Serum creatinine, blood urea nitrogen (BUN), uric acid (UA), albumin (Alb), hemoglobin (Hb), Ca, phosphate, and intact parathyroid hormone (iPTH) levels were measured at SRL Inc. Japan using standard clinical methods. Serum FGF23 level was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Kinos Laboratories International; Tokyo, Japan). This second-generation, 2-site, monoclonal antibody ELISA has previously been shown to recognise biologically active, intact FGF23 [24]. Serum α-Klotho level was also measured using an ELISA kit (Immuno-Biological Laboratories Co; Tokyo, Japan), consisting of a solid-phase sandwich ELISA using 2 kinds of highly specific antibodies [22]. All data are presented as mean ± SD. Single AZD1480 linear univariate correlations were evaluated by Pearson’s correlation Omipalisib manufacturer coefficient. Groups were compared using 1-way

analysis of variance, Dunnett tests, and χ2 tests as appropriate. Multiple regression Compound C solubility dmso analysis with soluble α-Klotho level as dependent variables was conducted using a stepwise forward selection method. The F values for the inclusion and exclusion of variables was set at 4.0. Statistical significance was defined as P < 0.05. All statistical analyses were performed using the JMP (Ver. 6) statistical package. Results Characteristics of the study population Baseline characteristics of the study population are presented in Table 1. This study included patients aged 16–89 years; the mean age was 63.8 ± 16.0 years. The mean DOK2 serum Hb concentration was 11.9 ± 2.0 g/dL, creatinine 2.0 ± 1.7 mg/dL, BUN 28.6 ± 17.2 mg/dL, UA 6.7 ± 1.9 mg/dL, Alb 4.1 ± 0.5 g/dL, Ca 8.9 ± 0.6 mg/dL,

phosphate 3.6 ± 0.9 mg/dL, and iPTH 88.7 ± 77.8 pg/mL. The primary cause of CKD was primary chronic glomerulonephritis in 28 % of patients, nephrosclerosis in 21 %, diabetic nephropathy in 10 %, and other types of diseases or unknown in 41 %. Patients were divided into the 5 CKD stages according to their eGFR. The characteristics of patients in each stage are presented in Table 1. Table 1 Baseline characteristics of the study population and each CKD stage Variables  Total  Stage 1 (eGFR ≥ 90) Stage 2 (90 > eGFR ≥ 60) Stage 3A (60 > eGFR ≥ 45) Stage 3B (45 > eGFR ≥ 30) Stage 4 (30 > eGFR ≥ 15) Stage 5 (15 > eGFR) Number 292 18 56 38 55 69 56 Male (n, %) 167 (57.2) 4 (22.2) 26 (46.2) 22 (57.9)* 35 (63.6)* 43 (62.3)** 37 (66.1)*,# Age (years) 63.8 ± 16.0 33.4 ± 14.8 56.9 ± 14.4** 64.6 ± 12.5**,# 68.7 ± 13.3¶ 69.8 ± 12.5†,¶ 67.6 ± 12.9¶ BMI (kg/m2) 23.2 ± 3.7 20.7 ± 1.9 23.1 ± 3.9* 22.5 ± 3.8 23.4 ± 3.3* 23.8 ± 3.8* 24.0 ± 3.9* Hypertension (%) 52.7 33.3 57.1 55.3 72.7* 49.5‡ 37.5#,‡‡ Hyperlipidemia (%) 29.5 16.7 35.7 39.5 32.7 30.4 16.1#,†,‡ Diabetes mellitus (%) 15.4 5.6 5.6 7.9 27.3 17.4 8.9† ALB (g/dL) 4.1 ± 0.5 4.2 ± 0.5 4.2 ± 0.5 4.2 ± 0.