Brown, H

Deballi, P

Fung, JJ

Jain, A

McCauley, J

Starzl, TE

Todo, S

English

PubMed

Name not available

Renal function after conversion from cyclosporine to FK 506 in liver transplant patients

D-Scholarship@Pitt

ll,1 ~ ; i '. Renal Function After Conversion From Cyclosporine to FK 506 in Liver Transplant Patients J. McCauley, J.J. Fung, H. Brown, P. Oeballi, A. Jain, S. Todo, and T.E. Starzl PK 506. a macrolide antibiotic. is a powerful immuno-suppressant which is approximately 100 times more potent than cyclosporine (CyA). The first clinical experi-ence with this agent was attained in patients with refrac-tory hepatic rejection and complications of Cy A thera-py.l.2 Initial experience suggested that FK 506 was surprisingly effective in reversing rejection in these pa-tients. In the first patients. the combined nephrotoxicity of FK 506 and CyA was apparent. Serum creatinine (SCr) regularly increased and, at times, dramatically.3 This was termed the "crossover nephrotoxicity" of FK 506 and Cy A. FK 506 has now been used for approximately 2 years at the University of Pittsburgh. We will update our expe-rience with the changes in renal function after conversion from CyA to FK 506. PATIENTS AND METHODS The first 121 patients convened from CyA to FK 506 will be described. The reasons for conversion included: (a) refractory hepatic rejection (90 patients); (b) complications of CyA therapy (25 patients); (c) those in which a reduction in steroid dosage was desirable (6 patients). Initially. all patients received IV FK 506. 0.075 mglkg per day for several days. and 0.15 mglkg per day subsequently. Cy A was retained for the first day in some patients. but our policy later was to discontinue it the day FK 506 was started. Patients without hepatic rejection were usually convened with oral FK 506 0.1 to 0.15 mglkg per day. Patients with renal failure prior to conversion received the lower dose. Renal function was determined by daily BUN. creatinine. and electrolytes. Glomerular filtration rate (GFR) and ERPF were determined by iothalamate and hippuran clearance in some patients. RESULTS All patients experienced a rise in SCr at some time. Surprisingly, 25 patients (21%) experienced a fall in SCr during the first week. An increase in SCr of <0.9 mgldL occurred in 60 patients, < 1.8 mgldL in 21, and the remain-der experienced a rise in SCr > 2.0 mgldL during the first week. Fig 1 illustrates ~he change in SCr for all patients over time. Peak SCr occurred usually during the first 2 months, and decreased as FK 506 dosage was reduced. Patients rescued for acute hepatic rejection experienced the greatest rise in SCr and required higher FK 506 drug doses and levels. Interestingly, patients converted for renal insufficiency (Fig 2) noted an overall reduction in SCr at latest follow-up compared to pretreatment values (2.8 ± 1.8 vs 1.8 ± 0.8 mgldL). This probably reflects aggressive attempts to reduce FK 506 doses and preserve renal function. In all patients tested, ERPF ~d GFR fell in parallel after 3.50 3.25 3.00 :; 2.71 Ii ! 2.50 .. z 2.25 i ...... T"" ' .. ,,, ..... D~ ......... ' .. "'" T T ;: 2.00 c .. a:: 1.75 0 .. ,""/ .... , "J,""" ........ 1.50 1.21 ·1 0 7 14 2. 10 80 120 110 270 310 450 130 DAYS Fig 1. Change in creatinine for all rescue patients. starting FK 506. As FK 506 was tapered and drug levels fell, ERPF and GFR returned toward pretreatment values. Patients converted for hypertension, steroid intoler-ance, and chronic rejection had intermediate changes in SCr. Pretreatment and latest follow-up SCr were: 1.7 ± 0.7 vs 1.8 ± 1.2 mgldL for hypertension, 1.3 ± 0.6 vs 1.8 ± 0.4 4.50 4.13 3.71 ~ 3.31 a ! 3.02 w z 2.15 i >= 2.2. < w a: 1.11 () 1.54 1.17 0." ·1 0 7 14 21 10 10 120 110 270 310 450 550 DAYS Fig 2. Changes in creatinine for patients converted for renal insufficiency. From the Departments of Medicine and Surgery, University of Pittsburgh School of Medicine, PresbyteriarHJniversity Hospital. and Veterans Administration Medical Center, Pittsburgh, Pennsyl· vania. Address reprint requests to Jerry McCauley, MD, University of Pittsburgh School of Medicine, 11431 Scaife Hall, Renal-Electro-lyte Division, Pittsburgh, PA 15213. © 1991 by Appleton & Lange 0041-1345/91/$3.00/ + 0 3148 Transplantation Proceedings, Vol 23. No 6 (December), 1991: pp 3148-3149 RENAL FUNCTION AFTER CONVERSION FROM CvA , mWdL for steroid intolerance, and 1.4 ± 0.7 vs 1.9 ± 0.5 ffigldL, respectively. DISCUSSION The changes in renal function after conversion appear to be related primarily to the requirement for FK 506. Pa-tients experiencing acute hepatic rejection required the maximal doses to rescue the liver and, therefore. devel-oped the greatest reduction in renal function. Since these original cases, the initial doses of FK 506 have decreased progressively. No longer are large IV infusions performed, and the current policy is to progressively taper FK 506 3149 :.", doses to the minimal do~ needed to prevent rejection. These patients. however. demonstrated that the benefits of conversion from Cy A to FK 506 could be accomplished without permanently reducing renal function, if the doses of FK 506 were lowered in a deliberate and progressive manner. REFERENCES 1. Starzl TE, Abu-Elmagd. Tzakis A. et al: Transplant Proc 23:914. 1991 2. Fung J. Todo S. Jain A, et a1: Transplant Proc 22:6, 1990 3. McCauley J, Fung J. Jain A. et a1: Transplant Proc 22:17, 1990 

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Renal function after conversion from cyclosporine to FK 506 in liver transplant patients

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