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Background Fuzzy inference systems (FISs) based on fuzzy theory in mathematics were previously applied to infer supplementary points for the limited number of monitoring sites and improve the uncertainty of spatial data. Therefore we adopted the FIS method to simulate spatiotemporal levels of air pollutants [particulate matter Methods A Complex Health Screening program was launched during 2012–2013 and a total of 8284 community residents in Chiayi County, which is located in southwestern Taiwan, received a series of standard physical examinations, including measurement of estimated glomerular filtration rate (eGFR). CKD cases were defined as eGFR Results Participants with a high FRS (>10%), diabetes, heart disease, gout, arthritis or metabolic syndrome had significantly increased CKD prevalence. After adjustment for confounders, PM2.5 levels were significantly increased in CKD cases in both single- and two-pollutant models (prevalence ratio 1.31–1.34). There was a positive association with CKD in the two-pollutant models for NO2. However, similar results were not observed for SO2. Conclusions FIS may be helpful to reduce uncertainty with better interpolation for limited monitoring stations. Meanwhile, long-term exposure to ambient PM2.5 appears to be associated with an increased prevalence of CKD, based on a FIS model.

The incidence of hypocalcemia is high in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing denosumab treatment. Since 2018, we have carried out a “multidisciplinary integrated care program for osteoporosis among patients with CKD and ESRD” in our hospital. The aim of this study was to compare the incidence of denosumab-associated hypocalcemia among patients with advanced CKD and ESRD before and after the integrated care program. We retrospectively reviewed the records of patients on their first dose of denosumab treatment from January 2012 to December 2021. A total of 3208 patients were included in our study. Among the 3208 patients, there were 101 dialysis patients, 150 patients with advanced CKD (stage 4 and 5), and 2957 patients with an estimated glomerular filtration rate (eGFR) higher than or equal to 30. The incidence of post-treatment severe hypocalcemia (corrected calcium level less than 7.0 mg/dl) within 30 days was significantly higher in the dialysis and advanced CKD group than in patients with an eGFR higher than or equal to 30 (6.9% vs. 2.0% vs. 0.1%, respectively, p < 0.001). Based on the results of the multivariate regression model, poor renal function (p < 0.05) and lower baseline corrected calcium level (p < 0.05) were associated with severe hypocalcemia within 30 days following the first dose of denosumab treatment. The incidence of post-treatment severe hypocalcemia within 30 days in advanced CKD and dialysis patients was significantly lower after the integrated care program (6.8% vs. 0.8%, p < 0.05). Our study shows that multidisciplinary integrated care may reduce the incidence rate of denosumab-associated severe hypocalcemia among patients with advanced CKD and ESRD.

The elderly population is expanding rapidly, and that has become a major healthcare burden in terms of chronic kidney disease. The distribution patterns of kidney diseases in these elderly patients remain largely unclear. Here, we compared biopsy-based renal disease patterns between elderly and nonelderly patients. We performed a single-center, retrospective study (1992-2008) on biopsy-proven renal diseases to compare results between geriatric patients (age ≥ 65 years; n = 254) and nongeriatric patients (18 ≤ age 65 years; n = 2592). Renal pathology was interpreted by pathologists based on light microscopy, immunofluorescence, and electron microscopy. The ages of the geriatric and nongeriatric groups were 71.8 ± 4.5 (65.1-87.3) and 39.7 ± 17.6 (18-64.9) years, respectively, and 74% and 41% of them, respectively, were men. In the geriatric group, the most frequent diagnosis was membranous nephropathy (46.1%), followed by minimal change disease/focal segmental glomerulosclerosis (16.9%), diabetic nephropathy (8.3%), hypertensive nephrosclerosis (7.5%), and IgA nephropathy (5.9%). The geriatric group had more membranous nephropathy and less lupus nephritis and IgA nephropathy than the nongeriatric group. Furthermore, the 5-year survival rate of the geriatric group was significantly low. Our results demonstrated the different distributions of renal biopsy patterns in geriatric patients diagnosed with acute or chronic progressive kidney injury and proteinuria through renal biopsy.

Background: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis. Methods: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011. Definition of peritonitis, the primary outcome, simultaneously met the diagnosis of peritonitis (International Classification of Diseases, Ninth Revision, Clinical Modification 567) and antibiotic use. Secondary outcomes included the impact of peritonitis on PD discontinuation and survival. Cox proportional hazards models with and without time-dependent variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: There were 7634 peritonitis episodes in 4245 patients during the follow-up period. The overall incidence of peritonitis was 0.18 episodes per patient-year. Peritonitis-associated risk factors included older age, female gender, chronic heart failure, cerebrovascular disease, liver cirrhosis and lower monthly income. In an adjusted Cox hazard proportional regression with the time-dependent model, peritonitis patients had a higher risk of PD discontinuation (HR 2.71, 95% CI 2.52–2.92) and mortality (HR 1.68, 95% CI 1.57–1.81) compared to patients without peritonitis. The adjusted HRs for mortality increased with each prior episode: one episode, two episodes and more than two episodes (all p < 0.05). The adjusted HRs for PD discontinuation also increased with the frequency of peritonitis. These negative effects were greatest during the first year and persisted significantly after 5 years. In a sensitivity analysis in which peritonitis within 30 days of death or PD discontinuation was excluded, peritonitis patients still had significantly increased risk of PD discontinuation and mortality compared to patients without peritonitis. Conclusions: Although peritonitis incidence was low, our findings reveal that peritonitis carried acute and long-term sequelae of higher PD discontinuation and lower patient survival.

Chun-Yi Wu,1,2 Chia-Tien Hsu,1 Mu-Chi Chung,1,3 Cheng-Hsu Chen,1,4– 6 Ming-Ju Wu1,3– 5,7– 9 1Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Nursing, Asia University, Taichung, Taiwan; 3PhD Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 5School of Medicine, China Medical University, Taichung, Taiwan; 6Department of Life Science, Tunghai University, Taichung, Taiwan; 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Graduate Institute of Clinical Medical Sciences, School of Medicine, China Medical University, Taichung, Taiwan; 9RongHsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanCorrespondence: Ming-Ju Wu, Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Xitun Dist, Taichung City, 407219, Taiwan, Email wmj530@gmail.comIntroduction: Air pollution is a novel environmental risk factor for chronic kidney disease (CKD). Air quality improved during COVID-19 lockdowns; however, the effects of these lockdowns on PM2.5 concentrations and renal function remain unclear.Methods: We conducted a retrospective cohort study to compare air pollution and estimated glomerular filtration rate (eGFR) decline in patients with stage 5 CKD between a year-long period of lockdown (2020; n = 724) and a similar period before lockdown (2019, n = 758).Results: Compared with 2019, a 17.5% reduction in the average PM2.5 concentration (from 17.36% to 14.32%; P < 0.001) and a 45.1% reduction (from 20.56% to 11.25%; P < 0.001) in cumulative days with PM2.5 concentration > 35 μg/m3 were noted in 2020. Moreover, a 93% reduction in PM2.5 air quality index > 150 per station-day (from 0.43% to 0.03%) was observed in 2020. From 2019 to 2020, the yearly incidence of eGFR decline ≥ 5 mL/min/1.73 m2 decreased by 33.7% (24.6% vs 16.3%; P < 0.001). Similarly, the proportion of patients who started undergoing regular dialysis also decreased by 32.7% in 2020 (from 20.8% to 14.0%; P = 0.001).Conclusion: Our findings suggest that fewer events of renal function decline during the COVID-19 pandemic may be associated with a decline in PM2.5 concentrations, supporting the global strategy of reducing air pollution to prevent CKD progression.Keywords: COVID-19 pandemic, chronic kidney disease, air pollution, PM2.5, air quality index

The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case-control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.

ImportanceThe association between sodium-glucose transport protein 2 inhibitor (SGLT2i) use and the incidence of acute kidney injury (AKI) remains controversial. The benefits of SGLT2i use in patients to reduce AKI requiring dialysis (AKI-D) and concomitant diseases with AKI as well as improve AKI prognosis have not yet been established.ObjectiveTo investigate the association between SGLT2i use and AKI incidence in patients with type 2 diabetes (T2D).Design, Setting, and ParticipantsThis nationwide retrospective cohort study used the National Health Insurance Research Database in Taiwan. The study analyzed a propensity score–matched population of 104 462 patients with T2D treated with SGLT2is or dipeptidyl peptidase 4 inhibitors (DPP4is) between May 2016 and December 2018. All participants were followed up from the index date until the occurrence of outcomes of interest, death, or the end of the study, whichever was earliest. Analysis was conducted between October 15, 2021, and January 30, 2022.Main Outcomes and MeasuresThe primary outcome was the incidence of AKI and AKI-D during the study period. AKI was diagnosed using International Classification of Diseases diagnostic codes, and AKI-D was determined using the diagnostic codes and dialysis treatment during the same hospitalization. Conditional Cox proportional hazard models assessed the associations between SGLT2i use and the risks of AKI and AKI-D. The concomitant diseases with AKI and its 90-day prognosis, ie, the occurrence of advanced chronic kidney disease (CKD stage 4 and 5), end-stage kidney disease, or death, were considered when exploring the outcomes of SGLT2i use.ResultsIn a total of 104 462 patients, 46 065 (44.1%) were female patients, and the mean (SD) age was 58 (12) years. After a follow-up of approximately 2.50 years, 856 participants (0.8%) had AKI and 102 (P P = .005) compared with DPP4i users. The numbers of patients with AKI with heart disease, sepsis, respiratory failure, and shock were 80 (22.73%), 83 (23.58%), 23 (6.53%), and 10 (2.84%), respectively. SGLT2i use was associated with lower risk of AKI with respiratory failure (hazard ratio [HR], 0.42; 95% CI, 0.26-0.69; P P = .048) but not AKI with heart disease (HR, 0.79; 95% CI, 0.58-1.07; P = .13) and sepsis (HR, 0.77; 95% CI, 0.58-1.03; P = .08). The 90-day AKI prognosis for the risk of advanced CKD indicated a 6.53% (23 of 352 patients) lower incidence in SGLT2i users than in DPP4i users (P = .045).Conclusions and RelevanceThe study findings suggest that patients with T2D who receive SGLT2i may have lower risk of AKI and AKI-D compared with those who receive DPP4i.

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&amp, E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg, p &lt, 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&amp, E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm2, db/db: 6538.5 ± 1818.6 μm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm2p &lt, 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial–mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.

Background Previous studies have shown inconsistent results regarding the impact of traffic pollution on the prevalence of chronic obstructive pulmonary disease (COPD). Therefore, using frequency matching and propensity scores, we explored the association between traffic pollution and COPD in a cohort of 8284 residents in a major agricultural county in Taiwan. Methods All subjects completed a structured questionnaire interview and health checkups. Subjects with COPD were identified using Taiwan National Health Insurance Research Databases. A hybrid kriging/LUR model was used to identify levels of traffic-related air pollutants (PM2.5 and O3). Multiple logistic regression models were used to calculate the prevalence ratios (PRs) of COPD and evaluate the role played by traffic-related indices between air pollutants and COPD. The distributed lag nonlinear model was applied in the analysis; we excluded current or ever smokers to perform the sensitivity analysis. Results Increased PRs of COPD per SD increment of PM2.5 were 1.10 (95% CI 1.05–1.15) and 1.25 (95% CI 1.13–1.40) in the population with age and sex matching as well as propensity-score matching, respectively. The results of the sensitivity analysis were similar between the single and two pollutant models. PM2.5 concentrations were significantly associated with traffic flow including sedans, buses, and trucks (p 2.5 concentrations near the subject’s residence correlated with a greater risk of developing COPD (p for interaction Conclusions Our results suggest that long-term exposure to traffic-related air pollution may be positively associated with the prevalence of COPD. Graphical abstract

We analyzed database from the Taiwan National Health Insurance to investigate whether primary aldosteronism (PA) increases the risk of bladder stones. This retrospective nationwide population-based cohort study during the period of 1998–2011 compared patients with and without PA extracted by propensity score matching. Cox proportional hazard models and competing death risk model were used to estimate the hazard ratios (HRs), sub-hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs). There were 3442 patients with PA and 3442 patients without PA. The incidence rate of bladder stones was 5.36 and 3.76 per 1000 person-years for both groups, respectively. In adjusted Cox hazard proportional regression models, the HR of bladder stones was 1.68 (95% CI 1.20–2.34) for patients with PA compared to individuals without PA. Considering the competing risk of death, the SHR of bladder stones still indicates a higher risk for PA than a comparison cohort (SHR, 1.79; 95% CI 1.30–2.44). PA, age, sex, and fracture number were the variables significantly contributing to the formation of bladder stones. In conclusion, PA is significantly associated with risk of bladder stones.

Background Combined peritoneal dialysis (PD) and hemodialysis (HD) therapy (combined therapy) has numerous clinical benefits and should be emphasized for PD patients encountering technique failure. Methods This 12-year nationwide retrospective study was conducted to compare long-term outcomes (including admission and mortality risks) between combined therapy patients (combined group) and patients directly transferred from PD to HD (transfer group). Results All 12,407 incidental PD patients from 2000 to 2010 were enrolled and followed up until the end of 2011. A total of 688 patients in the combined group and 688 patients in the transfer group were selected after 1:1 frequency matching based on age, sex, and PD duration. The overall admission and mortality risks of the two groups were comparable in a Cox proportional hazards model (adjusted hazard ratio [HR] = 1.06 [95% confidence interval (CI) = 0.95–1.19] and 1.02 [95% CI = 0.80–1.30]), respectively). Compared with the transfer group, combined group patients with recent peritonitis or frequent hemodialysis (four HD sessions per month) had significantly higher risk of admission while combined group patients without peritonitis had significantly lower risk. The number of incidents in the combined group increased over time. On average, patients stayed on combined therapy for 2 years. Conclusions Combined therapy (two HD sessions per month) is not redundant but a rational and cost-effective treatment, particularly for patients without recent peritonitis. Dialysis staff should be familiar with the advantages and disadvantages of combined therapy and consider it an essential part of integrated dialysis care.

BACKGROUND: Polycystic kidney disease (PKD) is suggested to be likely associated with underlying immunological dysregulation. This lymphopenia poses a risk of viral infection. Data to elucidate the herpes virus infection risk in patients with PKD are lacking; therefore, we conducted a national-wide population-based cohort study to investigate the herpes virus risk in PKD patients. METHODS: From the Taiwan National Health Insurance Research Database (NHIRD), patients who were hospitalized with a diagnosis of polycystic kidney disease were defined as case group of PKD patients; patients without any diagnosis of PKD during the study period were grouped into the non-PKD cohort. The index date was set as the date when the patients were newly diagnosed with PKD. All study patients were followed up until the occurrence of herpes zoster infection, death, withdrawal from the NHIRD for other reasons, or until December 31, 2013. RESULTS: We included 4366 PKD patients and 4366 non-PKD patients. The incidence rate and the risk of developing herpes zoster infection were estimated using multivariate stratified analyses. PKD patients had a 1.97-fold risk of herpes zoster virus infection (aHR = 1.97, 95% CI 1.17-3.31) compared with the non-PKD cohort. On multi-layer stratification, PKD patients without any comorbidities had a significantly increased risk of herpes zoster infection (aHR = 3.10, 95% CI 1.37-7.00). CONCLUSION: This is the first study to reveal a high risk of severe herpes zoster infection in patients with PKD. High index suspicion of severe herpes zoster infection should be maintained in clinical professionals.

Cigarette smoke is a known risk factor for urothelial carcinoma (UC). However, there is limited information about the distributions and effects of volatile organic compounds (VOCs) on smoking-related UC risk. With this hospital-based case-control study, we explored the associations between urinary levels of cotinine and VOC metabolites (acrylamide, 1,3-butadiene, and benzene) and the risk of UC. Urological examinations and pathological verifications were used to confirm the diagnoses of UC. All study participants provided smoking-related information via questionnaires and face-to-face interviews; they also provided urine samples for the measurement of VOC metabolites, cotinine, and 8-hydroxydeoxyguanosine (8-OHdG), which was used as an indicator of oxidative stress. We applied multiple logistic regression analysis to estimate the risk of UC, and we found that levels of urinary cotinine and 8-OHdG were higher in the UC group than in the control group. Furthermore, urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine-3, trans,trans-muconic acid (t,t-MA), and S-phenylmercapturic acid (SPMA), increased with increasing levels of urinary cotinine. After adjusting for potential risk factors, dose–response relationships were observed between UC risk and urinary levels of AAMA, t,t-MA, SPMA, and 8-OHdG. Participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG had risks of UC that were 3.5- to 6-fold higher than those of participants with lower levels. Future, large-scale investigations of the risks of UC should be explored, and repeated measurement of VOC metabolites should be assessed.

Environmental exposure to heavy metals is suspected to result in neuropathology damage and cognitive impairment. We aimed to explore the association of Alzheimer's disease (AD) risk with the internal dose of heavy metals by constructing a hospital-based case-control study and using propensity-score-matching methods. We investigated 170 patients with AD and 264 controls from the Department of Neurology and Family Medicine, China Medical University Hospital in Taiwan. All patients with AD received clinical neuropsychological examination and cognitive-function assessments, including the mini-mental status examination and clinical dementia rating scale. We also constructed a propensity-score-matched population of 82 patients with AD and 82 controls by matching age, gender, education, and AD-related comorbidity. Blood levels with cadmium, lead, mercury, selenium, and urinary arsenic profile were measured. Logistic regression models and 95% confidence intervals (CIs) were applied to estimate AD risk. After stratification by respective quartile cutoffs of heavy metals, the AD risk of study participants with high urinary inorganic arsenic (InAs%) or low dimethylarsinic acid (DMA%) significantly increased (p 0.05), as similarly found in the propensity-score-matched population. In addition, people with a low median level of selenium and high median level of InAs%, or/and a low median level of DMA% had approximately two- to threefold significant AD risk. Urinary arsenic profiles may be associated with increased AD risk. Repeat measurements of heavy metals with large sample size and the surveying of potential exposure sources are recommended in future studies.

Key Points Question Is the use of a sodium-glucose transport protein 2 (SGLT2) inhibitor for patients with type 2 diabetes associated with the incidence of gout? Findings In this Taiwan nationwide cohort study, there was a significant 11% risk reduction in the incidence of gout in 47 405 patients with type 2 diabetes who received an SGLT2 inhibitor compared with 47 405 propensity score–matched individuals receiving dipeptidyl peptidase 4 inhibitors, particularly for patients using dapagliflozin. The benefits of SGLT2 inhibitor use in patients with type 2 diabetes for a lower gout risk were not different across subgroups. Meaning The findings of this study suggest that use of SGLT2 inhibitors may help to decrease the incidence of gout in patients with type 2 diabetes., Importance The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels. However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established. Objective To investigate whether prescribed SGLT2 inhibitors are associated with lower gout incidence in patients with T2DM. Design, Setting, and Participants In a cohort study, all patients with incident T2DM in Taiwan National Health Institution databases between May 1, 2016, and December 31, 2018, were retrospectively analyzed. As a comparator, patients using dipeptidyl peptidase 4 (DPP4) inhibitors were included. A total of 47 905 individuals receiving an SGLT2 inhibitor and 183 303 receiving a DPP4 inhibitor were evaluated, along with 47 405 pairs of patients using an SGLT2 inhibitor or DPP4 inhibitor in 1:1 propensity score–matched analyses. Data analysis was conducted from April 1 to June 30, 2021. Main Outcomes and Measures A gout diagnosis was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Multiple Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs. Results In total, 231 208 patients with T2DM were included in the population; 113 812 individuals (49.22%) were women, and the mean (SD) age was 61.53 (12.86) years. The overall gout incidence was 20.26 per 1000 patient-years for SGLT2 inhibitor users and 24.30 per 1000 patient-years for DPP4 inhibitor users. When potential risk factors were adjusted in the propensity score–matched population, use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95). A sensitivity analysis, performed when a gout diagnosis was ascertained using the ICD-9-CM or ICD-10-CM code with gout-related medication, also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97). Subgroup analysis indicated that SGLT2 inhibitor benefits in patients with T2DM to achieve a lower gout risk were not different across subgroups. Conclusions and Relevance The findings of this study suggest that patients with T2DM who are receiving SGLT2 inhibitors may have a lower risk for gout compared with those receiving DPP4 inhibitors., This cohort study examines the use of sodium/glucose cotransporter 2 inhibitor therapy in patients with type 2 diabetes at risk for gout.

PurposeData for elucidating post-kidney transplantation (KT) acute pancreatitis (AP) risk are limited and no large-scale cohort study has investigated the impact of AP after KT.MethodData from Taiwan National Health Insurance (NHI) Research Database (NHIRD) were calculated through the method of propensity score matching to compare the pancreatitis risk in patients with and without KT.ResultsThe overall pancreatitis incidence rates were 1.71 and 0.61 per 1,000 person-years in the KT and non-KT groups, respectively and corresponding adjusted HR (aHR [95% CI]) for pancreatitis was 2.48 (1.51-4.09) in the KT group. In the multivariable model, AP risk was higher in transplant patients with alcohol-related illnesses (aHR: 3.78, 95% CI: 1.32-10.8), gall stone disease (aHR: 3.53, 95% CI: 1.48-8.44), or past history of pancreatitis (aHR: 10.3, 95% CI: 5.08-20.8). Of note, recurrent AP risk was significantly higher in the KT group (aHR: 8.19, 95% CI: 2.89-23.2). Patients with post-KT AP demonstrated shorter patient and allograft survival than did those without (both P < 0.001, respectively).ConclusionIn conclusion, KT recipients are very likely to be associated with AP. Moreover, their inferior outcomes are strongly associated with post-KT AP.

There are no specific therapies for autosomal dominant polycystic kidney disease (ADPKD), and clinical data evaluating the effects of non-specific therapies on ADPKD patients are scarce. We therefore evaluated those effects using data from a longitudinal health insurance database collected from 2000-2010. We individually selected patients with and without ADPKD from inpatient data files as well as from the catastrophic illness registry in Taiwan based on 1:5 frequency matching for sex, age, and index year. The hazard ratios (HR) of all-cause mortality, ischemic stroke, hemorrhagic stroke and end-stage renal disease (ESRD) in ADPKD inpatients were elevated as compared to the controls. Similarly, ADPKD patients from the catastrophic illness registry had an increased risk of hemorrhagic stroke and ESRD. Allopurinol users also had an increased risk of all-cause mortality. The HR for developing ESRD after medication exposure was 0.47-fold for statin and 1.93-fold for pentoxifylline. These results reveal that patients with ADPKD (either inpatient or from the catastrophic illness registry) are at elevated risk for hemorrhagic stroke and ESRD, and suggest that allopurinol and pentoxifylline should not be prescribed to ADPKD patients due to possible adverse effects.

Background: The incidence of stroke after kidney transplantation is poorly understood. Our study aimed to determine the incidence and predictors of stroke as well as mortality from stroke in kidney transplant recipients (KTRs). Methods: This retrospective cohort study used the National Health Insurance Research Database in Taiwan to study KTRs (N = 4635), patients with end-stage renal disease (ESRD, N = 69,297), and patients from the general population who were chronic kidney disease (CKD)-free and matched by comorbidities (N = 69,297) for the years 2000 through 2010. The risk of stroke was analyzed using univariate and multivariate Cox regression models and compared between study cohorts. Findings: Compared with the ESRD subgroup, KTRs had a significantly lower risk of overall stroke (adjusted hazard ratio (aHR) = 0.37, 95% confidence interval (CI) = 0.31&ndash, 0.44), ischemic stroke (aHR = 0.45, 95% CI = 0.37&ndash, 0.55), and hemorrhagic stroke (aHR = 0.20, 95% CI = 0.14&ndash, 0.29). The risk patterns for each type of stroke in the KTR group were not significantly different than those of the CKD-free control subgroup. The predictors of stroke were age and diabetes in KTRs. All forms of stroke after transplantation independently predicted an increased risk of subsequent mortality, and the strongest risk was related to hemorrhagic events. Interpretation: KTRs had a lower risk of stroke than ESRD patients, but this risk was not significantly different from that of the CKD-free comorbidities-matched general population group. Although stroke was relatively uncommon among cardiovascular events, it predicted unfavorable outcome in KTRs.

Background Hospital accreditation in Taiwan encourages greater use of shared decision making (SDM) in health care. This study aimed to explore the distribution change of treatment modalities for renal replacement therapy (RRT) before and after the use of SDM in newly diagnosed end-stage renal disease (ESRD) patients. Methods The processes of SDM for RRT were designed with Internet-based patient educational program and smart system. The project of SDM was reviewed by departmental consensus meeting and continuously executed since January 2017. Patients received long-term RRT between January 2016 and December 2017 were enrolled. Results In 2017, 310 patients (187 male, average 63.9 years old) received long-term RRT. Of them, 220 (71%) patients completed SDM for RRT. Sixty-six patients received peritoneal dialysis (PD), 67 patients entered the evaluation of living related kidney transplantation (KT) program, while 18 patients finally received operation for living KT. Compared to 2016, execution of SDM for RRT was associated with drastically increase of the number of living KT (38.5%) and PD (112.9%) after the implementation of SDM for RRT in 2017. The number of preemptive living KT was also increased from 1 patient to 5 patients. Moreover, 91.3% patients were satisfied with the process of SDM for RRT. Conclusion Our findings suggest that the implementation of SDM before patients entering long term RRT lead to more ESRD patients receiving living KT and entering PD therapy. The increasing trend of living KT could be reasonably expected if SDM for RRT could be carried out nationwide.

// Peir-Haur Hung 1, 2 , Hung-Bin Tsai 3 , Kuan-Yu Hung 4 , Chih-Hsin Muo 5 , Mu-Chi Chung 6 , Chao-Hsiang Chang 7 , Chi-Jung Chung 8, 9 1 Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan 2 Department of Applied Life Science and Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan 3 Department of Tramatology, National Taiwan University Hospital, Taipei, Taiwan 4 Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu City, Taiwan 5 Management Office for Health Data, China Medical University and Hospital, Taichung, Taiwan 6 Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 7 Department of Urology, China Medical University and Hospital, Taichung, Taiwan 8 Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan 9 Department of Medical Research, China Medical University Hospital, Taichung, Taiwan Correspondence to: Chi-Jung Chung, email: cjchung@mail.cmu.edu.tw Keywords: chronic kidney disease, end stage renal disease, nephrouretectomy, urothelial carcinoma Received: March 04, 2016 Accepted: July 27, 2016 Published: August 11, 2016 ABSTRACT The association between urothelial carcinoma (UC) and subsequent ESRD incidence has not been confirmed. This was a population-based study using claims data from the Taiwan National Health Institutes from 1998 to 2010. The study cohort consisted of 26,017 patients with newly diagnosed UC and no history of ESRD, and the comparison cohort consisted of 208,136 matched enrollees without UC. The incidence of ESRD was ascertained through cross-referencing with a registry for catastrophic illnesses. Cox proportional hazard regression analysis was used to estimate the risk of ESRD associated with UC and UC subtype. A total of 979 patients (3.76%) from the UC group and 1,829 (0.88%) from the comparison group developed ESRD. Multivariable analysis indicated that compared with the comparison group, the hazard ratios (HRs) for ESRD were 7.75 (95% confidence interval [CI]: 6.84 to 8.78) and 3.12 (95% CI: 6.84 to 8.78) in the cohort with upper urinary tract UC (UT-UC) and bladder UC (B-UC), respectively. In addition, there were significantly increased risks for ESRD in UC patients receiving and not receiving nephrouretectomies or aristolochic acids (AA). Moreover, the UC patients receiving segmental ureterectomy and ureteral reimplantation had approximately 1.3-fold and 2.4-fold increased risk for ESRD after control for confounders, respectively. Thus, our data indicate that UT-UC and B-UC independently increased the risk for ESRD in patients after considering about nephrouretectomies or aristolochic acids (AA). In addition, UC patients receiving segmental ureterectomy and ureteral reimplantation had increased risk for ESRD.

Escherichia coli is a generic indicator of fecal contamination, and certain serotypes cause food- and water-borne illness such as O157:H7. In the clinic, detection of bacteriuria, which is often due to E. coli, is critical before certain surgical procedures or in cases of nosocomial infection to prevent further adverse events such as postoperative infection or sepsis. In low- and middle-income countries, where insufficient equipment and facilities preclude modern methods of detection, a simple, low-cost diagnostic device to detect E. coli in water and in the clinic will have significant impact. We have developed a simple paper-based colorimetric platform to detect E. coli contamination in 5h. On this platform, the mean color intensity for samples with 10(5)cells/mL is 0.118±0.002 (n=4), and 0.0145±0.003 (P

Dysnatremias are the common problems in chronic kidney disease (CKD) patients anda sso c iat ed with neurologic symptoms. Thus, the purpose of this study was to determinethe association between dysnatremias (either hypernatremia or hyponatremia) and risk ofstroke in CKD population. A retrospective cohort study was constructed using the claimsdata of the entire insured residents covered by Taiwan’s universal health insurance from2000 to 2011. Severe hypona tremia and hypernatremia are defined as the need of 3% sodiumchloride treatment and the need of admission respectively. A total of 365 hyponatremia and137 hypernatremia patients and 1983 matched comparisons were recruited. The incidenceof stroke was defined using the International Classification of Diseases, 9th Revision, ClinicalModification. Cox proportional hazard regression and Kaplan–Meier curves were usedfor the analyses. In the analysis, CKD with dysnatremias were with more diabetes, heart fai lure, men tal illness, liver cirrhosis, cancer history and diuretics treatment. Compared withcomparisons, patients with dysnatremias, hyponatremia or hypernatremia patients had a 2.57(95% CI: 1.91-3.46), 2.35 (95% CI: 1.67-3.29) and 3.35 (95% CI: 2.04-5.50) fold risks of stroke afteradjusting for potential factors. There was similarly increased risk for ischemic stroke but not for hemorrhagic stroke. In addition, patients with rec urrent dysnatremias, the risk of str okemuch increased [9.19 (95% CI: 5.79-14.6) for hyponatremia and 11.4 (95% CI: 5.66-23.1) forhypernatremia]. In conclusion, we suggest more intensive surveillance to prevent recurrentdysnatremias and ischemic stroke should be emphasized.

Data regarding the risk of various liver diseases among different hepatitis viruses in kidney transplantation have not yet been identified.We selected individuals with kidney transplantation (ICD-9-CM V420 or 996.81) from 2000–2009 from the catastrophic illness registry of National Health Insurance Research Database (NHIRD)as the study cohort. The two end-points in the study included overall death and post-transplant occurrence of hepatic disease. After adjustment for other risk factors, the risk of mortality was increased in patients with HBV infection (N = 352) and with HCV infection (N = 275) compared to those with neither HBV nor HCV infection (N = 3485). In addition,renal transplant recipients with HBV alone,HCV alone and both with HBV and HCVinfectionrespectively had an approximately 10-fold hazard ratio (HR) = 9.84, 95% confidence interval (CI): 4.61–21.0, 4-fold increased risk (HR = 4.40, 95% CI: 1.85–10.5)and 5-fold increased risk (HR = 4.63, 95% CI: 1.06–20.2)of hepatocellular carcinoma (HCC)compared to those with neither HBV nor HCV infection. Our findings showed a significant risk of de novo liver disease in recipients with hepatitis virus infection. Based on our findings, we reinforce the importance and impact of hepatitis virus in renal transplantation.

This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs) using 5-methylcytosine (5-MeC) immunohistochemistry (IHC). We examined the relationship among 5-MeC levels, DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288). Both 5-MeC and DNMT1 were low in approximately 50% (76/150) of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110, 59%) than in normal urothelia (2/23, 13%) and non-invasive UC (18/40, 45%). Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II–IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478). Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365). Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

Hyponatremia is the most common electrolyte disorder and also a predictor of mild cognition impairment. However, the association between hyponatremia and dementia in long follow up periods is rarely investigated. A retrospective cohort study was performed using the claims data of all insured residents who were covered by Taiwan's universal health insurance from 2000 to 2011. A total of 4900 hyponatremia patients and 19545 matched comparisons were recruited for the analysis. The incidences of hyponatremia and dementia were diagnosed with clinical protocol and defined using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. Independent of adjusting factors, hyponatremia patients had 2.36-fold higher chances of suffering dementia, including Alzheimer's disease (AD) and non-AD dementia, than the comparisons. Severe hyponatremia patients had higher risks of suffering dementia than the non-severe hyponatremia patients (adjusted hazard ratio: 4.29 (95% CI: 3.47-5.31) versus 2.08 (95% CI: 1.83-2.37)). A dose response relationship was observed between hyponatremia and dementia. Those hyponatremia patients with baseline or incident stroke had significantly higher chances of suffering dementia compared with those patients without hyponatremia and stroke. Stroke is a significant modifier of the relationship between hyponatremia and dementia. Cerebrovascular disease after incident hyponatremia must be prevented to reduce the incidence of dementia.

Background Data on long-term maternal outcomes in patients with systemic lupus erythematosus (SLE) are lacking. The study aimed to explore the relationships among SLE, pregnancy, outcomes of end-stage renal disease (ESRD), and overall mortality. Methods We established a retrospective cohort study consisting of four cohorts: pregnant (case cohort) and nonpregnant SLE patients, as well as pregnant and nonpregnant non-SLE patients. One case cohort and three comparison cohorts were matched by age at first pregnancy and index date of pregnancy by using the Taiwan National Health Insurance Research Dataset. All study subjects were selected based on the index date to the occurrence of ESRD or overall death. Cox proportional hazard regression models and Kaplan–Meier curves were used in the analysis. Results SLE pregnant patients exhibited significantly increased risk of ESRD after adjusting for other important confounders, including immunosuppressant and parity (HR = 3.19, 95% CI: 1.35–7.52 for pregnant non-SLE; and HR = 2.77, 95% CI: 1.24–6.15 for nonpregnant non-SLE patients). No significant differences in ESRD incidence were observed in pregnant and nonpregnant SLE patients. Pregnant SLE patients exhibited better clinical condition at the baseline and a significantly lower risk of overall mortality than nonpregnant SLE patients. Conclusions Our data support current recommendations for SLE patients to avoid pregnancy until disease activity is quiescent. Multicenter recruitment and clinical information can be used to further examine the association of SLE and ESRD (or mortality) after pregnancy.

The effect of renal cell carcinoma (RCC) on the risk for end-stage renal disease (ESRD) has not been confirmed. The present population-based study used the claims data from the Taiwan National Health Institutes from 1998 to 2010 to compare the risk for ESRD in patients with and without RCC. The study cohort consisted of 2940 patients who had newly diagnosed with RCC but no history of ESRD; the control cohort consisted of 23,520 matched patients without RCC. Cox proportional hazard regressions were performed to compute ESRD risk after adjusting for possible confounding factors. Kaplan–Meier analysis and the log-rank test were also used to compare patients and controls. A total of 119 patients in the RCC group (incidence rate: 119/2940; 4.05%) and 160 patients in the control group (incidence rate: 160/23,520; 0.68%) were diagnosed with ESRD during the follow-up period. After adjusting for potential confounders, the RCC group had an ESRD hazard ratio (HR) of 5.63 [95% confidence interval (CI): 4.37–7.24] relative to the control group. In addition, among patients with RCC, females (adjusted HR: 6.95, 95% CI: 4.82–10.1) had a higher risk for ESRD than males (adjusted HR: 4.79, 95% CI: 3.37–6.82). Finally, there were significant joint effects of chronic kidney disease and diabetes on increasing the risk of ESRD in patients with and without RCC (P