Allopurinol and Progression of CKD and Cardiovascular Events- Long-term Follow-up of a Randomized Clinical Trial.Am J Kidney Dis. 2015 Apr Background:Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk. Study Design:Post hoc analysis of a long-term follow-up after completion of the 2-year trial. Setting & Participants:113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years. Intervention: Continuation of allopurinol treatment, 100 mg/d, or standard treatment. Outcome:Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or$50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease). Results:During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P50.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88;P50.02; adjusted for age, sex, and baseline kidney function). Limitations:Small sample size, single center, not double blind, post hoc follow-up and analysis. Conclusions: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

1. Original Investigation
Allopurinol and Progression of CKD and Cardiovascular Events:
Long-term Follow-up of a Randomized Clinical Trial
Marian Goicoechea, MD, PhD, Soledad Garcia de Vinuesa, MD, Ursula Verdalles, MD,
Eduardo Verde, MD, Nicolas Macias, MD, Alba Santos, MD,
Ana Pe´rez de Jose, MD, PhD, Santiago Ceden˜o, MD, Tania Linares, MD, and
Jose Lun˜o, MD, PhD
Background: Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously
conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved
estimated glomerular filtration rate and reduced CV risk.
Study Design: Post hoc analysis of a long-term follow-up after completion of the 2-year trial.
Setting & Participants: 113 participants (57 in the allopurinol group and 56 in the control group) initially
followed up for 2 years and 107 participants followed up to 5 additional years.
Intervention: Continuation of allopurinol treatment, 100 mg/d, or standard treatment.
Outcome: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or $50%
decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction,
coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and pe-
ripheral vascular disease).
Results: During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with
6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking
allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up,
an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an
additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus,
during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a
renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P 5 0.004;
adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system
blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the
control group (HR, 0.43; 95% CI, 0.21-0.88; P 5 0.02; adjusted for age, sex, and baseline kidney function).
Limitations: Small sample size, single center, not double blind, post hoc follow-up and analysis.
Conclusions: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and
reduce CV risk.
Am J Kidney Dis. -(-):---. ª 2015 by the National Kidney Foundation, Inc.
INDEX WORDS: Chronic kidney disease (CKD) progression; allopurinol treatment; hyperuricemia; uric acid
concentration; cardiovascular (CV) risk; renal disease.
In a randomized study published in 2010, we
demonstrated that treatment with allopurinol pre-
vents progressive declines in glomerular filtration rate
(GFR) in patients with chronic kidney disease
(CKD).1
In that study, 113 patients were randomly
assigned to treatment with allopurinol or their stan-
dard medication (control group) and were followed up
for 2 years. The main results were as follows: (1)
treatment with allopurinol reduced levels of inflam-
matory markers and risk of hospitalization, (2) treat-
ment with allopurinol decreased the risk of
cardiovascular events in 71% of patients, (3) esti-
mated GFR (eGFR) increased 1.2 mL/min/1.73 m2
in
the allopurinol treatment group and decreased
3.4 mL/min/1.73 m2
in the control treatment group
(P 5 0.02), and (4) allopurinol led to a 47% reduction
in progression of CKD (defined as a decrease in
eGFR . 0.2 mL/min/1.73 m2
per month).
Recent epidemiologic studies have shown a rela-
tionship between uric acid level and progression of
kidney disease2-6
; however, to our knowledge, no
data have been published about the effect of
decreasing uric acid levels with allopurinol on long-
term progression of kidney disease.
We report a post hoc analysis of our previous
study, including long-term follow-up for 5 additional
years. Our aim was to determine whether continued
lowering of serum uric acid levels with allopurinol
From the Department of Nephrology, Hospital General
Universitario Gregorio Marañón, Madrid, Spain.
Received August 20, 2014. Accepted in revised form November
2, 2014.
Address correspondence to Marian Goicoechea, MD, PhD,
Department of Nephrology, Hospital General Universitario
Gregorio Marañón, C/Dr Esquerdo 46, 28007 Madrid, Spain.
E-mail: marian.goicoechea@gmail.com
Ó 2015 by the National Kidney Foundation, Inc.
0272-6386
http://dx.doi.org/10.1053/j.ajkd.2014.11.016
Am J Kidney Dis. 2015;-(-):--- 1

2. could maintain the positive effect of allopurinol on
slowing progression of kidney disease.
METHODS
Study Design
The design of the previous randomized controlled trial (RCT)
has been described elsewhere.1
Briefly, 113 patients with
eGFRs , 60 mL/min/1.73 m2
, stable clinical condition (no hos-
pitalizations or cardiovascular events within the 3 months before
screening), and stable kidney function were randomly assigned
according to a computer-generated list to continue with their
standard treatment (control group) or to treatment with allopurinol
at 100 mg/d. The dosage of antihypertensive drugs, lipid-lowering
agents, and antiplatelet drugs was continued with adjustment ac-
cording to the individual patient’s clinical condition. Participants
were followed up for a mean of 23.4 6 7.8 (standard deviation)
months. The end points analyzed were as follows: (1) hospitali-
zations, (2) cardiovascular events (defined as myocardial infarc-
tion, coronary revascularization or angina pectoris, congestive
heart failure, cerebrovascular disease, and peripheral vascular
disease), (3) end-stage renal disease requiring dialysis therapy, and
(4) mortality.
Congestive heart failure was diagnosed by x-ray examination
(pulmonary edema) and echocardiogram (left ventricular
dysfunction). Patients with congestive heart failure were consid-
ered symptomatic and in New York Heart Association class II to
IV with left ventricular ejection fraction # 45%. Patients were
considered to have cerebrovascular disease when they had a his-
tory of ischemic or hemorrhagic stroke, transient ischemic attack
(verified using computed tomography), or carotid artery sten-
osis . 70% (verified using Doppler ultrasound). The diagnosis of
peripheral vascular disease was based on the presence of inter-
mittent claudication, angiography or ultrasonography proven ste-
nosis of the major arteries of the lower limbs, and ulcers caused by
atherosclerotic disease or by surgery.
When the initial study finished, patients returned to community-
or hospital-based nephrology care, with no attempt to maintain
previously randomly assigned therapy; any changes in their
treatment during the long-term follow-up period were made by
their attending physicians. For the post hoc study, we redefined
progression of kidney disease (renal event) as initiating dialysis
therapy and/or doubling serum creatinine level and/or $50%
decrease in eGFR. Cardiovascular events were defined as in the
initial study. A compound outcome was analyzed as cardiovas-
cular and/or renal event.
The same independent researcher (M.G.) assessed renal and
cardiovascular events from the clinical history. The researcher
obtained full documentation on all putative outcomes from hos-
pitals. The researcher did not know whether the patient belonged
to the allopurinol group or the control group.
Follow-up Assessment
Serum creatinine, uric acid, daily urinary protein excretion, he-
moglobin, and C-reactive protein were monitored at least yearly
after the trial. The isotope-dilution mass spectrometry–traceable 4-
variable MDRD (Modification of Diet in Renal Disease) Study
equation was used to estimate GFR. Routine clinical and
biochemical variables were measured on autoanalyzers using stan-
dardized methods. High-sensitivity C-reactive protein in plasma
was measured using a latex-based turbidimetric immunoassay on a
Hitachi analyzer (Sigma Chemical Co). Daily urinary albumin
excretion was measured using an immunonephelometric method.
Statistical Analysis
Statistical analysis was performed by intention to treat. All
statistical analyses were performed using IBM SPSS, version 21.0
(IBM Corp) for Windows XP. Values are expressed as mean6
standard deviation or median with interquartile range. Categorical
data were compared using c2
test; continuous variables, using t
test. Two-way analysis of variance (ANOVA) was used to
examine the influence of 2 different categorical independent var-
iables on 1 dependent variable. Kaplan-Meier curves and log-rank
test were used to analyze renal and cardiovascular survival. Cox
proportional hazard models were used to evaluate the risk of
cardiovascular events and progression of kidney disease, and re-
sults were adjusted for several covariates. Age, sex, and baseline
kidney function were entered into the model as potential con-
founding covariates. Univariate Cox regression was used to
determine which covariates should be introduced in the multi-
variable model. Statistical significance is defined as 2-tailed
P , 0.05.
RESULTS
Patient Flow
Baseline characteristics, previous cardiovascular
diseases, concomitant medication, and laboratory pa-
rameters have been described elsewhere1
and are lis-
ted in Table 1. In the original study, 113 participants
(57 in the allopurinol group and 56 in the control
group) initially were followed up for 2 years. In the
long-term follow-up reported here, 107 participants
were followed up to 5 additional years (56 in the
allopurinol group because 1 patient was lost to
follow-up and 51 in the control group because 3 pa-
tients were lost to follow-up and 2 patients died).
Overall median follow-up was 84 (interquartile range,
54-84) months from time of randomization. A patient
flow chart (initial and post hoc study) is shown in
Fig 1A and B.
During the long-term follow-up, 10 patients from
the control group received allopurinol. Two patients
in the allopurinol group stopped treatment during the
RCT phase owing to gastrointestinal symptoms and
12 additional patients stopped treatment during the
long-term follow-up owing to unknown cause.
Progression of Kidney Disease
After a median follow-up of 84 months, serum uric
acid levels were significantly decreased in the allo-
purinol group, from 7.8 6 2.1 to 6.6 6 1.5 mg/dL
(P 5 0.04), but were unchanged throughout the study
in the control group (baseline, 7.3 6 1.6 mg/dL; 84
months, 7.1 6 1.35 mg/dL). eGFRs in the allopurinol
and control groups decreased by 6.5 6 1.6 and
13.3 6 5.0 mL/min/1.73 m2
, respectively, after 84
months (P 5 0.001). eGFRs decreased over time
(P 5 0.001), and this decrease differed significantly
between groups (P 5 0.001; 2-way ANOVA).
Follow-up averages of uric acid and eGFR values
during the RCT and long-term follow-up are shown in
Table S1.
In a post hoc analysis of the initial study, a renal
event (initiating dialysis therapy and/or doubling
serum creatinine and/or $50% decrease in eGFR)
Goicoechea et al
2 Am J Kidney Dis. 2015;-(-):---

3. was recorded in 2 of the 57 allopurinol group patients
(1 initiated dialysis therapy and serum creatinine
doubled in 1) and 6 of the 56 control group patients (1
initiated dialysis therapy and serum creatinine level
doubled in 5; log-rank, 2.912; P 5 0.09). During
long-term follow-up, an additional 7 and 18 partici-
pants from the original allopurinol and control groups,
respectively, experienced a renal event. Thus, during
the entire 84-month follow-up, renal events were
recorded in 9 of 57 patients in the allopurinol group: 7
initiated dialysis therapy and 2 had eGFRs that had
decreased by $50%. In the control group, during the
full 84-month follow-up, a renal event was recorded
in 24 of the 56 patients: 13 patients started dialysis
therapy and 11 showed serum creatinine values that
had doubled or eGFRs that decreased by $50%.
Renal events are shown in the Kaplan-Meier curves
(log-rank, 9.487; P 5 0.002; Fig 2). Treatment with
allopurinol reduced the hazard rate for renal events by
68% compared to the control group (hazard ratio
[HR], 0.32; 95% confidence interval [CI], 0.15-0.69;
P 5 0.004).
Cardiovascular Risk
During the initial 2-year follow-up, 7 of 57 in the
allopurinol group and 15 of 56 in the control group
experienced a cardiovascular event. During long-term
follow-up, an additional 9 and 8 participants in the
allopurinol and control groups, respectively, had a
cardiovascular event. Thus, during the entire 84-
month follow-up, 39 patients had a cardiovascular
event (16 in the allopurinol group, 23 in the control
group). Cardiovascular events were as follows: 11
congestive heart failures, 16 ischemic coronary
events, 10 cerebrovascular accidents, and 2 cases of
peripheral artery disease. The distribution of cardio-
vascular events in the 2 groups of patients during the
84-month follow-up is shown in Table S2. After
adjustment for potential confounders, allopurinol
reduced the hazard rate for cardiovascular risk by
57% (HR, 0.43; 95% CI, 0.21-0.88; P 5 0.02).
Mortality and Adverse Events
There were 17 and 19 deaths in the allopurinol and
control groups, respectively. Causes of death were
cardiovascular disease (n 5 12), infection (n 5 2),
malignancy (n 5 8), and other (n 5 14). Patients in
the allopurinol group had a lower composite renal and
cardiovascular event rate compared with the control
group (log-rank, 11.04; P 5 0.001; Fig S1).
During the RCT, allopurinol was withdrawn in 2
patients because of gastrointestinal symptoms. No
abnormalities in liver function, hematologic alter-
ations, or serious adverse events associated with
allopurinol were recorded in the RCT or the long-term
follow-up.
DISCUSSION
This post hoc intention-to-treat analysis of previ-
ously published study data shows that the beneficial
effect of treatment with allopurinol on progression of
kidney disease and cardiovascular risk was main-
tained in the long term.1
After a median follow-up of
7 years, allopurinol was shown to reduce the risk of
Table 1. Baseline Characteristics
Control
(n 5 56)
Allopurinol
(n 5 57)
Age (y) 71.4 6 9.5 72.1 6 7.9
Cystatin C (mg/L) 1.9 6 0.7 1.9 6 0.5
Serum creatinine (mg/dL) 1.8 6 0.6 1.7 6 0.4
eGFR (mL/min/1.73 m2
) 39.5 6 12.4 40.6 6 11.3
Uric acid (mg/dL) 7.3 6 1.6 7.8 6 2.1
hs-CRP (mg/L) 3.4 [1.8-7.0] 4.4 [2.5-7.0]
Serum fibrinogen (mg/dL) 374 6 78 381 6 79
ESR (mm/h) 15 [8-29] 17 [8-32]
Hemoglobin (g/dL) 14.5 6 4.6 13.6 6 1.7
Serum albumin (g/dL) 4.4 6 0.3 4.3 6 0.3
Albuminuria (mg/d) 35 [11-436] 36 [15-356]
Renal pathology
Diabetes mellitus 10 (18) 9 (16)
Hypertensive kidney disease 25 (45) 28 (49)
Glomerulonephritis 5 (9) 1 (2)
Polycystic kidney disease 1 (2) 2 (3)
Interstitial nephropathy 2 (3) 8 (14)
Systemic vasculitis 2 (3) 0 (0)
Unknown-cause kidney disease 11 (20) 9 (16)
Diabetes mellitus 20 (36) 22 (39)
Ischemic cardiopathy 10 (18) 16 (28)
Cerebrovascular disease 2 (4) 2 (3)
Peripheral vascular disease 1 (2) 5 (9)
Diuretic use 30 (54) 36 (63)
Thiazide diuretics 13 (23) 15 (27)
Loop diuretics 17 (30) 21 (37)
RAAS blockers 41 (73) 47 (82)
Calcium channel blockers 20 (36) 13 (23)
Statin treatment 24 (43) 27 (47)
Antiplatelet treatment 18 (32) 15 (26)
Double treatment 28 (50) 32 (56)
Triple treatment 11 (20) 8 (14)
Note: Values for categorical variables are given as number
(percentage); values for continuous variables are given as
mean 6 standard deviation or median [interquartile range]. No
significant differences were observed between the different
analyzed variables. Conversion factors for units: creatinine in
mg/dL to mmol/L, 388.4; uric acid in mg/dL to mmol/L, 359.48;
fibrinogen in mg/dL to mmol/L, 30.0294.
Abbreviations and definitions: double treatment, RAAS
blockers and statins or antiplatelet treatment; eGFR, estimated
glomerular filtration rate; ESR, erythrocyte sedimentation rate;
hs-CRP, high-sensitivity C-reactive protein; RAAS, renin-
angiotensin-aldosterone system; triple treatment, RAAS
blockers and statins and antiplatelet treatment.
Am J Kidney Dis. 2015;-(-):--- 3
Allopurinol and CKD Progression

4. Figure 1. (A) Patient flow chart of the initial study. In the allopurinol treatment group, 2 patients stopped the treatment during ran-
domized controlled trial (RCT) because of gastrointestinal symptoms. In the initial RCT, 3 patients from the allopurinol group and 6
patients from the control group were lost to follow-up. Five patients (allopurinol group, 2; control group, 3) who had moved to other
hospitals were rescued and followed up in the post hoc analysis. (B) Patient flow chart of the post hoc study. One patient in the control
group was lost to follow-up and 3 patients in the control group (2 deaths and 1 lost to follow-up); 12 patients stopped the treatment
during the post hoc study in the allopurinol group, and in the control group, 10 patients initiated treatment with allopurinol.
4 Am J Kidney Dis. 2015;-(-):---
Goicoechea et al

5. renal events by 68% and the risk of cardiovascular
events by 57%. Our study design is strengthened by
the use of a renal end point that included initiation of
dialysis therapy and doubling of serum creatinine
level. Based on a long follow-up period, we demon-
strated that patients with CKD treated with allopurinol
have a lower risk of kidney disease progression.
Although numerous epidemiologic studies have
shown an association between hyperuricemia and risk
of kidney disease,7-11
this finding is not universal. For
example, an analysis of 840 individuals with CKD
stages 3 to 4 participating in the MDRD Study did not
find uric acid level to be an independent risk factor for
progression to chronic kidney failure despite a 10-
year follow-up.12
Very few interventional studies have shown a causal
relationship between hyperuricemia and kidney dis-
ease progression. Siu et al13
randomly assigned 54
patients with CKD (stages 3 and 4) to receive allopu-
rinol, 100 to 300 mg/d, for 12 months or to continue
with their usual therapy and found that allopurinol
slowed the progression of kidney disease. Kanbay
et al14
subsequently performed a study of 105 patients
(72 hyperuricemic patients and 33 normouricemic
patients with normal kidney function). The 72 hyper-
uricemic patients were randomly assigned to receive
allopurinol, 300 mg/d, for 4 months or no treatment.
Treatment with allopurinol led to a decrease in uric
acid levels that was associated with improved endo-
thelial function (P 5 0.003), GFR (P 5 0.001), and
systolic blood pressure (P 5 0.001). In an open-label
randomized controlled study, Shi et al15
evaluated
treatment with allopurinol in 40 patients with immu-
noglobulin A nephropathy. After 6 months, treatment
with allopurinol had not affected progression of CKD
or proteinuria, although it had improved blood pres-
sure significantly. However, 6 months is too short a
period to assess the effect on progression of kidney
disease.
In addition to small-scale randomized interven-
tional studies, post hoc analyses have corroborated the
effect of decreased uric acid level on progression of
CKD. In a post hoc analysis of the RENAAL
(Reduction of Endpoints in Non2Insulin Dependent
Diabetes With the Angiotensin II Antagonist Los-
artan) Study,16
which included 1,232 diabetic patients
randomly assigned to receive losartan or placebo, 6-
month uric acid levels predicted renal events, which
were defined as progression to dialysis therapy or a
50% increase in creatinine levels. Therefore, these
findings confirm that uric acid level may be a modi-
fiable factor in progression of CKD. However,
although current data are insufficient to assess
whether the beneficial effect of allopurinol is from the
reduction in uric acid level or the antioxidant effect
produced when xanthine oxidase is inhibited, exper-
imental studies suggest that endothelial function,
diabetes, cardiac insufficiency, and decreased kidney
function improve when uric acid level decreases with
allopurinol, but not with other hypouricemic
drugs.17,18
In addition to its beneficial effect in patients with
kidney disease, treatment with allopurinol reduces
cardiovascular risk regardless of previous coronary
artery disease, diabetes, inflammation, age, sex, and
baseline kidney function. In a recent epidemiologic
study19
of NHANES (National Health and Nutrition
Examination Survey; 1988-1994 and 1999-2002;
10,956 participants), a U-shaped association was
observed between uric acid level and cardiovascular
mortality in both women and men, although the
lowest risk of cardiovascular mortality was recorded
at a lower uric acid level for women than for men. The
authors also observed an association between the
highest quartile of uric acid level and cardiovascular
mortality, even after adjustment for potential con-
founders (HR, 1.48; 95% CI, 1.13-1.96); however,
this association was attenuated after adjustment for
albumin-creatinine ratio and eGFR (HR, 1.25; 95%
CI, 0.89-1.75). Other epidemiologic studies also have
shown an association between uric acid level and
cardiovascular risk.20-22
However, interventional studies are scarce. Uric
acid can induce growth of cardiomyocytes and car-
diac interstitial fibrosis, an observation that is
corroborated in a study conducted in Japan in which
patients with higher uric acid levels had a higher
prevalence of left ventricular hypertrophy.23
A
Figure 2. Kaplan-Meier curves for renal events. Differences
were evaluated using log-rank test.
Am J Kidney Dis. 2015;-(-):--- 5
Allopurinol and CKD Progression

6. randomized crossover study (65 patients with chronic
stable angina receiving placebo or high-dose allopu-
rinol [600 mg/d]) published some years ago showed
that when patients were treated with allopurinol, ex-
ercise capacity and time to onset of chest pain
improved.24
In a post hoc analysis of the RENAAL
Study and IDNT (Irbesartan Diabetic Nephropathy
Trial), Cox regression analysis was used to determine
whether the short-term effect of losartan and of irbe-
sartan on uric acid level is associated with long-term
cardiovascular outcome. The main finding was that
the reduction in uric acid level accounts for some of
the cardiovascular effect of losartan, thus supporting
the hypothesis that uric acid level is a modifiable risk
factor in cardiovascular disease, at least in individuals
with type 2 diabetes with nephropathy.25
To our
knowledge, our study is the first randomized trial to
demonstrate that treatment with allopurinol reduces
long-term cardiovascular risk in patients with CKD.
Our study is subject to a series of limitations. First,
it was not double blind. Second, the sample size is too
small for robust conclusions to be drawn and data are
from a single center. Third, despite the beneficial re-
sults of treatment with allopurinol in the progression
of CKD in the previous RCT, participants were not
required to adhere to randomly assigned treatment
during the long-term follow-up and crossovers may
bias toward the null. Nevertheless, despite these
limitations, the long follow-up time and the signifi-
cant differences in progression of kidney disease be-
tween patients treated with allopurinol and those who
continued with their standard treatment could validate
and reinforce our findings. In addition, we provide
sufficient evidence to support large-scale controlled
interventional trials to prove the hypothesis that
lowering uric acid levels with allopurinol could pre-
vent progression of CKD.
ACKNOWLEDGEMENTS
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Contributions: Research idea and study design: MG, SMGdV,
JL; data acquisition: MG, SMGdV, UV, EV, NM, AS, APdJ, SC,
TL; statistical analysis: MG, JL; supervision or mentorship: MG,
SMGdV, LJ. Each author contributed important intellectual con-
tent during manuscript drafting or revision and accepts account-
ability for the overall work by ensuring that questions pertaining to
the accuracy or integrity of any portion of the work are appro-
priately investigated and resolved. MG takes responsibility that
this study has been reported honestly, accurately, and trans-
parently; that no important aspects of the study have been omitted;
and that any discrepancies from the study as planned have been
explained.
SUPPLEMENTARY MATERIAL
Table S1: Follow-up averages of uric acid and eGFR during the
RCT and post hoc study.
Table S2: Distribution of cardiovascular events during the RCT
and post hoc study.
Figure S1: Kaplan-Meier curves for composite outcome: renal
and cardiovascular events.
Note: The supplementary material accompanying this article
(http://dx.doi.org/10.1053/j.ajkd.2014.11.016) is available at
www.ajkd.org
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Allopurinol and CKD Progression