Mycophenolate mofetil causing deep venous thrombosis in a renal transplant patient with factor V Leiden

Mycophenolate mofetil (MMF) is a drug that is commonly used as a post-transplant immunosup-pressive agent. The mechanism of action of MMF is via non-competitive, reversible inhibition of inosine monophosphate dehydrogenase (IMPDH). IMPDH is required for purine synthesis during lymphocyte activation w1x. Although effective for treating allograft rejection w2±5x, MMF has well known side effects including gastrointestinal upset, lymphopenia, and the risk of opportunistic infections w6±7x. Hepatotoxicity and nephrotoxicity are not common w8x. The factor V Leiden mutation involves a single adenine-for-guanine mutation at position 506, ®rst described in 1993 w9±10x. Mutated factor V is resistant to degradation by activated protein C, predisposing patients to thrombosis w9x. In this paper, we describe a case of proven deep venous thrombosis (DVT) in a 62-year-old cadaveric renal transplant recipient several days after starting MMF. The MMF was administered on two separate occasions, several months apart, and 4 years post-transplant because of episodes of chronic allograft nephropathy (CAN). The patient developed a DVT soon after receiving the MMF on both occasions. A haematological investigation revealed that the patient (P.F.) was heterozygous for factor V Leiden. The timing and reproducible relationship between the administration of MMF and the development of DVT strongly suggest a causal relationship between the drug and the occurrence of thrombosis. In this paper we describe what we think is a rare case of DVT as a complication of MMF. Case P.F. is a 62 year-old woman who was diagnosed with primary membranous glomerulonephritis in 1992. Her renal function declined and by March 1995 she required peritoneal dialysis. On 25 July 1995 the patient underwent a right-sided cadaveric renal transplant. An ultrasound performed prior to discharge revealed a normal transplant kidney. Her creatinine decreased from a pre-operative level of 586 mmolul to 78 mmolul by the time of discharge. Her discharge medications included cyclosporine A micro-immulsion 100 mg PO bid, azathioprine, and a tapering dose of prednisone. The patient's post-operative course was uneventful except for a nasal abscess, and the development of type 2 diabetes mellitus secondary to her immuno-suppressive medications. Her creatinine stabilized at 130±135 mmolul until April 1999, when her creatinine was noted to be 160 mmolul, and continued to increase slowly, reaching 236 mmolul by the beginning of June 1999. A renal biopsy that was performed 7 June 1999 demonstrated CAN, Grade III, with features of chronic transplant glomerulopathy and severe inter-stitial ®brosis. There was no evidence of membranous …