High Protein-Diet Induced Renal Hyperfiltration is Associated with Rapid Decline Rate of Renal Function: Community Based Prospective Cohort Study

Abstract

Background: High protein intake is associated with increased risk of renal hyperfiltration (RHF). However, the effect of high protein-diet induced RHF on decline of kidney function has never been explored. To investigate the association between a high protein diet, RHF, and declining kidney function. Methods: A total of 9,226 subjects were enrolled from the Korean Genome and Epidemiology Study, a community based prospective cohort study, and classified into quartiles according to daily amount of protein intake. 40,113 subjects from the Korean National Health and Nutrition Examination Survey (KNHANES) were enrolled for a sensitivity analysis. RHF was defined as eGFR with residuals > 95th percentile after adjustment for age, sex, and history of hypertension and/or diabetes. Decline of renal function over time was calculated by the slope of linear regression analysis of serial eGFR measurements for each subject. Findings: The prevalence and relative risk of RHF was higher in the highest than in the lowest protein intake quartile (odds ratio [OR], 3.19; 95% CI, 1.30 to 7.85). The mean eGFR decline rate was faster as quartiles of protein intake increased (-2.01, -2.05, -2.19, and -2.34 mL/min/1.73 m2/year in Q1, 2, 3, and 4, respectively). Furthermore, the highest quartile was associated with an increased risk of rapid eGFR decline (annual decline rate > 3 mL/min/1.73 m2/year; OR, 1.35; 95% CI, 1.03 to 1.78). When subjects were divided into two groups with or without RHF, highest quartile was associated with a rapid decline in renal function, only in RHF subjects. In the sensitivity analysis of the KNHANES data, higher quartile was associated with higher OR of RHF. Interpretation: A high protein intake is significantly associated with RHF and high protein diet-induced RHF increases the risk of rapid renal function decline in the general population. Funding Statement: The epidemiologic data used in this study were obtained from the KoGES from 2001 to 2014 and KNHANES (IV, V, and VI) from 2008 to 2015, Republic of Korea. This study was supported by a research grant from Inha University Hospital. Declaration of Interests: Authors have disclosed no conflicts of interest. Ethics Approval Statement: All subjects voluntarily participated in the study and provided informed consent. The study protocol was approved by the Ethics Committee of KoGES at the Korean National Institute of Health. This study was performed in accordance with the Declaration of Helsinki and approved by the institutional review board (IRB) of Yonsei University Health System Clinical Trial Center (4-2016-0900).