ACE and chronic kidney disease: Third, several prior studies limited the comparison between chlorthalidone and hydrochlorothiazide to their use as first-line agents,15,16 whereas they are recommended and commonly used as add-on therapy.4,5,6 Non–first-line thiazide use is particularly relevant in CKD, in which alternative agents, such as ACE inhibitors and ARBs, have well-established protective associations for the kidneys and are preferentially prescribed as first-line therapy.