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Objective: It has been suggested that the increase in blood pressure observed in transplant patients treated with ciclosporine A is mediated by sympathoexcitation induced by CICLOSPORINE A. However, the chronic effects of CICLOSPORINE A on sympathetic outflow in renal transplant patients (RTX) has not been investigated. Therefore, we studied sympathetic nerve activity and blood pressure before and 6 months after withdrawal of CICLOSPORINE A in RTX. Design and Methods: 18 RTX with histologically proven allograft nephropathy (age 49 2 yr, 72 9 months after transplantation, data are mean SEM) were included in the prospectives study and randomized to either withdrawal (n 11) or continuation (n 7) of CICLOSPORINE A treatment (average throgh levels 72 9 ng/ml and 6.0 ng/ml for ciclosporine and tacrolimus, respectively).Both groups received mycophenolate mofetil (MMF) and prednisolone as additional immunosuppressants. At entry and 6 months later, blood pressure, muscle sympathetic nerve activity (MSNA, microneurography at the peroneal nerve) and plasma catecholemines were measured. Results: MAP decreased significantly in the CICLOSPORINE Awithdrawal group (96 3 vs. 108 4 mmHg 6 vs. 0 months, p 0.05) but not in the CICLOSPORINE A continuation group (101 3 vs. 104 6 mmHg, n.s.). However, sympathetic nerve activity -as measured by MSNA and Norepinephrine plasma levelsdid not change significantly in either group (MSNA: 51 4 vs. 49 4 bursts/min and 43 7 vs. 45 5 bursts/min in the CICLOSPORINE A-withdrawal and CICLOSPORINE A-continuation goup, respectively; n.s.). Serum creatinine concentrations were stabel in both groups. Conclusions: CICLOSPORINE A withdrawal in renal transplant patients -receiving relatively low doses of CICLOSPORINE Aresults in a substantial decrease in blood pressure. However, this reduction in blood pressure was not attributable to decreases in sympathetic nerve activity suggesting either that CICLOSPORINE A treatment does not cause chronic sympathoexcitation in RTX or that the CICLOSPORINE A-induced sympathoexcitation is not reversible within 6 months.

Impact of ciclosporine a withdrawal on sympathetic nerve activity and blood pressure in renal tranplant recipients