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

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

Financial strain and social support as moderators of the relationship between living alone and depressive symptoms in older people.

This study investigated the moderating effect of financial strain or social support on depressive symptoms among older people living alone in Taiwan. Data were collected from the "Taiwan Longitudinal Study on Aging (TLSA)," which included 1513 participants aged 65 and over, among them, 153 (10.1%) were living alone, while 1360 (89.9%) were living with others. Measurement tools included the Depression scale (CES-D), financial stress scale, social support scale, ADL scale, IADL scale, and stress scale, with Cronbach's α coefficients were 0.85, 0.78, 0.67, 0.91, 0.90, and 0.70 respectively. Hierarchical multiple regression was used to examine the moderator effect. The findings revealed that (1) Financial strain was found to moderate the relationship between living alone and depressive symptoms, acting as a promotive moderator among older men living alone. For older women, financial stress does not moderate the relationship between living alone and depressive symptoms. However, financial strain was also identified as a significant factor associated with depressive symptoms among older women living alone. (2) Social support does not moderate effect on the relationship between living alone and depressive symptoms in older men or older women. These results underscore the importance of considering financial stress in mental health policy development by government agencies. It is imperative to address the unique challenges faced by older individuals living alone, particularly in relation to financial strain, in order to promote their mental well-being.

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

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

Shared decision-making for renal replacement treatment and illness perception in patients with advanced chronic kidney disease.

BACKGROUND: Current healthcare trends emphasize the use of shared decision-making (SDM) for renal replacement treatment (RRT) in patients with chronic kidney disease (CKD). This is crucial to understand the relationship between SDM and illness perception of CKD patients. Few studies have focused on SDM and illness perception status of CKD patients and the impact of illness perception on RRT after SDM. METHODS: In this cross-sectional study, we used a questionnaire with purposive sampling from March 2019 to February 2020 at the nephrology outpatient department of a medical center in southern Taiwan. The nephrology medical team in this study used the SHARE five-step model of SDM to communicate with the patients about RRT and Brief Illness Perception Questionnaire (BIPQ) was applied to evaluate illness perception of these patients at the beginning of SDM. According to the SDM decision time, the study participants were classified general and delayed SDM groups. The distribution between SDM groups was estimated using independent two sample t-test, chi-squared test or Fisher's exact test. The correlation between illness perception and SDM decision time were illustrated and evaluated using Spearman's correlation test. A p-value less than 0.05 is statistically significant. RESULTS: A total of 75 patients were enrolled in this study. The average time to make a dialysis decision after initiating SDM was 166.2 ± 178.1 days. 51 patients were classified as general group, and 24 patients were classified as delayed group. The median SDM decision time of delayed group were significantly longer than general group (56 vs. 361 days, P < 0.001). Our findings revealed that delayed group was significantly characterized with not created early surgical assess (delayed vs. general: 66.7% vs. 27.5%, p = 0.001) compared to general group. The average BIPQ score was 54.0 ± 8.1 in our study. We classified the patients into high and low illness perception group according to the median score of BIPQ. The total score of BIPQ in overall participants might increase by the SDM decision time (rho = 0.83, p = 0.830) and the linear regression line also showed consistent trends between BIPQ and SDM decision time in correspond cohorts. However, no statistically significant findings were found. CONCLUSIONS: The patients with advanced chronic kidney disease took an average of five and a half months to make a RRT decision after undergoing SDM. Although there is no statistical significance, the trend of illness perception seems correlated with decision-making time. The stronger the illness perception, the longer the decision-making time. Furthermore, shorter decision times may be associated with earlier establishment of surgical access. We need more research exploring the relationship between illness perception and SDM for RRT in CKD patients.

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

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

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

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

Evolutionary seroepidemiology of viral hepatitis and the gap in hepatitis C care cascades among uraemic patients receiving haemodialysis in Taiwan-the Formosa-Like Group.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895.

Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis.

BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.

The Association of Targeted Gut Microbiota with Body Composition in Type 2 Diabetes Mellitus.

The association between body composition and gut microbiota in type 2 diabetes mellitus (DM) remains unknown. To elucidate the correlation of body composition and gut microbiota, we conducted a clinical study to enroll 179 patients with type 2 DM. Body composition of lean tissue index (LTI) and fat tissue index was measured by Body Composition Monitor. Eight pairs of 16S rRNA gene primers specific to Firmicutes, Bacteroidetes, the Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, Escherichia coli, and Faecalibacterium prausnitzii were used to measure their abundance by quantitative polymerase chain reaction. The results showed that type 2 DM with higher abundance of phylum Firmicutes and a higher ratio of phyla Firmicutes to Bacteroidetes (phyla F/B ratio) had higher LTI. This significant correlation between phyla F/B ratio and LTI was especially evident in type 2 DM with high body mass index, and independent of glycemic control or dipeptidyl peptidase-4 inhibitor usage. In conclusion, our study demonstrated the positive association of LTI with the abundance of phylum Firmicutes and the phyla F/B ratio in type 2 DM.

Blood pressure modifies outcomes in patients with stage 3 to 5 chronic kidney disease.

Observational studies have demonstrated that low blood pressure is related to poor clinical outcomes in patients with chronic kidney disease (CKD). Subgroup analyses from the SPRINT trial showed that targeting systolic blood pressure under 120 mmHg is less beneficial for patients with CKD. Although malnutrition and inflammation are common in patients with advanced CKD, such patients are usually excluded from clinical trials. Therefore, we hypothesized that malnutrition-inflammation-cachexia syndrome could explain this J-shaped relationship. To test this, we studied 2441 patients with CKD stages 3-5 who received anti-hypertensive treatment for at least one year. Averaged blood pressures of the first year were used in the analyses. Fine-Gray competing risks regression showed a J-shaped relationship between continuous systolic blood pressure and end-stage kidney disease (ESKD) with a nadir risk at a systolic blood pressure of 120 mmHg. Adjusted sub-distribution hazard ratios of categorical systolic blood pressure 100-109 and 110-119 mmHg were 2.17 (95% confidence interval: 1.21-3.89) and 1.37 (0.94-1.99) for ESKD, respectively, compared with systolic blood pressures of 120-129 mmHg. Cox regression also showed J-shaped relationships between continuous systolic or diastolic blood pressures, and the composite outcomes of cardiovascular events and all-cause mortality. Logistic regression demonstrated the odds ratios of blood pressure components for Malnutrition-Inflammation Scores over 4 were J-shaped. Sub-distribution hazard ratios of systolic blood pressure 100-119 mmHg for ESKD was higher in those with a Malnutrition-Inflammation Score over 4, compared to 0.93 (0.53-1.63) in those with a score of 4 or under with significant interaction. Thus, malnutrition-inflammation-cachexia syndrome is associated with low blood pressure and modifies the J-shaped relationship in patients with advanced CKD.

Rapid Quantification of Gut Microbial Short-Chain Fatty Acids by pDART-MS.

Short-chain fatty acids (SCFAs) are small molecules ubiquitous in nature. In mammalian guts, SCFAs are mostly produced by anaerobic intestinal microbiota through the fermentation of dietary fiber. Levels of microbe-derived SCFAs are closely relevant to human health status and indicative to gut microbiota dysbiosis. However, the quantification of SCFA using conventional chromatographic approaches is often time consuming, thus limiting high-throughput screening tests. Herein, we established a novel method to quantify SCFAs by coupling amidation derivatization of SCFAs with paper-loaded direct analysis in real time mass spectrometry (pDART-MS). Remarkably, SCFAs of a biological sample were quantitatively determined within a minute using the pDART-MS platform, which showed a limit of detection at the µM level. This platform was applied to quantify SCFAs in various biological samples, including feces from stressed rats, sera of patients with kidney disease, and fermentation products of metabolically engineered cyanobacteria. Significant differences in SCFA levels between different groups of biological practices were promptly revealed and evaluated. As there is a burgeoning demand for the analysis of SCFAs due to an increasing academic interest of gut microbiota and its metabolism, this newly developed platform will be of great potential in biological and clinical sciences as well as in industrial quality control.

ß-blocker dialyzability and the risk of mortality and cardiovascular events in patients undergoing hemodialysis.

BACKGROUND: ß-blocker (BB) dialyzability has been proposed to limit their efficacy among hemodialysis (HD) patients. We attempted to confirm this hypothesis by comparing health outcomes associated with the initiation of dialyzable or nondialyzable BBs in a nationwide cohort of HD patients. METHODS: We created a prospective cohort study of 15 699 HD patients who initiated dialyzable BBs (atenolol, acebutolol, metoprolol and bisoprolol) and 20 904 hemodialysis patients who initiated nondialyzable BBs (betaxolol, carvedilol and propranolol) between 2004 and 2011 in Taiwan healthcare. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs, a composite of the acute coronary syndrome, ischemic stroke and heart failure) between users of dialyzable versus nondialyzable BBs during a 2-year follow-up. RESULTS: New users of dialyzable BBs were younger, more often men, with diabetes mellitus, hypertension and hyperlipidemia compared with users of nondialyzable BBs. Compared with nondialyzable BBs, initiation of dialyzable BBs was associated with lower all-cause mortality {hazard ratio [HR] 0.82 [95% confidence interval (CI) 0.75-0.88]} and lower risk of MACEs [HR 0.89 (95% CI 0.84-0.93)]. Results were confirmed in subgroup analyses, censoring at BB discontinuation or switch, after 1:1 propensity score matching, reclassifying bisoprolol or excluding bisoprolol/carvedilol users. CONCLUSIONS: This study does not offer support for the hypothesis that the dialyzability of BBs reduces their efficacy in HD patients.

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes.

BACKGROUND: Incidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy. METHODS: Totally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria. RESULTS: The glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups (p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups (p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients. CONCLUSION: Pre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes.

Patient assessment of chronic kidney disease self-care using the chronic kidney disease self-care scale in Taiwan.

AIM: Self-care represents the 'action' element of self-management. This study aimed to use the chronic kidney disease self-care (CKDSC) scale to examine factors associated with self-care and aspects of self-care deficits among CKD patients in Taiwan. METHODS: A cross-sectional investigation was conducted using the CKDSC scale with 449 CKD patients in Taiwan. The CKDSC is a 16-item questionnaire with five subscales, including medication adherence, diet control, exercise, smoking behaviours and blood pressure monitoring. Patient demographic and clinical factors taht may affect CKD self-care were analyzed in the multivariable regression models. RESULTS: Overall CKDSC scores were significantly higher for women (P = 0.020), older patients (P < 0.001), higher education (P = 0.033), BMI <24 kg/m2 (P = 0.005), later CKD stage or participants in the CKD care programme. Early-stage CKD patients had significantly lower for medication adherence, diet control, and blood pressure monitoring. Patients who participated in the CKD care programme had higher for medication adherence, diet control and regular exercise habits. CONCLUSION: The CKDSC scale is a tool to assess patient self-care. However, given the CKDSC tool is in Chinese, future studies should validate it in CKD patients in other languages or countries before it can be considered for general use.

Decreased incidence of gout in diabetic patients using pioglitazone.

Objective: The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population. Methods: We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population. Results: The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (<40, 40-59 and ⩾60 years) revealed that the HRs of both the 40-59 years [aHR 0.78 (95% CI 0.73, 0.83)] and the ⩾60 years [aHR 0.85 (95% CI 0.80, 0.91)] age groups were significantly lower among pioglitazone users than non-pioglitazone users. Conclusion: Compared with the non-pioglitazone users, the incidence of gout in the diabetic population using pioglitazone was less.

Decreased incidence of diabetes in patients with gout using benzbromarone.

Objective: Insulin resistance is inversely correlated with the clearance rate of uric acid, which may indicate that improvement in the clearance rate of uric acid could reduce insulin resistance. Considering the increased prevalence of diabetes mellitus (DM) in the gout population, this study evaluated the effects of benzbromarone, a uricosuric agent, on the incidence of DM in the gout population. Methods: We used data from the Taiwan National Health Insurance program. The benzbromarone user cohort included 8678 patients; each patient was age- and sex-matched with one benzbromarone non-user who was randomly selected from the gout population. The Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of DM in the gout population. Results: The incidence of DM was significantly lower in benzbromarone users than in benzbromarone non-users [adjusted hazard ratio (HR) = 0.86; 95% CI: 0.79, 0.94]. The HR for the incidence of DM was lower in male benzbromarone users (adjusted HR = 0.77; 95% CI: 0.69, 0.86) than in benzbromarone non-users. An analysis of three age groups (<40, 40-59 and ⩾60 years) indicated that the HRs of the age groups of 40-59 years (adjusted HR = 0.86; 95% CI: 0.76, 0.98) and ⩾60 years (adjusted HR = 0.82; 95% CI: 0.71, 0.94) were significantly lower among benzbromarone users than among benzbromarone non-users. Conclusion: In the gout population, the incidence of DM was lower in benzbromarone users than in benzbromarone non-users.

Angiopoietin-2, Renal Deterioration, Major Adverse Cardiovascular Events and All-Cause Mortality in Patients with Diabetic Nephropathy.

BACKGROUND/AIMS: Diabetic nephropathy is the leading cause of end-stage renal disease and accounts for 30∼40% of patients requiring maintenance dialysis, thereby increasing the burden on health insurance programs. Diabetic nephropathy is also the strongest predictor of cardiovascular morbidity and mortality. The aim of this study was to examine whether angiopoietin-2 (Angpt2), a modulator of endothelial function, affects the clinical outcomes of diabetic patients. METHODS: This study enrolled 236 patients with diabetes mellitus with estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2 from January 2006 to December 2011, who were followed until June 2017. Clinical outcomes included renal outcomes (commencing dialysis and rapid decline in renal function (eGFR decline > 3 ml/min per 1.73 m2/year)), major adverse cardiovascular events (MACEs), and all-cause mortality. RESULTS: Over a mean follow-up period of 3.9±2.7 years, 135 (57.2%) patients commenced dialysis, 106 (44.9%) had rapid decline in renal function, and 50 (21.2%) had MACEs or died from all-causes. Log-formed Angpt2 was significantly associated with increased risks of commencing dialysis (HR: 3.91, 95% CI: 1.56-9.76), rapid renal function decline (OR: 6.81, 95% CI: 1.06-43.88), and MACEs or all-cause mortality (HR: 6.34, 95% CI: 1.18-33.97) in the adjusted analysis. Patients in the highest quartile had hazard ratios of 2.90 and 3.11 for commencing dialysis and rapid renal function decline, respectively, compared to those in the lowest quartile after adjustments. Similar significant dose-response results were found in composite outcomes of either MACEs or all-cause mortality. CONCLUSION: Angpt2 is an independent predictor of adverse clinical outcomes in diabetic patients. Further studies are needed to identify the pathogenic role of Angpt2 in renal deterioration and cardiovascular complications of diabetes mellitus.

Independent Association of Overhydration with All-Cause and Cardiovascular Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and E/E' Ratio in Maintenance Hemodialysis Patients.

BACKGROUND/AIMS: Fluid overload is common and associated with morbidity and mortality in patients with end-stage renal disease. The relationship between fluid overload and cardiac function is complex, and whether fluid overload is associated with adverse outcomes in patients undergoing hemodialysis (HD) independently of systolic and diastolic function of the left ventricle (LV) remains unclear. METHODS: The present study aimed to investigate the relationship between overhydration and all-cause and cardiovascular (CV) mortality after adjusting for LV function in 178 maintenance HD patients. The relative hydration status (overhydration/ extracellular water, ∆HS) was measured using a body composition monitor, and then used to assess the fluid status. A ∆HS ≥7% was defined as fluid overload. Global left ventricular longitudinal systolic strain (GLS), and the early filling and early diastolic mitral annular velocity (E/E') ratio were assessed using speckle-tracking and tissue Doppler echocardiography. RESULTS: During a mean follow-up period of 2.7 years, 24 patients died, including 11 CV deaths. An increased ∆HS was significantly associated with all-cause and CV mortality in the univariate analysis. This prognostic significance remains after multivariate adjusting for GLS and E/E' ratio for all-cause (HR, 1.123; 95% CI, 1.063-1.186; p-value < 0.001) and CV (HR, 1.088; 95% CI, 1.005-1.178; p-value =0.037) mortality. Moreover, ∆HS significantly improved the prognostic value beyond conventional clinical and echocardiographic parameters. CONCLUSION: A higher ∆HS was independently associated with increased all-cause and CV mortality after adjusting for systolic and diastolic function of the LV. This suggests that ∆HS may be a relevant target for improving outcomes in maintenance HD patients.

Prognostic Cardiovascular Markers in Chronic Kidney Disease.

Chronic kidney disease (CKD), including end-stage renal disease (ESRD), is a public health issue worldwide, and is associated with high rates of morbidity and mortality. In addition, cardiovascular disease is a major cause of mortality in these patients. Both traditional and nontraditional risk factors associated with CKD can lead to remodeling of the myocardium and blood vessels, thereby resulting in cardiomyopathy, atherosclerosis and arterial stiffness. This can subsequently lead to ischemic heart disease, heart failure, cardiovascular death, rapid renal progression and progression to ESRD. Identifying these risk factors to allow for aggressive preventive and interventional strategies is important for the management of patients with CKD. This aim of this review was to survey the clinical outcomes of CKD using cardiac and vascular markers including echocardiographic parameters, systolic time intervals, electrocardiography, heart rate variability, ankle-brachial index, pulse wave velocity, differences between interarm and interankle blood pressure, and vascular calcification.

Economic evaluation of a pre-ESRD pay-for-performance programme in advanced chronic kidney disease patients.

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.