ARTHRITIS & RHEUMATISM
Vol. 43, No. 1, January 2000, pp 103–108
© 2000, American College of Rheumatology
THE EFFECT OF MINI-DOSE ASPIRIN ON RENAL FUNCTION AND
URIC ACID HANDLING IN ELDERLY PATIENTS
D. CASPI, E. LUBART, E. GRAFF, B. HABOT, M. YARON, and R. SEGAL
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 plate-
let aggregation inhibitor, no studies have been pub-
lished 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
Methods. The study included 49 elderly inpa-
tients (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. Pre-
vious 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 excre-
tion, 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 signifi-
cant 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 statisti-
cally significant [P ? 0.038]). Generally, creatinine and
UA clearance rates paralleled each other during aspirin
treatment. However, 1 week after aspirin was discontin-
ued, creatinine clearance remained decreased while UA
clearance returned to baseline. Plasma aspirin concen-
trations were low and variable. However, patients with
above-median aspirin levels had significantly greater
changes in serum creatinine levels, urinary UA excre-
tion rates, and UA clearance rates following the first
week of aspirin treatment. Hypoalbuminemia and con-
comitant treatment with diuretics enhanced the effects
of aspirin on renal function and UA retention.
Conclusion. Mini-dose aspirin, even at a dosage
of 75 mg/day, caused significant changes in renal func-
tion and UA handling within 1 week in a group of elderly
inpatients, mainly in those with preexisting hypoalbu-
minemia. Given the widespread (and often unmoni-
tored) 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 under-
lying these phenomena.
Though high-dose aspirin, once the king of anti-
inflammatory drugs, has lost its monarchy to modern
nonsteroidal antiinflammatory drugs (NSAIDs), the use
of low-dose and very-low-dose (mini-dose) aspirin for
the prevention of thrombosis has been greatly expanded
during the last decade. Current consumption of aspirin
in the US is estimated to be 10,000–20,000 tons per year
(1), and in Israel, with a population of ?6 million, 5 tons
of the 100-mg enteric coated preparation alone were
distributed during 1997. The drug is taken, often as an
over-the-counter remedy, by many patients and by
healthy subjects as well. Data on the influence of aspirin
on uric acid (UA) kinetics are based on the classical
studies by Yu and Gutman from 1959 (2) and by Yu et
al from 1963 (3), involving dosages of ?1 gm/day. Those
investigators found that while aspirin dosages of ?3
gm/day tend to promote uricosuria, lower dosages (1–2
gm/day) may cause UA retention. The effects of mini-
D. Caspi, MD, E. Graff, PhD, M. Yaron, MD: Tel Aviv
University, Tel Aviv, Israel; E. Lubart, MD, B. Habot, MD, R. Segal,
MD: Shmuel Harofeh Geriatric Medical Center, Beer Yaacov, Israel.
Address reprint requests to D. Caspi, MD, Rheumatology
Day Care Unit, Tel Aviv (Sourasky) Medical Center, 6 Weizmann
Street, Tel Aviv 64239, Israel.
Submitted for publication December 2, 1998; accepted in
revised form August 17, 1999.
(Table 2). Unsurprisingly, patients receiving diuretics
concomitant with aspirin tended to have further impair-
ment of renal function induced by mini-dose aspirin.
The influence of hypoalbuminemia in the same direction
may be explained by the known role of albumin in
binding salicylate (1), and thus by the higher serum
levels of the drug in hypoalbuminemic patients.
In conclusion, aspirin at dosages of 75–325 mg/
day was found to impair renal function and UA handling
in elderly inpatients. These effects were already noted at
the week-1 dosage of 75 mg/day. Concomitant diuretic
treatment and especially low serum albumin seem to
increase the susceptibility to these side effects. The
mechanisms underlying urate retention and renal im-
pairment appear to be at least partially independent.
Although further studies of clinical and biochemical
mechanisms are needed, we suggest that clinicians be
alert to possible mini-dose aspirin treatment phenomena
for elderly patients.
We thank the nursing and laboratory staff of Shmuel
Harofeh Medical Center for their patient patients’ care, Dr. J.
Atzmon for his helpful advice, Mr. Elon Neumann, MSc, for
his friendly guidance in statistics, and the anonymous reviewer
no. 1 for Arthritis & Rheumatism for helpful comments.
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108 CASPI ET AL