Ciclosporin-associated arteriolopathy: the renin producing vascular smooth muscle cells are more sensitive to ciclosporin toxicity.
The pathogenesis of ciclosporin (Cs) induced renal vasoconstriction and CS-associated arteriolopathy (CAA) has not been fully explained. CAA affects the part of the afferent arteriole where renin is most abundant, and an effect by Cs on the renin producing smooth muscle cells leading to necrosis has been suggested. Forty transplant biopsies with CAA of different degrees were compared with 10 transplant biopsies from Cs treated patients without CAA, and with 10 "zero-hour" control biopsies (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 renin positive arterioles in the Cs treated group without CAA, but with increasing CAA there was a decrease in the proportion of renin positive arterioles. In the group of arterioles with CAA, we found that with increase in the severity of CAA, there was an increase in renin negative arterioles, indicating a loss of renin containing cells in these arterioles. 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.
Strøm
E H
EH
Institute of Pathology, University of Basel, Switzerland.
Epper
R
R
Mihatsch
M J
MJ
D001160:Arterioles / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D001706:Biopsy; D003524:Cyclosporins / Q000009:adverse effects*; D006651:Histocytochemistry; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D009336:Necrosis; D012083:Renin / Q000096:biosynthesis*
D003524:Cyclosporins; D012083:Renin