Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension

Abstract

Although mycophenolate mofetil (MMF) monotherapy has been successfully used in liver transplant recipients suffering from calcineurin-inhibitor (CNI)-related chronic toxicity, still no consensus has been reached on its safety, efficacy and tolerability. We attempted the complete weaning off CNI in 42 individuals presenting chronic renal dysfunction and/or dyslipidemia and/or arterial hypertension and simultaneously introduced 1.5 gm/day MMF. CNI could be completely withdrawn in 41 cases. A total of 32 (75%) patients are currently on Յ1.5 gm/day of MMF. Mean follow-up from the introduction of MMF is 31.5 months and mean length of follow-up from the beginning of MMF monotherapy is 27.3 months. Renal function improved in 31/36 (89%) cases. Blood levels of cholesterol and triglycerides decreased in 13 of 17 (76%) and 15 of 17 (89%) patients, respectively. Arterial hypertension improved in 4 of 5 (80%) cases. A total of 8 patients showed a single episode of fluctuation of liver function tests during tapering off CNI. This feature was interpreted as an acute rejection (AR), based on the resolution of the clinical setting after escalation of MMF daily dose to 2 gm. A further patient developed a biopsy-proven AR insensitive to MMF adjustment, requiring reinstitution of the CNI dose. No deaths or major toxicity requiring MMF discontinuation occurred. In conclusion, low dose MMF monotherapy is safe, effective, and well tolerated. Liver Transpl 13: 46-54, 2007.

Chronic Kidney Disease after Nonrenal Solid-Organ Transplantation

“…[82][83][84] Similarly, in liver recipients in whom immunosuppression requirements are less stringent, emerging data suggest that elimination of CNIs and replacement by MMF may also achieve these goals. 85 In contrast, there is growing recognition that sirolimus is not devoid of nephrotoxicity, as originally hoped. Sirolimus potentiates nephrotoxicity of CNIs, especially CsA.…”

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“…High-dose MMF and delayed tacrolimus treatment may suppress the immune responses in the liver transplant recipient, and occasionally tacrolimus may be unnecessary. 15,16 Considering the toxicity of tacrolimus, we attempted to use MMF alone as the antirejection agent for 2 months, but eventually it was not effective. Currently, tacrolimus is not being used in this patient.…”

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

“…13,47 Discussion with the transplant center for reduction in the dose of CNIs, combining low-dose CNIs with renal-sparing MMF with or without concomitant glucocorticoids, could be considered. 48 Complete withdrawal of CNI and using only MMF and glucocorticoids is associated with significant risk of graft dysfunction. 19 Conversion to sirolimus-based immunosuppression may show a benefit to renal function if converted before 1 to 2 years of deteriorating renal function (as long as no proteinuria is noted) 49 ; otherwise, it is not effective in improving renal function in LT recipients.…”