The effects of long term eplerenone treatment in pediatric renal transplant patients
Esra Baskin1, Kaan Gulleroglu1, B. Handan Ozdemir2, Aysun Caltik Yilmaz1, Ebru H. Ayvazoglu Soy3, Gokhan Moray3, Mehmet A. Haberal3.
1Pediatric Nephrology, Baskent University, Ankara, Turkey; 2Pathology, Baskent University, Ankara, Turkey; 3Transplantation, Baskent University, Ankara, Turkey
Introduction: Experimental and clinical data strongly suggest that mineralocorticoid receptor (MCR) antagonists prevents acute kidney injury, proteinuria and progressive renal disease. However, there is little information about this approach in renal transplant patients. Eplerenone is a potent and high selective MCR antagonist. In this study we aimed to investigate the effect of long-term eplerenone administration in children with chronic allograft dysfunction.
Patients and Methods: Twenty-five of 165 renal transplant children with biopsy-proven chronic allograft dysfunction and GFR>40 ml/min per 1.73 m2 were included to the study. All patients had significant proteinuria and who were under treatment with enalapril plus losartan. Eight patients received additional 25 mg/day eplerenone for 3 years (Group 1), 17 patients did not receive eplerenone (Group 2). Patients were examined in the renal transplant outpatient clinic every 2 week for the first month and once a month thereafter. At each visit, a complete clinical examination was performed and serum creatinine, electrolytes, transaminases, complete blood cell count, and urinalysis, spot urine protein- creatinine ratio were measured. Kidney biopsy samples were evaluated at baseline and after 36 months. The outcomes and laboratory findings of patients in group 1 and 2 were compared.
Results: Twenty-five children were analyzed. There was 8 patients (F/M:7/1) in group 1, and 17 patients in group 2. Mean age at the time of transplantation was 11.2±4.8 years in group 1and 13.4±4.3years in group 2(p>0.05). There were no differences in age, sex, type of immunosuppression, donor type, follow-up time and acute cellular rejection episode. Serum potassium levels were similar between groups, eplerenone did not alter them. At the beginning of the study, both groups displayed similar serum creatinine levels (1.47±0.5 mg/dl in group 1, versus 1.09±0.4 mg/dl in group 2, P=0.68). At 36 months mean serum creatinine level had significantly higher in Group 2 than in the eplerenone group, (2.8±0.9 mg/dl versus 2.05±0.71 mg/dl respectively (P=0.04). The baseline eGFR was similar in both groups (60.7 ±17.9 versus 71.9±14 ml/min per 1.73 m2, p>0.05). At 36 months eGFR stayed stable level in group1, but significantly decreased in group 2(57.1±8.2 and 44.3±11.4 ml/min per 1.73 m2 respectively). The spot urine protein-creatinine ratio decreased from 2.3±0.4 to 1.2±0.6 in group1 at 36 month. In contrast this ratio increased significantly from1.9±0.9 to 3.8±0.8 in group 2(p<0.05)
Conclusions: Our study showed that the long-term eplerenone administration decreased proteinuria and attenuates the progression of chronic allograft dysfunction in selected pediatric transplant patients. Further studies are needed for determining the potential benefit of MCR antagonists in this pediatric patients.
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