Conversion From Calcineurin Inhibitor to Either Mycophenolate Mofetil or Sirolimus Improves Renal Function in Liver Transplant Recipients With Chronic Kidney Disease: Results of a Prospective Randomized Trial

• Published in: Transplantation proceedings Vol. 42; no. 10; pp. 4441 - 4448
• Main Authors: Herlenius, G, Felldin, M, Nordén, G, Olausson, M, Bäckman, L, Gustafsson, B, Friman, S
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01-12-2010; Elsevier
• Subjects: Adult; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Calcineurin Inhibitors; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glomerular Filtration Rate; Humans; Hypertension - complications; Hypertension - drug therapy; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Kidney - physiopathology; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - physiopathology; Kidneys; Kirurgi; Liver Transplantation; Medical sciences; MEDICIN; MEDICINE; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - adverse effects; Mycophenolic Acid - analogs & derivatives; Nephrology. Urinary tract diseases; Prospective Studies; Sirolimus - administration & dosage; Sirolimus - adverse effects; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Urinary system involvement in other diseases. Miscellaneous; Antineoplastic agent; Mofetil; Graft(material); Mycophenolic acid; Renal function; Calcineurin inhibitor; Sirolimus; Liver; Transplantation; Homotransplantation; Kidney; Macrocycle; Result; Prospective; Improvement; Randomization; Surgery; Antiviral; Clinical trial; Graft; Protein synthesis inhibitor; Kidney disease; Urinary system disease; Digestive system; Enzyme; IMP dehydrogenase; Enzyme inhibitor; Lactone; Chronic kidney disease; Macrolide; Conversion; Immunomodulator; Drug conversion; Antibiotic; Treatment; Urinary system; Renal failure; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Antibacterial agent
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2010.09.113

Abstract Background Chronic kidney disease (CKD) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD. CNI discontinuation or minimization protocols with replacement of the CNI with non-nephrotoxic drugs, such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to preserve or recover renal function. Patients and Methods In this prospective, randomized, single-center study with CNI discontinuation, OLT recipients with CKD (measured glomerular filtration rate [GFRm] 15–45 mL/min/1.73 m2 ) were randomized to either SRL or MMF-based immunosuppression. The main objective was to study the effect of CNI discontinuation on renal function. Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline, 3 months, and 1 year. Patients were stratified according to baseline GFRm > versus <30 mL/min/1.73 m2 . The 25 patients were enrolled for MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25–66) and the median number of years after OLT was 4.4 (range, 1–13). Twenty-two patients were followed up for a year; MMF (n = 12) and SRL (n = 10). Results Mean GFRm for the whole cohort (n = 25) was 31+/−8 mL/min/1.73 m2 at baseline. After 3 months the GFRm (n = 23) increased to 40+/−10 mL/min/1.73 m2 ( P = .0001) and at 1 year 42 +/− 11 mL/min/1.73 m2 (n = 22). There was not significant difference between the MMF and the SRL study arms. The cohort (n = 8) with baseline GFRm <30 mL showed a 63% ( P = .003) increased filtration after 1 year. There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm, both probably unrelated to the change in immunosuppression. There were no BPAR episodes. Conclusion CNI discontinuation and replacement with either MMF or SRL resulted in a significant improvement in renal function even in those patients with severe CKD. The protocol was effective with no acute rejection episodes. The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia. Future studies addressing long-term renal function after CNI discontinuation are needed.