Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does not result in sustained improvement in kidney function and causes cellular and ductopenic rejection
✍ Scribed by William J. Sandborn; J. Eileen Hay; Michael K. Porayko; Gregory J. Gores; Jeffery L. Steers; Ruud A. F. Krom; Russell H. Wiesner
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 906 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Twelve consecutive liver transplant recipients with stable allograft function and cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an attempt to halt and possibly reverse renal damage. Only patients who met the following criteria were included: (a) triple immunosuppression with cyclosporine, azathioprine and prednisone; (b) stable graft function for at least 1 F without rejection; and (C)
During the 198Os, combination therapy with cycloserum mater than 2*1 mfddl Or renal sporine and prednisone became the standard immuno- less than 35 drnin. c ~c l O ~r i n e was re-suppression regimen for liver transplant recipients after duced by 50 mg every 3 wk until discontinuation, studies demonstrated better patient survival with this prednieone was temporarily increased from 10 to 20 mg/day and azathioprine was maintained at approach than with treatment with azathioprine and 2 m M & y . Sustained improvement in kidney hc-prednisone (1-2). Unfortunately, this improvement in tion in the 12 patients was minimal, with the mean patient survival has been accompanied by the frequent serum creatinine level decreasing from 2.5 f 0.6 mg/dl occurrence of cyclosporine-associated nephrotoxicity (mean f S.D.) at study entry to 2.4 * 1.2 mddl after a and hypertension (3-8). mean follow-up Of 18 f 6 mo. In six Patient& ~O l O d -We have previously reported that conversion from CallY confumed Cellular rejection developed after a standard immunosuppression with cyclosporine and was begun' Two Of six patients with re-dose cyclosporine (maintenance of whole blood cyclojection responded to bolus steroid therapy and are in stable condition at this writing with low-dose cycle-sporine levels between 80 and 120 ng/ml) in combination qorine (2.8 and 3.2 mg/kg/day). %o patients initially with azathioprine and prednisone results in initial regponded to bolus steroids but later eghfbited due-improvement of kidney fUnCtiOn in liver tmnsplant topenic rejection; one responded to treatment with FK recipients with cyclosporine nephrotoxicity (9). 508 and the other died of sepsis. The two remaining However, long-term follow-up of these patients has patients were steroid unresponsive. One responded to shown that the improvement in kidney function is not treatment with OE'I'3 and is now stable 011 low-dose sustained (10). Our institution has subsequently CYClqdne (2.3 m@kddaY), but in the other dUC-adopted a protocol of primary therapy with triple dection developen and the patient died Of immunosuppression for liver transplantation. Three--rescue therapy with FK 508* By ' Omyear follow-up of patients treated in this protocol showed that, on average, kidney function declined by 25% during parison, in none of 12 matched control patients did rejection develop during a similar follow-up period. We the first year and then stabilized (11). Of significant concern, however, was the finding that some patients had progressive loss of kidney function over the 3-yr Experience in kidney transplantation Suggests that withdrawal of cyclosporine from triple immunosupcombination of prednisone and azathioprine (15-18) will improve kidney function but may result in rejection rates of up to 40%. One study suggested that slowly conclude that cycloqmrine withdrawal for nephrotoxicity in liver transplant recipients does not reault in sustained improvement in kidney function and causes a high incidence of cellular rejection, which can progress to ductopenic rejection or death from infection. (HEPM'fXQGY 1994;19:926-932.) mean of 5 * 6 mo from the time that 'doW*e prdnisone to "triple immunosuppression" with low-