The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients.
OBJECTIVE
Aspirin is known to have a bimodal effect on the renal handling of uric acid (UA). High dosages (>3 gm/day) are uricosuric, while low dosages (1-2 gm/day) cause UA retention. Although very-low-dose (mini-dose) aspirin is used increasingly as a platelet aggregation inhibitor, no studies have been published on whether aspirin's renal effects occur at dosages of <0.5 gm/day. The aim of the present study was to evaluate the effects of commonly used mini-dosages of aspirin on renal function and UA handling in elderly patients.


METHODS
The study included 49 elderly inpatients (age 61-94). Patients were excluded if they had renal failure, hyperuricemia, gout, or a history of bleeding, or if they were receiving anticoagulants, aspirin, or nonsteroidal antiinflammatory drugs. Previous medications and diet were kept unchanged. Aspirin was administered as follows: 75 mg/day (week 1), 150 mg/day (week 2), 325 mg/day (week 3), and 0 mg/day (week 4). Baseline and weekly samples of blood and urine were evaluated for UA, creatinine, blood urea nitrogen, creatinine clearance, UA excretion, UA clearance, and plasma levels of aspirin.


RESULTS
At the lowest dosage, aspirin caused a 15% decrease in the rate of UA excretion (P = 0.045 by t-test), which was associated with a slight but significant increase in serum levels of UA (P = 0.009). These effects on UA levels were gradually reduced with increasing dosages of aspirin (multivariate analysis of variance with repeated measures showed no statistically significant difference in the rate of UA excretion between weeks 1-3 and week 0 [baseline], but the difference in serum UA levels for the same comparison was statistically significant [P = 0.038]). Generally, creatinine and UA clearance rates paralleled each other during aspirin treatment. However, 1 week after aspirin was discontinued, creatinine clearance remained decreased while UA clearance returned to baseline. Plasma aspirin concentrations were low and variable. However, patients with above-median aspirin levels had significantly greater changes in serum creatinine levels, urinary UA excretion rates, and UA clearance rates following the first week of aspirin treatment. Hypoalbuminemia and concomitant treatment with diuretics enhanced the effects of aspirin on renal function and UA retention.


CONCLUSIONS
Mini-dose aspirin, even at a dosage of 75 mg/day, caused significant changes in renal function and UA handling within 1 week in a group of elderly inpatients, mainly in those with preexisting hypoalbuminemia. Given the widespread (and often unmonitored) use of mini-dose aspirin, especially among the elderly, these findings call for clinician alertness as well as for further studies to clarify the mechanisms underlying these phenomena.
Caspi
D
D
Tel Aviv University, Israel.
Lubart
E
E
Graff
E
E
Habot
B
B
Yaron
M
M
Segal
R
R
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood; D001241:Aspirin / Q000008:administration & dosage* / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood / Q000652:urine; D004232:Diuretics / Q000008:administration & dosage; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012709:Serum Albumin; D014527:Uric Acid / Q000097:blood* / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D012709:Serum Albumin; D014527:Uric Acid; D005665:Furosemide; D003404:Creatinine; D001241:Aspirin