Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study.

The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

The screening, diagnosis, and management of patients with autosomal dominant polycystic kidney disease: A national consensus statement from Taiwan.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.

AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. MATERIALS AND METHODS: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. RESULTS: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. CONCLUSION: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Environmental melamine exposure and adverse kidney outcomes in patients with type 2 diabetes mellitus.

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 µg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function.

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.

The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1-4.

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1-4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1-4.

Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial.

BACKGROUND: We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. METHODS: This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. RESULTS: A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). CONCLUSIONS: Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Multidisciplinary care program in pre-end-stage kidney disease from 2010 to 2018 in Taiwan.

BACKGROUND: The Taiwanese government launched a universal pay-for-performance (P4P) program in 2006 to promote multidisciplinary care for patients with stage 3b-5 chronic kidney disease (CKD). This study aimed to understand the enrollments, care processes, and outcomes of the P4P program between 2010 and 2018. METHODS: We conducted a population-based study using the Taiwan National Health Insurance Research Data. We divided the incident dialysis population into joining and not joining P4P groups based on whether patients had joined the pre-ESRD program before dialysis or not. Trends in the medications prescribed, anemia correction, vascular access preparation before dialysis initiation, and cumulative survival rate were compared. RESULTS: The program included more than 100,000 patients with late-stage CKD. Enrollment increased by almost 100% from 2010 to 2018, with increases seen in those over 75 years old (127.5%), male (96.7%), and earlier CKD stages (≥35% stage 3b in 2018). Females were more likely to stay being enrolled. The joining P4P group was prescribed more appropriate medications, such as erythropoietin-stimulating agents and statins. However, a high number of patients were still prescribed metformin (≥40%) and non-steroidal anti-inflammatory drugs (≥20%). Compared to the not joining P4P group, the patients in the P4P group had better anemia management, dialysis preparation, and post-dialysis survival. CONCLUSION: The patients in the joining P4P program group were delivered more appropriate CKD care and were associated with better survival outcomes. Polices and action plans are needed to extend the coverage of and enrollment in the P4P program.

Generation of induced pluripotent stem cells from a Bardet-Biedl syndrome patient carrying a homologous BBS2 c.534 + 1G > T mutation.

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition.

The Relationship between Subtypes of Health Literacy and Self-Care Behavior in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global public health issue that is associated with high rates of morbidity and mortality. Self-care behavior has been associated with clinical outcomes in chronic diseases, and adequate self-care behavior may mitigate adverse outcomes. Health literacy may be an important factor associated with self-care. The aim of this study was to examine the relationships between different domains of self-care behavior and health literacy in patients with CKD. This study enrolled 208 patients with CKD stages 1-5 who were not undergoing renal replacement therapy at Kaohsiung Medical University Hospital from April 2019 to January 2020. Health literacy was measured using a multidimensional health literacy questionnaire covering the following five dimensions: accessing, understanding, appraising, and applying health information, and communication/interaction. The CKD Self-Care scale, which is a 16-item questionnaire with five domains including medication adherence, diet control, exercise, smoking behavior, and home blood pressure monitoring was used to assess self-care behavior. Among the 208 patients, 97 had sufficient or excellent health literacy, and 111 had inadequate or limited/problematic health literacy. A higher health literacy score was significantly correlated with greater self-care behavior. Among the five domains of self-care behavior, the patients who had sufficient or excellent health literacy had higher diet, exercise, and home blood pressure monitoring scores than those who had inadequate or limited/problematic health literacy. This study demonstrated that health literacy was significantly and positively correlated with self-care behavior in patients with CKD.

Melamine exposure threshold in early chronic kidney disease patients - A benchmark dose approach.

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR≥30 ml/min per 1.73 m2. The patients were enrolled 2006-2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose-response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 µg/kg_bw/day after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.

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.

The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients.

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C-C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

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.

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. METHODS: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. RESULTS: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). CONCLUSION: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

OBJECTIVE: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. DESIGN: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up). RESULTS: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. CONCLUSION: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. CLINICALTRIALSGOV IDENTIFIER: NCT03803410 and NCT03891550.

Lung Cancer Cell-Derived Secretome Mediates Paraneoplastic Inflammation and Fibrosis in Kidney in Mice.

Kidney failure is a possible but rare complication in lung cancer patients that may be caused by massive tumor lysis or a paraneoplastic effect. Clinical case reports have documented pathological characteristics of paraneoplastic syndrome in glomeruli, but are short of molecular details. When Lewis lung carcinoma 1 (LLC1) cells were implanted in mice lungs to establish lung cancer, renal failure was frequently observed two weeks post orthotopic xenograft. The high urinary albumin-to-creatinine ratio (ACR) was diagnosed as paraneoplastic nephrotic syndrome in those lung cancer mice. Profiling the secretome of the lung cancer cells revealed that the secretory proteins were potentially nephrotoxic. The nephrotoxicity of lung cancer-derived secretory proteins was tested by examining the pathogenic effects of 1 × 106, 2 × 106, and 5 × 106 LLC1 cell xenografts on the pathogenic progression in kidneys. Severe albuminuria was present in the mice that received 5 × 106 LLC1 cells implantation, whereas 106 cell and 2 × 106 cell-implanted mice have slightly increased albuminuria. Pathological examinations revealed that the glomeruli had capillary loop collapse, tumor antigen deposition in glomeruli, and renal intratubular casts. Since IL-6 and MCP-1 are pathologic markers of glomerulopathy, their distributions were examined in the kidneys of the lung cancer mice. Moderate to severe inflammation in the kidneys was correlated with increases in the number of cells implanted in the mice, which was reflected by renal IL-6 and MCP-1 levels, and urine ACR. TGF-ß signaling-engaged renal fibrosis was validated in the lung cancer mice. These results indicated that lung cancer cells could provoke inflammation and activate renal fibrosis.

Associations of Bone Turnover Markers with Cognitive Function in Patients Undergoing Hemodialysis.

BACKGROUND: Patients undergoing hemodialysis experience a greater risk of cognitive impairment than the general population, but limited data elucidates the biomarkers on this. We evaluated the association of bone turnover markers on cognitive function among 251 prevalent hemodialysis enrollees in a cross-sectional study. METHODS: 251 hemodialysis patients (median age = 57.8, 55% men) and 37 control subjects (mean age = 61.2, 56% men) without a prior stroke or dementia diagnosis were enrolled. Serum concentrations of 8 bone markers were analyzed as the association of cognitive function (Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI)) using linear regression analysis. RESULTS: A lower cognitive function was noted in hemodialysis patients compared to control subjects. The receptor activator of nuclear factor kappa-B ligand (RANKL) was the only bone marker found to be associated with cognitive function (MoCA and CASI tests) in hemodialysis patients without a prior stroke or dementia diagnosis. In stepwise multiple linear regression analysis, the association remained significant in MoCA (ß = 1.14, 95% CI 0.17 to 2.11) and CASI (ß = 3.06, 95% CI 0.24 to 5.88). Short-term memory (ß = 0.52, 95% CI 0.01 to 1.02), mental manipulation (ß = 0.51, 95% CI 0.05 to 0.96), and abstract thinking (ß = 0.57, 95% CI 0.06 to 1.09) were the significant subdomains in the CASI score related to RANKL. CONCLUSIONS: Serum RANKL levels were potentially associated with better cognitive function in hemodialysis patients. Further large-scale and prospective studies are needed to confirm our findings.

Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients: A Cross-Sectional Study.

: Protein-bound uremic toxin is a cardiovascular (CV) risk factor for patients with end-stage renal disease. Indole-3-acetic acid (IAA) was found to be associated with CV disease but the detailed pathophysiology remains unknown. Moreover, mitogen-activated protein kinase (MAPK) signaling cascades play an important role in the pathogenesis of CV disease. Thus, we explored the association between circulating IAA levels and forty MAPK cascade associated proteins in patients undergoing hemodialysis (HD). Circulating total form IAA was quantified by mass spectrometry and forty MAPK cascade associated proteins by a proximity extension assay in 331 prevalent HD patients. Accounting for multiple testing, and in multivariable-adjusted linear regression models, circulating total form IAA levels were positively associated with stem cell factor (ß coefficient 0.13, 95% confidence interval 0.04 to 0.21, p = 0.004). A bioinformatics approach using the search tool for interactions of chemicals (STITCH) tool provided information that IAA may be involved in the regulation of cell proliferation, hematopoietic cells, and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. The knowledge gained here can be generalized, thereby impacting the non-traditional CV risk factors in patients with kidney disease. Further in vitro work is necessary to validate the translation of the mechanistic pathways.

Coenzyme Q10 status, glucose parameters, and antioxidative capacity in college athletes.

BACKGROUND: Glycemia is related to energy production during exercise. Coenzyme Q10 is an antioxidant that participates in adenosine triphosphate synthesis in mitochondria. The aim of this study was to investigate the level of coenzyme Q10, glucose parameters, and antioxidant capacity in athletes. METHODS: This study was designed as a cross-sectional study. Well-trained college athletes (n = 43) and age-gender matched healthy subjects (n = 25) were recruited from a college. The levels of glucose parameters, oxidative stress, antioxidant enzymes activity, Trolox equivalent antioxidant capacity (TAC), and coenzyme Q10 status were measured in the present study. RESULTS: The athletes had a significantly lower level of white blood cells (WBC) coenzyme Q10 than the healthy subjects (0.34 ± 0.24 vs. 0.65 ± 0.43 nmol/g, p < 0.01); however, no significant difference was detected in plasma coenzyme Q10 between the two groups. Regarding the glucose parameters, the athletes had significantly higher values for HbA1c (5.5 ± 0.3 vs. 5.3 ± 0.3%, p < 0.05) and quantitative insulin sensitivity check index (QUICKI, 0.37 ± 0.03 vs. 0.34 ± 0.03, p < 0.05), and lower homeostatic model assessment-insulin resistance (HOMA-IR, 1.5 ± 0.8 vs. 2.9 ± 3.8, p < 0.05) than the healthy subjects. A higher level of TAC was found in the athletes (serum, 5.7 ± 0.3 vs. 5.4 ± 0.2 mM Trolox; erythrocyte, 10.5 ± 0.6 vs. 10.0 ± 0.5 mM Trolox, p < 0.05). In addition, WBC coenzyme Q10 status was significantly correlated with catalase activity (r = 0.56, p < 0.01), GPx activity (r = 0.56, p < 0.01), serum TAC (r = 0.54, p < 0.01), fasting glucose (ß = - 1.10, p < 0.01), HbA1c (ß = - 0.82, p < 0.01), HOMA-IR (ß = - 1.81, p < 0.01), and QUICK (ß = 0.08, p < 0.01). CONCLUSIONS: Athletes may suffer from a marginal coenzyme Q10 deficiency, and the level was related to glycemic control and antioxidant capacity. Further interventional studies are needed to clarify an adequate dose of coenzyme Q10 supplementation in athletes to optimize their coenzyme Q10 status and athletic performance or recovery during exercise.