Kidney volume increases during long-term ciclosporin a treatment.
OBJECTIVE
Previously, we have for the first time reported enlargement of the pig kidney during long-term ciclosporin (CsA) treatment. In this paper, we summarize our findings of renal enlargement during long-term protocols with various dosages and durations of CsA administration as well as discuss possible pathogenetic mechanisms.


METHODS
Twenty-two adolescent Gottingen minipigs were allocated into four groups: group A (n = 6) served as controls for 6 months; group B (n = 5) were treated with CsA (10 mg/kg per day) for 6 months, group C (n = 4), with CsA (20 mg/kg per day) for 6 months, and group D (n = 7) with CsA (10 mg/kg per day) orally for 12 months. At regular intervals, renal length and total volume were measured using magnetic resonance imaging; renal biopsies were performed for histological examination.


RESULTS
A significant increase in kidney volume occurred in all CsA-treated pigs (groups B, C, and D); whereas the volume remained stable in the control animals (group A). A small but significant rise in kidney length was observed in groups A, B, and C, probably due to the normal growth of the animals. Histological examination was normal after treatment with CsA doses of 10 and 20 mg/kg per day for 6 months but showed definite interstitial fibrosis and glomerulosclerosis after treatment with 10 mg/kg per day CsA for 12 months.


CONCLUSIONS
Long-term CsA treatment produced renal enlargement in pigs before the development of histological changes in the kidney. Thus, renal enlargement may represent an early stage of chronic CsA nephrotoxicity.
Cibulskyte
D
D
Department of Renal Medicine, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark.
Engberg
A
A
Pedersen
M
M
Marcussen
N
N
Hansen
H E
HE
Madsen
M
M
Mortensen
J
J
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000033:anatomy & histology* / Q000187:drug effects; D007700:Kinetics; D023421:Models, Animal; D013552:Swine; D013556:Swine, Miniature
D016572:Cyclosporine