin as add-on therapy to hypoglycemic drugs for T2D patients is synergistically effective for lowering blood glucose, reducing body weight, and stabilizing blood pressure. Additionally, there was no significant difference in efficacy between dapagliflozin and empagliflozin, even with the administration of different doses of these agents.

Sex Difference in the Associations among Obesity-Related Indices with Incident Hypertension in a Large Taiwanese Population Follow-Up Study.

Hypertension is a major risk factor for stroke, atherosclerosis, and other cardiovascular diseases, and obesity is a major risk factor for hypertension. The aim of this longitudinal study was to investigate sex differences in the correlations among obesity-related indices and incident hypertension in a large Taiwanese cohort. We included 21,466 enrollees in the Taiwan Biobank and followed them for 4 years. Of the 21,466 patients enrolled in this study, 6899 (mean age, 49.6 ± 10.9 years) were male and 14,567 (mean age, 49.7 ± 10.0 years) were female. Data on visceral adiposity index (VAI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), lipid accumulation product (LAP), conicity index (CI), body roundness index (BRI), body mass index (BMI), body adiposity index (BAI), and abdominal volume index (AVI) were collected and analyzed. The results showed that all of the studied obesity-related indices were significantly associated with incident hypertension. Among them, WHtR was the strongest predictor of hypertension in both sexes. In addition, interactions between VAI, LAP, CI, BMI, and AVI with sex on incident hypertension were also statistically significant. CI and AVI were more strongly associated with hypertension in the men than in the women, while VAI, LAP, and BMI were more strongly associated with hypertension in the women. In conclusion, the studied obesity-related indices were found to be predictors of incident hypertension, and there were differences in the associations between the male and female participants. Our findings may imply that reducing body weight may be associated with a lower risk of developing hypertension.

Hepatic Steatosis Is Associated with High White Blood Cell and Platelet Counts.

The incidence of hepatic steatosis is increasing globally, and it is important to identify those at risk to prevent comorbidities. Complete blood count is a simple, convenient, and inexpensive laboratory examination which can be used to obtain white blood cell (WBC) and platelet counts. The aims of this study were to investigate the relationships between WBC and platelet counts with hepatic steatosis, and whether WBC and platelet counts were associated with the severity of hepatic steatosis. We enrolled 1969 participants residing in southern Taiwan who took part in a health survey from June 2016 to September 2018 in this cross-sectional study. None of the participants were heavy alcohol users or had a history of hepatitis B or C. We collected laboratory data, and the severity of hepatic steatosis was determined by abdominal ultrasound. The overall prevalence rate of hepatic steatosis was 42.0%. There were significant trends of stepwise increases in WBC count (p < 0.001) corresponding to the severity of hepatic steatosis. After multivariable linear regression analysis, hepatic steatosis was significantly associated with high WBC count (coefficient ß, 0.209; 95% confidence interval (CI), 0.055 to 0.364; p = 0.008) and high platelet count (coefficient ß, 12.213; 95% CI, 6.092 to 18.334; p < 0.001); also, higher WBC counts corresponded with the severity of hepatic steatosis.

Using herbs medically without knowing their composition: are we playing Russian roulette?

Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.

Betel Nut Chewing Increases the Risk of Metabolic Syndrome and Its Components in a Large Taiwanese Population Follow-Up Study Category: Original Investigation.

Betel nut chewing is a popular habit in Taiwan, and it is associated with adverse metabolic effects. The aim of this study was to investigate correlations between betel nut chewing with metabolic syndrome (MetS) and its components in a longitudinal study using data from the Taiwan Biobank. A total of 121,423 participants were included in the baseline study, and 27,002 received follow-up examinations after a median of 4 years. The association between betel nut chewing and MetS was analyzed using multiple logistic regression after controlling for confounders. The baseline prevalence of MetS was 22.5%. Multivariable analysis showed that a history of chewing betel nut was significantly associated with baseline MetS (odds ratio (OR) = 1.629; 95% confidence interval (CI) = 1.535 to 1.730, p < 0.001) and five components of MetS in all participants. A long history of chewing betel nut (per 1 year; OR = 1.008; 95% CI = 1.004 to 1.013, p < 0.001) was associated with baseline MetS, abdominal obesity, hypertriglyceridemia and low high-density lipoprotein (HDL) cholesterol. In addition, high cumulative dose (per 1 year × frequency × daily score; OR = 1.001; 95% CI = 1.001−1.002; p < 0.001) was significantly associated with baseline MetS. At the end of the follow-up, a history of chewing betel nut (OR = 1.352; 95% CI = 1.134 to 1.612, p = 0.001) was significantly associated with MetS and its components including abdominal obesity, hypertriglyceridemia and low HDL-cholesterol in the participants without baseline MetS. In addition, a longer history of betel nut chewing was associated with MetS (per 1 year; OR = 1.021; 95% CI = 1.008 to 1.035, p = 0.002), abdominal obesity and hypertriglyceridemia at follow-up. However, cumulative dose (p = 0.882) was not significantly associated with follow-up MetS. Chewing betel nut and a long history of betel nut chewing were associated with baseline MetS and its components. In the participants without MetS at baseline, chewing betel nut and a long history of chewing betel nut were associated with the development of MetS after 4 years of follow-up. However, a cumulative dose of betel nut chewing was not associated with follow-up MetS. Betel nut chewing cessation programs are important to reduce the incidence of MetS in Taiwan.

Generation of endoplasmic reticulum stress-dependent reactive oxygen species mediates TGF-ß1-induced podocyte migration.

Podocyte migration results in proteinuria and glomerulonephropathy. Transforming growth factor-ß1 (TGF-ß1), endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) can mediate podocyte migration; however, the crosstalk between them is unclear. This study determined the relationships between these factors. ER stress biomarkers (GRP78, p-eIF2α or CHOP), intracellular ROS generation, integrin-ß3 and cell adhesion and migration were studied in a treatment of experiment using TGF-ß1 with and without the ER stress inhibitors: 4-phenylbutyric acid (4-PBA, a chemical chaperone), salubrinal (an eIF2α dephosphorylation inhibitor) and N-acetylcysteine (NAC, an antioxidant). ER stress biomarkers (p-eIF2α/eIF2α and GRP78), ROS generation and intergrin-ß3 expression increased after TGF-ß1 treatment. NAC down-regulated the expression of GRP78 after TGF-ß1 treatment. 4-PBA attenuated TGF-ß1-induced p-eIF2α/eIF2α, CHOP, ROS generation and intergrin-ß3 expression. However, salubrinal did not inhibit TGF-ß1-induced p-eIF2α/eIF2α, CHOP, ROS generation or integrin-ß3 expression. NAC abrogated TGF-ß1-induced integrin-ß3 expression. At 24 h after treatment with TGF-ß1, podocyte adhesion and migration increased. Furthermore, NAC, 4-PBA and an anti-interin-ß3 antibody attenuated TGF-ß1-induced podocyte adhesion and migration. This study demonstrated that TGF-ß1-induced ER stress potentiates the generation of intracellular ROS to a high degree through the PERK/eIF2α/CHOP pathway. This intracellular ROS then mediates integrin-ß3 expression, which regulates podocyte migration.

U-Shaped Association between Waist-to-Hip Ratio and All-Cause Mortality in Stage 3-5 Chronic Kidney Disease Patients with Body Mass Index Paradox.

The obesity paradox, referring to the association of high body mass index (BMI) with low all-cause mortality risk, is found in patients with chronic kidney disease (CKD). Central obesity is associated with metabolic syndrome and may have better prognostic value than BMI for all-cause mortality. Whether central obesity is associated with all-cause mortality in cases of obesity paradox in CKD patients remains unknown. We included 3262 patients with stage 3-5 CKD, grouped into five quintiles (Q1-5) by waist-to-hip ratio (WHR). Low WHR and BMI were associated with malnutrition and inflammation. In Cox regression, high BMI was not associated with all-cause mortality, but BMI < 22.5 kg/m2 increased the mortality risk. A U-shaped association between central obesity and all-cause mortality was found: WHR Q1, Q4, and Q5 had higher risk for all-cause mortality. The hazard ratio (95% confidence interval) of WHR Q5 and Q1 for all-cause mortality was 1.39 (1.03-1.87) and 1.53 (1.13-2.05) in male and 1.42 (1.02-1.99) and 1.28 (0.88-1.85) in female, respectively. Waist-to-height ratio and conicity index showed similar results. Low WHR or low BMI and high WHR, but not high BMI, are associated with all-cause mortality in advanced CKD.

The MicroRNA Prediction Models as Ancillary Diagnosis Biomarkers for Urothelial Carcinoma in Patients With Chronic Kidney Disease.

Urothelial carcinoma is a common urological cancer in chronic kidney disease patients. Cystoscopy and urine cytology are the clinical diagnostic tools for UC. However, cystoscopy is an invasive procedure, while urine cytology showed low sensitivity for low-grade urothelial tumors. High accuracy with non-invasive tools for UC is needed for CKD patients. Our study collected a total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from CKD patients. Seventeen candidate miRNAs of biofluids were selected and confirmed by qRT-PCR. Our results showed that urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378, and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595. Two miRNA classifiers and the nomograms could improve the drawbacks of current UC biomarker screenings for patients with CKD.

Mobile Health, Disease Knowledge, and Self-Care Behavior in Chronic Kidney Disease: A Prospective Cohort Study.

Mobile health (mHealth) management is an emerging strategy of care for patients with chronic diseases. However, the effect of mHealth management on clinical outcomes of patients with chronic kidney disease (CKD) has not been well-studied. The aim of this study was to investigate the additional influence of mHealth on disease knowledge and self-care behavior in CKD patients who had received traditional education. We designed and developed a new healthcare mobile application, called iCKD, which has several major features, including home-based physiological signal monitoring, disease health education, nutrition analysis, medication reminder, and alarms and a warning system. Trained nurses interviewed patients with CKD using structured questionnaires of disease knowledge and self-care behavior. After propensity score matching, we analyzed 107 patients who used iCKD and traditional education, and 107 who received traditional education. The patients who used iCKD had higher disease knowledge scores than those who received traditional education. In multivariate analysis, iCKD was significantly and positively associated with disease knowledge scores. Patients with high education levels could have greater disease knowledge through using mHealth. There was no significant difference in total scores of self-care behavior between the two groups. In conclusion, mHealth can significantly increase disease knowledge in patients with CKD.

Association of glomerular filtration rate slope with timely creation of vascular access in incident hemodialysis.

The factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = - 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < - 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27-0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48-1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.

Tackling Dialysis Burden around the World: A Global Challenge.

CKD is a global problem that causes significant burden to the healthcare system and the economy in addition to its impact on morbidity and mortality of patients. Around the world, in both developing and developed economies, the nephrologists and governments face the challenges of the need to provide a quality and cost-effective kidney replacement therapy for CKD patients when their kidneys fail. In December 2019, the 3rd International Congress of Chinese Nephrologists was held in Nanjing, China, and in the meeting, a symposium and roundtable discussion on how to deal with this CKD burden was held with opinion leaders from countries and regions around the world, including Australia, Canada, China, Hong Kong, Singapore, Taiwan, the UK, and the USA. The participants concluded that an integrated approach with early detection of CKD, prompt treatment to slow down progression, promotion of home-based dialysis therapy like peritoneal dialysis and home HD, together with promotion of kidney transplantation, are possible effective ways to combat this ongoing worldwide challenge.

Low serum iron is associated with anemia in CKD stage 1-4 patients with normal transferrin saturations.

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1-4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 µg/dL in men, 60 µg/dL in women). Our results confirmed low TIBC (< 200 µg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both "normal TSAT low iron" and "low TSAT low iron" groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13-2.16 and OR 2.36; 95% CI 1.76-3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00-2.83 and OR 1.94; 95% CI 1.11-3.40, respectively). In conclusion, CKD stage 1-4 patients with normal TSAT but low serum iron are still at risk for anemia.

Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics.

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study.

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

The interaction between self-care behavior and disease knowledge on the decline in renal function in chronic kidney disease.

Multidisciplinary care can improve the outcomes of chronic kidney disease (CKD), however the contribution of self-care behavior and knowledge about CKD is unclear. This study enrolled 454 participants with CKD stages 1-5 not on dialysis. Structured questionnaires were used to evaluate self-care behavior and kidney disease knowledge. Rapid decline in renal function was defined as the decline in estimated filtration rate > 3 ml/min per 1.73 m2/year within 1-year prior to enrollment. The mean age of all study participants was 65.8 ± 12.1 years and 55.9% were male. The elderly had better self-care behavior while younger participants had better disease knowledge. Both high self-care and high disease knowledge scores were significantly associated with and had a synergistic effect on decreasing the risk of rapid decline in renal function. CKD patients with better self-care behavior and better kidney disease knowledge had lower risk of rapid decline in renal function.