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Purpose: To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD)., Design: Nationwide, population-based cohort study., Methods: This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis., Results: In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence = 1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio = 1.17, 95% CI = 1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence = 21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio = 1.89, 95% CI = 1.07-3.36)., Conclusions: Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.

The level of di-(2-ethylhexyl) phthalate (DEHP) is elevated in chronic kidney disease patients undergoing dialysis. However, statins are unable to reduce the cardiovascular events in chronic dialysis patients. In this study, we investigated the effects of DEHP on statin-conferred pleiotropic effects and the underlying molecular mechanism in peritoneal dialysis (PD) patients and endothelial cells (ECs). In PD patients with serum DEHP level ≥0.0687 μg/mL, statin treatment was not associated with lower risk of cardiovascular disease. In ECs, exposure to DEHP abrogated the simvastatin-induced NO bioavailability and EC-related functions. Additionally, DEHP abolished the anti-inflammatory effect of simvastatin on the tumor necrosis factor α-induced upregulation of adhesion molecules and monocyte adhesion to ECs. Mechanistically, DEHP blunted the activation of transient receptor potential vanilloid type 1 (TRPV1), which is required for NO production by simvastatin in ECs. Notably, DEHP increased the activity and expression of protein phosphatase 2B (PP2B), a negative regulator of TRPV1 activity. The effect of DEHP on PP2B activation was mediated by the activation of the NADPH oxidase/reactive oxygen species (NOX-ROS) pathway. Inhibition of PP2B activity by pharmacological antagonists prevented the inhibitory effects of DEHP on simvastatin-induced Ca 2+ influx, NO bioavailability, and EC migration, proliferation, tube formation, and anti-inflammatory action. Collectively, DEHP activates the NOX-ROS-PP2B pathway, which in turns inhibits TRPV1/Ca 2+ -dependent signaling and abrogates the statin-conferred pleiotropic protection in ECs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A valid diet quality assessment scale has not been investigated in hemodialysis patients. We aimed to adapt and validate the alternative healthy eating index in hemodialysis patients (AHEI-HD), and investigate its associations with all-cause mortality. A prospective study was conducted on 370 hemodialysis patients from seven hospital-based dialysis centers. Dietary data (using three independent 24-hour dietary records), clinical and laboratory parameters were collected. The construct and criterion validity of original AHEI-2010 with 11 items and the AHEI-HD with 16 items were examined. Both scales showed reasonable item-scale correlations and satisfactory discriminant validity. The AHEI-HD demonstrated a weaker correlation with energy intake compared with AHEI-2010. Principle component analysis yielded the plateau scree plot line in AHEI-HD but not in AHEI-2010. In comparison with patients in lowest diet quality (tertile 1), those in highest diet quality (tertile 3) had significantly lower risk for death, with a hazard ratio (HR) and 95% confidence intervals (95%CI) of HR: 0.40; 95%CI: 0.18 - 0.90; p = 0.028, as measured by AHEI-2010, and HR: 0.37; 95%CI: 0.17-0.82; p = 0.014 as measured by AHEI-HD, respectively. In conclusion, AHEI-HD was shown to have greater advantages than AHEI-2010. AHEI-HD was suggested for assessments of diet quality in hemodialysis patients.

Chronic kidney disease (CKD) and its complications are major global public health issues. Vegetarian diets are associated with a more favorable profile of metabolic risk factors and lower blood pressure, but the protective effect in CKD is still unknown. We aim to assess the association between vegetarian diets and CKD. A cross-sectional study was based on subjects who received physical checkups at the Taipei Tzu Chi Hospital from 5 September 2005, to 31 December 2016. All subjects completed a questionnaire to assess their demographics, medical history, diet pattern, and lifestyles. The diet patterns were categorized into vegan, ovo-lacto vegetarian, or omnivore. CKD was defined as an estimated GFR <60 mL/min/1.73 m² or the presence of proteinuria. We evaluated the association between vegetarian diets and CKD prevalence by using multivariate analysis. Our study recruited 55,113 subjects. CKD was significantly less common in the vegan group compared with the omnivore group (vegan 14.8%, ovo-lacto vegetarians 20%, and omnivores 16.2%, P < 0.001). The multivariable logistic regression analysis revealed that vegetarian diets including vegan and ovo-lacto vegetarian diets were possible protective factors [odds ratios = 0.87 (0.77⁻0.99), P = 0.041; 0.84 (0.78⁻0.90), P < 0.001]. Our study showed a strong negative association between vegetarian diets and prevalence of CKD. If such associations are causal, vegetarian diets could be helpful in reducing the occurrence of CKD.

Background: Spironolactone has been shown to reduce cardiovascular death in patients with mild-to-moderate chronic kidney disease (CKD), but its risks and benefits in advanced CKD remain unsettled. We aimed to assess whether spironolactone reduces cardiovascular mortality and morbidity in pre-dialysis stage 5 CKD patients., Methods: Using Taiwan's National Health Insurance Research Database from January 2000 to June 2009, we enrolled 27,213 pre-dialysis stage 5 CKD adult patients, in whom 1363 patients were treated with spironolactone (user) and 25,850 were not (nonuser). Outcomes were all-cause mortality, hospitalization for heart failure (HHF) and major adverse cardiac event (MACE, the composite of acute myocardial infarction and ischemic stroke). Patients were followed up till December 31, 2009., Results: Over 85,758 person-years of follow-up, spironolactone users had higher incidence for all-cause mortality (24.7/100 person-years vs. 10.6/100 person-years), infection-related death (4.4/100 person-years vs. 1.7/100 person-years) and HHF (4.0/100 person-years vs. 1.4/100 person-years). Multivariable Cox hazards model showed that spironolactone users were associated with higher risks of all-cause mortality (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.24-1.46), infection-related death (aHR 1.42, CI 1.16-1.73) and HHF (aHR 1.35, CI 1.08-1.67) as compared to nonusers. The risks for cardiovascular mortality, MACE and hyperkalemia-associated hospitalization were similar between two groups. After matching users and nonusers (1:3 ratio) by propensity scores, the results were consistent in matched cohort and across subgroups., Conclusions: Spironolactone may be associated with higher risks for all-cause and infection-related mortality and HHF in pre-dialysis stage 5 CKD patients. Spironolactone should be used with caution in advanced CKD patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair. Clinically, indoxyl sulfate is associated with total and cardiovascular mortality in patients with CKD. Recent studies have indicated that in addition to coronary and cerebral arteries, indoxyl sulfate plays a role in peripheral artery disease (PAD) and dialysis graft thrombosis. Emerging evidence suggests that indoxyl sulfate is implicated via novel mechanisms, including progenitor cell-related neovascularization and tissue factor-related hypercoagulability. These findings raise the possibility that strategies targeting serum indoxyl sulfate may have the potential to improve the outcomes of PAD and dialysis vascular access in patients with CKD., Competing Interests: The authors declare no conflict of interest.

A combination therapy of pentoxifylline with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) decreased proteinuria or glomerular filtration rate decline in early chronic kidney disease (CKD). Whether adding pentoxifylline to ACEI/ARB provides additional benefits on outcome is unclear in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND). A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 14,117 CKD 5 ND with serum creatinine levels >6 mg/dL and hematocrit levels <28% and who have been treated with ACEI/ARB. All patients were divided into pentoxifylline users and nonusers. Patient follow-up took place until dialysis, death before initiation of dialysis or December 31, 2009. Finally, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before dialysis. After propensity score-matching, use of pentoxifylline was associated with a lower risk for long-term dialysis or death in ACEI/ARB users (HR, 0.94; 95% CI, 0.90-0.99) or ARB users (HR, 0.91; 95% CI, 0.85-0.97). In conclusion, pentoxifylline exhibited a protective effect in reducing the risk for the composite outcome of long-term dialysis or death in ACEI/ARB treated CKD 5 ND.

Background: A risk/benefit analysis of iron supplementation in pre-dialysis advanced chronic kidney disease (CKD) patients has not been conducted. We aim to assess the effectiveness and the safety of iron supplementation in patients with CKD Stage 5 who have not yet received dialysis (CKD 5 ND)., Methods: A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From 1 January 2000 to 30 June 2009, we enrolled 31 971 adult patients who had a serum creatinine >6 mg/dL and a haematocrit <28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without iron supplementation within 90 days after starting ESA therapy. Patient follow-up took place until dialysis, death before initiation of dialysis or 31 December 2009. The primary outcomes were death before initiating dialysis, hospitalization before death or long-term dialysis., Results: After propensity score matching, the patients who received iron supplementation were associated with a lower risk of all-cause death [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.80-0.90] compared with non-users. The survival benefit of iron use was consistent across the majority of dosage groups, except for those who were treated with monthly IV iron >200 mg. Moreover, compared with the non-users, the iron users were associated with a lower risk of hospitalizations (HR, 0.97; 95% CI, 0.94-0.99) but with a higher risk of faster progression to end-stage renal disease (HR, 1.05; 95% CI, 1.01-1.08)., Conclusions: Iron supplementation is associated with 15% risk reduction in death among CKD 5 ND patients who received ESA treatment. Randomized studies are needed to validate this association., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Metformin is recommended as a first-line treatment for patients with type 2 diabetes. However, use of this drug has been contraindicated in individuals with impaired kidney function because of the perceived risk of lactic acidosis. Evidence now supports cautious use of metformin in people with mild-to-moderate chronic kidney disease. However, studies examining the use of metformin in patients with advanced chronic kidney disease are lacking. We aimed to assess the safety of metformin in patients with type 2 diabetes and advanced (approximately stage 5) chronic kidney disease., Methods: We did a retrospective, observational, cohort study of patients with type 2 diabetes who were enrolled prospectively in Taiwan's national health insurance research database between Jan 1, 2000, and June 30, 2009, and had follow-up data until Dec 31, 2009. We included individuals with a serum creatinine concentration greater than 530 μmol/L, which is approximately equivalent to stage 5 chronic kidney disease. From a consecutive sample of 12 350 patients with type 2 diabetes and chronic kidney disease, 1005 used metformin and 11 345 were non-users. We matched users and non-users of metformin by propensity score in a 1:3 ratio. Our primary outcome was all-cause mortality., Findings: 813 metformin users were matched by propensity score to 2439 non-users. The two groups of patients did not differ significantly by 30 baseline clinical and socioeconomic variables. Median follow-up in the matched cohort was 2·1 years (range 0·3-9·8). All-cause mortality was reported in 434 (53%) of 813 metformin users and in 1012 (41%) of 2439 non-users. After multivariate adjustment, metformin use was an independent risk factor for mortality (adjusted hazard ratio 1·35, 95% CI 1·20-1·51; p<0·0001). The increased mortality risk was dose-dependent and was consistent across all subgroup analyses. However, metformin use compared with no use was associated with a higher but non-significant risk of metabolic acidosis (1·6 vs 1·3 events per 100 patient-years; adjusted hazard ratio 1·30, 95% CI 0·88-1·93; p=0·19)., Interpretation: Use of metformin in people with type 2 diabetes and a serum creatinine concentration greater than 530 μmol/L is associated with a significantly increased risk of all-cause mortality compared with non-users. Metformin use should not be encouraged in this patient group., Funding: Taipei Tzu Chi Hospital, Taipei Veterans General Hospital, Foundation for Poison Control, National Health Research Institutes, Ministry of Science and Technology of Taiwan., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.

Background: Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood., Methods and Results: A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes., Conclusions: Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

The introduction of erythropoiesis-stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non-dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin-α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10-11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation., (© 2014 Asian Pacific Society of Nephrology.)

The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (<27), and the L allele represents long repeats (≥27). The primary renal end points consisted of sustained serum creatinine doubling and/or ESRD requiring long-term RRT. The secondary end points were major adverse cardiovascular events and mortality. At the end of study, the adjusted hazard ratios (95% confidence intervals) for each L allele in the additive model were 1.99 (1.27 to 3.14; P=0.003) for the renal end points, 1.70 (1.27 to 2.27; P<0.001) for major adverse cardiovascular events, and 1.36 (1.04 to 1.79; P=0.03) for mortality. With cardiac events as time-dependent covariates, the adjusted hazard ratio for each L allele in the additive model was 1.91 (1.20 to 3.06; P=0.01) for the renal end points. In conclusion, a greater number of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with higher risk for CKD, cardiovascular events, and mortality among patients with coronary artery disease., (Copyright © 2014 by the American Society of Nephrology.)

High-dose intravenous iron supplementation is associated with adverse cardiovascular outcomes in patients with CKD, but the underlying mechanism is unknown. Our study investigated the causative role of iron sucrose in leukocyte-endothelium interactions, an index of early atherogenesis, and subsequent atherosclerosis in the mouse remnant kidney model. We found that expression levels of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and adhesion of U937 cells increased in iron-treated human aortic endothelial cells through upregulated NADPH oxidase (NOx) and NF-κB signaling. We then measured mononuclear-endothelial adhesion and atherosclerotic lesions of the proximal aorta in male C57BL/6 mice with subtotal nephrectomy, male apolipoprotein E-deficient (ApoE(-/-)) mice with uninephrectomy, and sham-operated mice subjected to saline or parenteral iron loading. Iron sucrose significantly increased tissue superoxide production, expression of tissue cell adhesion molecules, and endothelial adhesiveness in mice with subtotal nephrectomy. Moreover, iron sucrose exacerbated atherosclerosis in the aorta of ApoE(-/-) mice with uninephrectomy. In patients with CKD, intravenous iron sucrose increased circulating mononuclear superoxide production, expression of soluble adhesion molecules, and mononuclear-endothelial adhesion compared with healthy subjects or untreated patients. In summary, iron sucrose aggravated endothelial dysfunction through NOx/NF-κB/CAM signaling, increased mononuclear-endothelial adhesion, and exacerbated atherosclerosis in mice with remnant kidneys. These results suggest a novel causative role for therapeutic iron in cardiovascular complications in patients with CKD., (Copyright © 2014 by the American Society of Nephrology.)

Volume overload is a predictor of mortality in dialysis patients. However, the fluid status of patients with chronic kidney disease (CKD) but not yet on dialysis has not been accurately characterized. We used the Body Composition Monitor, a multifrequency bioimpedance device, to measure the level of overhydration in CKD patients, focusing on the association between overhydration and cardiovascular disease risk factors. Overhydration was the difference between the amount of extracellular water measured by the Body Composition Monitor and the amount of water predicted under healthy euvolemic conditions. Volume overload was defined as an overhydration value at and above the 90th percentile for the normal population. Of the 338 patients with stages 3-5 CKD, only 48% were euvolemic. Patients with volume overload were found to use significantly more antihypertensive medications and diuretics but had higher systolic blood pressures and an increased arterial stiffness than patients without volume overload. In a multivariate analysis, male sex, diabetes, pre-existing cardiovascular disease, systolic blood pressure, serum albumin, TNF-α, and proteinuria were independently all associated with overhydration. Thus, volume overload is strongly associated with both traditional and novel risk factors for cardiovascular disease. Bioimpedance devices may aid in clinical assessment by helping to identify a high-risk group with volume overload among stages 3-5 CKD patients.

Importance: The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined., Objective: To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. DESIGN Prospective cohort study., Setting: Taiwan., Participants: From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents., Interventions: Users (n = 14,117) and nonusers (n = 14,380) of ACEIs/ARBs., Main Outcomes and Measures: We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers., Results: In a median follow-up of 7 months, 20,152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30)., Conclusions and Relevance: Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.