Spironolactone reduces estimated glomerular filtration rate (eGFR) soon after initiating treatment, but mineralocorticoid receptor antagonists (MRA) may prevent longer-term decline in eGFR. We studied the effect of spironolactone (compared to usual care) on eGFR changes and its biomarker correlations in 527 people at risk of developing heart failure enrolled in the HOMAGE trial. eGFR was determined at baseline, one and nine months. Compared to usual care, spironolactone reduced eGFR from baseline to month one: -3 (-4 to -2) ml/min/1.73m2, P <0.001 (corresponding to a -4% change on average). Spironolactone caused no further reduction in eGFR from month one to month nine: -1 (-3 to 0) ml/min/1.73m2, P=0.085. eGFR decrease between baseline and one month was positively correlated with brain natriuretic peptide and kidney injury molecule 1. Thus, spironolactone induces a small, early eGFR decrease without evidence of renal tubular injury, suggesting an early hemodynamic effect.