Renal side effects of high and low cyclosporin A doses in patients with rheumatoid arthritis.
Thirty-nine patients with classical or definite rheumatoid arthritis (RA) entered a randomized double-blind placebo controlled study with low dose cyclosporin A (CyA) (mean whole blood CyA level after 26 weeks 282 +/- 33 micrograms/l) or placebo treatment for 48 weeks. The placebo treatment had to be withdrawn before 48 weeks in 9 out of 19 patients because of a deterioration of their arthritis symptoms. All 20 patients in the CyA group completed 26 weeks of treatment. Fourteen of them were followed up for 48 weeks of treatment on CyA and then 12 weeks after CyA treatment was withdrawn. The side effects in the CyA group were compared with the results from another study with high CyA doses (mean whole blood CyA level 419 +/- 71 micrograms/l) for 26 weeks in 11 other patients with RA. Serum creatinine increased 19.7% (p less than 0.01) in the low CyA dose group after 26 weeks as compared with 59.5% in the high CyA dose group. Creatinine clearance was reduced by 17.9% (low dose) (p less than 0.01) and 26.2% (high dose), respectively. Twelve weeks after withdrawal of the low dose CyA treatment, serum creatinine values were still higher than before treatment (p less than 0.05), but creatinine clearance had normalized. Eight of the 20 patients treated with low CyA doses also started with nonsteroidal anti-inflammatory drugs (NSAIDs) after 20-36 weeks of CyA treatment. Serum creatinine was 16.6% above baseline 4 weeks before NSAIDs compared with an increase of 40.4% (p less than 0.05) 4 weeks after start of NSAID treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Berg
K J
KJ
Medical Department B, Rikshospitalet, Oslo, Norway.
Førre
O
O
Djøseland
O
O
Mikkelsen
M
M
Narverud
J
J
Rugstad
H E
HE
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003524:Cyclosporins / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D011897:Random Allocation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003524:Cyclosporins