G- 02: nutrition
F-08: cardiovascular complications
Relationship Between Serum Uric Acid and All-Cause and
Cardiovascular Mortality in Patients Treated With Peritoneal
Dialysis
Xi Xia, MD∗ ,Feng He, MD∗,Xianfeng Wu, MD, Fenfen Peng, MD ,Fengxian Huang, MD, PhD
,Xueqing Yu, MD, PhD
American Journal of Kidney Diseases
Volume 64, Issue 2, Pages 257–264, August 2014
Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou,
China
ABSTRACT
Although serum uric acid level appears to be associated with mortality in individuals treated
with hemodialysis, the relationship between serum uric acid level and death is uncertain in
patients treated with peritoneal dialysis (PD).
Study Design
Cohort study.
Setting & Participants
985 patients from a single PD center in South China followed up for a median of 25.3
months.
Predictor
Serum uric acid level.
Outcomes & Measurements
The association of baseline sex-specific uric acid level with all-cause and cardiovascular
mortality was evaluated. Models were adjusted for age, body mass index, comorbidity score,
residual kidney function, total Kt/V, allopurinol and angiotensin-converting enzyme
inhibitor/angiotensin receptor blocker use, and laboratory test results, including hemoglobin,
serum albumin, creatinine, calcium, phosphorus, triglycerides, low-density lipoprotein
cholesterol, and high-sensitivity C-reactive protein.
Results
Mean age was 48.3 ± 15.4 (SD) years, and 23% had diabetes. Mean uric acid level was 7.0 ±
1.3 (range, 3.8-19.8) mg/dL. During follow-up, 144 deaths were recorded, of which 64 were
due to cardiovascular events. In multivariable models, the highest sex-specific tertile of uric
acid level was associated with increased risk of all-cause mortality (HR, 1.93; 95% CI, 1.272.93; P = 0.004) and cardiovascular mortality (HR, 3.31; 95% CI, 1.70-6.41; P < 0.001)
compared to the lowest tertile. Adjusted Cox regression models showed that the HRs per 1mg/dL higher uric acid level for all-cause and cardiovascular mortality were 1.33 (95% CI,
1.14-1.56; P < 0.001) and 1.44 (95% CI, 1.17-1.77; P = 0.001) for men and 1.03 (95% CI,
0.86-1.24; P = 0.8) and 1.16 (95% CI, 0.97-1.38; P = 0.1) for women, respectively. A formal
test for interaction indicated that the association of uric acid level with all-cause and
cardiovascular mortality differed by sex (β = −0.06 [P = 0.02] and β = −0.10 [P = 0.02],
respectively).
Limitations
Single measurement of uric acid at baseline. Cause of death determined by death certificates
and expert consensus.
Conclusions
Elevated serum uric acid level is an independent risk factor for all-cause and cardiovascular
mortality in men treated with PD.
Index Words:
Serum uric acid, peritoneal dialysis, all-cause mortality, cardiovascular mortality
COMMENTS
Uric acid is the final product of purine nucleotide metabolism in humans. 4 Increased serum
uric acid levels have been shown to be related to kidney disease, CVD, hypertension, and
metabolic syndrome.
The large multicenter international study (DOPPS [Dialysis Outcomes & Practice Patterns
Study]) found that higher uric acid levels were associated with a lower risk of all-cause and
CV mortality in the hemodialysis population1 The studie mainly focused on hemodialysis
settings; however, the relationship of serum uric acid level and mortality is uncertain in
patients treated with PD. In addition, sex-related differences in serum uric acid level–
mortality have been reported, and some studies have shown serum uric acid level to be a
predictor of mortality in women only.
It is unclear whether uric acid level is an independent risk factor for increased all-cause and
CV mortality in both male and female patients treated with PD
From January 1, 2006, to November 30, 2010, a total of 985 consecutive patients were
recruited from a single PD center of the First Affiliated Hospital of Sun Yat-sen University.
Enrollment included all patients aged 18-80 years who had received continuous ambulatory
PD for more than 3 months, except those who had malignant disease or refused to give
written consent.
CVD was defined as history of angina pectoris, myocardial infarction, angioplasty, coronary
artery bypass, heart failure, or stroke. The Davies score assigns 1 point for each of the
following conditions: ischemic heart disease (defined as prior myocardial infarction, angina,
or ischemic changes on electrocardiogram), left ventricular dysfunction (defined as clinical
evidence of pulmonary edema not due to errors in fluid balance, or history of congestive
heart failure), peripheral vascular disease (includes distal aortic, lower extremity, and
cerebrovascular disease), malignancy, diabetes, collagen vascular disease, and other
significant pathology (eg, chronic obstructive pulmonary disease).24 The theoretical range is
0-7. Each score was categorized into 4 levels: 0, 1, 2, and >2.
The primary outcome of interest was all-cause mortality, and the second outcome of interest
was CV mortality. CV events contributing to CV mortality included acute myocardial
infarction, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest,
congestive heart failure, cerebrovascular accident (including intracranial hemorrhage),
ischemic brain damage, anoxic encephalopathy, and peripheral vascular disease.
Participants were stratified into tertiles of serum uric acid levels, which were calculated
separately in men (tertile 1 [lowest], <6.67; tertile 2 [middle], 6.67-7.56; and tertile 3 [highest],
>7.56 mg/dL) and women (tertile 1, <6.19; tertile 2, 6.19-7.13; and tertile 3, >7.13 mg/dL,
respectively).
A total of 985 patients were enrolled in this study (mean age, 48.3 ± 15.4 [SD] years; 58%
men; 23% with diabetes), with a median follow-up of 25.3 (maximum, 71.8) months. Mean
serum uric acid value was 7.0 (range, 3.8-19.8) mg/dL for all patients, and male patients had
a significantly higher mean serum uric acid level than female patients (7.2 ± 1.2 vs 6.8 ± 1.4
mg/dL, respectively; P < 0.001).
With each 1-mg/dL increase in serum uric acid level, adjusted HRs of all-cause and CV
mortality were 1.33 (95% CI, 1.14-1.56; P < 0.001) and 1.44 (95% CI, 1.17-1.77; P = 0.001)
for men and 1.03 (95% CI, 0.86-1.24; P = 0.8) and 1.16 (95% CI, 0.97-1.38; P = 0.1) for
women, respectively. As further support of this apparent difference by sex, they tested the
interaction between sex and serum uric acid level on all-cause and CV mortality among all
participants and observed a significant interaction (β = −0.06; [P = 0.02] and β = −0.10 [P =
0.02], respectively).
So, higher serum uric acid concentrations are associated with higher all-cause and CV
mortality only in male patients treated with PD. The association remained robust despite
adjustment for metabolic and CV risk factors. Further studies will be necessary not only to
determine whether uric acid–lowering regimens improve survival in patients treated with PD.
Pr. Jacques CHANARD
Professor of Nephrology