Materials and Methods Patients and Laboratory Measurements The study design and population were previously described.6 Briefly, 338 patients with stage 3 to 5 CKD who were referred to the nephrology clinic at Taipei Tzu Chi Hospital, Taiwan between September 1, 2011, and December 31, 2012, were enrolled in the study and were followed until June 30, 2014. In all of the patients, a thorough medical history was taken and the medical chart was reviewed at the time of study enrollment. Diabetes mellitus was assumed to be present in patients who reported the current or past use of insulin and/or oral antidiabetic agents. Hypertension was defined on the basis of a blood pressure (BP) ≥140/90 mm Hg or current therapy for hypertension. The presence of CVD was defined as a medical history and clinical findings of congestive heart failure, coronary artery disease, as documented by coronary angiography or a history of myocardial infarction, and/or cerebrovascular disease. The primary outcome was the first occurrence of a decline in the estimated glomerular filtration rate (eGFR) ≥50% or ESRD needing chronic dialysis. The secondary outcome, morbidity and mortality from cardiovascular causes, was a composite of the first occurrence of myocardial infarction, hospitalization for congestive heart failure or unstable angina, or death from cardiovascular causes. Changes in the eGFR were confirmed at least 4 weeks after the treatment of potentially reversible factors. The timing of the initiation of chronic dialysis was determined according to the regulations of the National Health Insurance Administration of Taiwan. CVD deaths included fatal myocardial infarction, congestive heart failure, arrhythmia, and sudden death. The patients were followed every 3 months. For the primary outcome, patients were censored at the time of their last outpatient visit, death, or end of follow-up period, whereas for the secondary outcome, patients were censored at the time of their last outpatient visit, noncardiovascular death, or end of follow-up period. The study protocol was approved by the Institutional Review Board of Taipei Tzu Chi Hospital. Informed consent was obtained from all of the participants, and our study complies with the Declaration of Helsinki.
BP was measured by use of an automated oscillometric sphygmomanometry (Welch Allyn, Series 300). All of the study personnel were trained to use the device, to select an appropriately sized arm cuff, and to start the measurements after 10 minutes of rest with the subject having voided and being seated quietly in a straight-back chair with the arm at heart level. The plasma levels of interleukin 6 (IL-6), tumor necrosis factor a (TNF-a) (R&D Systems), and N-terminal probrainnatriureticpeptide(NT-proBNP)(RocheDiagnostics)were measuredbyusingcommerciallyavailableELISAkitsaccording tothemanufacturer’sinstructions.Theserumalbuminlevelwas determined by using a bromocresol purple (BCP) assay. Proteinuria was expressed as the ratio of urine protein to creatinine (UPCR) determined by using the first morning void.