The efficiency of dapagliflozin as add-on therapy in obese patients with resistant hypertension and chronic kidney disease
Authors: Obertynska O 
Published: October 2021

Abstract

Background
Obesity, insulin resistance, renal dysfunction, hyperuricemia are some of the most common causes of resistant hypertension (RH). A close relationship exists between RH and fluid retention. Currently, there is no consensus regarding pathogenetic therapy of RH and there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors in obese patients with RH and chronic kidney disease (CKD).
The aim was to evaluate the effects of dapagliflozin (D) in obese P with RH and CKD stages 3a.

Methods
45 obese P (mean body mass index (BMI) 34.2 kg/m2, waist circumference (WC) 104 cm) with true RH and CKD 3a (eGFR 45–59 mL/min/1.73m2) were included in the study under conventional therapy full doses of appropriate combinations (mean 3.7 antihypertensive drugs). The D at daily doses of 10 mg was added to previous treatment. The blood pressure (BP) was measured in the office and by ambulatory BP monitoring. Anthropometry, metabolic profile, including oral glucose tolerance test with insulin, homeostatic model assessment HOMA-R, hematocrit (Hct), uric acid, potassium (K), serum creatinine, calculated GFR were performed at baseline and after 12 weeks treatment.

Results
At baseline were excellent correlations between BMI and SBP (r=0.45, P&lt;0.01), eGFR and DBP (r=−0.33, P&lt;0.05), eGFR and Hct (r=0.31, P&lt;0.05), BMI and HOMA-R (r=0.34, P&lt;0.05). At baseline mean HOMA-R was 2,8±0.7, eGFR 53.50±3.26 ml/min/1.73 m2, uric acid 469±23 nmol/L, K 4,9±0.9 mmol/L. The asymptomatic hyperuricemia was observed in 57%, impaired glucose tolerance in the 37%.
After 12 weeks administration of D, the mean 24 h ambulatory BP effectively decreased (−7.6/−4.3 mmHg; P&lt;0.05 for both; respectively. Also, there were significant decreases in BMI (−2,1 kg/m2, P&lt;0.01), WC (−4,8 cm, P&lt;0.01), fasting glucose (−0,8 mmol/L, P&lt;0.01) and uric acid (−42 nmol/L, P&lt;0.01) without changes in insulin secretion and not significant improvement in HOMA-R (2,8±0.7 versus 2.4±0.4). Mean eGFR and K on D remained unchanged, however, the albumin/creatinine ratio decreased significantly (P&lt;0.05). Also, the Hct significantly increased after start of D (P&lt;0.01).
By linear regression analysis, the independent associated factor for the change SBP was baseline BMI (P&lt;0.05) and for the change DBP baseline eGFR (P&lt;0.05).

Conclusion
Dapagliflozin shows an additional antihypertensive effect when added to the prior combination therapy in obese patients with RH and CKD 3a without risk of hyperkalemia. Dapagliflozin increase hematocrit, possibly due to its diuretic effects and hemoconcentration. So, positive antihypertensive effect D is due to natriuretic effect and decrease fluid retention. Furthermore, there is also a strong indication that the BP effect is also influenced by weight loss and dapagliflozin administration decreased body mass index, waist circumference, fasting glucose and uric acid, with a tendency to decrease the insulin resistance without changes in insulin secretion.

Funding Acknowledgement
Type of funding sources: None.