UNLABELLED: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Acute nephrotoxicity due to TAC in kidney transplant patients is either similar to, or significantly more frequent than that of cyclosporin A (CsA). In this study we describe the clinico-morphologic characteristics 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 nephrotoxicity. We also studied retrospectively the clinico-morphologic profiles of the acute TAC nephrotoxicity with 16 kidney transplant recipients under TAC immunosuppression, 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 nephrotoxicity and non-nephrotoxicity groups about age, sex, donor source, age of donor, the proportion of ABO incompatible and the number of human leukocyte antigen (HLA) mismatches. Of 27 acute TAC nephrotoxicity recipients, 7 patients (26%) had moderate-to-severe grade arteriosclerosis in their allograft arteries. The onset of TAC nephrotoxicity occurred 8-69 days post-operatively. The baseline 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 whole 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 level 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-to-severe arteriosclerosis in allograft arteries was seen in 5 (31%) patients. CONCLUSION: The high trough level of the whole blood TAC and the existence of moderate-to-severe arteriosclerosis in allograft arteries have the potential of causing TAC nephrotoxicities. A reduction of TAC dosage may be effective in improving allograft functions.
UNLABELLED: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Acute nephrotoxicity due to TAC in kidney transplant patients is either similar to, or significantly more frequent than that of cyclosporin A (CsA). In this study we describe the clinico-morphologic characteristics 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 nephrotoxicity. We also studied retrospectively the clinico-morphologic profiles of the acute TAC nephrotoxicity with 16 kidney transplant recipients under TAC immunosuppression, 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 nephrotoxicity and non-nephrotoxicity groups about age, sex, donor source, age of donor, the proportion of ABO incompatible and the number of human leukocyte antigen (HLA) mismatches. Of 27 acute TAC nephrotoxicity recipients, 7 patients (26%) had moderate-to-severe grade arteriosclerosis in their allograft arteries. The onset of TAC nephrotoxicity occurred 8-69 days post-operatively. The baseline 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 whole 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 level 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-to-severe arteriosclerosis in allograft arteries was seen in 5 (31%) patients. CONCLUSION: The high trough level of the whole blood TAC and the existence of moderate-to-severe arteriosclerosis in allograft arteries have the potential of causing TAC nephrotoxicities. A reduction of TAC dosage may be effective in improving allograft functions.
Authors: Gerold Thölking; Katharina Schütte-Nütgen; Julia Schmitz; Alexandros Rovas; Maximilian Dahmen; Joachim Bautz; Ulrich Jehn; Hermann Pavenstädt; Barbara Heitplatz; Veerle Van Marck; Barbara Suwelack; Stefan Reuter Journal: J Clin Med Date: 2019-10-02 Impact factor: 4.241