The basic research protocol of the iDIC Study
The present study was planned as a prospective multi-center cohort study in a specific region, Ibaraki Prefecture, called the Ibaraki Dialysis Initiation Cohort Study, iDIC Study. Sixty tertiary care institutions (universities, referring hospitals and dialysis clinics; see Appendix) participated in this cohort study, enrolling consecutive patients with newly initiated dialysis and following each patient for 24 months. The inclusion criteria of this study were first, consecutive patients with newly initiated dialysis at each participating institute from January 2013 to December 2015; second, patients who needed continuous maintenance dialysis at each participating institute. As the outcome assessment, the primary outcomes of this study were all-cause, cardiovascular and infection-related mortality after dialysis initiation; the secondary outcomes were the rates of admission caused by infection, malignancy and cardiovascular and arteriovenous fistula-related events. In conducting the cohort study, we followed the Declaration of Helsinki and the Ethical Guidelines for Epidemiological Research in Japan. Written informed consent was obtained from each participant for participation, publication, availability of data and materials, and the study protocol was approved by the ethics committee at each participating hospital (the main institute being the University of Tsukuba Hospital, H24-116). This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000010806). Patient clinical records and blood and urine samples were collected at baseline. The chief investigators of this cohort (KY), the officer of the research center (JU) and investigators at the top 5 institutes in terms of enrollment numbers (IE, TI, MK, YM, HK) comprised the study’s steering committee.
The diagnosis of primary diseases
The primary cause of ESKD in each participant, e.g., diabetic nephropathy, chronic glomerulonephritis and hypertensive nephrosclerosis, was diagnosed on the basis of medical history and renal biopsy. As the standard clinical practice, the clinical diagnosis of diabetic nephropathy was based on the following criteria: first, the duration of diabetes for 10 years or more, the confirmation of diabetic retinopathy, typically neo-vascular proliferative lesion, and neuropathy, typically sensory disorders of the distal portion of limbs; third, the observation of overt proteinuria, typically nephrotic syndrome; fourth, the exclusion of other primary causes, such as primary glomerulonephritis, other secondary glomerulonephritis including collagen disorder or vasculitis, hereditary kidney disease, cystic kidney disease and drug-induced kidney injury and so on. The clinical diagnosis of hypertensive nephrosclerosis was based on the following criteria: first, the duration of hypertension 10 years or more; second, the lack of overt proteinuria; third, the confirmation of hypertensive retinopathy; fourth, the exclusion of other primary causes, such as primary glomerulonephritis, other secondary glomerulonephritis including diabetic nephropathy, collagen disorder or vasculitis, hereditary kidney disease, cystic kidney disease, drug-induced kidney injury and so on.
Baseline characteristics and comorbidities
Clinical information and laboratory data were collected at study entry via a uniform questionnaire. Baseline information included age, gender, primary cause of ESKD, renal histological diagnosis, complications including diabetes [The International Classification of Diseases, Tenth Revision (ICD-10) codes E10 to E14] and hypertension (ICD-10 codes I10 to I15), prior history of cardiovascular disease and malignancy, kidney disease in family, regular medical checkup, health insurance, motive for consultation, duration between the referral and dialysis initiation, estimated glomerular filtration rate (eGFR) value at 3 time points just before dialysis initiation, duration between operation of arteriovenous fistula to dialysis initiation, and method of continuous dialysis treatment (hemodialysis, peritoneal dialysis or both). Physical status at the baseline included height, body weight, body mass index, blood pressure and daily urine volume. The laboratory data included (from blood) hemoglobin, hematocrit, urea nitrogen, creatinine, albumin, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, hemoglobin A1c, glucose, uric acid, calcium, phosphate, beta 2-microgloblin, intact-parathyroid hormone, whole-parathyroid hormone and (from urine) protein, blood, urea nitrogen and creatinine. Medication categories at dialysis initiation included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, statins, anti-platelet drugs including aspirin, active vitamin D analogues, erythropoiesis-stimulating agents, insulin and other anti-diabetic agents. Prior treatments for primary glomerulonephritis included glucocorticoids, immunosuppressive reagents and tonsillectomy. The qualitative data were reported as number of cases and rate (%). The quantitative data were written as mean value ± standard deviation (SD).