Aims: This study aimed to explore the effect of discontinuation of long-term spironolactone treatment on markers of kidney function in individuals with type 2 diabetes (T2D) at high risk of kidney disease enrolled in the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study.
Materials and methods: An observational study following the nested randomised part of the PRIORITY study was conducted. A total of 115 individuals with T2D and normoalbuminuria but high risk for progression based on urinary proteomics, randomised to daily spironolactone (n = 50) or placebo (n = 65) for a median of 2.5 years, were re-examined approximately 6 weeks after the final visit in the PRIORITY study. Primary endpoint was relative change in geometric mean of urinary albumin-creatinine ratio (UACR) between the final visit in PRIORITY (baseline) and follow-up. Secondary endpoints were change in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP) and serum potassium.
Results: No change in UACR was observed in neither the spironolactone (geometric mean change: 17%; 95% CI -12, 55; p = 0.28) nor the placebo (5%; 95% CI -13, 26; p = 0.63) group at follow-up. No difference in UACR between the groups was observed at follow-up (relative difference in geometric mean: 11%, 95% CI -26, 67; p = 0.60). For eGFR and SBP, an increase after discontinuation of spironolactone was observed, as well as for SBP after placebo discontinuation. Potassium levels were lower after discontinuation of spironolactone, but higher after placebo discontinuation (all p < 0.05).
Conclusions: UACR did not change after discontinuation of long-term treatment with spironolactone. However, an increase in eGFR was observed supporting a haemodynamic effect of spironolactone in the kidneys.
Keywords: chronic kidney disease; diabetes complications; drug mechanism; observational study; type 2 diabetes.
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