Acute declines in kidney function with thiazide plus loop diuretics vs loop diuretics alone in acute decompensated...

The association between acute declines in estimated glomerular filtration rate (eGFR) among individuals admitted for acute decompensated heart failure (ADHF) and cardiovascular outcomes has been inconsistent. Our objective was to examine whether eGFR decline, and the timing of these declines, are associated with mortality and a composite outcome of mortality or heart failure (HF) hospitalization.

We used data from the CLOROTIC Trial, which randomized patients admitted for ADHF to thiazide versus placebo. We examined %eGFR change at 2-days (n = 225) and at 4-days (n = 218) after randomization. Multivariable Cox models were used to evaluate the association between % eGFR change and a primary outcome of mortality and secondary outcome of composite of mortality or HF hospitalization.

Median %eGFR change was -9.7% (IQR -22.1, 5.4) and -14.4% (-25.1, 7.8) in the thiazide arm at 2-days and 4-days respectively, compared to -0.3% (-7.5, 10.1) and 0% (-10.0, 16.2) in the placebo arm at 2-days and 4-days, respectively. Over a median 3-month follow-up, of those with 2-day eGFR change available, 41 (18%) patients died and 98 (44%) met the composite outcome, and of those with 4-day eGFR change available, 38 (17.4%) died and 95 (43.6%) met the composite outcome. The eGFR decline at 2-days was not associated with risk of mortality (HR = 0.96 [95% CI 0.47, 1.97] and HR = 0.89 [0.37, 2.10] per 30% eGFR decline in the thiazide and placebo arms, respectively). The eGFR decline at 4-days was not associated with risk of mortality in the thiazide arm (HR = 0.86 [0.48, 1.55] per 30% eGFR decline) nor in the placebo (HR = 1.63 [0.82, 3.26] per 30% eGFR decline). Associations were similar for the composite outcome.

Among patients admitted for ADHF and randomized to thiazide vs placebo, early acute declines in eGFR had no association with increased risk of cardiovascular outcomes.

Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36.