Abstract
Introduction: Hypertension (HTN) is not uncommon in patients with chronic kidney disease (CKD). Thiazide diuretics (THZ) are widely used for the management of HTN. The clinical outcomes of THZ usage in patients with CKD remain uncertain. Hypothesis: The aim of this study is to examine the clinical effects of THZ usage in patients with CKD by utilizing a nationwide cohort. Methods: The THZ cohort included 8501 patients; each patient was age- and sex-matched with one THZ nonuser in the CKD population. The Cox proportional hazard regression analysis was conducted to estimate the effects of THZ on the mortality, incidence of end-stage renal disease (ESRD), congestive heart failure (CHF), acute myocardial infarction (AMI), peripheral arterial occlusive disease (PAOD) and stroke. Results: The mortality rate was significantly lower in THZ users than in THZ nonusers (hazard ratio [HR] = 0.65; 95% confidence interval [CI] = 0.60-0.71, p <0.001). The HR for the incidences of ESRD, AMI, PAOD and stroke were significantly ( p <0.05) lower in THZ users (HR=0.71, CI= 0.66-0.77; HR=0.82, CI=0.76-0.89; HR=0.68, CI=0.63-0.74; HR=0.91, CI=0.84-0.98) than in THZ nonusers. In THZ subgroup analysis, clothalidone users had significantly lower incidences of mortality, ESRD, and PAOD (HR=0.62, CI= 0.40-0.97, p =0.037; HR=0.54, CI=0.36-0.82, p =0.004; HR=0.60, CI=0.39-0.94, p =0.026) than nonusers. Indapamide users had significant lower incidences of mortality, ESRD, AMI and PAOD (HR=0.64, CI= 0.57-0.71, p <0.001; HR=0.72, CI=0.65-0.79, p <0.001; HR=0.89, CI=0.81-0.98, p =0.018; HR=0.69, CI=0.62-0.78, p <0.001) than nonusers. However, Metolazone users had significantly higher incidences of ESRD, CHF, and AMI (HR=1.28, CI= 1.06-1.54, p =0.009; HR=1.60, CI=1.33-1.92, p <0.001; HR=1.41, CI=1.08-1.59, p =0.007) than nonusers. Conclusions: In patients with CKD who receive therapy with THZ, both clothalidone and Indapamide users exhibit significantly beneficial effects of mortality, ESRD, and PAOD. Indapamide users revealed significantly advantageous results of AMI. However, Metolazone users had significantly higher incidences of ESRD, CHF, and AMI. A further randomized control trial to clarify the effect of THZ usage in patients with CKD is a necessity.
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