title: Early withdrawal of calcineurin inhibitors and rescue immunosuppression with sirolimus-based therapy in renal transplant recipients with moderate to severe renal dysfunction.
abstract: Mammalian Target-of-Rapamycin inhibitors (mTOR inhibitors) can be used to replace the calcineurin inhibitors (CNIs) to prevent progression in chronic kidney disease (CKD) following organ transplantation. Discontinuation of tacrolimus in 136 recipients of kidney transplants with progressive renal dysfunction significantly decreased the rate of loss of estimated glomerular filtration rate (eGFR, mL/min/1.73 m(2)) (pre-intervention vs. post-intervention slopes, -0.013 vs. -0.002, p < 0.0001). Discontinuation of tacrolimus was associated with a sustained and significant improvement in graft function (pre-eGFR vs. post-eGFR; 26.0 +/- 1.1 vs. 47.4 +/- 2.1, p < 0.0001) in 74% of patients. This intervention was ineffective if the mean and (median) values of creatinine (mg/dL) and eGFR were 3.8 +/- 0.2 (3.4) and 18.4 +/- 1.9 (22.4), respectively, at the time of conversion therapy. During the follow-up (range, 1.5-34.6, months), a total of 13 patients had their first acute rejection following the conversion therapy, an annual incidence of less than 10% and none of these episodes resulted in graft loss. The salutary effects of sirolimus therapy following discontinuation of tacrolimus in patients with moderate to severe graft dysfunction due to allograft nephropathy even in high-risk patients improves kidney function and prevents acute rejection.
authors.affiliation: Division of Nephrology, Department of Medicine, Unniversity of Maryland School of Medicine, Baltimore, MD, USA. rwali@medecine.umaryland.edu
authors.forename: R K
authors.initials: RK
authors.lastname: Wali
authors.forename: V
authors.initials: V
authors.lastname: Mohanlal
authors.forename: E
authors.initials: E
authors.lastname: Ramos
authors.forename: S
authors.initials: S
authors.lastname: Blahut
authors.forename: C
authors.initials: C
authors.lastname: Drachenberg
authors.forename: J
authors.initials: J
authors.lastname: Papadimitriou
authors.forename: M
authors.initials: M
authors.lastname: Dinits
authors.forename: A
authors.initials: A
authors.lastname: Joshi
authors.forename: B
authors.initials: B
authors.lastname: Philosophe
authors.forename: C
authors.initials: C
authors.lastname: Foster
authors.forename: C
authors.initials: C
authors.lastname: Cangro
authors.forename: J
authors.initials: J
authors.lastname: Nogueira
authors.forename: M
authors.initials: M
authors.lastname: Cooper
authors.forename: S T
authors.initials: ST
authors.lastname: Bartlett
authors.forename: M R
authors.initials: MR
authors.lastname: Weir
mesh_terms: D001706:Biopsy; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000276:immunology* / Q000517:prevention & control; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus