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Introduction: Serum creatinine is crucial in glomerular filtration rate (GFR) estimation. Various methods of measuring GFR have been developed, which vary in their ability to estimate the prevalence of chronic kidney disease (CKD) and predict consequences associated with CKD. The use of different laboratory devices also results in uncertainty in estimated GFR (eGFR). The purpose of our study was to discuss the effect of differences in laboratory devices on eGFR when performing serum creatinine measurements.Methods: 163 participants aged 51.22 ± 18.66 years were enrolled during a community health screening programme conducted on 18 June 2011. Samples were sent to four different hospitals using four different devices to check serum creatinine by the Jaffe and enzymatic creatinine methods.Results: Using Roche Cobas Integra 400, Beckman LX20, Hitachi 7180 and Toshiba TBA - c8000, the proportion of the population with eGFR < 60 mL/min/1.73 m2 was 11.04%, 6.75%, 20.25% and 20.86%, respectively. Moreover, 3.68% of the participants had eGFR < 60 mL/min/1.73 m2 in the laboratory when Roche Cobas Integra 400 was used with the enzymatic creatinine method and compensated Jaffe method.Conclusion: Although standardisation of serum creatinine measurement has been achieved by using isotope dilution mass spectrometry, differences in measurement devices still cause substantial bias in the overall results. This affects the application of GFR in the estimation of CKD progression and outcomes associated with CKD. [ABSTRACT FROM AUTHOR]

Background: The clinical consequences of starting chronic peritoneal dialysis (PD) after emergent dialysis via a temporary hemodialysis (HD) catheter has rarely been evaluated within a full spectrum of treated end-stage renal disease (ESRD). We investigated the longer-term outcomes of patients undergoing emergent-start PD in comparison with that of other practices of PD or HD in a prospective cohort of new-onset ESRD.Methods: This was a 2-year prospective observational study. We enrolled 507 incident ESRD patients, among them 111 chose PD (43 planned-start, 68 emergent-start) and 396 chose HD (116 planned-start, 280 emergent-start) as the long-term dialysis modality. The logistic regression model was used to identify variables associated with emergent-start dialysis. The Kaplan-Meier survival analysis was used to determine patient survival and technique failure. The propensity score-adjusted Cox regression model was used to identify factors associated with patient outcomes.Results: During the 2-year follow-up, we observed 5 (4.5%) deaths, 15 (13.5%) death-censored technique failures (transfer to HD) and 3 (2.7%) renal transplantations occurring in the PD population. Lack of predialysis education, lower predialysis estimated glomerular filtration rate and serum albumin were predictors of being assigned to emergent dialysis initiation. The emergent starters of PD displayed similar risks of patient survival, technique failure and overall hospitalization, compared with the planned-start counterparts. By contrast, the concurrent planned-start and emergent-start HD patients with an arteriovenous fistula or graft were protected from early overall death and access infection-related mortality, compared with the emergent HD starters using a central venous catheter.Conclusions: In late-referred chronic kidney disease patients who have initiated emergent dialysis via a temporary HD catheter, post-initiation PD can be a safe and effective long-term treatment option. Nevertheless, due to the potential complications and cost concerns, such practice of PD initiation would better be replaced with a planned-start mode by employing more effective predialysis therapeutic education and timely catheter placement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Background: Chronic kidney disease (CKD) is highly prevalent in Taiwan. More than two-thirds of end-stage renal disease is associated with diabetes mellitus (DM) or hypertension (HTN). Therefore, the formulation of a special preventative policy of CKD in these patients is essential. This study surveyed 14 traditional risk factors and identified their effects on CKD in patients with HTN/DM and compared these with their effects in the general population. Methods: This study included 5328 cases and 5135 controls in the CKD/HTN/DM outpatient and health centres of 10 hospitals from 2008 to 2010. Fourteen common effect factors were surveyed (four demographic, five disease and five lifestyle), and their effects on CKD were tested. Significance tests were adjusted by the Bonferroni method. Results of the stratified analyses in the variables were presented with significant heterogeneity between patients with different comorbidities. Results: Male, ageing, low income, hyperuricemia and lack of exercise habits were risk factors for CKD, and their effects in people with different comorbidities were identical. Anaemia was a risk factor, and there was an additive effect between anaemia and HTN on CKD. Patients with anaemia had a higher risk when associated with HTN [odds ratio (OR) = 6.75, 95 % confidence limit (95 % CI) 4.76-9.68] but had a smaller effect in people without HTN (OR 2.83, 95 % CI 2.16-3.67). The association between hyperlipidaemia-related factors and CKD was also moderated by HTN. It was a significant risk factor in people without HTN (OR = 1.67, 95 % CI 1.38-2.01) but not in patients with HTN (OR =1.03, 95 % CI 0.89-1.19). Hepatitis B, hepatitis C, betel nut chewing, smoking, alcohol intake and groundwater use were not associated with CKD in multivariate analysis. Conclusions: We considered that patients with HTN and anaemia were a high CKD risk population. Physicians with anaemic patients in outpatient clinics need to recognise that patients who also have HTN might be latent CKD cases. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is highly prevalent in Taiwan. More than two-thirds of end-stage renal disease is associated with diabetes mellitus (DM) or hypertension (HTN). Therefore, the formulation of a special preventative policy of CKD in these patients is essential. This study surveyed 14 traditional risk factors and identified their effects on CKD in patients with HTN/DM and compared these with their effects in the general population. Methods: This study included 5328 cases and 5135 controls in the CKD/HTN/DM outpatient and health centres of 10 hospitals from 2008 to 2010. Fourteen common effect factors were surveyed (four demographic, five disease and five lifestyle), and their effects on CKD were tested. Significance tests were adjusted by the Bonferroni method. Results of the stratified analyses in the variables were presented with significant heterogeneity between patients with different comorbidities. Results: Male, ageing, low income, hyperuricemia and lack of exercise habits were risk factors for CKD, and their effects in people with different comorbidities were identical. Anaemia was a risk factor, and there was an additive effect between anaemia and HTN on CKD. Patients with anaemia had a higher risk when associated with HTN [odds ratio (OR) = 6.75, 95 % confidence limit (95 % CI) 4.76–9.68] but had a smaller effect in people without HTN (OR 2.83, 95 % CI 2.16–3.67). The association between hyperlipidaemia-related factors and CKD was also moderated by HTN. It was a significant risk factor in people without HTN (OR = 1.67, 95 % CI 1.38–2.01) but not in patients with HTN (OR =1.03, 95 % CI 0.89–1.19). Hepatitis B, hepatitis C, betel nut chewing, smoking, alcohol intake and groundwater use were not associated with CKD in multivariate analysis. Conclusions: We considered that patients with HTN and anaemia were a high CKD risk population. Physicians with anaemic patients in outpatient clinics need to recognise that patients who also have HTN might be latent CKD cases. [ABSTRACT FROM AUTHOR]

Background Mineral disorders are associated with adverse renal outcomes in chronic kidney disease (CKD) patients. Previous studies have associated hypercalcemia and hypocalcemia with mortality; however, the association between serum calcium and renal outcome is not well-described. Whether adding calcium besides phosphorus or in the form of calcium-phosphorus (Ca × P) product into the model of survival analysis could improve the prediction of renal outcomes is not known. Methods A prospective cohort of 2144 outpatients with CKD stages 3-4 was evaluated. Cox proportional hazard analysis was performed according to calcium quartiles. Results The mean calcium level was 9.2 ± 0.7 mg/dL. Low serum calcium (<9.0 mg/dL) was associated with increased risk of requiring renal replacement therapy (RRT) (hazards ratio [HR]:2.12 (95% CI:1.49-3.02, P <0.05) and rapid renal function progression (odds ratio [OR]: 1.65 (95%CI: 1.19-2.27, P <0.05) compared with high serum calcium (>9.8 mg/dL). Adding calcium into the survival model increased the integrated discrimination improvement by 0.80% (0.12% - 1.91%) while calcium-phosphorus product did not improve risk prediction. The combination of high serum phosphorus (>4.2 mg/dL) and low serum calcium (<9.1 mg/dL) was associated with the highest risk of RRT (HR:2.31 (95%CI: 1.45-3.67, P < 0.05). Conclusion Low serum calcium is associated with increased risk of RRT and rapid renal function progression in CKD stage 3-4 patients. The integration of serum calcium and phosphorus, but not calcium-phosphorus product should be considered in a predictive model of renal outcome. [ABSTRACT FROM AUTHOR]

Background Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Inflammatory diseases are characterized by immunological dysfunction, and monocyte recruitment underlies the mechanism of cell damage. Chemokines attract inflammatory cells to sites of inflammation. Interleukin-8 (IL-8/CXCL8); the monocyte chemoattractant protein-1 (MCP-1/CCL2); the regulated on activation, normal T cell expressed, presumably secreted protein (RANTES/CCL5); the macrophage inflammatory protein (MIP)-1α (CCL3); and MIP-1β (CCL4) are involved in the pathogenesis of inflammation. However, whether mTOR inhibitors moderate the production of chemokines in monocytes remains unclear. Methods A human monocyte cell line, THP-1, and primary monocytes obtained from human volunteers, were stimulated using lipopolysaccharide (LPS), and then treated with sirolimus. The expression of the MCP-1, RANTES, IL-8, MIP-1α, MIP-1β, and TNF-α proteins was measured using enzyme-linked immunosorbent assays, and intracellular signalling was examined using western blotting. Results Sirolimus significantly suppressed the LPS-induced expression of MCP-1, IL-8, RANTES, MIP-1α, and MIP-1β in the THP-1 cells and human primary monocytes. The mitogenactivated protein kinase (MAPK) inhibitors that were examined suppressed the LPS-induced expression of MCP-1, IL-8, RANTES, MIP-1α, and MIP-1β. In addition, sirolimus suppressed the LPS-induced phosphorylation of p38 and p65 in the THP-1 and human primary monocytes. Conclusion Sirolimus downregulates the expression of chemokines in monocytes, including MCP-1, RANTES, IL-8, MIP-1α, and MIP-1β, by inhibiting the NF-кB-p65 and MAPK-p38 signalling pathways. [ABSTRACT FROM AUTHOR]

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the -2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Coxmodel, a smaller initial eGFR AUC%_12M (P < 0.001), a smaller peak eGFR AUC%_12M (P < 0.001), and a larger negative eGFR slope 12M (P < 0.001) were associatedwith a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope 12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC%_is associated with the higher risk of progression to RRT. [ABSTRACT FROM AUTHOR]

Background and Aim: Metabolic syndrome (MetS) and albuminuria increase cardiovascular risk. However, in occupational drivers, the clinical significance of albuminuria and its association with MetS remain unclear. We investigated the prevalence of MetS, albuminuria and cardiovascular risk, and its associated risk factors in occupational drivers; Methods: 441 occupational drivers and 432 age- and sex-stratified matched counterpart controls were enrolled. MetS was defined using Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio = 30 mg/g. Cardiovascular disease risk was evaluated by Framingham Risk Score (FRS); Results: A significantly higher prevalence of MetS (43.1% vs. 25.5%, p < 0.001), albuminuria (12.0% vs. 5.6%, p = 0.001) and high FRS risk ≥ 10% of 10-year risk (46.9% vs. 35.2%, p < 0.001) was found in occupational drivers compared with their counterpart controls. Multiple logistic regression analysis showed that old age, a history of diabetes, gout and betel nut chewing, less exercise and albuminuria (odds ratio [OR], 2.75; p = 0.01) were risk factors for MetS, while a history of renal disease, diabetes and hypertension, and MetS (OR, 2.28; p = 0.01) were risk factors for albuminuria in occupational drivers; Conclusions: Our study demonstrated that MetS and albuminuria were public health problems in occupational drivers. An education program for promoting healthy lifestyle and a regular occupational health visit for early detection and interventions should be established. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection and chronic kidney disease (CKD) have high prevalences in Taiwan and worldwide, but the role of HCV infection in causing CKD remains uncertain. This cohort study aimed to explore this association. Methods: This nationwide cohort study examined the association of HCV with CKD by analysis of sampled claims data from Taiwan National Health Insurance Research Database from 1998 to 2004. ICD-9 diagnosis codes were used to identify diseases. We extracted data of 3182 subjects who had newly identified HCV infection and no traditional CKD risk factors and data of randomly selected 12728 matched HCV-uninfected control subjects. Each subject was tracked for 6 years from the index date to identify incident CKD cases. Cox proportional hazard regression was used to determine the risk of CKD in the HCV-infected and control groups. Results: The mean follow-up durations were 5.88 years and 5.92 years for the HCV-infected and control groups, respectively. Among the sample of 15910 subjects, 251 subjects (1.6%) developed CKD during the 6-year follow-up period, 64 subjects (2.0%) from the HCV-infected group and 187 subjects (1.5%) from the control group. The incidence rate of CKD was significantly higher in the HCV-infected group than in the control group (3.42 vs. 2.48 per 1000 person-years, p = 0.02). Multivariate analysis indicated that the HCV-infected group had significantly greater risk for CKD (adjusted hazard ratio: 1.75, 95% CI: 1.25-2.43, p = 0.0009). This relationship also held for a comparison of HCV-infected and HCV-uninfected subjects who were younger than 70 years and had none of traditional CKD risk factors. Conclusions: HCV infection is associated with increased risk for CKD beyond the well-known traditional CKD risk factors. HCV patients should be informed of their increased risk for development of CKD and should be more closely monitored. [ABSTRACT FROM AUTHOR]

Chronic hypoxia has been recognized as a common mechanism driving the progression of many glomerular diseases. Glomerular cells, although susceptible to hypoxic injuries, are less studied to unravel the hypoxia-related influences. In the present study, we showed that both lipopolysaccharide (LPS) and hypoxia induced B7-1 and hypoxia-inducible factor (HIF)-1α expression in podocytes. B7-1, an essential player in the regulation of podocyte stress fibers, interacted directly with the NH2-terminal oxygenation domain of HIF-1α protein and, therefore, might interfere with the HIF-related oxidative events. The suggestion was supported by the changes in the expression of inducible nitric oxide synthase and nitric oxide. The orderly arranged stress fibers in differentiated podocytes were disrupted by either LPS or hypoxic stimulation, and the disruption could be rescued if they were brought back to normal oxygen tension. Cell motility increased with the stimulation by LPS and hypoxia, most probably mediated by the induction of B7-1 and HIF-1α, respectively. We generated a B7-1 knockdown podocyte cell line using the lentiviral small interfering RNA system. The LPS- and hypoxia-induced stress fiber disruption was largely prevented in the B7-1 knockdown podocytes. The increased cell motility by LPS and hypoxia stimulations was also ameliorated in the B7-knockdown podocytes. In summary, we found that both B7-1 and HIF were upregulated by LPS and hypoxic stimulations in podocytes and they interacted with each other. Hypoxia disrupted the abundant stress fibers and increased cell motility. These hypoxia-induced changes were prevented in B7-knockdown podocytes, and they highlighted the importance of B7-1 expression in the hypoxia-related podocyte injuries. [ABSTRACT FROM AUTHOR]

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope<- 6 ml/min/1.73 m2/y) in 3303 patients with stage 3-5 CKD. In all subjects, the mean hsCRP, WBC count, and ferritin levels were 1.2 (0.4, 5.4) mg/L, 7.2±2.3±103 cells/μL, and 200 (107,349) ng/mL, respectively. During a mean 3.2-year follow-up, there were 1080 (32.7%) subjects commencing RRT, and 841(25.5%) subjects presenting rapid renal progression. Both hsCRP and ferritin were associated with increased risk for RRT with the adjusted HR (tertile 3 versus tertile 1:1.17 1.01-1.36 and 1.20 1.03-1.40 , respectively). Both hsCRP and ferritin were associated with increased odds for rapid renal progression with the adjusted OR (tertile 3 versus tertile 1:1.40 1.13-1.77 and 1.32 1.06-1.67 , respectively). hsCRP and ferritin stratified by albumin were also associated with RRT and rapid renal progression. Instead, WBC count was not associated with renal outcome. In conclusion, elevated levels of hsCRP and ferritin are risk factors associated with RRT and rapid renal progression in advanced CKD patients. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). In Taiwan, CVD is dominated by strokes but there is no robust evidence for a causal relationship between CKD and stroke. This study aimed to explore such causal association. Methods: We conducted a nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database from 2004 to 2007. Each patient identified was individually tracked for a full three years from the index admission to identify those in whom any type of stroke developed. The study cohort consisted of patients hospitalized with a principal diagnosis of CKD and no traditional cardiovascular risk factors at baseline (n = 1393) and an age-matched control cohort of patients hospitalized for appendectomies (n = 1393, a surrogate for the general population). Cox proportional hazard regression and propensity score model were used to compare the three-year stroke-free survival rate of the two cohorts after adjustment for possible confounding factors. Results: There were 256 stroke patients, 156 (11.2%) in the study cohort and 100 (7.2%) in the control cohort. After adjusting for covariates, patients with primary CKD had a 1.94-fold greater risk for stroke (95% CI, 1.45-2.60; p<0.001) based on Cox regression and a 1.68-fold greater risk for stroke (95% CI, 1.25-2.25; p = 0.001) based on propensity score. This was still the case for two cohorts younger than 75 years old and without traditional cardiovascular risk factors. Conclusions: This study of Taiwanese patients indicates that CKD itself is a causal risk factor for stroke beyond the traditional cardiovascular risk factors. Primary CKD patients have higher risk for stroke than the general population and all CKD patients, irrespective of the presence or severity of traditional cardiovascular risk factors, should be made aware of the stroke risk and monitored for stroke prevention. [ABSTRACT FROM AUTHOR]

Aims. Patients with diabetic nephropathy are reported to have a high prevalence of left ventricular structural and functional abnormalities. This study was designed to assess the determinants of left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF) in diabetic patients at various stages of chronic kidney disease (CKD). Methods. This cross-sectional study enrolled 285 diabetic patients with CKD stages 3 to 5 from our outpatient department of internalmedicine. Clinical and echocardiographic parameters were compared and analyzed. Results.We found a significant stepwise increase in LVMI (P < 0.001), LVH (P < 0.001), and LVEF < 55% (P = 0.013) and a stepwise decrease in LVEF (P = 0.038) corresponding to advance in CKD stages. Conclusions. Our findings suggest that increases in LVMI and decreases in LVEF coincide with advances in CKD stages in patients with diabetes. [ABSTRACT FROM AUTHOR]

17&agr;-hydroxylase/17, 20-lyase deficiency (17OHD) is an autosomal recessive disease causing congenital adrenal hyperplasia and a rare cause of hypertension with hypokalemia. The CYP17A1 gene mutation leads to 17OHD and its clinical features. We described an 18 y/o female with clinical features of 17&agr;-hydroxylase/17, 20-lyase deficiency and characterized the functional consequences of an intronic CYP17A1 mutation. The coding regions and flanking intronic bases of the CYP17A1 gene were amplified by PCR and sequenced. The patient is a compound heterozygote for the previously described p.R358X and IVS1 +2T>C mutations. A first intron splice donor site mutation was re-created in minigene and full-length expression vectors. Pre-mRNA splicing of the variant CYP17A1 intron was studied in transfected cells and in a transformed lymphoblastoid cell line. When the full-length CYP17A1 gene and minigene containing the intronic mutation was expressed in transfected cells, the majority (>90%) of mRNA transcripts were incorrectly spliced. Only the p.R358X transcript was detected in the EBV-transformed lymphoblastoid cell line. The IVS1 +2T>C mutation abolished most 17&agr;-hydroxylase/17, 20-lyase enzyme activity by aberrant mRNA splicing to an intronic pseudo-exon, causing a frame shift and early termination. [ABSTRACT FROM AUTHOR]

OBJECTIVE--An association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS--We enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria. RESULTS--We found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88-1.87), 1.44 (0.99-2.08), and 1.52 (1.06-2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93-2.02), 1.66 (1.12-2.47), and 1.76 (1.20-2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively. CONCLUSIONS--According to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Overseas kidney transplantation has often been reported to have unsatisfactory outcomes. This study aims to compare post-transplantation outcomes between overseas and domestic kidney transplant (KT) recipients in Taiwan. The Taiwanese National Health Insurance Research Database was used to identify 310 domestic and 643 overseas KT recipients, who survived for longer than 1 month after the transplantation, in a cohort of 45 453 chronic haemodialysis patients in 1997-2002. Cox proportional hazards models were used to assess risks of mortality and graft failure. The 1, 3 and 5 year survival rates for domestic KT recipients were 96.5%, 93.3% and 91.6%, respectively, while those for overseas KT recipients were 94.9%, 87.9% and 77.1%, respectively ( P = 0.015). For the overseas group, those who received a KT before 2001 had significantly higher hazard ratios of mortality and graft failure (2.85 and 1.71, respectively). However, for those receiving a KT in 2001-2002, no significant outcome difference could be found between overseas and domestic recipients. The risk disparity between overseas and domestic KT recipients is mainly attributable to when the transplantation was performed. In attempting to dissuade potential recipients from organ trafficking, merely emphasizing the previously acknowledged poor outcomes no longer suffices as a valid reason. In this paper, Hsu and colleagues from Taiwan analyze the outcome of kidney transplantation performed overseas in two time periods, before and after 2001, and show the outcome of kidney transplants performed outside Taiwan after 2001 are comparable to those performed in Taiwan. The implication of this paper is that emphasis on poor mortality and graft outcome from 'transplant tourism' is less sustainable than before and new strategies to deter this will need to be developed. [ABSTRACT FROM AUTHOR]

Aims. The SLC2A9 gene encodes the glucose transporter 9, with the abilities of transporting both glucose and uric acid and is involved in the pancreatic glucose-stimulated insulin secretion. The single nucleotide polymorphisms (SNPs) of SLC2A9 accounted for 5% variance of serum uric acid (UA). UA was identified as a risk factor for type 2 diabetes mellitus (DM). We investigated whether the SLC2A9 gene variations are associated with type 2 DMin Han Chinese. Methods. Three common SNPs of the SLC2A9, rs1014290, rs2280205, and rs3733591, were genotyped in 1003 Han Chinese randomly selected from Kaohsiung, Taiwan. Results. The variant SNP rs1014290 is associated with decreased 0.12-fold risk of type 2 DM (P = .002). Per-copy increase in the minor C-allele results in 0.13mmol/L (P = .037) and 10.03 µmol/L (P = .016) decrease in serum glucose and UA, respectively. Conclusions. The SNP rs1014290 within the SLC2A9 gene is associated with type 2 DM in Han Chinese. [ABSTRACT FROM AUTHOR]

Background. Glomerular filtration rate (GFR) and co-morbidity at dialysis initiation in relation to mortality in end-stage renal disease is still controversial. We studied factors potentially related to the mortality in incident haemodialysis (HD) patients. [ABSTRACT FROM PUBLISHER]

Chronic kidney disease (CKD) has emerged as a global public health burden. Taiwan has the highest incidence and prevalence rates of end-stage renal disease (ESRD) in the world. In this review, the following key issues of CKD in Taiwan are addressed: epidemiological data, underlying diseases patterns, risk factors, public health concerns and a preventive project. Prevalence of CKD are reported to be 6.9% for CKD stage 3–5, 9.83% for clinically recognized CKD and 11.9% for CKD stage 1–5. However, overall awareness of CKD is low, 9.7% for CKD stage 1–3 and 3.5% for stage 1–5. Diabetes mellitus (43.2%), chronic glomerulonephritis (25.1%), hypertension (8.3%) and chronic interstitial nephritis (2.8%) are four major underlying renal diseases of ESRD. Older age, diabetes, hypertension, smoking, obesity, regular use of herbal medicine, family members (both relatives and spouses), chronic lead exposure and hepatitis C are associated with higher risk for CKD. Impact of CKD increases risk of all-cause mortality and cardiovascular diseases, especially in those with overt proteinuria and advanced CKD stages. These impacts lead to increased medical costs. The nationwide CKD Preventive Project with multidisciplinary care program has proved its effectiveness in decreasing dialysis incidence, mortality and medical costs. It is crucially significant from Taiwan experience on CKD survey and preliminary outcome of the preventive project. Provision of a more comprehensive public health strategy and better care plan for CKD should be achieved by future international collaborative efforts and research. [ABSTRACT FROM AUTHOR]

Background. Quality of life (QOL) may be associated with morbidity and survival in end-stage renal disease (ESRD), and is considered to be an important outcome measure for patients with chronic kidney disease (CKD). However, the prognostic role of QOL for survival in CKD remains unclear. We studied the relationship between QOL and risks of ESRD and mortality in CKD patients. [ABSTRACT FROM PUBLISHER]

Aim: The ankle brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and haemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end-stage renal disease. The aim of this study was to investigate the predictors for mortality by using ABI value in patients with CKD and undergoing haemodialysis in Taiwan. Methods: One hundred and sixty-nine patients with CKD stage 3–5 and 231 haemodialysis patients were enrolled in one regional hospital. The mean follow-up period was 23.3 ± 3.3 months. Patients were stratified into three groups according to ABI value (<0.9, ≥0.9 to <1.3, and ≥1.3). The relative mortality risk was analyzed by Cox-regression methods. Results: In multivariate analysis, an ABI of 1.3 or more (hazard ratio, 3.846; P = 0.043) and coronary artery disease ( P = 0.012) were positively associated with overall mortality, and serum low-density lipoprotein cholesterol level ( P = 0.042) was negatively associated with overall mortality. In addition, an ABI of less than 0.9 ( P = 0.049), an ABI of 1.3 or more ( P = 0.033), coronary artery disease ( P = 0.024) and haemodialysis treatment ( P = 0.043) were strong predictors for cardiovascular mortality. Conclusion: Our findings show that an ABI of 1.3 or more predicts for both overall and cardiovascular mortality, and an ABI of less than 0.9 predicts for cardiovascular mortality in CKD and haemodialysis patients. Screening patients with chronic renal failure by means of ABI may help to identify a high-risk group for increased mortality. [ABSTRACT FROM AUTHOR]

A CKD Care Program is found to help pre-ESRD patients prepare for dialysis initiation and is associated with a reduced probability of emergency dialysis and hospitalization and lowered medical costs. Aim: Multidisciplinary care of patients with chronic kidney disease (CKD) provides better care outcomes. This study is to evaluate the effectiveness of a CKD care program on pre-end-stage renal disease (ESRD) care. Methods: One hundred and forty incident haemodialysis patients were classified into the CKD Care Group ( n = 71) and the Nephrologist Care Group ( n = 69) according to participation in the CKD care program before dialysis initiation. The ‘total observation period’ was divided into ‘6 months before dialysis’ and ‘at dialysis initiation’. Quality of pre-ESRD care, service utilization and medical costs were evaluated and compared between groups. Results: The mean estimated glomerular filtration rates at dialysis initiation were low in both groups; but the levels of haematocrit and serum albumin of the CKD Care Group were significantly higher. The percentages of patients initiating dialysis with created vascular access, without insertion of double-lumen catheter and without hospitalization were 57.7%, 50.7% and 40.8%, respectively, in the CKD Care Group, and 37.7%, 29.0% and 18.8% in the Nephrologist Care Group ( P < 0.001). Participation in the CKD care program, though with higher costs during the 6 months before dialysis ($US1428 ± 2049 vs US$675 ± 962/patient, P < 0.001), was significantly associated with lower medical costs at dialysis initiation ($US942 ± 1941 vs $US2410 ± 2481/patient, P < 0.001) and for the total period of observation ($US2674 ± 2780 vs $US3872 ± 3270/patient, P = 0.009). The cost-saving effect came through the early preparation of vascular access and the lack of hospitalization at dialysis initiation. Conclusion: CKD care programs significantly improve quality of pre-ESRD care, decrease service utilization and save medical costs. [ABSTRACT FROM AUTHOR]

Aim: Late referral of chronic kidney disease (CKD) patients to nephrologists is associated with increased morbidity and mortality and is still quite common and seldom studied in Taiwan because of unique sociocultural factors. We aimed to study the decline in renal function and factors related to the change in renal function before and after referral. Methods: We retrospectively reviewed the changes of estimated glomerular filtration rate (eGFR) in 213 new referrals of patients with CKD stages 3–5 to the nephrology divisions of one medical centre and one regional hospital from 2001–2006. Data on demographics and laboratory investigations were collected for study. Results: The rates of annual eGFR decline slowed significantly from −7.38 ± 0.84 before referral to −1.02 ± 0.45 mL/min per 1.73 m2/year after referral (mean ± standard error of the mean, P < 0.001). The nephrology referral was the most significant factor associated with the slowing of renal function progression, as was younger age and female sex. After nephrology referral, patients with diabetes had an increase in eGFR compared to those without diabetes ( P = 0.034). Patients had better control of diastolic blood pressure, sugar and lipid, more frequent use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins, less frequent use of non-steroidal anti-inflammatory drugs, and more serum creatinine measurements after nephrology referral. Conclusion: Slowing renal functional decline in CKD patients after referral addresses the importance of nephrology referral for CKD care, which should be strongly promoted in CKD prevention projects in Taiwan. [ABSTRACT FROM AUTHOR]

OBJECTIVES: There is growing evidence with regard to the association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). However, the mutual link and related virological implication have not been fully clarified. The impact of hepatitis B virus (HBV) infection on the epidemiological link remains unclear. This study aimed to elucidate the link between T2DM and viral hepatitis infections, especially HCV infection. It also aimed to analyze the associated virological characteristics and implication. METHODS: Cross-sectional analysis of a computer-sampling survey among 10,975 participants (aged 40–65 yr) was performed in an area endemic for HBV and HCV infections in Taiwan. Outcome measures included prevalence of T2DM among different groups of viral hepatitis infection, and comparison of related biochemical and virological profiles. RESULTS: Of 10,975 participants studied, 9,932 eligible participants were analyzed. The prevalence of T2DM, seropositivity for HBV surface antigen (HBsAg) and HCV antibodies (anti-HCV), and HCV viremia was 12.5%, 13.1%, 6.5%, and 4.8%, respectively. Prevalence of HCV viremia showed significant difference between T2DM and non-T2DM subjects (6.9% vs 4.5%, P < 0.001), whereas anti-HCV seropositivity showed borderline significance (7.8% vs 6.3%, P= 0.047). There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM. On the other side, the prevalence of HBsAg (+) did not differ between T2DM and non-T2DM subjects (12.5% vs 13.9%, P= 0.19). The prevalence of T2DM among HCV viremic subjects (18.0%, 86/478) was significantly higher than HBsAg (+) subjects (11.4%, 155/1,363, P= 0.001) and those negative for both viral hepatitis markers (12.5%, 997/8,004, P= 0.001). Multivariate logistic regression analyses showed that HCV viremia was the leading significant factor associated with T2DM, followed by male gender, hypertension, body mass index, and age. CONCLUSIONS: HBV infection did not increase the association with T2DM. A significant mutual link between T2DM and HCV viremia existed in this HBV/HCV endemic area. There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM. [ABSTRACT FROM AUTHOR]

Objective: To evaluate losartan and conventional antihypertensive therapy (CT) compared with CT alone on the cost associated with end-stage renal disease (ESRD) in Hong Kong, Japan, Korea, Malaysia, Singapore and Taiwan. Methods: Reduction of end-points in non-insulin-dependent diabetes mellitus with the angiotensin II antagonist losartan (RENAAL) was a multinational, double-blind, randomized, placebo-controlled trial to evaluate the renal protective effects of losartan on a background of CT in patients with type 2 diabetes and nephropathy. The primary composite end-point was a doubling of serum creatinine, ESRD or death. Data on the duration of ESRD for the Asian subgroup of patients enrolled in RENAAL were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the number of days each patient experienced ESRD with the average daily cost of dialysis from the third-party payer perspective in Hong Kong, Japan, Korea, Malaysia, Singapore and Taiwan. Total cost, converted to US dollars, was the sum of ESRD and losartan costs. Results: Losartan plus CT reduced the number of days with ESRD by 37.9 per patient over 3.5 years compared with CT alone. This reduction in ESRD days resulted in a decrease in the cost associated with ESRD, which ranges from $910 to $4346 per patient over 3.5 years across the six countries or regions. After accounting for the cost of losartan, the reduction in ESRD days resulted in net savings in each of the six countries or regions, ranging from $55 to $515 per patient. Conclusion: Treatment with losartan in patients with type 2 diabetic nephropathy not only reduced the incidence of ESRD among Asian patients, but resulted in direct medical cost savings in countries or regions representing Asia. [ABSTRACT FROM AUTHOR]

In this investigation, we tried to find the incidence and characteristics of tuberculosis (TB) in dialysis patients previously found only in a small number of cases. We collected the cases of newly diagnosed TB patients in Taiwan during 1997. Simultaneously, all dialysis patients were collected and matched with the TB cases to identify the dialysis patients who had also contracted TB. The annual incidence of the dialysis population was 493.4/100,000, 6.9 times that of the general population (71.1/100,000). The annual incidence for the male dialysis population was 573.3, the incidence was 479.2 for the female dialysis population. The incidence for the general population was 97.1 and 43.7/100,000, respectively. Although the 1-year mortality rate due to TB (1.7 vs. 1.9%, p > 0.05) was similar in both populations, the non-TB mortality was much higher in the dialysis population than that in the general population (25.6 vs. 11.1%, p < 0.05). Finally, the 1-year mortality rate of dialysis patients with TB is 3.3 times higher than that in dialysis patients without TB (27.3 vs. 8.3%, p < 0.05). The findings suggest that uremia modifies the behavior of TB, jeopardizes female and younger dialysis patients, poses a higher risk of extrapulmonary dissemination, and predicts a higher overall mortality.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Incident and prevalent (I&P) rates in dialysis end-stage renal disease (ESRD) patients in Taiwan increased rapidly following the launch of National Health Insurance (NHI) in 1995. Our aim was to explore the impact of NHI on the status and trends of ESRD epidemiology in Taiwan. Methods. This study was conducted using retrospective cohort analysis of data collected from the Taiwan national dialysis registry. Results. From 1990 to 2001, I&P rates of ESRD patients increased 2.6 times from 126 to 331 per million populations (pmp) and 3.46 times from 382 to 1322 pmp, respectively. Increasing ESRD was seen in patients who were middle-aged, elderly and who had diabetic nephropathy as their primary renal disease. The mean age of I&P patients increased by 7.2 years and 7.1 years, respectively. All of these parameters increased markedly in 1995, the year of NHI implementation. First-year mortality decreased to 7.8 per 1000 patient-months in 1994, and then increased to 18.0 in 2001. The cumulative survival rate of the elderly subgroup (age >65) in the incident 1990–1994 cohort was greater than in the 1995–1999 cohort. These data indicated that NHI implementation significantly influenced the inflow and the mortality of ESRD patients. Conclusion. In addition to presenting ESRD epidemiology in Taiwan, this study demonstrated that NHI implementation stimulated the growth of treated ESRD populations. Preventive plans mounted against chronic kidney diseases will be essential to reduce the growth of ESRD patient numbers and consequent economic burdens. [ABSTRACT FROM AUTHOR]

Background. Taiwan has the worlds highest incidence and second highest prevalence of end-stage renal disease (ESRD), particularly in older age groups. However, the transition from chronic kidney disease (CKD) to death or ESRD remains unclear. This study aimed to investigate the impact of late-stage CKD on all-cause and cause-specific mortality by identifying the CKD population. Methods. This was an observational cohort study (n = 35 529), mean age 75.7 years (SD = 5.3), of participants in the Elderly Health Examination Program (EHEP) in Kaohsiung City, Taiwan, between 2002 and 2004. Estimated glomerular filtration rate (eGFR) was calculated by the simplified modified diet in renal disease equation. Proportional hazard ratios (HR) of mortality associated with late-stage CKD were assessed by Cox regression. Results. The crude prevalence rate of CKD stages 3–5 was 39.4%; 1840 participants (5.18%) died within 2-year follow-up, a mortality rate of 20.3 per 1000 person-years overall and 16.4 per 1000 person-years in the reference group. Higher HR for all-cause and cause-specific mortality were found in the groups with decreased eGFR. Compared with the reference group (eGFR > 60 mL/min/1.73 m2), adjusted HR for all-cause mortality were 1.5, 2.1 and 2.6 for groups with eGFR 30–44, 15–29 and P P Conclusion. Late-stage CKD is a significant risk factor for mortality, especially due to cardiovascular and renal diseases, in elderly Taiwanese. Given the higher prevalence rate of late-stage CKD in the study area, CKD patient mortality was relatively lower, which might reflect underestimation of renal function for patients at early stages of CKD, or partly explain the high ESRD population. [ABSTRACT FROM AUTHOR]