Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study)

Abstract

Background The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. Methods We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0–10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m 2 , and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. Results Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 ( P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP − 8.32 ± 11.42/− 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP − 9.57 ± 12.08/− 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP − 2.38 ± 7.82/− 1.17 ± 5.39 mmHg ( P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. Conclusions In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018. Electronic supplementary material The online version of this article (10.1186/s12933-019-0912-3) contains supplementary material, which is available to authorized users.

Exercise-induced albuminuria increases over time in individuals with impaired glucose metabolism

“…A reduction in albuminuria is related to favorable cardiovascular and renal outcomes, especially in patients with diabetes [26][27][28]. While novel treatment strategies for cardio-renal outcomes such as SGLT-2 inhibitors are effective in lowering rest albuminuria [29,30], their effect on exercise induced excretion of albumin is not entirely clear. We suggest that monitoring exercise induced levels of albuminuria may serve as a screening tool for pre-diabetic and diabetic individuals who require early initiation of such renal protective therapies [31,32].…”

Possible Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Reducing Effects of Blood Glucose and also Blood Pressure

“…Patients with Type 2 Diabetes Study (Y-AIDA Study) [10]. As the results of 85 patients for home blood pressure on 24 weeks later, changes in the morning, evening, and nocturnal home BP showed -8.3/-4.2 mmHg, -9.6 /-4.5 mmHg, -2.4/-1.2 mmHg (all p>0.05).…”

“…In the former, renal protective effect was examined in cases of renal function deterioration, where the degree of blood pressure reduction was lower compared with that of CANVAS. From these results, the usefulness of SGLT-2i for BP control would be considered [10,18]. The degree of BPlowering effect was not so large.…”

“…As the results of 85 patients for home blood pressure on 24 weeks later, changes in the morning, evening, and nocturnal home BP showed -8.3/-4.2 mmHg, -9.6 /-4.5 mmHg, -2.4/-1.2 mmHg (all p>0.05). In addition, the reduction in urine albuminto-creatinine ratio (UACR) has a significant correlation with the BP improvement profile [10].…”

“…Carbohydrate load increases the risk of non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and dyslipidemia. SGLT2i has been reported to have the function of lowering blood sugar in diabetes and also lowering blood pressure [10]. In this article, a general overview of SGLT2i and the effect on blood pressure would be described.…”