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Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population. [ABSTRACT FROM AUTHOR]

Background: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. Methods: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. Results: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. Conclusions: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI. [ABSTRACT FROM AUTHOR]

The clinical efficacy of ticagrelor versus clopidogrel has not been replicated in East Asian populations. The pronounced bleeding risk with ticagrelor was of concern given the increased bleeding tendency in Asian populations. This study evaluated efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI) in the entire Taiwan. We used the Taiwan National Health Insurance Research Database to identify 6203 patients aged ≥ 20 years with NSTEMI hospitalization and prescription of dual antiplatelets at discharge between January 2014 and December 2014. Cohorts of ticagrelor and clopidogrel were matched 1:1 based on propensity score matching to balance baseline covariates. The primary composite efficacy endpoints included death from any cause, non-fatal myocardial infarction, and non-fatal stroke. The secondary efficacy endpoints were the individual components. The primary safety endpoint was major bleeding requiring hospitalization. The incidence of primary efficacy endpoint was 20.3% in the ticagrelor users and 20.7% in the clopidogrel users (adjusted HR 0.94; 95% CI 0.73–1.22), with the median (interquartile range, IQR) follow-up period of 5.2 (2.3–8.5) months. The incidence of primary safety endpoint was 2.3% in the ticagrelor users and 3.2% in the clopidogrel users (adjusted HR 0.67; 95% CI 0.33–1.35). Regarding the secondary efficacy endpoint, patients treated with ticagrelor had significantly lower incidence of stroke (adjusted HR 0.44; 95% CI 0.21–0.94; p = 0.033). In this nationwide Taiwanese cohort of NSTEMI, treatment with ticagrelor after discharge, as compared to clopidogrel, had similar rates of ischemic composite events and major bleeding. Nevertheless, the median follow-up time was only 5.2 months, and the reduced stroke events with ticagrelor compared to clopidogrel needs further verification. [ABSTRACT FROM AUTHOR]

Aim: Previous investigations have shown that end‐stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age. Methods: We analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1 000 000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age‐, gender‐ and diabetes‐matched controls were selected from the database (n = 12 220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy. Results: The incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40 years, 40–49 years, 50–59 years and 60–69 years, respectively. Conclusion: The patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan. SUMMARY AT A GLANCE: End‐stage kidney disease is associated with an increased risk of many malignancies. This epidemiological study from Taiwan reviews the incidence rates of malignancies in a large haemodialysis cohort compared to a control group, revealing a higher cumulative risk of malignancies especially in those of a young age on dialysis. [ABSTRACT FROM AUTHOR]

Background: Dialyzed patients are vulnerable to coronavirus infection disease 2019 (COVID-19). The incidence and outcome of COVID-19 in hemodialysis (HD) patients in Taiwan remain unclear. A series of preventive measures were executed to combat COVID-19 transmission among HD patients. Methods: We carried out a series of forward-looking and practical preventive strategies of COVID-19 control in our HD center. Incidences of COVID-19 of our HD unit were compared with those of national and local estimates from a community outbreak from 15 May to 30 June 2021. Prognostic factors associated with mortality were analyzed. Results: The national incidence of COVID-19 was 0.062%; being highest in Taipei City (0.173%), followed by New Taipei City (0.161%) and Keelung (0.083%). The overall incidence in Keelung HD patients was 0.666%. One patient of our HD center contracted COVID-19 from the household; however, we have contained secondary transmission in our HD center by implementing strict preventive measures. The mortality rate of HD patients in Keelung was 66.6%. The median Ct value of HD patients was 17.53 (11.75–27.90) upon diagnosis. The deceased patients had a higher cardiac/thoracic ratio than alive (0.61 vs. 0.55, p = 0.036). Conclusions: Taking aggressive and proactive infection preventive measures impedes the secondary transmission of COVID-19 in HD facilities. COVID-19-associated mortality was high in HD patients, being the high cardiac-thoracic ratio, an important prognostic factor for clinical outcome of infected HD patients. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear. Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan's National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis. Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p -value <0.001), and the risk of mortality was 0.42 (95% CI: 0.36–0.49; p -value <0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55–0.63; p -value <0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.) , Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf. , Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs. Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. Methods: A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan–Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. Results: Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9–15.0] and 16.6% for nonusers (95% CI: 16.0–17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1–34.6) and 49.2% for nonusers (95% CI: 48.5–49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78–0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47–0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6–59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4–30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. Conclusions: The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed. [ABSTRACT FROM AUTHOR]

Background & Aims: Metabolism dysregulation and protein energy wasting occur in patients with chronic kidney disease (CKD) and are associated with poor survival, especially in patients prior to starting dialysis. Accumulating evidence indicates that dietary supplementation with ketoanalogues (KAs, a mixture of branched-chain amino acids) exerts a variety of beneficial effects for patients with CKD. However, the role of KAs in diabetic kidney disease (DKD), one of the major causes of CKD, is still controversial. The aim of this study was to explore the impact of KA supplements on survival in patients with stage 5 DKD who have not yet started dialysis (DKD-5-ND)., Methods: We analyzed a nationwide cohort retrieved from the National Health Insurance Research Database in Taiwan to study the long-term impact of KA supplements in patients with DKD-5-ND. We enrolled 15,782 incident pre-dialysis DKD patients between January 1, 2004 and December 31, 2007. Landmark analysis was used to eliminate immortal bias, and overlap weighting was used to balance differences between the KA users and nonusers in the beginning. The primary study endpoint was all-cause mortality, and the occurrence of permanent dialysis (presenting the end-stage renal disease, ESRD) and major adverse cardiovascular events (MACEs) was also evaluated. All patients were followed for five years or until death., Results: The prevalence of KA usage in the DKD-5-ND patients was 6.3%. The 5-year all-cause mortality rate in the KA users was lower than that in the nonusers (34.7% vs 42.7%). After adjusting for known covariates, the KA users still had a lower risk of mortality (adjusted hazard ratio [aHR]: 0.73, 95% confidence interval [CI]: 0.66-0.82). In addition, the incidence of ESRD was also slightly lower among the KA users (90.9% for users vs 91.2% for nonusers, adjusted cause-specific hazard ratio [aCSHR]: 0.65, 95% CI: 0.61-0.69), and the occurrence of MACEs was lower (adjusted incidence rate ratios [aIRR]: 0.76, 95% CI: 0.67-0.86). Although the all-cause mortality was higher among patientsolder than 70 years (60.5% for KA users vs 46.5% for nonusers) the risk reduction seemed prominent among older patients (aHR: 0.65, 95% CI: 0.56-0.76 for patients aged ≥70 years; aHR: 0.82, 95% CI: 0.71-0.96 for patients aged < 70 years). The reduction in risks of mortality was consistent in subgroup analysis and sensitivity tests., Conclusions: The use of KA supplements seemed to be beneficial for patients with DKD-5-ND; further in-depth analysis of using KA for these patients is warranted., Competing Interests: Conflicts of Interest The authors declare that they have no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: Discrepancies in blood pressure (BP) estimates lead to incomparable BP assessment., Objective: To determine intraindividual discrepancies in BP estimates and classifications based on different BP estimation protocols., Design, Setting, and Participants: This cross-sectional study was a secondary analysis of data from the May Measurement Month Taiwan in 2017 and 2018, which were cross-sectional survey campaigns at pharmacies nationwide to raise awareness of high BP. Participants were volunteers aged 20 years or older. Analysis was conducted from February 2 to August 7, 2020., Exposure: Pharmacist-measured sitting BP using oscillometric sphygmomanometers., Main Outcomes and Measures: A total of 7 BP estimation protocols were assessed according to the latest American College of Cardiology (ACC), Chinese Hypertension League (CHL), European Society of Cardiology (ESC), International Society of Hypertension, Japanese Society of Hypertension, and National Institute of Health and Care Excellence (NICE) hypertension guidelines, and the proposed Averaging the Lowest Two systolic readings protocol. According to BP classification schemes of ESC and ACC guidelines, intraindividual discrepancies were identified if classification inconsistencies among 7 BP estimates were present., Results: Of 81 041 participants, 62 647 adults with 3 BP readings were included. The median (interquartile range) age was 59.0 (46.0-69.0) years, and 31 922 (51.5%) were women. The intraindividual maximum mean (SD) differences in systolic/diastolic BP estimates among the seven protocols were 4.8 (4.3)/3.3 (3.1) mm Hg. The highest prevalence of BP of 140/90 mm Hg or higher was by CHL (16 405 participants [26.2%]) and the lowest was by Averaging the Lowest Two (13 996 participants [22.3%]; P < .001); while the highest prevalence of 130/80 mm Hg or higher was by NICE (37 232 participants [59.4%]) and the lowest prevalence was by Averaging the Lowest Two (32 788 participants [52.4%]; P < .001). Compared with the other 6 estimates, Averaging the Lowest Two reclassified 7.3% to 15.8% of participants designated as 140/90 mm Hg or higher to less than 140/90 mm Hg, and 4.9% to 14.1% of those as 130/80 mm Hg or higher to less than 130/80 mm Hg. Intraindividual discrepancies in classifications occurred in 19 815 participants (31.6%) with the ESC classification and 16 401 participants (26.2%) with the ACC BP classification. Classification agreements were the lowest between NICE (κ coefficient, 0.667 [95% CI, 0.662-0.671]) and ESC protocols (κ coefficient, 0.705 [95% CI, 0.701-0.709])., Conclusions and Relevance: This cross-sectional study of adults in Taiwan found that different BP estimation protocols led to considerable intraindividual discrepancies in BP estimates and classifications. These findings suggest that the Averaging the Lowest Two protocol is less likely to overestimate BP and could serve as a prudent recommendation for BP estimation.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022-1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Background: Liver transplantation can prolong survival in patients with end-stage liver disease. We have proposed that the Sequential Organ Failure Assessment (SOFA) score calculated on post-transplant day 7 has a great discriminative power for predicting 1-year mortality after liver transplantation. The Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, a modified SOFA score, is a newly developed scoring system exclusively for patients with end-stage liver disease. This study was designed to compare the CLIF-SOFA score with other main scoring systems in outcome prediction for liver transplant patients., Methods: We retrospectively reviewed medical records of 323 patients who had received liver transplants in a tertiary care university hospital from October 2002 to December 2010. Demographic parameters and clinical characteristic variables were recorded on the first day of admission before transplantation and on post-transplantation days 1, 3, 7, and 14., Results: The overall 1-year survival rate was 78.3% (253/323). Liver diseases were mostly attributed to hepatitis B virus infection (34%). The CLIF-SOFA score had better discriminatory power than the Child-Pugh points, Model for End-Stage Liver Disease (MELD) score, RIFLE (risk of renal dysfunction, injury to the kidney, failure of the kidney, loss of kidney function, and end-stage kidney disease) criteria, and SOFA score. The AUROC curves were highest for CLIF-SOFA score on post-liver transplant day 7 for predicting 1-year mortality. The cumulative survival rates differed significantly for patients with a CLIF-SOFA score ≤8 and those with a CLIF-SOFA score >8 on post-liver transplant day 7., Conclusion: The CLIF-SOFA score can increase the prediction accuracy of prognosis after transplantation. Moreover, the CLIF-SOFA score on post-transplantation day 7 had the best discriminative power for predicting 1-year mortality after liver transplantation.