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CLINICAL STATEMENTS AND GUIDELINES September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e158 5.2.9 Kidney Dysfunction/Injury Synopsis Estimated GFR using serum creatinine should be measured 2 to 4 weeks after initiation or dose titration of antihypertensive medications. Renin-angiotensinaldosterone system inhibitor (RAASi) (including ACEi, ARB, and MRA) may lead to an expected reduction, or dip, in eGFR of up to 30% via vasodilation of efferent arterioles.1–3 This expected short-term dip in eGFR is associated with preservation of kidney function in the long-term4–10 and should not lead to discontinuation of the RAASi unless the decline in eGFR is persis tently >30%. A referral to a nephrologist is appro priate for evaluation for other causes of AKI, CKD progression, and possible renal artery stenosis. The presence of new kidney dysfunction/injury may also be observed with the addition or dose increase of diuretics. This should prompt evaluation of volume status to rule out hypovolemia and other possible causes of kidney dysfunction. It may be appropriate to initially hold or reduce the diuretic dose and then advance more slowly. 5.3 Comorbidities Synopsis Hypertension-related target organ damage describes adverse structural or functional changes in major organ Table 16. Pharmacokinetic Drug–Drug Interactions With Antihypertensive Medications Blood Pressure Drug Potential Interacting Drug Clinical Effect Absorption Thiazide-type diuretics Cholestyramine Decreased absorption leading to reduced BP lowering Amlodipine, furosemide, metoprolol, carvedilol, bisoprolol, nebivolol, telmisartan Potassium binder (patiromer) Decreased absorption of antihypertensives leading to reduced BP-lowering effects. To mitigate this, administer the antihypertensives at least 3 h before or after taking the potassium binder Furosemide Potassium binder (sodium zirconium cyclosilicate) Increased absorption of furosemide due to increased gastric pH leading to in creased clinical effects (eg, diuresis or risk of hypokalemia); effect diminished with separation of administration by 2 h Methyldopa Iron salts Decreased absorption of methyldopa leading to reduced BP lowering Metabolism Bisoprolol, carvedilol, metoprolol CYP2D6 inhibitors (eg, amiodarone, cimetidine, diphenhydramine, fluoxetine, paroxetine, terbinafine) Increased BB concentration leading to enhanced clinical effects (eg, hypo tension and bradycardia) Diltiazem, verapamil CYP3A4 inhibitors (eg, clarithromycin, erythromycin itraconazole, ketoconazole) Increased nondihydropyridine concentration leading to enhanced clinical ef fects (eg, hypotension and bradycardia) Diltiazem, verapamil CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, St. John’s Wort, rifampin) Decreased nondihydropyridine CCB concentration leading to reduced clini cal effects (eg, minimization of blood pressure and pulse lowering) CYP3A4 inhibition via amlodipine, verapamil, or diltiazem or other CYP3A4 inhibitors Tacrolimus, cyclosporine Increased calcineurin inhibitor concentration leading to increased risk for side effects (eg, renal impairment) Dabigatran, rivaroxaban Increased concentration leading to increased risk for bleeding Atorvastatin, simvastatin Increased statin concentration leading to increased risk for side effects (eg, myopathy) Colchicine Increased colchicine concentration leading to increased risk for adverse ef fects (eg, neuromuscular toxicity) Eplerenone Increased risk of hypotension and hyperkalemia Using a lower dose of eplerenone when combined with diltiazem could be considered a productive interaction, as the inhibition of eplerenone’s metabo lism might allow for lower doses to be effective, reducing the risk of adverse effects while maintaining efficacy Elimination Thiazide-type diuretics, RAS blockers Lithium Reduced lithium clearance leading to increased lithium toxicity risk P-glycoprotein (P-gp) Verapamil via P-gp inhibition Dabigatran Reduced P-gp efflux of dabigatran leading to increased dabigatran levels, which results in a higher risk of bleeding Verapamil and carvedilol via P-gp inhibition Digoxin Reduced P-gp efflux of digoxin leading to increased digoxin levels, resulting in a higher risk of digoxin toxicity Modified with permission from Fravel et al.1 Copyright 2021 Springer Nature. BB indicates beta blocker; BP, blood pressure; CCB, calcium channel blocker; h, hour; and P-gp, P-glycoprotein. Downloaded from http://ahajournals.org by on October 7, 2026