Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients – assessment of renal and allograft function, cardiovascular risk factors and immune monitoring

• Published in: Alimentary Pharmacology and Therapeutics 2007-11, Vol.26 (9), p.1195-1208
• Main Authors: CICINNATI, V. R., YU, Z., KLEIN, C. G., SOTIROPOULOS, G. C., SANER, F., MALAGÓ, M., FRILLING, A., GERKEN, G., BROELSCH, C. E., BECKEBAUM, S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Calcineurin Inhibitors; Cardiology. Vascular system; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Creatinine - blood; Digestive system; Drug Therapy, Combination; Female; Gastroenterology. Liver. Pancreas. Abdomen; Glomerular Filtration Rate - physiology; Humans; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - prevention & control; Liver Transplantation; Male; Medical sciences; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Pharmacology. Drug treatments; Prospective Studies; Risk Factors
• ISSN: 0269-2813; 1365-2036; 0953-0673
• DOI: 10.1111/j.1365-2036.2007.03466.x

Summary Background  Calcineurin inhibitor (CNI)‐related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation. Methods  In this prospective study, liver transplantation patients with renal dysfunction were randomized either to receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI‐trough levels (MMF group), or to continue their maintenance CNI dose (control group). Immune monitoring was performed in a subgroup of the patients. Results  In the MMF group (n = 50), renal function assessed by serum creatinine improved >10% in 62% of patients, was stable in 36% and deteriorated >10% in 2% after 12 months compared with baseline values. Mean serum creatinine levels (± s.d.) significantly decreased from 1.90 ± 0.44 mg/dL to 1.61 ± 0.39 mg/dL and the corresponding calculated glomerular filtration rate significantly increased from 38.8 ± 9.6 mL/min/1.73 m2 to 47.0 ± 11.8 mL/min/1.73 m2 over a 12‐month follow‐up period. Blood pressure and levels of liver enzymes significantly decreased. In the control group (n = 25), there were no significant changes with respect to the investigated parameters. The MMF group had significantly lower numbers of circulating cytotoxic T cells compared with the controls; whereas regulatory T cells significantly increased. Conclusion  Combined MMF and minimal dose CNI therapy after liver transplantation is nephroprotective and may promote allograft tolerance.