limited. A review of the Cambridge experience with CsA indi-After liver transplantation, long-term cyclosporin A cated that some patients with nephrotoxicity could be man-(CsA) administration is commonly complicated by renal aged with azathioprine and prednisone alone, but details insufficiency and other side effects. To manage these about the regimen and its complications were lacking. 3 A problems, 1.5 to 2.0 mgrkg 01 rday 01 of azathioprine for recent report from the Mayo Clinic suggests that discontinuaat least 6 weeks was prescribed; CsA was then discontion of CsA along with increased doses of azathioprine and tinued or reduced to ยฐ2.5 mgrkg 01 rday 01 for several prednisone often results in rejection with graft loss and is months. The dose of prednisone was kept constant. CsA not usually associated with sustained improvement in renal was discontinued in 14 patients because of nephrotoxicfunction. 11 We report here that discontinuation of CsA and ity (three or more serum creatinine levels of ยข1.5 mg/ conversion of patients to therapy with azathioprine and pred-dL), in 1 patient because of headaches and in 1 patient nisone alone resulted in few complications and substantial because of a generalized sensory neuropathy; 1 patient improvement in CsA-related side effects, particularly nephrorefused to continue taking the drug. The CsA dose was toxicity and headaches. reduced in 13 patients, 12 because of nephrotoxicity and 1 because of headaches. One patient in whom adminis-PATIENTS AND METHODS tration of CsA was stopped developed azathioprine hepatotoxicity, whereas 1 patient whose dose was reduced Identification of Patients With CsA Nephrotoxicity. Records maindeveloped acute cellular rejection. These complications tained on each post-OLT patient were reviewed to identify subjects with possible CsA nephrotoxicity. Patients with at least three serum were controlled by discontinuing azathioprine and recreatinine values of ยข1.5 mg/dL were considered to have possible initiating CsA. In the patients in whom CsA was discon-CsA nephrotoxicity. The diagnosis was considered to be established tinued, the mean serum creatinine level decreased from if there was no clinical evidence of other types of renal injury, based 2.42 { 0.48 to 1.72 { 0.39 mg/dL (P ร
.00004); in the paon microscopic examination of the urine sediment; ultrasonography
tients in whom CsA was reduced, the mean serum creatiexamination of the kidneys, ureters, and bladder; and discontinua- nine level decreased less markedly. This report suggests tion of potentially nephrotoxic drugs besides CsA. Hypertension, de- that discontinuation of CsA along with increased doses fined as three or more systolic blood pressure measurements of ยข140 of azathioprine is safe for some patients and may be mm Hg and/or diastolic blood pressure measurements of ยข90 mm effective in managing CsA-related nephrotoxicity and Hg often complicated the course of CsA nephrotoxicity. This problem was managed with diuretics and b-blockers or calcium channel blocknous OKT