In:
Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 8 ( 2017-8), p. 1291-1300
Abstract:
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 m 2 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 m 2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m 2 , 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.
Type of Medium:
Online Resource
ISSN:
1555-9041
,
1555-905X
DOI:
10.2215/CJN.05300516
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2216582-4
detail.hit.zdb_id:
2226665-3
