The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis.
Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.
Weinblatt
M
M
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, MA 02115.
Helfgott
S
S
Coblyn
J
J
Spragg
J
J
Uedelhoven
W M
WM
Tumeh
S
S
Sperling
R
R
Lorenz
R
R
Maier
A
A
Weber
P
P
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000009:adverse effects*; D015777:Eicosanoids / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D003524:Cyclosporins; D015777:Eicosanoids; D013929:Thromboxane B2; C028965:2,3-dinor-thromboxane B2; D003404:Creatinine