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Mineralocorticoid receptor blockade reduced oxidative stress in renal transplant recipients: a double-blind,
Marcos Ojeda-Cervantes1, Jonatan Barrera-Chimal, Josefina Alberú
1Nephrology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Background:
Previous experimental studies from our laboratory have demonstrated that aldosterone plays a central role in renal ischemic processes. This study was designed to evaluate the effect of mineralocorticoid receptor blockade in renal transplant recipients from living donors.
Methods:
20 adult kidney transplant recipients from living donors were included in a double-blind, randomized, placebo-controlled clinical pilot study that compared spironolactone and placebo. Placebo or spironolactone (25 mg) was administered 1 day before and 3 days posttransplantation. Renal function and urinary kidney injury molecule-1, interleukin-18, and heat shock protein 72 as well as urinary hydrogen peroxide (H2O2) levels were quantified.
Results:
No significant differences were seen between the groups studied regarding age, gender, indication for kidney transplantation, residual renal function, renal replacement therapy, or warm and cold ischemia periods. In contrast, spironolactone administration significantly reduced the oxidative stress assessed by the urinary H2O2 excretion, in spite of no differences in renal function or reduction in tubular injury biomarkers.
Conclusions:
The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H2O2 as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.
Insights
Mineralocorticoid receptor blockade with spironolactone reduced oxidative stress in kidney transplant recipients. This study suggests aldosterone promotes oxidative stress, and spironolactone mitigates it by reducing reactive oxygen species formation post-transplant.
Area of Science:
- Nephrology
- Transplantation immunology
- Cardiovascular endocrinology
Background:
- Aldosterone is implicated in renal ischemia.
- Mineralocorticoid receptor blockade's role in kidney transplantation requires further investigation.
Purpose of the Study:
- To evaluate the effect of mineralocorticoid receptor blockade using spironolactone in renal transplant recipients from living donors.
Main Methods:
- A double-blind, randomized, placebo-controlled pilot study involving 20 adult kidney transplant recipients.
- Administration of spironolactone (25 mg) or placebo pre- and post-transplantation.
- Quantification of renal function, urinary biomarkers (kidney injury molecule-1, interleukin-18, heat shock protein 72), and urinary hydrogen peroxide (H2O2).
Main Results:
- No significant differences in patient demographics or transplant characteristics between groups.
- Spironolactone significantly reduced urinary H2O2 excretion, indicating decreased oxidative stress.
- No significant differences in renal function or tubular injury biomarkers were observed.
Conclusions:
- Aldosterone appears to promote oxidative stress in the context of renal ischemia-reperfusion.
- Spironolactone administration effectively reduces oxidative stress, as evidenced by decreased urinary H2O2 levels.
- This suggests a potential therapeutic role for spironolactone in mitigating ischemia-reperfusion injury in kidney transplantation.
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