Dietary phosphorus is associated with greater left ventricular mass
2013; Elsevier BV; Volume: 83; Issue: 4 Linguagem: Inglês
10.1038/ki.2012.303
ISSN1523-1755
AutoresKalani T. Yamamoto, Cassianne Robinson‐Cohen, Márcia C.C. de Oliveira, А. N. Kostina, Jennifer A. Nettleton, Joachim H. Ix, Ha Nguyen, John Eng, João A.C. Lima, David S. Siscovick, Noel S. Weiss, Bryan Kestenbaum,
Tópico(s)Nutrition and Health in Aging
ResumoDietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function, which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals who were free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1167mg/day in men and 1017mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1g greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1g greater LVM compared with the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies. Dietary phosphorus consumption has risen steadily in the United States. Oral phosphorus loading alters key regulatory hormones and impairs vascular endothelial function, which may lead to an increase in left ventricular mass (LVM). We investigated the association of dietary phosphorus with LVM in 4494 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based study of individuals who were free of known cardiovascular disease. The intake of dietary phosphorus was estimated using a 120-item food frequency questionnaire and the LVM was measured using magnetic resonance imaging. Regression models were used to determine associations of estimated dietary phosphorus with LVM and left ventricular hypertrophy (LVH). Mean estimated dietary phosphorus intake was 1167mg/day in men and 1017mg/day in women. After adjustment for demographics, dietary sodium, total calories, lifestyle factors, comorbidities, and established LVH risk factors, each quintile increase in the estimated dietary phosphate intake was associated with an estimated 1.1g greater LVM. The highest gender-specific dietary phosphorus quintile was associated with an estimated 6.1g greater LVM compared with the lowest quintile. Higher dietary phosphorus intake was associated with greater odds of LVH among women, but not men. These associations require confirmation in other studies. Phosphorus is an essential mineral that plays a key role in cell signaling and bone metabolism. The consumption of phosphorus has risen steadily in the United States over the past decades and now considerably exceeds the recommended daily intake in men and women, and across all age groups.1.Calvo M.S. Park Y.K. Changing phosphorus content of the US diet: potential for adverse effects on bone.J Nutr. 1996; 126: 1168S-1180SPubMed Google Scholar,2.Ross A.C. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Food and Nutrition Board (FNB) and the Institute of Medicine (IOM).Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press, Washington, DC2011Google Scholar The increase in dietary phosphorus has been driven, in part, by greater consumption of phosphorus-containing food additives, from which intake alone has nearly doubled over the past decade.1.Calvo M.S. Park Y.K. Changing phosphorus content of the US diet: potential for adverse effects on bone.J Nutr. 1996; 126: 1168S-1180SPubMed Google Scholar,3.Kemi V.E. Rita H.J. Karkkainen M.U. et al.Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women.Public Health Nutr. 2009; 12: 1885-1892Crossref PubMed Scopus (64) Google Scholar Estimating the phosphorus content of such additives is difficult; hence, the size of the increase may be underestimated.4.Oenning L.L. Vogel J. Calvo M.S. Accuracy of methods estimating calcium and phosphorus intake in daily diets.J Am Diet Assoc. 1988; 88: 1076-1080PubMed Google Scholar Despite tight hormonal regulation of phosphorus balance, excess dietary phosphorus may adversely affect cardiac structure and function. In controlled feeding studies of healthy volunteers, dietary phosphorus loading stimulates the phosphaturic hormone fibroblast growth factor-23 (FGF-23) and lowers circulating concentrations of 1,25-dihydroxyvitamin D.5.Antoniucci D.M. Yamashita T. Portale A.A. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men.J Clin Endocrinol Metab. 2006; 91: 3144-3149Crossref PubMed Scopus (355) Google Scholar, 6.Burnett S.M. Gunawardene S.C. Bringhurst F.R. et al.Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.J Bone Miner Res. 2006; 21: 1187-1196Crossref PubMed Scopus (392) Google Scholar, 7.Ferrari S.L. Bonjour J.P. Rizzoli R. Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men.J Clin Endocrinol Metab. 2005; 90: 1519-1524Crossref PubMed Scopus (449) Google Scholar Lower vitamin D and higher FGF-23 concentrations are associated with left ventricular hypertrophy (LVH) in experimental models and clinical studies.8.Bodyak N. Ayus J.C. Achinger S. et al.Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals.Proc Natl Acad Sci USA. 2007; 104: 16810-16815Crossref PubMed Scopus (299) Google Scholar, 9.Li Y.C. Kong J. Wei M. et al.1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.J Clin Invest. 2002; 110: 229-238Crossref PubMed Scopus (1766) Google Scholar, 10.Mirza M.A. Larsson A. Melhus H. et al.Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population.Atherosclerosis. 2009; 207: 546-551Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar, 11.Faul C. Amaral A.P. Oskouei B. et al.FGF23 induces left ventricular hypertrophy.J Clin Invest. 2011; 121: 4393-4408Crossref PubMed Scopus (1477) Google Scholar Dietary phosphorus loading also acutely impairs flow-mediated vascular dilatation in healthy men.12.Shuto E. Taketani Y. Tanaka R. et al.Dietary phosphorus acutely impairs endothelial function.J Am Soc Nephrol. 2009; 20: 1504-1512Crossref PubMed Scopus (287) Google Scholar Although serum phosphorus concentrations are generally protected from fluctuations in dietary phosphorus intake, higher serum phosphorus concentrations are associated with greater left ventricular mass (LVM), clinical heart failure, and cardiovascular events in general population studies.13.Dhingra R. Gona P. Benjamin E.J. et al.Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community.Eur J Heart Fail. 2010; 12: 812-818Crossref PubMed Scopus (78) Google Scholar,14.Tonelli M. Sacks F. Pfeffer M. et al.Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.Circulation. 2005; 112: 2627-2633Crossref PubMed Scopus (705) Google Scholar Given the plausible effects of dietary phosphorus on ventricular mass, we evaluated associations of dietary phosphorus consumption with LVM, assessed by gold standard and cardiac magnetic resonance imaging (MRI), among 4494 participants in a community-based, multiethnic study population that was free of known cardiovascular disease. Compared with the 2320 participants who were excluded because of noncompletion of cardiac MRI, missing food frequency questionnaire (FFQ), or implausible dietary data, the 4494 included participants were, on average, younger (61.6 vs. 63.2 years), had lower systolic blood pressures (125 vs. 129mmHg), and were more likely to be White (40.5% vs. 35.1%) or Asian (13.9% vs. 7.3%). Overall, men consumed more dietary phosphorus than women (mean 1167mg/day; interquartile range 746–1435 vs. 1017mg/day; interquartile range 634–1261mg/day). Subjects who consumed more dietary phosphorus tended to be younger, consumed more alcohol, were more likely to be White or Hispanic, exercised more, and had greater body mass index and lower systolic blood pressures (Table 1). Estimated dietary phosphorus was highly correlated with total kilocalories (Pearson's correlation coefficient (PCC)=0.86), dietary protein (PCC=0.83), and dietary sodium (PCC=0.61). There was no meaningful relationship between estimated dietary phosphorus intake and the serum phosphorus concentrations among the subset of 947 participants who had serum phosphorus measurements available (Table 1; correlation coefficient -0.055).Table 1Baseline characteristics by sex-specific dietary phosphorus quintileaAll values expressed as mean±s.d. (percent).Dietary phosphorus quintileQ1 (N=898)Q2 (N=898)Q3 (N=900)Q4 (N=898)Q5 (N=898)Estimated dietary phosphorus (mg/day) men270–687688–917918–11661167–15531554–5032Estimated dietary phosphorus (mg/day) women251–585586–775776–10091010–13451346–4069Age63.2±10.262.1±10.161.8±9.960.7±10.260.1±9.9Male433 (48)433 (48)434 (48)433 (48)434 (48)Race White244 (27)342 (38)405 (45)418 (47)411 (46) Black242 (27)218 (24)227 (25)208 (23)179 (20) Hispanic181 (20)173 (19)166 (18)199 (22)258 (29) Asian231 (26)165 (18)102 (11)73 (8)52 (6)Diabetes status Normal523 (58)535 (60)564 (63)539 (60)556 (62) Impaired glucose248 (28)251 (28)223 (25)244 (27)230 (26) Diabetes125 (14)108 (12)110 (12)113 (13)113 (13)Education High school or less183 (20)151 (17)110 (12)131 (15)161 (18) Some college408 (45)411 (46)408 (45)373 (42)411 (46) College or higher307 (34)335 (37)379 (42)392 (44)328 (36)Smoking Never493 (55)476 (53)453 (50)464 (52)433 (48) Former307 (34)319 (36)329 (37)326 (36)334 (37) Current98 (11)102 (11)115 (13)106 (12)133 (15)Alcohol use None498 (55)429 (48)427 (47)382 (43)383 (43) 0–7 drinks per week258 (29)285 (32)297 (33)311 (35)330 (37) >7 drinks per week138 (15)174 (19)163 (18)197 (22)178 (20)Physical activitybMetabolic equivalent task-min per week of moderate/vigorous physical activity/100.51.4±52.055.8±57.856.4±62.860.1±61.366.3±64.3Body mass index (kg/m2)26.8±4.627.2±4.727.7±5.027.8±5.028.9±5.1Systolic blood pressure (mmHg)127.0±22125.6±20125.6±22123.3±21124.8±21Diastolic blood pressure (mmHg)72.0±1071.8±1072.3±1171.1±1071.6±10Hypertension medication use347 (39)330 (37)319 (35)289 (32)294 (33)Estimated GFRcEstimated glomerular filtration rate (GFR) in ml/min per 1.73m2.79.0±16.279.2±15.978.8±17.279.4±16.180.6±16.9Estimated GFR <60ml/min per 1.73m292 (10)85 (10)88 (10)88 (10)68 (8)Serum phosphorus (mg/dl)dSerum phosphorus measurements available for a subset of 947 study participants.3.5±0.53.5±0.53.4±0.53.5±0.53.4±0.5Albuminuria (≥30mg/dl)77 (9)63 (7)94 (10)70 (8)64 (7)C-reactive protein (mg/l)3.6±7.33.1±4.53.3±5.03.6±5.83.8±5.4Total calories (kcal)949.3±2241255.6±2851562.3±3601918.5±4502701.5±867Sodium (mg/day)1232.4±4341726.2±5712184.2±7182738.8±9084002.8±1632Percent calories from protein15.0±3.816.0±3.816.2±3.516.4±3.317.3±3.6Percent calories from fat33.9±7.933.8±7.234.2±6.734.6±6.835.0±6.5a All values expressed as mean±s.d. (percent).b Metabolic equivalent task-min per week of moderate/vigorous physical activity/100.c Estimated glomerular filtration rate (GFR) in ml/min per 1.73m2.d Serum phosphorus measurements available for a subset of 947 study participants. Open table in a new tab The mean and s.d. LVM for men and women was 168.6±36.8 and 123.8±27.4g, respectively. Higher estimated dietary phosphorus intake was associated with greater LVM (Figure 1 and Table 2). After adjusting for height, weight, age, and race, and weighing model estimates by sex, each 20% greater estimated dietary phosphorus intake was associated with an estimated 0.42g greater LVM (95% confidence interval (CI): 0.14–0.70g). Progressive adjustment strengthened the association of estimated dietary phosphorus with LVM (Table 2). In the fully adjusted model, each 20% greater estimated dietary phosphorus was associated with an estimated 1.06g greater LVM (95% CI: 0.50–1.62g; P-value 0.2). There were too few cases of advanced kidney disease in Multi-Ethnic Study of Atherosclerosis (MESA) to permit testing for interaction across the full range of kidney dysfunction. The size of the association between estimated dietary phosphorus and LVM also did not differ appreciably across categories of age, race/ethnicity, or hypertension status.Table 4Association of estimated dietary phosphorus with LVM by subgroupSubgroupNMean LVM (g) ±s.d.Difference in LVM (g) per 20% greater dietary phosphorus (95% CI)aExcept for the covariate representing the subgroup of interest, all models weighed and combined by sex and adjusted for age, race, height, weight and weight0.5, total dietary calories, dietary sodium, smoking, alcohol use, education, moderate/vigorous physical activity, diabetes status, systolic blood pressure, antihypertensive medication use, urinary albumin-to-creatinine ratio, C-reactive protein, and estimated glomerular filtration rate.Overall cohort4494145±391.06 (0.50, 1.62) Men2167169±370.59 (-0.49, 1.67) Women2327124±271.24 (0.58, 1.89)Premenopausal women355122±250.42 (-1.27, 2.11)Postmenopausal women1878124±281.38 (0.65, 2.12)Age 45–64 years2467147±390.97 (0.27, 1.67)Age 65–84 years1847142±391.22 (0.29, 2.16)White1820144±380.89 (0.08, 1.71)Black1074158±410.76 (-0.70, 2.23)Asian623124±310.98 (-0.18, 2.15)Hispanic977148±381.55 (0.34, 2.76)HypertensionbHypertension models exclude adjustment for systolic blood pressure and antihypertensive medication use.2050153±411.05 (0.12, 1.98)No hypertensionbHypertension models exclude adjustment for systolic blood pressure and antihypertensive medication use.2442138±360.91 (0.22, 1.59)Chronic kidney disease421142±402.01 (0.24, 3.78)No chronic kidney disease4061146±390.99 (0.40, 1.99)Abbreviations: 95% CI, 95% confidence interval; LVM, left ventricular mass.a Except for the covariate representing the subgroup of interest, all models weighed and combined by sex and adjusted for age, race, height, weight and weight0.5, total dietary calories, dietary sodium, smoking, alcohol use, education, moderate/vigorous physical activity, diabetes status, systolic blood pressure, antihypertensive medication use, urinary albumin-to-creatinine ratio, C-reactive protein, and estimated glomerular filtration rate.b Hypertension models exclude adjustment for systolic blood pressure and antihypertensive medication use. Open table in a new tab Abbreviations: 95% CI, 95% confidence interval; LVM, left ventricular mass. The prevalence of LVH among male and female MESA participants was 7.7% and 9.2%, respectively. Greater estimated dietary phosphorus consumption was associated with progressively higher adjusted odds of LVH among women, but not men (Figure 2). We investigated whether the association of estimated dietary phosphorus with LVM might differ across different foods groups (Table 5; Supplementary Table S3 online). Our findings did not reveal any significant differences in the primary association according to the type of dietary protein or processed food status.Table 5Association of estimated dietary phosphorus with LVM within food groupsProtein typeProcessed food typeExamplesaThe complete categorization of all 120-food frequency questionnaire items is presented in Supplementary Table S3 online.Proportion dietary phosphorus (mg/day)Difference in LVM (mg)95% CIAnimalProcessedHamburger Fried chicken14% (146mg/day)+102–736, +939AnimalUnprocessedEggs Roast chicken16% (169mg/day)+82–614, +777DairyProcessedFlavored yogurt Ice cream5% (54mg/day)-153–1101, +795DairyUnprocessedMilk Cottage cheese22% (277mg/day)+219–150, +437VegetableProcessedFried rice Chili6% (66mg/day)-19–526, +488VegetableUnprocessedCold cereal Nuts11% (118mg/day)+673–52, +1398NonproteinProcessedCrackers Soda9% (96mg/day)-975–1983, +33NonproteinUnprocessedFruit Beer17% (164mg/day)+644–389, +1676Abbreviations: 95% CI, 95% confidence interval; LVM, left ventricular mass.Associations per 100mg greater dietary phosphorus within each food category. N=4405 for all models.All models weighed and combined by sex and adjusted for age, race, height, weight and weight0.5, total dietary calories, dietary sodium, smoking, alcohol use, education, moderate/vigorous physical activity, diabetes status, systolic blood pressure, antihypertensive medication use, urinary albumin-to-creatinine ratio, C-reactive protein, and estimated glomerular filtration rate.a The complete categorization of all 120-food frequency questionnaire items is presented in Supplementary Table S3 online. Open table in a new tab Abbreviations: 95% CI, 95% confidence interval; LVM, left ventricular mass. Associations per 100mg greater dietary phosphorus within each food category. N=4405 for all models. All models weighed and combined by sex and adjusted for age, race, height, weight and weight0.5, total dietary calories, dietary sodium, smoking, alcohol use, education, moderate/vigorous physical activity, diabetes status, systolic blood pressure, antihypertensive medication use, urinary albumin-to-creatinine ratio, C-reactive protein, and estimated glomerular filtration rate. In a community-based, multiethnic population without clinical cardiovascular disease, higher estimated dietary phosphorus consumption was associated with greater LVM, measured by cardiac MRI. Associations persisted after adjustment for known LVH risk factors. Higher estimated dietary phosphorus intake was also associated with a greater odds of LVH among women, but not men. If confirmed in other populations, these findings suggest the possibility that dietary phosphorus could have adverse cardiovascular consequences in the general population. An association of dietary phosphorus with LVM is supported by the hormonal response to dietary phosphorus. In animal models, and some human feeding studies, dietary phosphorus loading stimulates a rise in FGF-23 and a decline in 1,25-dihydroxyvitamin D.5.Antoniucci D.M. Yamashita T. Portale A.A. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men.J Clin Endocrinol Metab. 2006; 91: 3144-3149Crossref PubMed Scopus (355) Google Scholar, 6.Burnett S.M. Gunawardene S.C. Bringhurst F.R. et al.Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.J Bone Miner Res. 2006; 21: 1187-1196Crossref PubMed Scopus (392) Google Scholar, 15.Perwad F. Azam N. Zhang M.Y. et al.Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice.Endocrinology. 2005; 146: 5358-5364Crossref PubMed Scopus (343) Google Scholar These hormonal changes serve to maintain phosphorus homeostasis: FGF-23 enhances phosphorus excretion through the kidneys and diminished vitamin D activation slows phosphorus absorption through the gut. However, higher FGF-23 and lower 1,25-dihydroxyvitamin D concentrations may have adverse effects on the myocardium. Vitamin D potently suppresses the renin–angiotensin system; disruption of the vitamin D system leads to hypertension and LVH in experimental models.9.Li Y.C. Kong J. Wei M. et al.1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.J Clin Invest. 2002; 110: 229-238Crossref PubMed Scopus (1766) Google Scholar In human studies, higher FGF-23 concentrations are associated with greater LVM.10.Mirza M.A. Larsson A. Melhus H. et al.Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population.Atherosclerosis. 2009; 207: 546-551Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar,16.Gutierrez O.M. Januzzi J.L. Isakova T. et al.Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease.Circulation. 2009; 119: 2545-2552Crossref PubMed Scopus (679) Google Scholar Although a dietary phosphorus–hormone–LVM hypothesis is intriguing, this theory awaits further study. Given previous associations of serum phosphorus concentrations with LVM, incident heart failure, and cardiovascular events,13.Dhingra R. Gona P. Benjamin E.J. et al.Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community.Eur J Heart Fail. 2010; 12: 812-818Crossref PubMed Scopus (78) Google Scholar,14.Tonelli M. Sacks F. Pfeffer M. et al.Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.Circulation. 2005; 112: 2627-2633Crossref PubMed Scopus (705) Google Scholar it is tempting to connect associations for dietary phosphorus through serum phosphorus levels. However, animal models and human studies demonstrate extraordinarily tight regulation of the circulating phosphorus concentration, irrespective of dietary phosphorus intake.17.Isakova T. Gutierrez O. Shah A. et al.Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD.J Am Soc Nephrol. 2008; 19: 615-623Crossref PubMed Scopus (137) Google Scholar,18.Berndt T. Thomas L.F. Craig T.A. et al.Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption.Proc Natl Acad Sci USA. 2007; 104: 11085-11090Crossref PubMed Scopus (136) Google Scholar Among 15,513 participants in the Third National Health and Nutrition Examination Survey, no association of dietary phosphorus intake with the circulating phosphorus concentration was found across a wide range of phosphorus intake.19.de Boer I.H. Rue T.C. Kestenbaum B. Serum phosphorus concentrations in the third National Health and Nutrition Examination Survey (NHANES III).Am J Kidney Dis. 2009; 53: 399-407Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar Associations of estimated dietary phosphorus with LVM were modestly stronger among women and among participants who had CKD. A possible explanation for sex-specific differences could be a reduction in phosphorus excretion that occurs in postmenopausal women.20.Cirillo M. Ciacci C. De Santo N.G. Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults.N Engl J Med. 2008; 359: 864-866Crossref PubMed Scopus (83) Google Scholar CKD leads to diminished phosphorus clearance through the kidney, which could enhance relationships of dietary phosphorus intake with adverse outcomes. These subgroup findings require confirmation in other study populations, particularly those that include greater numbers of individuals who have CKD. Most participants in this study consumed more phosphorus than 700mg/day recommended by the Institute of Medicine.2.Ross A.C. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Food and Nutrition Board (FNB) and the Institute of Medicine (IOM).Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press, Washington, DC2011Google Scholar Currently, there are no FDA (Food and Drug Administration) requirements to list the phosphorus content of food products. In addition, standard nutritional software may not account for phosphorus derived from food additives.4.Oenning L.L. Vogel J. Calvo M.S. Accuracy of methods estimating calcium and phosphorus intake in daily diets.J Am Diet Assoc. 1988; 88: 1076-1080PubMed Google Scholar These factors likely contribute to significant underestimation of dietary phosphorus content in research studies. More rigorous methods are needed to increase precision of dietary phosphorus assessment, potentially validated against repeated 24-h urine phosphorus collections, which provide a reasonable estimate of total dietary phosphorus intake in the steady state.6.Burnett S.M. Gunawardene S.C. Bringhurst F.R. et al.Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.J Bone Miner Res. 2006; 21: 1187-1196Crossref PubMed Scopus (392) Google Scholar An important limitation of our study is potential misclassification of dietary phosphorus consumption using the FFQ and Nutrition Data Systems for Research d
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