CLINICAL RESEARCH
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Oxalate Intake and the Risk for Nephrolithiasis
Eric N. Taylor* and Gary C. Curhan*
*Renal Division and Channing Laboratory, Department of Medicine, Brigham and Womens Hospital, Harvard
Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
ABSTRACT
Most kidney stones consist of calcium oxalate, and higher urinary oxalate increases the risk for calcium
oxalate nephrolithiasis. However, the relation between dietary oxalate and stone risk is unclear. This
study prospectively examined the relation between oxalate intake and incident nephrolithiasis in the
Health Professionals Follow-up Study (n 45,985 men), the Nurses Health Study I (n 92,872 older
women), and the Nurses Health Study II (n 101,824 younger women). Food frequency questionnaires
were used to assess oxalate intake every 4 yr. Cox proportional hazards regression was used to adjust
for age, body mass index, thiazide use, and dietary factors. A total of 4605 incident kidney stones were
documented over a combined 44 yr of follow-up. Mean oxalate intakes were 214 mg/d in men, 185 mg/d
in older women, and 183 mg/d in younger women and were similar in stone formers and nonstone
formers. Spinach accounted for 40% of oxalate intake. For participants in the highest compared with
lowest quintile of dietary oxalate, the relative risks for stones were 1.22 (95% confidence interval [CI]
1.03 to 1.45; P 0.01 for trend) for men and 1.21 (95% CI 1.01 to 1.44; P 0.05 for trend) for older
women. Risk was higher in men with lower dietary calcium (P 0.08 for interaction). The relative risks for
participants who ate eight or more servings of spinach per month compared with fewer than 1 serving
per month were 1.30 (95% CI 1.08 to 1.58) for men and 1.34 (95% CI 1.10 to 1.64) for older women.
Oxalate intake and spinach were not associated with risk in younger women. These data do not implicate
dietary oxalate as a major risk factor for nephrolithiasis.
J Am Soc Nephrol 18: 2198 2204, 2007. doi: 10.1681/ASN.2007020219
Kidney stones are common, costly, and painful. The
lifetime prevalence of symptomatic nephrolithiasis
is approximately 10% in men and 5% in women,1,2
and more than $2 billion is spent on treatment each
year.3,4 Approximately 80% of kidney stones contain calcium, and the majority of calcium stones
consist primarily of calcium oxalate.5 Small increases in urinary oxalate can have a major effect on
calcium oxalate crystal formation,6 and higher levels of urinary oxalate are a major risk factor for the
formation of calcium oxalate kidney stones.5,7 Because oxalate is a metabolic end product and is excreted unchanged in the urine after absorption in
the gastrointestinal tract, clinicians routinely recommend a low-oxalate diet to patients with calcium oxalate nephrolithiasis.8
However, the role of dietary oxalate in the
pathogenesis of calcium oxalate nephrolithiasis is
unclear.9 Uncertainty about the impact of dietary
oxalate on stone risk centers around the contribu2198
ISSN : 1046-6673/1807-2198
tion of oxalate intake to urinary oxalate excretion. A
large amount of urinary oxalate is derived from the
endogenous metabolism of glycine, glycolate, hydroxyproline, and dietary vitamin C,10,11 and the
proportion of urinary oxalate derived from dietary
oxalate is unclear (estimates range from 10 to
50%12). Studies of dietary oxalate and stone risk
also must account for the intake of other dietary
factors. For example, the intake of calcium and
magnesium may modulate the intestinal absorption of dietary oxalate.9 Observational data showing
an inverse relation between dietary calcium and the
Received February 20, 2007. Accepted April 9, 2007.
Published online ahead of print. Publication date available at
www.jasn.org.
Correspondence: Dr. Eric N. Taylor, Channing Laboratory, Third
Floor, Brigham and Womens Hospital, 181 Longwood Avenue,
Boston, MA 02115. Phone: 617-525-2043; Fax: 617-525-2008;
E-mail:
[email protected]Copyright 2007 by the American Society of Nephrology
J Am Soc Nephrol 18: 2198 2204, 2007
www.jasn.org
risk for incident kidney stones1315 suggested that dietary calcium may bind to oxalate in the gut, thereby limiting intestinal
oxalate absorption (and subsequent urinary oxalate excretion). Indeed, the inhibitory effect of calcium ingestion on urinary oxalate excretion has been demonstrated in oxalate loading studies.16 18 Magnesium intake may also decrease urinary
oxalate in a similar manner.19 21
To examine the relation between oxalate intake and the incidence of kidney stones, we conducted a prospective study of
three large cohorts: the Health Professionals Follow-up Study
(HPFS) and the Nurses Health Studies I and II (NHS I and
NHS II).
RESULTS
During a combined 44 yr of follow-up, we documented 4605
new symptomatic kidney stones in the three cohorts. In HPFS
(men), NHS I (older women), and NHS II (younger women),
there were 1627, 1414, and 1564 incident kidney stones, respectively.
Table 1 displays mean oxalate intake for HPFS and NHS I in
1994 and for NHS II in 1995. In each cohort, there were no
substantial changes in oxalate intake over time. On average,
men without kidney stones consumed 214 mg/d oxalate (median 191 mg; 10th to 90th percentile range 106 to 329 mg),
older women without kidney stones consumed 185 mg/d oxalate (median 165 mg; 10th to 90th percentile range 87 to 287
mg), and younger women without kidney stones consumed
183 mg/d oxalate (median 158 mg; 10th to 90th percentile
range 86 to 293 mg). There was no statistically significant difference in oxalate intake between participants with and without kidney stones.
The main sources of dietary oxalate were vegetables, fruits,
nuts, and grains. The 10 foods that contribute most to total
oxalate intake are listed in Table 2. Many foods that are high in
oxalate, such as rhubarb, did not contribute substantially to
oxalate intake because they were consumed relatively infre-
CLINICAL RESEARCH
quently. In each cohort, spinach was the highest contributor to
total oxalate intake. Consumption of spinach (cooked plus
raw) constituted 40.4% of oxalate intake in men, 44.2% of
oxalate intake in older women, and 42.3% of oxalate intake in
younger women. Consumption of potatoes (not mashed or
French fried) constituted 10.2% of oxalate intake in men,
11.1% of oxalate intake in older women, and 9.9% of oxalate
intake in younger women. All other foods contributed 5% to
oxalate intake.
After adjustment for age, oxalate intake was inversely associated with the risk for incident kidney stones in all three cohorts (Table 3). However, after multivariate adjustment, oxalate intake was associated with a modest increase in risk in
HPFS and NHS I. The multivariate relative risk for men in the
highest as compared with lowest quintile of dietary oxalate was
1.22 (95% confidence interval [CI] 1.03 to 1.45; P 0.01 for
trend) and the multivariate relative risk for older women was
1.21 (95% CI 1.01 to 1.44; P 0.05 for trend). After multivariate adjustment, no association with risk was observed in
younger women. We also evaluated kidney stone risk associated with extreme categories, rather than quintiles, of oxalate
intake. The multivariate relative risk for men who consumed
350 mg/d oxalate (median intake 445 mg) compared with
100 mg/d (median intake 87 mg) was 1.35 (95% CI 1.05 to
1.73; P 0.009 for trend). The multivariate relative risks in
identical categories for older and younger women were 1.28
(95% CI 0.97 to 1.68; P 0.10 for trend) and 1.11 (95% CI 0.86
to 1.45; P 0.28 for trend), respectively.
Because of the importance of spinach as a contributor to
total oxalate intake, we evaluated the association between spinach intake and kidney stone risk (Table 4). Spinach contains
many dietary factors that are associated with risk (e.g., calcium,
potassium, magnesium, vitamin C), thereby complicating the
interpretation of multivariate stone risk that is associated with
spinach intake. However, spinach contributed to 2% of calcium, potassium, magnesium, and vitamin C intake in each
cohort. Total spinach intake was associated with risk in men
Table 1. Oxalate intake (mg/d) in men (HPFS), older women (NHS I), and younger women (NHS II)a
Parameter
HPFS
mean (SD)
median
10th to 90th percentile range
NHS I
mean (SD)
median
10th to 90th percentile range
NHS II
mean (SD)
median
10th to 90th percentile range
Stone
Formers
NonStone
Formers
215 (117)
194
107 to 342
214 (121)
191
106 to 329
0.84
184 (109)
166
86 to 291
185 (112)
165
87 to 287
0.94
179 (121)
151
81 to 283
183 (121)
158
86 to 293
0.45
For illustrative purposes, oxalate values were derived from responses to the 1994 (men and older women) and 1995 (younger women) dietary questionnaires.
Updated period-specific values were used for prospective analyses. Oxalate values were adjusted for total caloric intake. HPFS, Health Professionals Follow-up
Study; NHS I, Nurses Health Study I; NHS II, Nurses Health Study II.
J Am Soc Nephrol 18: 2198 2204, 2007
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Table 2. Foods that contribute to oxalate intake in men (HPFS), older women (NHS I), and younger women (NHS II)a
HPFS
NHS I
NHS II
Food
Food
Food
Cooked spinach
Raw spinach
Potatoes (whole)
Cold cereal
Oranges
French fries
Mixed nutsb
Navy beans (canned)
Cookiesc
Peanuts
23.1
17.3
10.2
4.4
2.9
1.9
1.7
1.7
1.6
1.6
Cooked spinach
Raw spinach
Potatoes (whole)
Cold cereal
Oranges
Coffee
Cooked carrots
Tea
Cookiesc
Pasta sauced
25.8
18.4
11.1
4.3
2.5
1.7
1.7
1.6
1.5
1.4
Cooked spinach
Raw spinach
Potatoes (whole)
Cold cereal
French fries
Oranges
Pasta
Pasta sauced
English muffins
Coffee
22.0
20.3
9.9
3.8
2.5
2.0
2.0
1.9
1.7
1.7
Expressed as percentage of total oxalate intake. Based on oxalate content and frequency of consumption. For illustrative purposes, values were derived from
responses to the 1994 (men and older women) and 1995 (younger women) dietary questionnaires.
b
With peanuts.
c
Chocolate chip.
d
Marinara.
Table 3. RR for incident kidney stones in men (HPFS), older women (NHS I), and younger women (NHS II) by quintile of
oxalate intakea
Parameter
HPFS
quintile median (mg/d)
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)b
NHS I
quintile median (mg/d)
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)b
NHS II
quintile median (mg/d)
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)b
Quintile
P for Trend
106
363
105,806
1.0
1.0
149
317
106,298
0.89 (0.76 to 1.03)
1.01 (0.86 to 1.17)
191
325
107,393
0.89 (0.77 to 1.04)
1.07 (0.92 to 1.25)
236
313
108,200
0.85 (0.73 to 0.99)
1.10 (0.94 to 1.29)
328
309
107,788
0.85 (0.73 to 0.99)
1.22 (1.03 to 1.45)
0.04
0.01
87
312
254,953
1.0
1.0
127
279
257,271
0.89 (0.76 to 1.05)
1.02 (0.86 to 1.20)
164
304
259,528
0.96 (0.82 to 1.12)
1.16 (0.99 to 1.36)
205
250
259,712
0.79 (0.67 to 0.93)
1.03 (0.87 to 1.23)
287
269
258,882
0.85 (0.72 to 1.00)
1.21 (1.01 to 1.44)
0.03
0.05
85
365
169,306
1.0
1.0
117
340
168,806
0.95 (0.82 to 1.10)
1.03 (0.88 to 1.20)
157
296
169,837
0.83 (0.71 to 0.96)
0.96 (0.82 to 1.13)
202
286
169,964
0.80 (0.69 to 0.94)
1.00 (0.85 to 1.18)
293
277
169,674
0.79 (0.67 to 0.92)
1.06 (0.89 to 1.27)
0.001
0.57
CI, confidence interval; RR, relative risk.
Results are adjusted for age; body mass index (BMI; six categories); use of thiazide diuretics (yes or no); fluid intake (in quintiles); alcohol use (seven
categories); calcium supplement use (four categories); and dietary intake of animal protein, calcium, potassium, sodium, phytate, vitamin C, and magnesium (all
in quintiles).
and older women but not in younger women. The multivariate
relative risk for men who consumed eight or more servings of
spinach per month compared with fewer than one serving was
1.30 (95% CI 1.08 to 1.58), and the multivariate relative risk for
older women was 1.34 (95% CI 1.10 to 1.64).
We also tested the hypothesis that the relation between
dietary oxalate and stone risk varied by calcium intake. Because we did not have data about the timing of calcium
supplement ingestion in relation to food intake, we performed these stratified analyses in participants who did not
consume calcium supplements. In men with dietary calcium
below the median (755 mg/d), the multivariate relative risk
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Journal of the American Society of Nephrology
in the highest as compared with lowest quintile of dietary
oxalate was 1.46 (95% CI 1.11 to 1.93; P 0.008 for trend).
In men with calcium intake at or above the median, the
multivariate relative risk in the highest as compared with
lowest quintile of dietary oxalate was 0.83 (95% CI 0.61 to
1.13; P 0.31 for trend). The P value for interaction between oxalate and calcium intake was 0.08. In contrast, the
relation between oxalate intake and stone risk did not vary
by calcium intake in older or younger women.
Stratified analyses of the relation between oxalate intake
and risk evaluating the lowest quintile of calcium intake, rather
than median calcium intake, did not result in higher estimates
J Am Soc Nephrol 18: 2198 2204, 2007
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CLINICAL RESEARCH
Table 4. Total spinach intake and the relative risk for incident kidney stones in men (HPFS), older women (NHS I), and
younger women (NHS II)
Spinach Servings
Parameter
HPFS
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)a
NHS I
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)a
NHS II
cases
person-years
age-adjusted RR (95% CI)
multivariate RR (95% CI)a
<1/mo
1 to 7/mo
>8/mo
541
174,589
1.0
1.0
936
307,680
0.95 (0.86 to 1.06)
1.11 (0.99 to 1.24)
150
53,214
0.89 (0.75 to 1.07)
1.30 (1.08 to 1.58)
468
411,253
1.0
1.0
807
753,777
0.92 (0.82 to 1.03)
1.09 (0.97 to 1.23)
139
125,316
0.95 (0.78 to 1.14)
1.34 (1.10 to 1.64)
684
328,525
1.0
1.0
766
445,464
0.84 (0.76 to 0.93)
0.96 (0.87 to 1.07)
114
73,598
0.76 (0.62 to 0.93)
1.00 (0.81 to 1.24)
Results adjusted for age; BMI (six categories); use of thiazide diuretics (yes or no); fluid intake (in quintiles); alcohol use (seven categories); calcium supplement
use (four categories); and dietary intake of animal protein, calcium, potassium, sodium, phytate, vitamin C, and magnesium (all in quintiles).
of risk. Finally, the relation between oxalate intake and risk did
not vary by magnesium intake or body size.
DISCUSSION
In men (HPFS) and older women (NHS I), oxalate intake and
spinach consumption were associated with small increases in
the risk for incident kidney stone formation. The magnitude of
risk was higher in men who consumed lower intakes of dietary
calcium. In contrast to men and older women, we observed no
relation between dietary oxalate or spinach and stone risk in
younger women (NHS II). Of note, we have reported previously that the relation between some dietary factors and stone
risk varies by cohort. For instance, potassium intake is inversely associated with risk in men and older women but not in
younger women.1315 It is possible that the association between
oxalate intake and stone risk varies by age, but there were not
enough older women in NHS II to permit age-stratified analyses.
The modest associations between dietary oxalate and stone
risk that were observed in our study may reflect the primacy of
endogenous oxalate synthesis in the pathogenesis of hyperoxaluria. The proportion of urinary oxalate that is derived from
dietary oxalate is unclear: estimates range from 10 to 50%.12
However, it is well established that a large proportion of urinary oxalate is derived from the endogenous metabolism of
glycine, glycolate, hydroxyproline, and dietary vitamin C.10,11
A recent metabolic study compared a controlled diet with 25%
of protein from gelatin (2.75 g of hydroxyproline) with the
same diet except with 25% of protein from whey (containing
no hydroxyproline).22 The diet that was high in hydroxyproline increased urinary oxalate excretion by 42%. Another metabolic trial demonstrated that 1000 mg of supplemental vitamin C consumed twice daily increased urinary oxalate
excretion by 20 to 33%.23
J Am Soc Nephrol 18: 2198 2204, 2007
To our knowledge, only two previous studies that used direct analytical techniques to measure food oxalate attempted
to quantify the oxalate content of the typical Western diet. One
study consisted of five healthy individuals (mean age 29 yr),
and the mean oxalate intake, as measured by a 3-d dietary
record, was 152 mg/d.24 The other study consisted of 186 calcium oxalate stone formers (mean age 48 yr), divided into two
groups on the basis of urinary oxalate excretion. The difference
in oxalate intake between the two groups was not statistically
significant, and the mean intakes, as measured by a 24-h dietary record, were 101 and 130 mg/d.25 No analysis was performed to determine whether oxalate intake varied by gender.
Our study suggests that oxalate intakes in free-living Western
populations are substantially higher and that men consume
more oxalate than women.
Our data do not exclude an important role for dietary oxalate in the pathogenesis of calcium oxalate kidney stone formation. Although oxalate intake did not differ substantially
between stone formers and nonstone formers, it is reasonable
to speculate that stone formers might absorb more dietary oxalate than their nonstone-forming counterparts. Indeed, increased absorption of dietary oxalate may be observed in up to
one third of patients with calcium oxalate nephrolithiasis.12
Another study found that mean oxalate absorption in normal
volunteers was 8%, compared with 10.2% in a group of calcium oxalate stone formers.26 Some data suggest that differential rates of colonization by Oxalobacter formigenes, an enteric
oxalate-degrading organism, may be responsible for such variation.2729 Finally, genetic difference between individuals
might result in differences in intestinal oxalate absorption.9
A limitation to this study is that the bioavailability of dietary
oxalate may vary substantially by food type. For example, bioavailability (as measured by the increase in urinary oxalate excretion 6 to 8 h after food ingestion) ranges from 0.6 to 2.4%
Oxalate Intake and the Risk for Nephrolithiasis
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for spinach and may be as high as 4% for rhubarb.30 32 Marked
differences in oxalate bioavailability between frequently consumed foods in our study would introduce error into our measurements of dietary oxalate exposure and would attenuate the
observed associations between dietary oxalate and stone risk.
Although some authors have proposed measuring soluble, instead of total, oxalate food content as a proxy for absorbable
oxalate, this contention is controversial.9 There is no accepted
assay, beyond oxalate loading studies, to determine the oxalate
bioavailability of individual foods.
Another limitation is that we do not have stone composition reports or 24-h urine collections from all of the stone
formers in our cohorts. However, the majority of stone composition reports in each cohort show kidney stones that contained 50% calcium oxalate. Furthermore, urinary oxalate is
a major risk factor for kidney stone formation in these cohorts.7 Finally, only a small proportion of our study population
is nonwhite, and we do not have data on stone formation in
men who are younger than 40 yr.
CONCLUSION
Our data do not support the contention that dietary oxalate is
a major risk factor for incident kidney stones. The risk that was
associated with oxalate intake was modest even in individuals
who consumed diets that were relatively low in calcium. We
hope that our study encourages additional research into the
relations between dietary oxalate, other dietary factors, endogenous oxalate production, urinary oxalate, and kidney stone
formation.
CONCISE METHODS
Study Population
HPFS.
In 1986, 51,529 male dentists, optometrists, osteopaths, pharmacists,
podiatrists, and veterinarians between the ages of 40 and 75 yr completed and returned an initial questionnaire that provided detailed
information on diet, medical history, and medications. This cohort,
like NHS I and NHS II, is followed by biennial mailed questionnaires,
which include inquiries about newly diagnosed diseases such as kidney stones. We limited the analysis to men who completed at least one
dietary questionnaire and excluded participants with a history of kidney stones before 1986. A total of 45,985 men remained in the study
group.
formation on phytate intake. After exclusion of women with kidney
stones before 1984, our study population included 92,872 women.
NHS II.
In 1989, 116,671 female registered nurses between the ages of 25 and
42 yr enrolled in NHS II by completing and returning an initial questionnaire. Dietary information was first collected from this cohort in
1991. We limited the analysis to women who completed at least one
dietary questionnaire and excluded participants with a history of kidney stones before 1991. A total of 101,824 women remained in the
study group.
Assessment of Diet and Measurement of Oxalate
The baseline semiquantitative food frequency questionnaires (FFQ)
for this study (mailed to HPFS in 1986, to NHS I in 1984, and to NHS
II in 1991) asked about the annual average use of more than 130 foods
and beverages. Subsequently, a version of this FFQ has been mailed to
study participants every 4 yr.
The oxalate content of the majority of foods on the FFQ, as well as
frequently consumed write-in foods, was measured by capillary electrophoresis in the laboratory of Dr. Ross Holmes. This assay has been
described in detail elsewhere.24 Each item of food was subject to at
least three measurements, and the final value was obtained by arithmetic mean. Commercial preparations (packaged, canned, etc.) were
purchased from different lots, and fresh produce was purchased on
three different days spaced at least 1 wk apart.
The resulting oxalate food database contained 283 direct values
from analysis, nine calculated values, 123 values imputed from analyzed food, and 59 values imputed from recipe compilations. Margarines were assigned zero on the basis of a former analysis that showed
no oxalate detection. Cereals were added to the database using 35
direct values from analysis and 18 imputed values from other analyzed cereals.
Intake of oxalate and other dietary factors was computed from the
reported frequency of consumption of each specified unit of food and,
with the exception of oxalate, from United States Department of Agriculture data on the content of the relevant nutrient in specified
portions. Nutrient values were adjusted for total caloric intake to
determine the nutrient composition of the diet independent of the
total amount of food eaten. Adjustment was performed using a regression model, with total caloric intake as the independent variable
and absolute nutrient intake as the dependent variable.33,34
The intake of supplements (e.g., calcium, vitamin C) in multivitamins or isolated form was determined by the brand, type, and frequency of reported use. The reproducibility and validity of the FFQ in
the HPFS and NHS I have been documented.35,36
Assessment of Nondietary Covariates
NHS I.
In 1976, 121,700 female registered nurses between the ages of 30 and
55 yr enrolled in NHS I by completing and returning an initial questionnaire. Because we first asked NHS I participants about their lifetime history of kidney stones in 1992, this analysis was limited to
women who answered questionnaires in 1992 or later. For this study,
we started follow-up in 1984, because before that date we lacked in2202
Journal of the American Society of Nephrology
For each cohort, information on age, weight, and height was obtained
on the baseline questionnaire, and age and weight were updated every
2 yr. Body mass index was calculated as the weight in kilograms divided by the square of height in meters. Information on thiazide diuretics was updated every 2 yr in HPFS and NHS II. In NHS I, thiazide
use was determined in 1980 and 1982 and then every 6 yr until 1994,
when biennial updates started.
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Outcomes and Their Measurement
The primary outcome was an incident kidney stone accompanied
by pain or hematuria. The participants reported on the interval
diagnosis of kidney stones every 2 yr. Any study participant who
reported a new kidney stone on the biennial questionnaire was sent
an additional questionnaire to determine the date of occurrence
and the symptoms from the stone. In HPFS, we obtained medical
records from 582 men who reported a kidney stone, and the diagnosis was confirmed in 95%. A total of 148 records contained a
stone composition report, and 127 (86%) men had a stone that
contained 50% calcium oxalate. In NHS I, we obtained medical
records from 194 women who reported a kidney stone, and 96% of
the records confirmed the diagnosis. A total of 78 records contained a stone composition report, and 60 (77%) women had a
stone that contained 50% calcium oxalate. In NHS II, we obtained medical records from 858 women who reported a kidney
stone, and 98% of the records confirmed the diagnosis. A total of
243 records contained a stone composition report, and 191 (79%)
women had a stone that contained 50% calcium oxalate.
Statistical Analyses
The study design was prospective; information on diet was collected before the diagnosis of the kidney stone. The relative risk
was used as the measure of association between oxalate intake and
incident kidney stones. Oxalate intake was divided into quintiles,
and the lowest quintile served as the referent group. The Mantel
extension test was used to evaluate linear trends across categories
of intake.
Dietary exposures were updated every 4 yr. We allocated person-months of follow-up according to exposure status at the start
of each follow-up period. When complete information on diet was
missing at the start of a time period, the subject was excluded for
that time period. For HPFS, person-months of follow-up were
counted from the date of the return of the 1986 questionnaire to
the date of a kidney stone or death or to January 31, 2002, whichever came first. For NHS I, person-months of follow-up were
counted from the date of the return of the 1984 questionnaire to
the date of a kidney stone or death or to May 31, 2002. For NHS II,
person-months of follow-up were counted from the date of the
return of the 1991 questionnaire to the date of a kidney stone or
death or to May 31, 2001.
We adjusted our analyses for potentially confounding variables
using Cox proportional hazards regression. The confounding variables considered were age (continuous); body mass index (six categories); alcohol intake (seven categories); the use of thiazide diuretics (yes or no); supplemental calcium use (four categories);
and the intake of fluid, potassium, sodium, animal protein, phosphorous, magnesium, sucrose, vitamin C, vitamin B6, phytate, vitamin D, and dietary calcium (quintile groups). We calculated
95% CI for all relative risks. All P values are two tailed.
All data were analyzed by using SAS software, version 9.1 (SAS
Institute, Cary, NC). The research protocol for this study was reviewed and approved by the institutional review board of Brigham
and Womens Hospital.
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CLINICAL RESEARCH
ACKNOWLEDGMENTS
Research support was obtained from grants DK73381, DK59583,
DK62270, CA87969, CA55075, and CA50385 from the National Institutes of Health.
Data from this article were presented at the annual meeting of the
American Society of Nephrology; November 14 through 19, 2006; San
Diego, CA.
We thank the study participants and Ross Holmes, Elaine
Coughlan-Gifford, Christine Iannaccone, and Adam Summerfield.
DISCLOSURES
None.
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