Clinical and histological analysis of acute tacrolimus (TAC) nephrotoxicity in renal allografts

Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Acute nephrotoxicity due to TAC in kidney transplant patie nts is either similar to, or significantly more frequent than that of cyclo sporin A (CsA). In this study we describe the clinico-morphologic character istics of acute TAC nephrotoxicity in kidney transplant recipients. Patients and methods. We studied retrospectively the clinical courses of 67 patients who underwent kidney transplantation under TAC immunosuppression at Tokyo Women's Medical University between July 1990 and January 1997. We compared the recipient's characteristics with and without acute TAC nephrot oxicity. We also studied retrospectively the clinico-morphologic profiles of the acu te TAC nephrotoxicity with 16 kidney transplant recipients under TAC immuno suppression, who were diagnosed with acute TAC nephrotoxicity by allograft biopsies between January 1996 and January 1997. Results. There were no significant differences between acute TAC nephrotoxi city and non-nephrotoxicity groups about age, sex. donor source, age of don or. the proportion of ABO incompatible and the number of human leukocyte an tigen (HLA) mismatches. Of 27 acute TAC nephrotoxicity recipients, 7 patien ts (26%) had moderate-to-severe grade arteriosclerosis in their allograft a rteries. The onset of TAC nephrotoxicity occurred 8 69 days post-operatively The bas eline creatinine level was 1.92 mg/dL (range 0.4-5.1 mg/dL) and rose by 38. 4% (range 0-84.6) during episodes of nephrotoxicity. The mean peak of the w hole blood TAC trough level during the toxic episodes was 32.5 ng/mL (range 21.2-58.5 ng/mL). The rise in creatinine level preceded the highest TAC le vel in 10 cases. A mean reduction in TAC dosage of 18.9% (range 0-50%) led to a fall of 17.2% (range 0-43%) in serum creatinine levels. The moderate-t o-severe arteriosclerosis in allograft arteries was seen in 5 (31%) patient s. Conclusion. The high trough level of the whole blood TAC and the existence of moderate-to-severe arteriosclerosis in allograft arteries have the poten tial of causing TAC nephrotoxicities. A reduction of TAC dosage may be effe ctive in improving allograft functions.