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This longitudinal cohort study investigated the associations of air pollutant exposures, including CO, NO, NO 2 , NO x , O 3 , PM 10 , PM 2.5 , and SO 2 , with long-term kidney function changes in patients with chronic kidney disease (CKD). We enrolled 447 CKD patients who took part in a universal hospital pre-ESRD care program during 2011-2015. The daily average air pollutant exposures and temperature were estimated for each patient, with different levels of air pollutant concentrations defined by 5-knot and restricted cubic spline function. Predicted annual estimated glomerular filtration (eGFR) slope values by one mixed model were considered as the study outcome. The average age of the study population was 77.1 ± 12.6 years, and the median annual eGFR decreased by 2.1 ml/min/1.73 m 2 per year from 30 ml/min/1.73 m 2 at baseline during a mean follow-up time of 3.4 years. The univariable and multivariable analyses revealed no significant linear and non-linear associations between 5-knot air pollutant concentrations and annual eGFR slope. In addition, the visualized spline effect plots show insignificant variation patterns in annual eGFR slope values with increased air pollutant concentrations. These results encourage more extensive studies to clarify the causal relationships and mechanisms of long-term specific air pollutant exposures and longitudinal kidney function change, especially in CKD populations., (© 2023. The Author(s).)

Background: Understanding renal function state transition risk and associated factors in community residences is vital for appropriate preventive and care actions. We aim to investigate factors affecting renal function state transitions through 10-year longitudinal community screening surveys., Methods: The prospective cohort study included participants who attended the screening program ≥2 times from 2001 to 2009 and were divided into two cohorts: those with baseline estimated glomerular filtration rate (eGFR) ≥60 ( n = 46,278) and those with eGFR 59-30 mL/min/1.73 m 2 ( n = 4,656). We applied the illness-death model to identify associated factors with eGFR <60 and death for the cohort with baseline eGFR ≥60 and eGFR <30 and death for that with baseline eGFR ≥59-30., Results: Among the followed-up participants, 3,018 (6.5%) in the cohort of baseline eGFR ≥60 mL/min/1.73 m 2 and 322 (6.9%) in the cohort of eGFR 59-30 mL/min/1.73 m 2 experienced renal function state transition during a median over 7-year follow-up. Besides eGFR and grade of proteinuria, diabetes mellitus (adding nearly 50% hazard rate) is the main factor associated with both state transitions. Other early-phase eGFR state transition risk factors were metabolic syndrome score, triglyceride, uric acid, fasting blood sugar, and high-density lipoprotein cholesterol. Males, poor hemoglobin, high triglyceride, and high low-density lipoprotein cholesterol were all linked with the late-phase eGFR state transition hazard rate., Conclusion: The study developed the state transition functions for community participants with varying renal function levels. Further actions to develop precision screening plans and services that incorporate personal risk factors and state transition risks are necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsai, Lin, Hsu, Yen, Chen, Chiu and Hwang.)

Introduction: The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region., Methods: We systematically searched MEDLINE, Embase and Google Scholar for observational studies and contacted national experts to estimate CKD prevalence in countries of Asia (Eastern, Southern and South Eastern Asia). CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 or the presence of proteinuria. For countries without reported data, we estimated CKD prevalence using agglomerative average-linkage hierarchical clustering, based on country-level risk factors and random effects meta-analysis within clusters. Published CKD prevalence data were obtained for 16 countries (of the 26 countries in the region) and estimates were made for 10 countries., Results: There was substantial variation in overall and advanced (eGFR <30 mL/min/1.73 m 2 ) CKD prevalence (range: 7.0%-34.3% and 0.1%-17.0%, respectively). Up to an estimated 434.3 million (95% CI 350.2 to 519.7) adults have CKD in Asia, including up to 65.6 million (95% CI 42.2 to 94.9) who have advanced CKD. The greatest number of adults living with CKD were in China (up to 159.8 million, 95% CI 146.6 to 174.1) and India (up to 140.2 million, 95% CI 110.7 to 169.7), collectively having 69.1% of the total number of adults with CKD in the region., Conclusion: The large number of people with CKD, and the substantial number with advanced CKD, show the need for urgent collaborative action in Asia to prevent and manage CKD and its complications., Competing Interests: Competing interests: TL, TT and KP have no relevant conflicts of interests to declare. MW declares consulting work for Amgen, Kyowa Kirin and Freeline, and was funded by an Australian National Health and Medical Research Council Investigator and Programme Grants. VP reports receiving personal fees for Advisory Boards or Scientific Presentations from Retrophin, Janssen, Merck, and Servier. VP also reports receiving fees for Advisory Boards, Steering Committee roles, or Scientific Presentations from Abbvie, Astellas, Astra Zeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Vifor and Tricida. HS-F was a full-time employee and shareholder of GlaxoSmithKline. VJ reports grant funding from NephroPlus, Baxter Healthcare and GSK and speaker fees and honoraria from Baxter Healthcare and AstraZeneca (all monies paid to the employing organisation). MJ reports receiving research support from (1) the Australian National Health and Medical Research Council and (2) VentureWise (a wholly-owned subsidiary of NPS MedicineWise) to conduct a project funded by AstraZeneca., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with chronic kidney disease (CKD) often have structural abnormalities of the heart due to pressure and volume overload. The aim of this study was to evaluate associations between echocardiographic parameters and renal outcomes (estimated glomerular filtration rate [eGFR] slope and progression to dialysis) in patients with stage 3-5 CKD., Methods: This longitudinal study enrolled 419 patients. Changes in renal function were assessed using the eGFR slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min/1.73 m 2 /year, and the renal endpoint was defined as commencing dialysis., Results: Increased left atrial diameter (LAD), ratio of left ventricular mass to body surface area (LVM/BSA), ratio of LVM to height 2.7 (LVM/ht 2.7 ), and ratio of observed to predicted LVM (o/p LVM) were associated with eGFR slope in an adjusted model, but left ventricular ejection fraction (LVEF) was not. Furthermore, LAD ≥ 4.7 cm, LVM/BSA > 115 g/m 2 in males and > 95 g/m 2 in females, and LVM/ht 2.7 > 48 g/ht 2.7 in males and > 44 g/ht 2.7 in females were correlated with progression to dialysis, but o/p LVM and LVEF were not. The maximum change in χ 2 change to predict renal outcomes was observed for LAD, followed by LVM/BSA and LVM/ht 2.7 ., Conclusions: A large LAD and increased LVM, regardless of how it was measured (LVM/BSA, LVM/ht 2.7 and o/p LVM), were correlated with adverse renal outcomes in patients with CKD stage 3-5. LAD had superior prognostic value to LVM and LVEF.

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 m 2 , 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 m 2 /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.

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.

Purpose: To examine the effects of health coaching on self-management and quality of life (QOL) in patients with chronic kidney disease (CKD) and to evaluate whether self-efficacy and patient activation mediate the effect of health coaching on self-management and QOL., Design and Methods: A single-center, parallel-group, randomized controlled trial. A total of 108 patients with stages 1 to 3a CKD participated in the study. Participants were randomly assigned to a health-coaching intervention group or a usual care control group. Participants' QOL (World Health Organization Quality of Life Scale), self-management (CKD Self-Management instrument), patient activation (Patient Activation Measure), and self-efficacy (CKD Self-Efficacy instrument) were measured at baseline, immediately after, and 6 weeks after the intervention., Findings: Health coaching improved QOL, self-management, patient activation, and self-efficacy at postintervention and at 12 weeks' follow-up. Health coaching had a significant indirect effect on QOL through improvements in patient activation. Health coaching exerted a significant indirect effect on self-management through improvements in self-efficacy and patient activation., Conclusions: The findings demonstrated that health coaching can effectively improve QOL and self-management. A health-coaching intervention can raise self-efficacy and activation levels through which self-management and QOL further improve., Clinical Relevance: Health-coaching strategies can be used to assist patients with early-stage CKD in reaching their health goals and becoming activated in self-management of their diseases., (© 2021 Sigma Theta Tau International.)

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., Competing Interests: Co-author Ping-Hsun Wu is a fellow of PLOS ONE Editorial Board Members. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.

Evidence-based studies have revealed outcomes in patients with chronic kidney disease that differed depending on the design of care delivery. This study compared the effects of 3 types of nephrology care: multidisciplinary care (MDC), nephrology care, and non-nephrology care. We studied their effects on the risks of requiring dialysis and the differences between these methods had on long-term medical resource utilization and costs.We conducted a retrospective cohort study involving patients with an estimated glomerular filtration rate of (eGFR) ≤45 mL/min/1.73 m from 2005 to 2007. Patients were divided into MDC, non-MDC, and non-nephrology referral groups. Between-group differences with regard to the risk of requiring dialysis and annual medical utilization and costs were evaluated using a 5-year follow-up period.In total, 661 patients were included. After other covariates and the competing risk of death were taken into account, we observed a significant (56%) reduction in the incidence of dialysis in both the MDC and non-MDC groups relative to the non-nephrology referral group. Costs were markedly lower in the MDC group relative to the other groups (average savings: US$ 830 per year; 95% confidence interval: 367-1295; P < .001).For patients without nephrology referrals, MDC can substantially reduce their risk of developing end-stage renal disease and lower their medical costs. We therefore strongly advocate that all patients with an eGFR of ≤45 mL/min/1.73 m should be referred to a nephrologist and receive MDC.

Late referral in chronic kidney disease (CKD) is associated with irregular care and poor prognosis. How the specialty of healthcare provider affect late referral and irregular CKD care remain unclear.We conducted a population-based cross-sectional study to include incident dialysis patients from 2002 to 2007 in Taiwan and observed for 1, 2, and 3 years before dialysis. The medical visits-related information was evaluated every 3 months, retrospectively. Irregular follow-up was defined as missing a follow-up during more than one interval every year.A total of 46,626 patients were included. At 1, 2, and 3 years prior to maintenance dialysis, 87%, 66%, and 50% of patients had regular medical visits; however, only 49%, 23%, and 12% had estimated glomerular filtration rate (eGFR) regularly monitored, respectively. Independent factors of less regular eGFR follow-up included age (adjusted odds ratio (OR) 0.995, 95% confidence interval 0.993-0.998), cardiac disorder (0.90, 0.82-0.99), and stroke (0.76, 0.69-0.84), as well as regular visits at some other specialties (adjusted OR range: from 0.77 to 0.88); whereas, independent factors of less regular visits at nephrology included diabetes mellitus (0.48, 0.46-0.51), cardiac disorder (0.61, 0.56-0.66), stroke (0.53, 0.48-0.58), and regular visits at any other specialty (adjusted OR range: from 0.22 to 0.78).Regular medical visits were quite common in late CKD patients, but they received regular eGFR measurement and visit at nephrology much less frequently. Physicians play a major role in the late referrals in CKD and its irregular care.

Background: The National Health Insurance Administration in Taiwan initiated a nationwide pre-end-stage renal disease (ESRD) pay-for-performance (P4P) programme at the end of 2006 to improve quality of care for chronic kidney disease (CKD) patients. This study aimed to examine this programme's effect on patients' clinical outcomes and its cost-effectiveness among advanced CKD patients., Methods: We conducted a longitudinal observational matched cohort study using two nationwide population-based datasets. The major outcomes of interests were incidence of dialysis, all-cause mortality, direct medical costs, life years (LYs) and incremental cost-effectiveness ratio comparing matched P4P and non-P4P advanced CKD patients. Competing-risk analysis, general linear regression and bootstrapping statistical methods were used for the analysis., Results: Subdistribution hazard ratio (95% confidence intervals) for advanced CKD patients enrolled in the P4P programme, compared with those who did not enrol, were 0.845 (0.779-0.916) for incidence of dialysis and 0.792 (0.673-0.932) for all-cause mortality. LYs for P4P and non-P4P patients who initiated dialysis were 2.83 and 2.74, respectively. The adjusted incremental CKD-related costs and other-cause-related costs were NT$114 704 (US$3823) and NT$32 420 (US$1080) for P4P and non-P4P patients who initiated dialysis, respectively, and NT$-3434 (US$114) and NT$45 836 (US$1572) for P4P and non-P4P patients who did not initiate dialysis, respectively, during the 3-year follow-up period., Conclusions: P4P patients had lower risks of both incidence of dialysis initiation and death. In addition, our empirical findings suggest that the P4P pre-ESRD programme in Taiwan provided a long-term cost-effective use of resources and cost savings for advanced CKD patients., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD., Methods: This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y)., Results: During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02)., Conclusions: Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13-1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics.

Background: Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients., Methods: This cross-sectional study enrolled 172 of CKD stages 1-5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status (extracellular water/total body water, ECW/TBW), lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method., Results: All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P<0.001 and P = 0.002). CKD patients with high FTI had lower handgrip strength and 30-second chair-stand than those with low FTI (P<0.001 and P = 0.002). These patients with low LTI had lower handgrip strength than those with high LTI (P = 0.04). In multivariate analysis, high ECW/TBW was positively associated with decreased handgrip strength (β = -41.17, P = 0.03) in CKD patients. High FTI was significantly correlated with decreased times of 30-second chair-stand (β = -0.13, P = 0.01). There was no significant relationship between body composition and 2-minute step test., Conclusions: Our results show a significant association of impaired upper and lower extremity muscle endurance with high fluid status and fat tissue. Evaluation of body composition may assist in indentifying physical dysfunction earlier in CKD patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Nonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan., Methods: We conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio., Results: The subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26-1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23-1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19-1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35-2.40, p< 0.001)., Conclusions: In this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.

Background: Leptospirosis is the most widespread zoonosis. Chronic human infection and asymptomatic colonization have been reported. However, renal involvement in those with leptospira chronic exposure remains undetermined., Methods and Findings: In 2007, a multistage sampling survey for chronic kidney disease (CKD) was conducted in a southern county of Taiwan, an area with a high prevalence of dialysis. Additionally, an independent cohort of 88 participants from a leptospira-endemic town was followed for two years after a flooding in 2009. Risks of CKD, stages of CKD, associated risk factors as well as kidney injury markers were compared among adults with anti-leptospira antibody as defined by titers of microscopic agglutination test (MAT). Of 3045 survey participants, the individuals with previous leptospira exposure disclosed a lower level of eGFR (98.3 ± 0.4 vs 100.8 ± 0.6 ml/min per 1.73 m2, P < 0.001) and a higher percentage of CKD, particularly at stage 3a-5 (14.4% vs 8.5%), than those without leptospira exposure. Multivariable linear regression analyses indicated the association of leptospiral infection and lower eGFR (95% CI -4.15 to -1.93, P < 0.001). In a leptospiral endemic town, subjects with a MAT titer ≥ 400 showed a decreased eGFR and higher urinary kidney injury molecule-1 creatinine ratio (KIM1/Cr) level as compared with those having lower titers of MAT (P < 0.05). Furthermore, two participants with persistently high MAT titers had positive urine leptospira DNA and deteriorating renal function., Conclusions and Significance: Our data are the first to show that chronic human exposure of leptospirosis is associated significantly with prevalence and severity of CKD and may lead to deterioration of renal function. This study also shed light on the search of underlying factors in areas experiencing CKD of unknown aetiology (CKDu) such as Mesoamerican Nephropathy.

Dipyridamole has been shown to decrease proteinuria and improve renal function progression especially in early chronic kidney disease (CKD) patients with glomerulonephropathy. A combination therapy of dipyridamole with aspirin could prevent second strokes in the general population. Whether these effects of dipyridamole are also true in advanced CKD patients and whether dipyridamole could improve renal outcomes or patient survival is unknown. We retrospectively analyzed an observational cohort of 3074 participants with CKD stage 3-5 from southern Taiwan, of whom 871 (28.3%) had received dipyridamole treatment ≥50 mg/d for ≥3 months and more than half of the observation period. The mean age was 63.6 ± 13.4 years and the mean estimated glomerular filtration rate (eGFR) was 25.5 mL/min/1.73 m(2). After inverse probability of treatment weighted adjustment by propensity score, there were no differences between the dipyridamole-treated and untreated groups. Dipyridamole treatment was associated with decreased odds for rapid eGFR decline [odds ratio, 0.755; 95% confidence interval (CI), 0.595-0.958; p = 0.007] and progression of urine protein-to-creatinine ratio (odds ratio, 0.655; 95% CI, 0.517-0.832; p = 0.002). In survival analysis, the dipyridamole-treated group was also associated with a decreased risk for end-stage renal disease (hazard ratio, 0.847; 95% CI, 0.733-0.980; p = 0.011) and all-cause mortality (hazard ratio, 0.765; 95% CI, 0.606-0.971; p = 0.001) but not for cardiovascular events. Our findings demonstrate that dipyridamole treatment is significantly associated with better renal outcomes and patient survival in patients with CKD stage 3-5. Further investigations are warranted to confirm these independent positive effects., (Copyright © 2014. Published by Elsevier Taiwan.)

Background: The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown., Methods: This study enrolled 621 patients with stages 3-5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m2/y) over follow-up of more than 3 years., Results: Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06-2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13-7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2., Conclusions: Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the -2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%&#95;12M (P < 0.001), a smaller peak eGFR AUC%&#95;12M (P < 0.001), and a larger negative eGFR slope&#95;12M (P < 0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%&#95;12M and eGFR slope&#95;12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

This cross-sectional research study explored differences in health-promoting behavior and resilience among three groups of chronic kidney disease patients (high-risk, early chronic kidney disease; early CKD and pre-end stage renal disease; pre-ESRD) treated at the Nephrology outpatient clinic in northern Taiwan. A total of 150 CKD outpatients were interviewed using structured questionnaires including a CKD Health to Promote Lifestyle Scale, and resilience scale. We found that the pre-ESRD group had lower resilience than either high-risk or early CKD groups. Factors affecting pre-ESRD resilience were gender, occupational status, diabetes and health-promoting behaviors. Factors affecting resilience of the high-risk group included level of education and health-promoting behaviors while factors affecting resilience in the early CKD group involved whether they are employed and health promoting behaviors. A significant positive correlation was found between health promoting behavior and resilience in all study subjects. Multiple regression analysis found that factors which could effectively predict resilience in patients at high-risk for CKD were gender, whether the patient had a job, nutrition, self-actualization, and stress level, accounting for 69.7% of the variance. Therefore, nursing education should focus on health promotion advocacy throughout the life of not only patients but also their families.

Background and Objectives: The risk factors for CKD in different age groups remain unknown. This community-based study aimed to identify the risk factors for CKD in elderly and nonelderly patients., Design, Setting, Participants, & Measurements: A multistage sampling survey for CKD was conducted in 2007 in Kaohsiung County, an area with the highest prevalence of dialysis in the world. CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR (eGFR) of <60 ml/min per 1.73 m(2). The factors for CKD in elderly and nonelderly patient groups were identified (with age 60 years as a cutoff value)., Results: The analyses included 3352 participants, of whom 687 had CKD. The weighted prevalence of CKD was 19.4% (95% confidence interval [CI], 18.0%-20.7%). Elderly patients typically presented with low eGFR and nonelderly patients, with proteinuria. Age, annual income, use of oral analgesics, metabolic syndrome, hyperuricemia, and hemoglobin were risk factors for CKD in both age groups. In elderly patients, risk factors were medical history of diabetes mellitus, CKD, stroke, and not using analgesic injection (odds ratios [95% CIs], 3.58 [2.06-6.22], 3.66 [1.58-8.43], 3.89 [1.09-13.87], 2.27 [1.21-4.17], respectively). In nonelderly patients, associated risk factors for CKD were gout, hepatitis B virus infection, and use of the Chinese herbal medicine Long Dan Xie Gan Tang (odds ratios [95% CIs], 3.15 [1.96-5.07], 1.66 [1.09-2.53], and 8.86 [1.73-45.45], respectively)., Conclusions: The risk factors for CKD vary by age.

Background: Depression is related to morbidity and mortality in patients with kidney failure treated by dialysis, but its influence on patients with earlier stages of chronic kidney disease (CKD) is uncertain. This study investigates the association of depressive symptoms with clinical outcomes in patients with CKD not requiring dialysis., Study Design: Prospective observational cohort study., Setting & Participants: 568 participants with CKD not requiring maintenance dialysis were recruited consecutively at a tertiary hospital in Southern Taiwan and followed up for 4 years., Predictors: Baseline status of depressive symptoms., Outcomes: The primary outcome is a composite of progression to end-stage renal disease (ESRD), defined as requiring maintenance dialysis treatment, or all-cause mortality; and secondary outcome was first hospitalization., Measurements: Depressive symptoms were assessed by Beck Depression Inventory. Estimated glomerular filtration rate (eGFR) was computed using the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation., Results: 428 participants completed the questionnaires and 160 (37%) had depressive symptoms. During a mean follow-up of 25.2 ± 11.9 months, 136 participants (32%) reached the primary outcome (119 reached ESRD and 17 died) and 110 participants (26%) were hospitalized. High depressive symptoms increased the risk of progression to ESRD or death (HR, 1.66; 95% CI, 1.14-2.44) and first hospitalization (HR, 1.59; 95% CI, 1.03-2.47). Participants with high depressive symptoms had more rapid GFR decrease (eGFR slopes of -2.3 [25th-75th percentile, -5.3 to -0.4] vs -1.2 [25th-75th percentile, -3.5 to 0.3] mL/min/1.73 m(2) per year; P = 0.001) and initial dialysis treatment at a higher eGFR (OR for initiation of dialysis at eGFR >5 mL/min/1.73 m(2), 4.45; 95% CI, 1.44-13.78)., Limitations: A single-center study of Taiwanese, Beck Depression Inventory evaluates only depressive symptom burden., Conclusions: Depressive symptoms in CKD are independent predictors of adverse clinical outcomes, including faster eGFR decrease, dialysis therapy initiation, death, or hospitalization. Depression should be evaluated early and treated in patients with CKD., (Copyright © 2012. Published by Elsevier Inc.)

Background: A higher prevalence of chronic kidney disease (CKD) has been found in genetic relatives of patients with end-stage renal disease. However, the risk of CKD in nongenetic spouses of patients with end-stage renal disease is still unknown., Study Design: Cross-sectional study., Setting & Participants: 196 first- and second-degree relatives and 95 spouses of 178 hemodialysis (HD) patients were enrolled. Two sex- and age-stratified matched counterpart controls were randomly selected from the population of a community screening program for CKD., Predictors: Relatives or spouses of HD patients and kidney disease risk factors., Outcomes: Prevalence of CKD (albuminuria or low estimated glomerular filtration rate)., Measurement: Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g), low estimated glomerular filtration rate (<60 mL/min/1.73 m(2)), and kidney disease risk factors of age, hypertension, diabetes mellitus, metabolic syndrome, and lifestyle., Results: A significantly higher prevalence of CKD was found in relatives (15.8% vs 7.5%; P = 0.01) and spouses (41.1% vs 15.8%; P < 0.001) of HD patients compared with their counterpart controls. Multiple logistic regression analysis showed that age (OR, 1.05) and hypertension (OR, 3.13) were significant independent risk factors for CKD in relatives of HD patients, whereas diabetes mellitus (OR, 3.51) was a significant risk factor for CKD in spouses of HD patients. For all pooled participants, being relatives (OR, 2.55) or spouses (OR, 2.80) of HD patients, age (OR, 1.06), female sex (OR, 1.81), diabetes mellitus (OR, 3.95), hypertension (OR, 1.85), and hyperuricemia (OR, 2.06) were independent significant risk factors for CKD., Limitations: Cross-sectional research design, single laboratory measurement, and limited numbers of participants., Conclusions: A comprehensive screening program for CKD is equally important in both relatives and spouses of HD patients, especially for participants with the renal risk factors of older age, hypertension, and diabetes mellitus. Spousal concordance of CKD suggests that the shared environmental factors and health behaviors might have important roles in the development of CKD., (Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Taiwan has the world's highest incidence and second highest prevalence of end-stage renal disease (ESRD), particularly in older age groups. However, the transition from chronic kidney disease (CKD) to death or ESRD remains unclear. This study aimed to investigate the impact of late-stage CKD on all-cause and cause-specific mortality by identifying the CKD population., Methods: This was an observational cohort study (n = 35 529), mean age 75.7 years (SD = 5.3), of participants in the Elderly Health Examination Program (EHEP) in Kaohsiung City, Taiwan, between 2002 and 2004. Estimated glomerular filtration rate (eGFR) was calculated by the simplified modified diet in renal disease equation. Proportional hazard ratios (HR) of mortality associated with late-stage CKD were assessed by Cox regression., Results: The crude prevalence rate of CKD stages 3-5 was 39.4%; 1840 participants (5.18%) died within 2-year follow-up, a mortality rate of 20.3 per 1000 person-years overall and 16.4 per 1000 person-years in the reference group. Higher HR for all-cause and cause-specific mortality were found in the groups with decreased eGFR. Compared with the reference group (eGFR > 60 mL/min/1.73 m(2)), adjusted HR for all-cause mortality were 1.5, 2.1 and 2.6 for groups with eGFR 30-44, 15-29 and < 15 mL/min/ 1.73 m(2), respectively (P < 0.001). Higher HR of mortality due to cardiovascular or renal diseases were also significantly associated with decreased eGFR (P < 0.05)., Conclusion: Late-stage CKD is a significant risk factor for mortality, especially due to cardiovascular and renal diseases, in elderly Taiwanese. Given the higher prevalence rate of late-stage CKD in the study area, CKD patient mortality was relatively lower, which might reflect underestimation of renal function for patients at early stages of CKD, or partly explain the high ESRD population.