Effect of cyclosporine on urinary kallikrein excretion in patients with rheumatoid arthritis.
The effect of cyclosporine (6 to 8 mg/kg/day) on urinary kallikrein excretion was examined in 10 patients with rheumatoid arthritis by using a radioimmunoassay for kallikrein, a product of renal tubular biosynthesis. All patients had baseline values of serum creatinine and blood urea nitrogen (BUN) within the normal range. The group had a mean baseline kallikrein excretion of 98.30 +/- 29.98 micrograms/24 hours (mean +/- SEM), and 3 and 6 months after therapy was initiated, kallikrein excretion was 44% and 46% of baseline, respectively (p less than 0.01). The five patients who had a normal mean baseline kallikrein excretion rate (106.60 +/- 15.21 micrograms/24 hr) excreted significantly less (p less than 0.05) kallikrein 3 and 6 months after therapy was initiated (56.60 +/- 3.98 micrograms/24 hr and 34.50 +/- 11.02 micrograms/24 hr, respectively), as did one patient with an elevated baseline kallikrein. All six of these individuals completed the protocol. In a subgroup of four patients with low baseline levels (28.25 +/- 5.06 micrograms/24 hr), two individuals experienced elevations of BUN such that cyclosporine was discontinued; in the two who completed the protocol, there was some further decrement in kallikrein excretion. Kallikrein excretion increased in all patients after a 3-month washout period. During a low-dose (3 mg/kg/day) open extension study that followed the initial trial, kallikrein excretion was determined monthly. Seven episodes in which kallikrein excretion decreased in six patients by 44% +/- 18% over a 1-month interval preceded any increase in serum creatinine by 1 to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Spragg
J
J
Department of Medicine, Harvard Medical School, Boston, MA.
Weinblatt
M E
ME
Coblyn
J
J
Fraser
P
P
Austen
K F
KF
D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000652:urine*; D007668:Kidney / Q000187:drug effects*
D003524:Cyclosporins; D003404:Creatinine; D007610:Kallikreins