Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease: A...

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Early-stage chronic kidney disease (CKD) is associated with increased cardiovascular risk.
• Spironolactone has shown potential in reducing cardiovascular complications, but its specific effects on cardiac and vascular remodeling in CKD require further investigation.
• Previous studies suggest spironolactone may reduce left ventricular mass and arterial stiffness, but the mechanisms are not fully understood.

Purpose of the Study:

• To compare the efficacy of spironolactone versus chlorthalidone in reducing left ventricular mass and arterial stiffness in patients with nondiabetic stage 2 and 3 CKD.
• To evaluate the effects of spironolactone and chlorthalidone on blood pressure and renal function in this patient population.
• To assess the safety profiles of spironolactone and chlorthalidone, including the incidence of hyperkalemia and decline in estimated glomerular filtration rate (eGFR).

Main Methods:

• A prospective, randomized, open-label, blinded end-point study was conducted in four UK centers.
• 154 participants with nondiabetic stage 2-3 CKD, on ACE inhibitor or ARB therapy with controlled BP, were randomized to receive either spironolactone 25 mg or chlorthalidone 25 mg daily for 40 weeks.
• Left ventricular mass by cardiac MRI, office and 24-hour ambulatory BP, pulse wave velocity, and eGFR were assessed.

Main Results:

• No significant difference was observed in left ventricular mass regression between spironolactone and chlorthalidone at 40 weeks (adjusted mean difference -3.8 g, P=0.08).
• Both drugs similarly reduced office and 24-hour ambulatory blood pressure and pulse wave velocity.
• Hyperkalemia (≥5.4 mEq/L) occurred significantly more frequently with spironolactone (12 vs. 2 participants, adjusted RR 5.5, P=0.02), but no severe hyperkalemia (≥6.5 mEq/L) was reported. A decline in eGFR >30% was more frequent with chlorthalidone (8 vs. 2 participants, adjusted RR 0.2, P=0.07).

Conclusions:

• Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, blood pressure, or arterial stiffness in patients with nondiabetic CKD.
• Both agents demonstrated comparable efficacy in improving cardiovascular and hemodynamic parameters.
• Spironolactone was associated with a higher incidence of hyperkalemia, while chlorthalidone was associated with a trend towards more frequent declines in eGFR.