RESUMO
BACKGROUND: Anemia associated with high mortality is a common complication of chronic kidney disease (CKD). Target hemoglobin (Hb) levels for CKD treatment remain controversial: Recent guidelines recommend a maximum of 13 g/dL to avoid increased risk of CVD. However, some smaller studies show slower progression of renal function loss with high Hb targets. Recently, darbepoetin alfa targeting Hb 11-13 g/dL was reported to improve renal composite outcome of Japanese patients compared with a low Hb group maintained at 9.0-11.0 g/dL using epoetin alfa (HR 0.66; 95% CI 0.47-0.93). The high Hb group showed significant reduction of left ventricular mass index and improved quality of life. Sub-analysis revealed greater beneficial effects in non-diabetic stage 5 CKD patients. This randomized controlled trial, PREDICT, aims to confirm the impact of targeting Hb levels of 11-13 g/dL using darbepoetin alfa with reference to a low Hb target of 9-11 g/dL. METHODS: We calculated the number of subjects (N = 440) necessary to detect a statistically significant level of α = 0.05 (two-sided) and statistical power of 80% for a minimum follow-up period of 2 years on the basis of a previous study. RESULTS: The study enrolled 498 non-diabetic Japanese patients with eGFR 8-20 mL/min/1.73 m(2). The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m(2) or less, 50% decrease in eGFR). Average follow-up period is 2 years and the study ends in 2016. CONCLUSION: PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD. (ClinicalTrials.gov No. NCT01581073).
Assuntos
Anemia/tratamento farmacológico , Darbepoetina alfa/uso terapêutico , Hematínicos/uso terapêutico , Hemoglobinas/metabolismo , Falência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Biomarcadores/sangue , Protocolos Clínicos , Darbepoetina alfa/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Hematínicos/efeitos adversos , Humanos , Japão , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Tamanho da Amostra , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
By using carbophilic Lewis acids, In(OTf)3, NiCl2, and AuCl(PPh3)/AgNTf2, a concise and efficient synthesis of 1,3-disubstituted 1,2-dihydroisoquinolines has been achieved via tandem nucleophilic addition and cyclization of 2-(1-alkynyl)arylaldimines. Addition of proton sources such as water, CF3CH2OH, and 2,6-di-tert-butyl-4-methoxyphenol was essential for the Lewis acid-catalyzed tandem reactions with organometallic reagents. By switching these catalysts, various types of nucleophiles such as allylstannanes, silyl enol ethers, alkenylboronic acids, and active methylene compounds could be introduced at the C1 position of 1,2-dihydroisoquinolines in this transformation. Furthermore, this method proved to be applicable to the synthesis of 1H-isochromene derivatives via the same tandem reaction of 2-(1-alkynyl)arylaldehydes.