CYCLOSPORINE-ASSOCIATED ARTERIOLOPATHY - THE RENIN PRODUCING VASCULARSMOOTH-MUSCLE CELLS ARE MORE SENSITIVE TO CYCLOSPORINE TOXICITY

The pathogenesis of ciclosporin (Cs) induced renal vasoconstriction an d CS-associated arteriolopathy (CAA) has not been fully explained. CAA affects the part of the afferent arteriole where renin is most abunda nt, and an effect by Cs on the renin producing smooth muscle cells lea ding to necrosis has been suggested. Forty transplant biopsies with CA A of different degrees were compared with 10 transplant biopsies from Cs treated patients without CAA, and with 10 ''zero-hour'' control bio psies (taken from the donor kidney at implantation). Immunoreactivity to renin by the ABC method was recorded in the arterioles. Compared to the control group there was a slight increase in the proportion of re nin positive arterioles in the Cs treated group without CAA, but with increasing CAA there was a decrease in the proportion of renin positiv e arterioles. In the group of arterioles with CAA, we found that with increase in the severity of CAA, there was an increase in renin negati ve arterioles, indicating a loss of renin containing cells in these ar terioles. This suggests that a large proportion of the necrotic cells in CAA has once been renin producing smooth muscle cells. Our findings support the possibility that Cs stimulates renin production, and that the renin producing cells are more sensitive to Cs toxicity.