J Am

Body

Size

and

GARY FRANK

Risk

of Kidney

C. CURHAN,*tII E. SPEIZER,*t

*Depart,nent Epidemiology,

and

Department

Channing

Laboratory,

Environmental

of Medicine,

Health,

Massachusetts

1998

Stones

WALTER C. WILLETT,*tt and MEIR J. STAMPFER*t

of Medicine,

Soc Nephrol 9: 1645-1652,

Brigham

Harvard

ERIC

Hospital;

Women

and

School

General

B. RIMM,*t ‘s Hospital;

of Public

Health;

and

Harvard

disease

Departments and

the

Medical

of Nutrition,

1Renal

School,

Unit,

Boston,

Massachusetts.

Abstract. cium

A variety

oxalate

excretion factors

be

a larger

stone

body

risk

factor

body

the

of kidney

risk

cohorts:

the the

exposures

during

during

horts,

the

Kidney calcium ily

diet

of

disease

vast

(4,5),

and

was

incident and

Several

).

oxalate

daily

stones,

urine

oxalate,

is derived

endogenous

acid,

both

from

production.

oxalate

generation

have

not been

it was

suggested

that

larger

is associated

with

higher

urinary

sumably due to increased endogenous Men, who on average have a larger have a lifetime risk of women. Therefore, body for

calcium

oxalate

stone

the

oxalate

in the contri-

it is likely endogenous endogenous Recently, lean excretion,

pre-

oxalate production (7). body size than women,

although

risk

to

decreases

the risk

this

found

the

varies

determine

but

These

results

risk

of stone

by

gender.

of stone

risks

for

for women associated

not

associated

suggest

that

formation

and

Additional

body

that

the

studies

a reduction

formation,

I .76

confiin men.

relative

was

mass

was

(95%

comparison

disease

whether

published

relation

data

in

body

particularly

are

weight

in women.

and

sparse.

Most

in weight

case-control

between

cases

studies

have

and controls

(8,9),

study that found a significantly compared with male control sub-

(10).

examine

between

and

cohorts:

the

Health

this

body

[BMI])

the

between

completed Nurses’ means

and

dietary

women

initial cohort

association mass

index

in two women)

=

5 1,529

121,700

female

(ti

large and

the

men).

The

Study male

first

dentists,

inquire

as well

population

for the current either

the

about

as the 1992

a history of kidney questionnaire since

the by

lifestyle

incidence

of

analysis or

the

was 1994

stones, and 1980 when

collected.

Follow-Up (HPFS)

which

states

and constitute cohort is followed

of interest, answered

registered

in one of I I U.S.

questionnaire (1 1). The

questionnaires,

who

was

Professionals 5 1,529

89,376

=

1976,

which inquired about at least one dietary

information

als Follow-up

In

exposures disease.

to the

Health among

mailed

other

questionnaires, who completed

formation

of 30 and 55 yr living

returned the Study (NHS)

diagnosed

the body

Methods Study.

of biennial

practices

studied and

stone Health Study (n Follow-up Study

the ages

and Health

we

weight,

of kidney

Nurses’

and

further,

(height,

risk

Study Population Nurses’ Health nurses

issue

size

Professionals

limited Received December 8, 1997. Accepted March 4, 1998. Correspondence to Dr. Gary C. Curhan, Channing Laboratory, Brigham Women’s Hospital, 181 Longwood Avenue. Boston, MA 021 15.

are

no difference

with the exception of one higher weight in male cases

newly

1046-6673/0909l645$03.00/0 Journal of the American Society of Nephrology Copyright 0 1998 by the American Society of Nephrology

of

Materials

body

stone formation three times that of size may be an important risk factor formation,

with

1 .38

1 .89 (1 .5 1 to 2.36) Height was inversely

stone

age-

body

kg/m2

but

the multivariate

formation.

and

the

with

21 to 22.9

to 2.07),

were in men. of

necessary

To

relative

formation,

stone

women

for the same

.

is associated

jects

concentra-

defined. (possibly

fam-

(1).

controversial, results from that influence size

as the

(2,3),

ingested

with

weight

Specifically,

for

1 .50

1 16 to 1.65)

prevalence

with

of the associations

women.

ratio

compared

the similar comparisons and 1.19 (0.83 to 1.70)

on

condi-

usually influence

oxalate

completely

body

costly

among

interval,

stone

associated

the magnitude

mci-

the

urinary

interval,

For incident

magnitude

stones

and

citrate

Although

bution of these two sources remains that at least half of urinary oxalate production (6). However, the factors

mass)

and

dence

directly

odds

kg/m2

size

cases in In both co-

diet

confidence

by mailed

of 956

factors

32

(95%

the

a total

and

index

incident

of kidney

greater

prevalence

with

=

were

However,

consistently

with

stone

calcium,

and

n

index.

forma-

kidney

including

large

women)

(HPFS;

history

volume,

uric

89,376

=

and

in two

confirmed.

important

oxalate

of

index)

cases

contain

adjusted

risk

Study

painful,

of stones

was

average

association

obtained

disease

is a common,

1

(

were

a stone

majority

of calcium,

Urinary

1078

8 yr of follow-up

of calcium

history

tions

of

prevalence

oxalate

formation

size,

14 yr of follow-up

stone The

body

of interest

A total

HPFS

tion.

on

The

mass

n

(NHS;

of these on

studied

Follow-up

mass

lifetime

body

was

of stone

body

be an important

formation.

Study

Information

questionnaires. in NHS

Health

men

may

and

dence

and

Several

higher

formation

Professionals

other

acid.

size

weight,

stone

Nurses’

men).

and

body stone

(height,

diet,

Because

a threefold

oxalate

size

Health

5 1 ,529 tion,

and

women,

for calcium

between

and

size

uric

size.

of calurinary

formation

gender,

and

to body

than

the

including

oxalate,

related

formation

influence

stones,

of calcium, may

have

of factors

kidney

Study.

is a longitudinal optometrists,

The Health study

of diet

osteopaths,

Professionand disease pharmacists,

Journal

1646

podiatrists. participants

of the

American

and veterinarians

who

returned

mation

on

followed

diet,

medical

by means lifestyle

about

history, and

of newly

of kidney

were

of Nephrology

in 1986

and

diagnosed

disease

infor-

The

questionnaires,

information

The

providing

medications.

mailed other

J Am Soc Nephrol

40 to 75 yr of age in 1986.

questionnaire

of biennial

practices

the incidence nosis

a mailed

Society

cohort

which

of interest,

including

is

inquire

as well

a physician

as

diag-

stones.

occurrence

and

symptoms.

random

sample

the diagnosis were

stones.

stones

each

biennial

weight

questionnaire.

(in kilograms)

validation

studies

self-reported

ments

of current

weights

(r

We

were

BMI

in NHS

highly

by

of the height

weight

0.96 and 0.97.

=

calculated

by the square

correlated

dividing

(12)

and

with

actual

In

HPFS

(13).

weight

answer

Assessment

of Diet

We asked complete

the NHS

participants

semiquantitative

in 1980,

1984,

food-frequency

1986,

and 1990 to

questionnaires

on

which

they reported the average use of specified foods and beverages during the past year. The HPFS participants completed the dietary questionnaires in 1986 and 1990. The 1980 NHS dietary questionnaire contamed

a list of 6 1 items,

cohorts

contained

and

the

approximately

subsequent

questionnaires

in both

130

We

nutrient

items.

computed

on the amount

carbonate)

ingested,

multimineral

of supplemental

both

as individual

preparations.

questionnaires

have

and HPFS

calcium

The

been

(such

supplements

reproducibility

documented

and

and

previously

as part

validity

in both

of (15)

adjusted regression

for total model

energy intake by taking with total caloric intake

the as

the independent variable and nutrient intake as the dependent variable (14,17). Energy-adjusted values thus reflect the nutrient composition of the diet independent of the total amount of food consumed. Follow-Up

and

Ascertainment

and

for

1986

were

analyzed

stone

disease

from the

were

the

Incident

goal

The

subjects’

reports,

of 90 of the confirmed HPFS. nosed were

women

who

stone

on

each

as those

that

baseline questionnaire. after the return of the

and 1986

was

reported

tary

form

The

response

medical

reported

records

from

a kidney

on a follow-up to confirm

the

biennial occurred

incident cases questionnaire. questionnaire. self-report

the

stone.

rate

The

or May 3 1 1994,

was

and updated

person-months return of the

status

by

of kidfor NHS

disease

and

prevalence

of

size

numbers

categories

of individuals

are the standard of BMI.

The

unadjusted using

study

tests

date-

Categorical

for trend

the Mantel

design

and

across

extension

for the incident size

in 1984,

1986,

and

of follow-up 1986 questionnaire

allocated

occurred

of interest

dietary

the

For

each

1990.

were calculated to the date occurred 1986 HPFS

person-months

at the start

first.

from

test

cases

was

intake

was

category

for

at the start

of a time

records

that

time

diag-

category

cases

parison

I 986

a supplemen-

follow-up

time

period.

period,

tension multiple

HPFS

then

on diet,

questionnaire participant, of the death,

first. Diet, weight, and other questionnaire were updated according

period

(e.g.,

to ex-

indicated

size information was assigned

If dietary

information

the subject

was excluded

by was to the was for

period. relative

risk-the

of exposure category-was

incidence divided used

test size

was

used

( 19). We risk factors

among

individuals

by the corresponding as the

adjusted relative risks were calculated 5-yr age categories for the respective body

of

that

1980

of follow-up

of each

missing

Information

from the date of a kidney stone,

to the

date

The

body

of the

of the

the

prevalent

cases.

the category of BMI and other variables). If body missing at the start of a time period, the individual

were those that occurred Whenever a kidney stone to ascertain

variables

missing

Prevalent return

other

sample

newly

(1980

of our analyses

whichever

.

weight,

The any

we mailed and

medical

a random

questionnaire. before

subject a to obtain

the validity

the diagnosis in all but one of the cases. The participants were asked to report

kidney defined

we obtained

if known.

the

collected before the onset of the kidney stone. For each NHS participant, person-months of follow-up were calculated from the date of the return of the 1980 questionnaire to the date of a kidney stone,

on the date

was 92%. To confirm

a history

questionnaire

on body

information

of stone,

subjects

to have

BMI

information

We

the type

Similarly,

examined

MA).

in 1990.

questionnaire

Only

using the test, and confidence interthe Robins-Breslow-Greenland variance

posure

and

prevalent

categories

was

supplementary

did not

with

sufficient

information supplementary conditions,

provide

participants

of having

3 1 , 1994, whichever of interest from the

relevant

to

they

period.

the incident

were calculated are two-tailed.

thus.

a participant

relevant

The

Cambridge,

Analyses.

for

imputed.

at baseline. The categories of height and the start of the analysis according to their

were performed calculated using

size categories All P values

was

who reported

dietary

was

BMI) before

not reported “missing”

or because

analyses.

considered

categories.

( 18) (StatXact,

death,

symptoms.

by the

stone.

from

or January variables

of occurrence,

Thus,

we use for the majority

comparisons vals were

the

the incident

baseline

with

prospective;

of Cases

the and

for

incident

separately

were labeled

the analyses of

Individuals

HPFS) at

for

failure

on the baseline

weight, and were selected

that

used

analyzed.

NHS. On the 1992 questionnaire. we inquired whether each woman had ever been diagnosed with a kidney stone and the date of the first occurrence. The 1994 biennial questionnaire asked about a new diagnosis of a kidney stone since 1992. Prevalent cases were defined as those that occurred before the return of the 1980 questionnaire. If a kidney stone reportedly occurred in 1980 (when dietary first collected) or later, we mailed questionnaire to confirm the diagnosis

confirmed

measurements

from

Analyses. disease

body (19).

3%

of self-reported

cases.

on a questionnaire,

was

after

ney stone

gories

(16).

Nutrient values were residuals from a linear

Prevalent

values

result

excluded

in the extreme

of the

NHS

were

distributions,

as calcium

confirmed

the remaining rate

to a category

questionnaire

event

censored

(height, weight

intake from the reported frequency of consumption of each specified unit of food or beverage and from published data on the nutrient content of the specified portions (14). Beginning in 1984, we collected information

disease

could

size

assigned

of the

biennial

stone

were

supplementary To confirm the records from a

records

all reports

to be true

body

or height

the

first

we assumed

were

None

values

their

respectively).

period

period.

Missing

measure-

The

of the cases;

the confirmation

so high,

for whom

a time

that

to the

1998

Analyses

Participants during

rate

cases.

in 97%

questionnaire

Statistical

the

(in meters).

stone

Because

was

supplementary

from the 1976 NHS and the on weight was obtained from

response

period was more than 92%. we obtained the medical

of 60 of the confirmed of a kidney

bladder

kidney

Assessment of Body Size We obtained information on height 1986 HPFS questionnaires. Information

The

questionnaire for each 2-yr validity of the self-report,

9: 1645-1652,

to evaluate

measure

in a particular rate

of association

in the com(20).

after stratification according cohorts (20). The Mantel linear

trends

across

used a proportional hazards model simultaneously (21). The selection

categories

Ageto exof

to adjust for of variables

J Am

Soc Nephrol

9: 1645-1652,

considered

in these

to calcium

stone

models

considered categories

in the models for NHS and

ries),

(seven

BMI

(five (0,

calcium,

animal

phosphorus.

P values

C (five

(eight

to be related

literature.

500+

potassium,

fiber.

D, and

we calculated

and

sodium,

vitamin

95%

vitamin

fluid

sucrose,

magnesium,

(quintile

groups).

For

(95%

Cl).

confidence

intervals

for

of

lence odds of kidney

to categories 1 . Of

the

question

about

lifetime

a history

of kidney

disease

decreased

89,376

with

in NHS weight,

women

history

stones with

increased

stones

of height,

in Table

and

who

before

stones,

1980.

The

height

increasing

BMI

responded

of kidney

increasing

at baseline

women

inches

shorter

were

1.96

respectively. to

The

189

pounds

than (1.13

weight

59

inches

to

3.38)

age-adjusted and

1. Frequency according

in men 21

(P. trend

and and

odds

190

to 234

of history

ratios pounds

of kidney

to categories

ratios

of stone

than