Dietary protein intake, kidney function, and survival in a nationally representative cohort

Abstract

Background: High-protein diets (e.g., Paleo, Atkins, South Beach, ketogenic) have gained popularity as a means to promote weight loss and avoid excess carbohydrate consumption. Yet in chronic kidney disease (CKD) patients, evidence suggests low dietary protein intake (DPI) leads to attenuation of kidney function decline, although concerns remain for risk of protein-energy wasting.

Objectives: To examine associations of DPI with mortality in a nationally representative cohort of US adults, stratified by kidney function.

Methods: We examined the association between daily DPI scaled to actual body weight (ABW), ascertained by 24-h dietary recall, with all-cause mortality among 27,604 continuous NHANES adult participants (1999-2010), stratified according to impaired versus normal kidney function (estimated glomerular filtration rates <60 compared with ≥60 ml/min/1.72 m2, respectively), using multivariable Cox models. We also examined the relation between high biological value (HBV) protein consumption with mortality.

Results: In participants with impaired kidney function, a high DPI of ≥1.4 g/kg ABW/day was associated with higher mortality, while lower DPI levels were not associated with mortality (reference, 0.6 to <1.0 g/kg ABW/day): the adjusted HRs (aHRs) were 1.09 (95% CI: 0.90, 1.32), 1.03 (95% CI: 0.82, 1.29), and 1.37 (95% CI: 1.02, 1.85) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. Yet in participants with normal kidney function, a low DPI of <0.6 g/kg ABW/day was associated with higher mortality, whereas higher DPI levels were not associated with death: the aHRs were 1.18 (95% CI: 1.04, 1.34), 0.92 (95% CI: 0.81, 1.04), and 0.99 (95% CI: 0.85, 1.16) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. The highest 2 tertiles of HBV consumption were associated with higher mortality in participants with impaired kidney function.

Conclusions: Among participants with impaired kidney function, a higher DPI and greater HBV consumption were associated with higher mortality, whereas a lower DPI was associated with higher mortality in those with normal kidney function. Further studies are needed to elucidate the specific pathways between higher DPI and mortality in CKD.

Keywords: chronic kidney disease; dietary protein; kidney function; mortality; survival, NHANES.

FIGURE 1

Association of DPI scaled to ABW with all-cause mortality risk, stratified by eGFR in participants with (A) impaired kidney function (n = 1994) and (B) normal kidney function (n = 25,605). Each plot shows HRs and their 95% CIs, estimated using Cox regression models incrementally adjusted with the following covariates: 1) unadjusted analyses; 2) case mix–adjusted analyses, adjusted for age, sex, race/ethnicity, family income status, educational status, and marital status; 3) expanded case mix–adjusted analyses, adjusted for case-mix covariates plus smoking status, alcohol status, CVD, cancer, diabetes, high blood pressure, and BMI; 4) expanded case mix + eGFR–adjusted analyses, adjusted for expanded case-mix covariates plus eGFR; 5) expanded case mix + eGFR + dietary intake–adjusted analyses, adjusted for expanded case-mix + eGFR covariates plus dietary energy intake and dietary sodium intake; and 6) expanded case mix + eGFR + dietary intake + health behavior + nutritional status–adjusted analyses, adjusted for expanded case-mix + eGFR + dietary intake covariates plus physical activity status, supplement status, and serum albumin levels. ABW, actual body weight; CVD, cardiovascular disease; DPI, dietary protein intake; eGFR, estimated glomerular filtration rate.

FIGURE 2

Association of absolute DPI with all-cause mortality risk, stratified by eGFR in participants with (A) impaired kidney function (n = 1994) and (B) normal kidney function (n = 25,605). Each plot shows HRs and their 95% CIs, estimated using Cox regression models incrementally adjusted with the following covariates: 1) unadjusted analyses; 2) case mix–adjusted analyses, adjusted for age, sex, race/ethnicity, family income status, educational status, and marital status; 3) expanded case mix–adjusted analyses, adjusted for case-mix covariates plus smoking status, alcohol status, CVD, cancer, diabetes, high blood pressure, and BMI; 4) expanded case mix + eGFR–adjusted analyses, adjusted for expanded case-mix covariates plus eGFR; 5) expanded case mix + eGFR + dietary intake–adjusted analyses, adjusted for expanded case-mix + eGFR covariates plus dietary energy intake and dietary sodium intake; and 6) expanded case mix + eGFR + dietary intake + health behavior + nutritional status–adjusted analyses, adjusted for expanded case-mix + eGFR + dietary intake covariates plus physical activity status, supplement status, and serum albumin levels. DPI quartiles 1, 2, 3, and 4 correspond to DPI of <52, 52 to <73, 73 to <100, and 100–718 g/d, respectively, based on the DPI distribution in the overall cohort. CVD, cardiovascular disease; DPI, dietary protein intake; eGFR, estimated glomerular filtration rate.

FIGURE 3

Association of DPI as a proportion of total energy intake with all-cause mortality risk stratified by eGFR in participants with (A) impaired kidney function (n = 1994) and (B) normal kidney function (n = 25,605). Each plot shows HRs and their 95% CIs, estimated using Cox regression models incrementally adjusted with the following covariates: 1) unadjusted analyses; 2) case mix–adjusted analyses, adjusted for age, sex, race/ethnicity, family income status, educational status, and marital status; 3) expanded case mix–adjusted analyses, adjusted for case-mix covariates plus smoking status, alcohol status, CVD, cancer, diabetes, high blood pressure, and BMI; 4) expanded case mix + eGFR–adjusted analyses, adjusted for expanded case-mix covariates plus eGFR; 5) expanded case mix + eGFR + dietary intake–adjusted analyses adjusted for expanded case-mix + eGFR covariates plus dietary energy intake and dietary sodium intake; and 6) expanded case mix + eGFR + dietary intake + health behavior + nutritional status–adjusted analyses, adjusted for expanded case-mix + eGFR + dietary intake covariates plus physical activity status, supplement status, and serum albumin levels. CVD, cardiovascular disease; DPI, dietary protein intake; eGFR, estimated glomerular filtration rate.

FIGURE 4

Association of proportion of HBV protein intake with all-cause mortality risk, stratified by eGFR, in participants with (A) impaired kidney function (n = 1994) and (B) normal kidney function (n = 25,605). Each plot shows HRs and their 95% CIs, estimated using Cox regression models incrementally adjusted with the following covariates: 1) unadjusted analyses; 2) case mix–adjusted analyses, adjusted for age, sex, race/ethnicity, family income status, educational status, and marital status; 3) expanded case mix–adjusted analyses, adjusted for case-mix covariates plus smoking status, alcohol status, CVD, cancer, diabetes, high blood pressure, and BMI; 4) expanded case mix + eGFR–adjusted analyses, adjusted for expanded case-mix covariates plus eGFR; 5) expanded case mix + eGFR + dietary intake–adjusted analyses, adjusted for expanded case-mix + eGFR covariates plus dietary energy intake and dietary sodium intake; and 6) expanded case mix + eGFR + dietary intake + health behavior + nutritional status–adjusted analyses, adjusted for expanded case-mix + eGFR + dietary intake covariates plus physical activity status, supplement status, and serum albumin levels. The HBV tertiles 1, 2, and 3 correspond to proportions of HBV protein intake of <47%, 47% to <69%, and 69–100%, respectively, based on HBV protein intake distribution in the overall cohort. CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HBV, high biological value.

FIGURE 5

Subgroup analyses of the association of DPI scaled to ABW (dichotomized as ≥1.4 compared with <1.4 g/kg ABW/day) with all-cause mortality risk among participants with (A) impaired kidney function (n = 1994) and (B) normal kidney function (n = 25,605). Each plot shows HRs and their 95% CIs, estimated using Cox regression models adjusted for expanded case-mix covariates, including age, sex, race/ethnicity, family income status, education status, marital status, smoking status, alcohol status, CVD, cancer, diabetes, high blood pressure, and BMI. P-interactions were explored through the addition of 2-way interaction terms with DPI (separately), using likelihood ratio tests. ABW, actual body weight; CVD, cardiovascular disease; DPI, dietary protein intake; eGFR, estimated glomerular filtration rate.