Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy
Por:
Cruzado, JM, Poveda, R, Ibernon, M, Diaz, M, Fulladosa, X, Carrera, M, Torras, J, Bestard, O, Navarro, I, Ballarin, J, Romero, R, Grinyo, JM
Publicada:
1 nov 2011
Resumen:
Background. There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models.
Methods. We performed a pilot, randomized controlled trial to evaluate the efficacy and safety of low-dose sirolimus in patients with a high-risk IgA nephropathy. Twenty-three patients with a glomerular filtration rate (GFR) within 30-60 mL/min and/or proteinuria > 1 g/day were randomly assigned to low-dose sirolimus plus enalapril and atorvastatin (SRL group, n = 14) or enalapril plus atorvastatin (CONTROL group, n = 9). Primary composite end point was variation of haematuria, proteinuria and blood pressure. Secondary end points were isotopic GFR, renal histology evaluated by Oxford classification and safety parameters evaluated at 6 and 12 months.
Results. Primary end point improved significantly in the SRL group at 12 months. Regarding isotopic GFR, patients included in the CONTROL group lost 8 mL/min/1.73m(2), whereas those in the SRL arm improved 5 mL/min/1.73m(2) (P = 0.03). Proteinuria decreased similarly in both study groups. At 1 year, SRL treatment was associated with a significant reduction of mesangial and endocapillary proliferation, whereas glomerular sclerosis, tubular atrophy and interstitial fibrosis were similar. Sirolimus was well tolerated; all patients remained on therapy at 12 months.
Conclusion. The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.
Filiaciones:
Cruzado, JM:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Poveda, R:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Ibernon, M:
Satut Hosp Germans Trias & Pujol, Fundacio Inst Invest Ciencies, Dept Nephrol, Badalona, Spain
Diaz, M:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Fulladosa, X:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Carrera, M:
Hosp Univ Bellvitge, IDIBELL, Dept Pathol, Barcelona, Spain
Torras, J:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Bestard, O:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Navarro, I:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
Ballarin, J:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Romero, R:
Satut Hosp Germans Trias & Pujol, Fundacio Inst Invest Ciencies, Dept Nephrol, Badalona, Spain
Grinyo, JM:
Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Dept Nephrol, Barcelona, Spain
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