Although thiazides are excreted by the kidney, no dose adjustment is recom- mended in patients with reduced GFR. As the GFR falls below , the ability of thiazides to over- come fluid retention is diminished, although their antihyper- tensive benefit may be preserved, at least according to small, short-term studies in humans.120 Most clinicians switch to a loop diuretic in patients with CKD 4, particularly if the BP is becoming resistant to therapy or edema becomes a problem. Drug combinations. Thiazides are often one of the first 2 or 3 drugs used for BP lowering in CKD, particularly if there is edema or if ACE-Is or ARBs have already been prescribed. Thiazides are known to potentiate the effect of other antihypertensive agents, particularly ACE-Is and and may also reduce the risk of hyperkalemia. The inclusion of thiazides in fixed-dose combinations with other antihypertensives is convenient for patients and may Loop diuretics. Furosemide (also called frusemide), bu- metanide, torsemide and ethacrynic acid are the most commonly used loop diuretics, with wide dose ranges and differing pharmacodynamics. In primary hypertension they are effective in the short term121 but less so than thiazides in the long term.115 Loop diuretics are particularly useful when treating edema and high BP in CKD 4 5 patients in addition or as an alternative to thiazide diuretics. Potassium-sparing diuretics. Triamterene and amiloride are usually avoided in patients with CKD because of the risk of hyperkalemia. They are less effective in reducing extra- cellular fluid volume than thiazides or loop diuretics. Aldosterone antagonists such as spironolactone and epler- enone are discussed separately, above. Beta-blockers Beta-blockers are one of the most extensively investigated class of agents, having been used to treat hypertension and CVD for over 40 years. 