The effects of chlorthalidone and furosemide on serum creatinine in Thai patients with stage 4 and 5 chronic kidney disease: Retrospective cohort study.

Abstract

Chlorthalidone has been shown to lower blood pressure in CKD stages 4–5 but may raise serum creatinine (SCr), particularly when combined with furosemide. Data in Asian populations remain limited. This retrospective cohort study, conducted at Ramathibodi Hospital, included patients with stage 4-5 CKD who were recruited between April 1, 2021 and December 31, 2022 and followed until January 31, 2024. From 904 screened patients, 30 participants receiving chlorthalidone were enrolled and categorized into three groups: (1) chlorthalidone with unchanged furosemide dose (n=8), (2) chlorthalidone with reduced or discontinued furosemide (n=8), and (3) chlorthalidone without furosemide (n=14). The primary endpoint was an increase in SCr >25% from baseline. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and adverse events, followed for up to 18 months. At baseline, mean eGFR was 22 ± 7 mL/min/1.73 m² and mean SCr was 2.6 ± 1.4 mg/dL. Group 1 showed the largest rise in SCr, with a 168.8% median increase (from 3.57 to 6.37 mg/dL) at 18 months and 100% (4/4) experiencing an SCr rise >25%. Group 2 maintained stable renal function with median SCr decreasing slightly from 1.79 to 1.73 mg/dL Group 3 had a mild upward median SCr from 1.94 to 2.41 mg/dL with 75% experiencing an SCr increase >25% in both groups. Adverse events occurred in 88%, 63%, and 86% of patients in Groups 1, 2, and 3, respectively. Concomitant chlorthalidone with unchanged furosemide accelerated renal function decline, whereas reducing or discontinuing furosemide appeared more protective. Careful adjustment of diuretic regimens may mitigate risk when combining these agents. However, larger prospective studies are warranted.