The Journal of Nutrition
Higher Biomarker-Calibrated Protein Intake
Is Not Associated with Impaired Renal Function
in Postmenopausal Women1,2
Jeannette M. Beasley,3* Aaron K. Aragaki,3Andrea Z. LaCroix,3Marian L. Neuhouser,3Lesley F. Tinker,3
Jane A. Cauley,4Kristine E. Ensrud,5Rebecca D. Jackson,6and Ross L. Prentice3
3Fred Hutchinson Cancer Research Center, Seattle, WA;4University of Pittsburgh, Pittsburgh, PA;5University of Minnesota,
Minneapolis, MN; and6Ohio State University, Columbus, OH
With aging, renal function tends to decline, as evidenced by reduced glomerular filtration rate. High-protein intake may
further stress the kidneys by causing sustained hyperfiltration. To investigate whether dietary protein is associated with
impaired renal function, we used data from 2 nested case-control studies within the Women’s Health Initiative
Observational Study (n = 2419). We estimated protein intake using a FFQ and estimated glomerular filtration rate (eGFR)
from cystatin C. To account for the original study designs, inverse probability weights were applied. Self-reported energy
and protein were calibrated using biomarkers of energy and protein intake. Associations between protein intake and renal
function were estimatedby weighted linear and logistic regressionmodels. Average calibrated protein intake (mean 6 SD)
was 1.1 6 0.2 g/(kg body weight×d).Twelve percent (n = 292) of women had impaired renal function. The odds of impaired
renal function,defined as eGFR ,60 mL/(min×1.73m2), was not associated withcalibrated protein intake. When eGFR was
modeled continuously, there was no association with calibrated protein when protein was expressed in absolute (g/d) or
relative to energy (protein % energy/d), but protein relative to body weight [g/(kg body weight×d)] was associated with
higher eGFR. There was no evidence for effect modification by age, BMI, or general health status. These data suggest
higher protein intake is not associated with impaired renal function among postmenopausal women without a diagnosis of
chronic kidney disease. J. Nutr. 141: 1502–1507, 2011.
Higher dietary protein intake causes hyperfiltration, as mea-
sured by elevated estimated glomerular filtration rate (eGFR),7
in the short term, but whether protein detrimentally affects renal
function is contentiously debated (1,2). Sustained hyperfiltration
may cause renal injury, leading to reduced renal function, and
the American Dietetic Association and American Diabetes
Association both recommend limiting protein intake to 0.8–
1.0 [g/(kg body weight×d)] (~ ,10–14% of energy from protein)
among individuals with renal damage (3). An alternative
hypothesis is that hyperfiltration is a normal, adaptive response
to higher protein intake having no impact on renal function (4).
Of critical importance to public health is whether diets higher in
protein have detrimental effects on renal function among older
adults without overt chronic kidney disease (CKD), i.e. having
an eGFR .60 mL/(min×1.73m2) (5). Clinicians commonly
prescribe higher protein intake in aging individuals to reduce
sarcopenia and preserve lean body mass, enhance immune
function, promote wound healing, and treat hypoalbuminemia.
Two serum markers, creatinine and cystatin C, are used in
clinical practice to measure eGFR (6,7). A systematic review of
24 studies comparing the diagnostic accuracy of both markers
for impaired renal function reported that cystatin C had higher
sensitivity compared with creatinine (81 vs. 69%) at a common
specificity (88%) (8). While measuring cystatin C as a biomarker
of renal function also has the advantage over creatinine of being
independent of muscle mass (9,10), cystatin C may be associated
with adiposity independent of renal function (11). Thus, studies
that carefully account for protein intake and BMI while
measuring renal function using cystatin C as a measure of renal
function are warranted.
Data from the Women’s Health Initiative Observational
Study (WHI-OS) can inform this question by examining asso-
ciations between protein intake and renal function among older
1Supportedby theNational Heart, Lung, and BloodInstitute,the NIH, and the U.S.
Department of Health and Human Services through contracts N01WH22110,
24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. The project described was supported by award
number K99AG035002 from the National Institute on Aging. The content is solely
the responsibility of the authors and does not necessarily represent the official
viewsof the National Institute onAgingor the NIH. This work was also supported
by PO1 CA53996 and 5R01AG025441-03.
2Author disclosures: J. M. Beasley, A. K. Aragaki, A. Z. LaCroix, M. L.
Neuhouser, L. F. Tinker, J. A. Cauley, K. E. Ensrud, R. D. Jackson, and R. L.
Prentice, no conflicts of interest.
7Abbreviations used: CKD, chronic kidney disease; eGFR, estimated glomerular
filtration rate; NHS, Nurses’ Health Study; WHI-OS, Women’s Health Initiative
* To whom correspondence should be addressed. E-mail: firstname.lastname@example.org.
ã 2011 American Society for Nutrition.
Manuscript received November 18, 2010. Initial review completed February 12, 2011. Revision accepted May 12, 2011.
First published online June 8, 2011; doi:10.3945/jn.110.135814.
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