title: Sirolimus attenuates the rate of progression of early chronic allograft nephropathy.
abstract: Optimal treatment for patients with chronic allograft nephropathy (CAN) is not known. Early intervention is preferred. We examined the benefit of adding sirolimus (SRL; C(0) 5-12 ng/mL: HPLC) on the rate of progression of early CAN. We identified patients with biopsy-confirmed Banff grade 1 CAN. After biopsy, patients were switched to SRL + CsA + prednisolone (SRL), MMF + CsA + prednisolone (MMF), or CsA + AZA + prednisolone (AZA). GFR was estimated by Cockcroft-Gault and MDRD formulae. The rate of GFR decline (delta GFR) was determined by calculating the slope of the regression line of estimated GFR (MDRD and Cockcroft-Gault method) at different times. Statistical analysis was performed by the Wilcoxon test. The 41 patients with CAN grade 1 were assigned to SRL: MMF: AZA = 12: 20: 9. Before biopsy; the graft age for SRL: MMF: AZA were 56 +/- 27: 70 +/- 48: 51 +/- 36 months; and the GFR (MDRD method), 38 +/- 8: 42 +/- 15: 36 +/- 14 mL/min; GFR (C-G method) 45 +/- 13, 42 +/- 12, 41 +/- 15 mL/min; trough CsA levels 152 +/- 36: 145 +/- 46: 177 +/- 61 ng/dL; delta GFR (MDRD method) -0.18 +/- 0.20: -0.15 +/- 0.59: -0.20 +/- 1.08; delta GFR (C-G method) -0.13 +/- 0.37: -0.19 +/- 0.24: -0.65 +/- 0.99. Follow-up time for SRL: MMF: AZA was 19 +/- 4: 35 +/- 32: 59 +/- 54 months. At last follow-up; GFR (MDRD method) for SRL: MMF: AZA were 39 +/- 13: 35 +/- 21: 40 +/- 24 mL/min; GFR (C-G method) 46 +/- 17, 37 +/- 18, 46 +/- 25 mL/min; BP 128 +/- 11/79 +/- 7: 131 +/- 22/80 +/- 14: 132 +/- 20/82 +/- 11 mm Hg; and CsA level 52 +/- 25: 122 +/- 41: 155 +/- 49. After biopsy, statin was prescribed in nine SRL, 10 MMF, and three AZA. ACEI was prescribed in two SRL, three MMF, and two AZA. Compared with the prebiopsy values, the delta GFR (MDRD method) changed to -0.04 +/- 0.31 (SRL; P = .04), -0.17 +/- 0.40 (MMF; P = .60), and -0.97 +/- 1.52 (AZA: P = .16). Delta GFR (C-G method) was also significantly improved in the SRL group (-0.02 +/- 0.47; P = .05) but not in the MMF (-0.13 +/- 0.51; P = .53) or AZA (-0.54 +/- 1.78; P = .44). We concluded that patients with early CAN who are switched to SRL and low-dose CsA have a significant attenuation of the rate of GFR declination when compared with patients who receive MMF or AZA addition.
authors.affiliation: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. ravsm@mahidol.ac.th
authors.forename: V
authors.initials: V
authors.lastname: Sumethkul
authors.forename: S
authors.initials: S
authors.lastname: Changsirikulchai
authors.forename: T
authors.initials: T
authors.lastname: Lothuvachai
authors.forename: P
authors.initials: P
authors.lastname: Chalermsanyakorn
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D001706:Biopsy; D001794:Blood Pressure; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus