The composite outcome of long-term dialysis or death referred to either the starting date of long-term dialysis or death, whichever came first. and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before progression to end-stage renal disease requiring dialysis. In comparison with the ARB-only users, dual blockade with ACEIs and ARBs was associated with a significantly higher risk of (1) death in all CKD patients (HR = 1.49, [95%CI, 1.30C1.71]; P = 0.02) and in diabetic subgroup (HR = 1.58, [95%CI, 1.34C1.86]; P Phthalic acid = Phthalic acid 0.02); (2) composite endpoint of long-term dialysis or Phthalic acid death in diabetic subgroup (HR = 1.10, [95%CI, 1.01C1.20]; P = 0.04); (3) hyperkalemia-associated hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05C7.15]; P = 0.04). However, ACEIs users were associated with higher mortality than ARBs users in all CKD patients (HR = 1.17, [95%CI, 1.07C1.27]; P = Phthalic acid 0.03) and in diabetic subgroup (HR = 1.32, [95%CI, 1.18C1.48]; P = 0.03). Monotherapy of RAS blockade, especially ARB, is more effective and safer than dual RAS blockade in pre-dialytic stage 5 CKD patients. Introduction Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) has been prescribed worldwide to improve proteinuria and delay the progression of chronic kidney disease (CKD) in both diabetic and non-diabetic patients. Several investigations have documented its benefit for renal protection to the patients with early CKD (serum creatinine level: 1.5C3.0 mg/dl)[1, 2] and non-diabetic stage 4 CKD (glomerular filtration rate:15C29 ml/min/1.73m2 or serum creatinine level: 3.0C5.0 mg/dl).[3] To explore whether ACEI/ARB therapy is the same effective to those patients with advanced CKD at the pre-dialytic stage, our task group developed a national-wide retrospective study by including all CKD patients diagnosed between January 1, 2000 and June 30, 2009 in Taiwan, who had serum creatinine level >6 mg/dl and hematocrit level <28%, and could receive erythropoiesis-stimulating agent (ESA). Among 28,497 advanced CKD patients, 14,117 ACEI/ARB users, as compared with nonusers, showed to run a significantly lower risk of long-term dialysis (HR, 0.94 [95% CI, 0.91C0.97]) and the composite outcome of long-term dialysis or death (0.94[0.92C0.97]).[4] Thus, the survival benefit of ACEI or ARB therapy can persist throughout the whole CKD stage, even in pre-dialytic patients. Previous investigations have disclosed that dual renin angiotensin system (RAS) blockade (combination therapy with an ACEI and an ARB) is more effective in proteinuria reduction, which may provide additional cardiovascular or renoprotective benefit, than either drug alone in renal disease.[5] However, in the Ongoing Telmisartan FAA Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), the authors found that combination therapy with an ACEI and an ARB, compared with monotherapy, did not provide more cardiovascular or renal benefits but increased risk of hyperkalemia and acute kidney injury in persons running an increased cardiovascular risk.[6] Another recent meta-analysis for patients with early CKD (stage 1C3) showed no significant difference, either, between dual ACEI plus ARB combination therapy and monotherapy in reducing mortality risk or delay ESRD development.[7] However, investigation focusing on the safety and effectiveness of dual RAS blockade in advanced CKD patients, especially at pre-dialytic stage, is lacking. To bridge the gap in Phthalic acid the transition from CKD to ESRD, we assessed the association of the choice of treatment (dual RAS blockade monotherapy) with the risk of long-term dialysis and/or death in this nationwide, large cohort of patients with pre-dialytic stage-5 CKD who had hypertension and anemia, and were treated with ESAs. Materials and methods Data source The present study used data from Taiwans National Health Insurance (NHI) Research Database which was launched in 1995, managed and released to the public by the National Health Research Institute of Taiwan, and up to the present covers more than 99%, approximating 23 million, of the residents in Taiwan. This mandatory universal program offers all their medical records, including date of birth, sex, diagnostic codes, medical procedure and prescription of drugs. Diseases are coded according to the 2001 International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM). Any information that would.