Effect of pioglitazone on serum FGF23 levels among patients with diabetic kidney disease: a randomized controlled trial.

AIM: Elevated fibroblast growth factor-23 (FGF23) is an established marker of cardiovascular disease among patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Recently, circulating FGF23 positively correlated with insulin resistance level among patients with CKD. Pioglitazone improves insulin sensitivity and it may have potential for treating CKD-related FGF23 overactivity. METHODS: A randomized, open-label, controlled trial was performed among patients with T2DM and CKD. Eligible participants were randomly assigned to either oral 15 mg/day of pioglitazone (N = 22) or control group (N = 24) for 16 weeks. Serum FGF23 and homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were measured. RESULTS: Forty-six patients completed the trial. After 16 weeks of treatment, significant decreases in serum intact FGF23 level (median change - 49.01 (IQR, - 103.51 to - 24.53) vs. 1.07 (IQR, - 22.4-39.53) pg/mL, P = 0.01) and HOMA-IR (mean change - 1.41 (95% CI, - 2.24 to - 0.57) vs. - 0.05 (95% CI, - 1.00-0.89), P = 0.031) were observed in the pioglitazone group compared with the control group. HemoglobinA1C also significantly decreased in the pioglitazone group compared with the control group. No difference was found in the changes of serum phosphorus, calcium and serum intact parathyroid hormone between the two groups. Changes of FGF23 were positively associated with changes of HOMA-IR (R = 0.47) and insulin levels (R = 0.47). No serious adverse event was reported during the study. CONCLUSION: This study confirmed that pioglitazone effectively reduced serum FGF23 levels and related to improved insulin sensitivity among patients with T2DM and CKD. CLINICAL TRIAL REGISTRATION: TCTR20210316009.

Arterial Stiffness Predicts Rapid Decline in Glomerular Filtration Rate Among Patients with High Cardiovascular Risks.

AIMS: Arterial stiffness is known to be an important surrogate marker for atherosclerosis and predictor of peripheral vascular and cardiovascular (CV) disease. Whether high cardio-ankle vascular index (CAVI) is associated with the development of rapid glomerular filtration rate (GFR) decline remains uncertain. The study aimed to determine the relationship between CAVI and renal function progression among patients with high CV risk. METHODS: This study employed a prospective cohort design with 1-year follow-up among patients with high CV risk. Arterial stiffness was measured using CAVI method. GFR was estimated using the chronic kidney disease (CKD) epidemiology collaboration equation, and rapid decline in GFR was defined with decrease in GFR ≥ 5 mL/min/1.73 m2 yearly. RESULTS: Of 352 patients with mean age 67.8±10.1 years, 224 patients (63.6%) were suspected to have arteriosclerosis (CAVI ≥ 9), and 208 patients (59.1%) had CKD (GFR ＜60 mL/min/1.73 m2). Annual decline of GFR was -0.75 [interquartile range (IQR), -1.16 to 6.08] mL/min/1.73 m2/year, and 30.1% of patients experienced a rapid decline in GFR. Compared with normal CAVI (CAVI ＜8), high CAVI (CAVI ≥ 9) and borderline CAVI (CAVI 8-8.9) in all subjects and subgroup of baseline GFR ＞60 mL/min/1.73 m2 were associated with rapid GFR decline. Multivariable analysis showed that high CAVI and borderline CAVI were associated with 2.47-fold (95% CI, 0.89-6.84; P=0.082) and 4.04-fold (95% CI, 1.46-11.18; P=0.007) increased odds ratio of rapid GFR decline, respectively. CONCLUSION: Among patients with high risk of CV with or without CKD, high CAVI (cut point of ≥ 9) was independently associated with a rapid decline in GFR, suggesting that systemic vascular stiffness predicted a decrease in renal function in this population.