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Updated: Mar 2, 2026
Robot-Assisted Kidney Transplantation
Published on: July 19, 2021
Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft
Mara Medeiros1,2, Luis Velásquez-Jones2, Ana M Hernández1
1Nephrology and Mineral Metabolism Research Unit.
Background And Objectives:
We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN).
Design, Setting, Participants, & Measurements:
Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1.73 m2 were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (n=10) or eplerenone 25 mg/d for 24 months (n=13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months.
Results:
The baseline eGFR was 80±6 in the placebo and 86±6 ml/min per 1.73 m2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m2, respectively (P=0.33; 95% confidence intervals, -18 to 33 at baseline, and -11 to 40 after 24 months). The albumin-to-creatinine ratio was 110±74 in the placebo, and 265±140 mg/g in the eplerenone group; and after 24 months it was 276±140 and 228±88 mg/g, respectively (P=0.15; 95% confidence intervals, -283 to 593, and -485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group.
Conclusions:
Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.
Insights
Mineralocorticoid receptor blockade (MRB) with eplerenone showed potential in preventing chronic allograft nephropathy (CAN) progression in pediatric kidney transplant recipients. Further studies are needed to confirm these promising findings in this population.
Area of Science:
- Nephrology
- Transplantation immunology
- Pharmacology
Background:
- Mineralocorticoid receptor blockade (MRB) has shown efficacy in preventing cyclosporine-induced nephropathy in rats.
- Chronic allograft nephropathy (CAN) remains a significant challenge in pediatric renal transplantation.
- Investigating long-term effects of MRB in children with CAN is crucial for improving graft survival.
Purpose of the Study:
- To evaluate the long-term effect of eplerenone, a selective MRB, on renal allograft function in pediatric patients with biopsy-proven CAN.
- To assess the impact of eplerenone on markers of kidney injury and fibrosis progression.
Main Methods:
- A randomized, placebo-controlled trial involving pediatric renal transplant recipients with biopsy-proven CAN.
- Patients received either eplerenone (25 mg/d) or placebo for 24 months.
- Glomerular filtration rate (GFR), albumin-to-creatinine ratio, and urinary biomarkers (HSP72, KIM-1) were monitored. Kidney biopsy analysis for tubulo-interstitial fibrosis (TIF) and glomerulosclerosis was performed.
Main Results:
- While not statistically significant due to underpowering, the eplerenone group showed a trend towards better preservation of GFR compared to placebo at 24 months.
- The eplerenone group exhibited lower levels of tubulo-interstitial fibrosis (TIF), glomerulosclerosis, and urinary heat shock protein 72 (HSP72) compared to the placebo group.
- Albumin-to-creatinine ratio did not show significant differences between groups.
Conclusions:
- Long-term eplerenone administration may attenuate the progression of chronic allograft nephropathy in pediatric kidney transplant patients.
- This study, despite being underpowered, provides a rationale for further investigation of MRB in this specific pediatric population.
- Eplerenone demonstrates a potential role in managing CAN, warranting larger, powered trials.
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