Abstract
629 Rapamycin (RAPA) has been reported to be as effective as Cyclosporine (CyA) as base therapy in a randomized trial (Groth CG et al (Transplantation: in press). From 8/97 to 8/98, 19 patients (age 22-63, male 63%) receiving a cadaveric (13) living related (4) or living unrelated (1) renal transplant and 1 kidney-pancreas, were switched to RAPA 5 mg/day 14 to 204 months after transplant for 17 patients and 2 within 2 weeks. The main indication for switch was chronic CyA or Tac nephrotoxicity (ChN)(8), ChN + chronic rejection (4), severe gum hyperplasia + hypertrichosis (2), acute CyA or Tac toxicity (2) lymphoma and Hodgkins disease while on CyA (both in remission) and new onset diabetes in 1. Follow up is 2 to 14 months. In the 12 patients switched because of ChN there was a significant decrease in serum creatinine from 233 umol/L to 202 umol/L (p<0.01) and 203 umol/L (p,0.05) at 2 and 3 months post switch respectively. Blood pressure (BP) remained stable after the switch (pre switch mean arterial BP 101 +/− 11 to 95 +/− 8 mmHg (p=0.16) 2 patients had a decrease in antihypertensive drugs. Facial dysmorphism improved in the 2 patients and diabetes in the one patient resolved 6 months after switch. Neither PTLD relapsed. Six patients developed pneumonia after the switch. Pneumocystis carinii 2, bronchiolitis obliterans organizing pneumonia 2, and atypical pneumonia 1. One patient had a pneumonia secondary to a primary EBV infection. Five patients required hospitalization. All recovered. Eight patients (42%) developed transient oral aphthous ulcers. RAPA was discontinued in 4 patients, (because of pneumonia in 2, EBV in 1, and herpetic infection 1) and 15 patients remain on rapamycin. There was one reversible acute rejection episode at 3 months in a patient switched to RAPA & MMF 2 weeks post transplant. There were no graft losses. The complications of over immunosuppression in patients switched late in their course appear to be related to the slow taper of cyclosporin and the continuation of azathioprine and/or MMF. Completely stopping CyA at conversion may be better than drug overlap. PCP and herpes prophylaxis should be included at conversion. Pharmacokinetics may be needed to adjust RAPA doses when stable long term patients are switched. Improvement in renal function and disappearance of other CyA toxicities was demonstrated in this small group of patients.
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