Renal Cyclosporine Clearance in Marrow Transplant Recipients: Age‐Related Variation

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Abstract
Cyclosporine is extensively metabolized in the liver and is subject to biliary elimination. Although only a small amount of the drug is eliminated unchanged in the urine, urine concentrations of the drug are much higher than blood or serum concentrations known to be associated with renal toxicity. Renal clearance (CL) of cyclosporine may be a sensitive correlate of nephrotoxicity, but renal CL studies of cyclosporine have not been reported in transplant patients. Therefore, we studied the renal CL of cyclosporine in 21 patients (median age, 27 yr) with hematologic malignancies undergoing allogeneic bone marrow transplantation. All patients received cyclosporine for prophylaxis or treatment of acute graft vs host disease. At the time of the study, all patients had normal renal function, as determined by serum creatinine concentration. Urine and serum cyclosporine concentrations were measured by high‐performance liquid chromatography. Renal cyclosporine CL in different patients ranged from 1.8 to 79.8 mL/min. However, serial renal CL studies performed one week apart in two patients showed minimal intrapatient variability. Patients 25 years old or younger had a higher mean renal cyclosporine CL (39.7 mL/min) than older patients (17.9 mL/min) (P < .05). These data show that renal cyclosporine CL is related to age and that renal CL in marrow transplant recipients is higher than the reported mean value in non‐marrow‐transplant patients. Further clinical studies are needed to evaluate renal cyclosporine CL in solid organ transplant recipients and the correlation between urinary cyclosporine (or cyclosporine metabolite) concentrations and renal dysfunction.