Higher protein intake associated with rapid decline of kidney function in healthy adults
High-protein diet with renal hyperfiltration is associated with rapid decline rate of renal function: a community-based prospective cohort study
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Introduction and methods
A high-protein diet has been associated with increased risk of renal hyperfiltration (RHF) in the general population [1-3] and can worsen progression of chronic kidney disease (CKD) [4-6]. In contrast, some studies have reported no association between dietary protein intake and estimated glomerular filtration rate (eGFR) .
RHF has been demonstrated as a novel marker of all-cause mortality in the general population , and an association between RHF and rapid renal function decline was shown in patients with diabetes [9,10]. Causes of RHF include medical conditions, such as diabetes hypertension and autosomal dominant polycystic kidney disease, as well as physiological conditions, such as pregnancy or obesity [2, 11-14].
This study examined the association between a high-protein diet and RHF with kidney function decline in a healthy adult population. RHF was adjusted for age, sex, history of diabetes and/or hypertension, height, and weight. In addition, the effect of time-averaged protein intake on the association between RHF and decline in kidney function was examined and the association between protein intake and RHF was validated using another community-based cohort data set.
Subjects with data on protein intake were recruited from the Korean Genome and Epidemiology Study (KoGES) (2001-2014), a prospective community-based cohort study consisting of residents of two South Korean cities between 40-69 years. Those with an eGFR <60 mL/min/1.73 m² or kidney disease at baseline, missing data and missing follow-up creatinine data were excluded, leaving 9226 subjects.
Dietary intake was assessed at baseline and the second follow-up examination using a semiquantitative food frequency questionnaire (FFQ) . Based on the FFQ, the subjects were categorized into four groups according to quartiles of daily amount of protein intake at baseline. RHF was defined as the logarithm transformed eGFR larger than the 95th percentile in the distribution of residuals from the multivariable linear regression after the adjustment for logarithm-transformed age, sex, history of hypertension and/or diabetes, height and weight. The exact eGFR value for the RHF was 94.4 mL/min/1.73 m². A rapid eGFR decline was defined as an annual eGFR decline rate 3 mL/min/1.73 m²/year.
The impact of mean protein intake over time (time-averaged amount of protein intake) on RHF and decline of kidney function was further evaluated in subjects for whom dietary intake data were available at the second follow-up (6906 subjects). The Korean National Health and Nutrition Examination Survey (KNHANES IV, V and VI,2008–15) was used to validate the association between high daily protein intake and RHF, of which 40113 participants were included for this analysis.
- Higher protein intake was associated with RHF (OR for Q4 compared to Q1: 3.48, 95%CI: 1.39–8.71, P=0.01).
- Higher protein intake was associated with rapid decline of eGFR (OR for Q4 compared to Q1: 1.32, 95%CI: 1.02-1.73, P=0.03).
- When subjects were divided based on RHF status, protein intake was higher in the RHF group (n=472) compared to the non-RHF group (n=8754) (1.07 g/kg vs. 1.02 g/kg, P=0.02). eGFR decline rate was faster in the RHF group compared to the non-RHF group (-3.1 vs. -2.1 mL/min/1.73 m²/year, P<0.001).
- When subjects were divided into quartiles in the RHF and non-RHF groups, the highest quartile in the RHF group showed the highest risk for rapid kidney function decline (OR for Q4 compared to Q1: 3.35, 95%CI: 1.07-10.51, P=0.04). In the non-RHF group, there was no difference for rapid kidney function decline between the different quartiles.
- When using time-averaged amount of protein intake, rapid eGFR decline was higher in the group with highest protein intake (OR for Q4 compared to Q1: 2.66, 95%CI: 1.37-5.17, P=0.01). This was also observed in the RHF group (OR: 1.55, 95%CI: 1.14–2.09, P=0.01), but in the non-RHF group no differencesin rapid eGFR decline were observed between quartiles.
- An analysis of data from the KNHANES cohort also showed that higher protein intake was associated with higher prevalence of RHF.
In a Korean community-based prospective study, higher intake of protein was associated with RHF and rapid decline of eGFR compared to lower protein intake in healthy adults. These findings suggest that a high protein diet can have deleterious effects on kidney function in the general population.
In the same journal the results of a study on dietary protein intake and kidney function decline in stable patients after myocardial infarction (MI) was reported: Dietary protein intake and kidney function decline after myocardial infarction: the Alpha Omega Cohort Esmeijer K et al Nephrol Dial Transplant 2019. Post-MI patients have an increased annual risk of kidney function decline (double compared to general population), and are therefore at risk of CKD. Although KDIGO guidelines recommend to limit daily total protein intake in adults at risk for CKD [16,17], it is unknown whether protein restriction in post-MI patients slows down kidney function decline. The Alpha Omega Cohort was used, a prospective cohort of Dutch patients aged 60-80 years with a diagnosis of MI, 10 years before study entry. Data on food intake was collected using a 203-item food frequency questionnaire (FFQ) at baseline. Using data of 2255 patients with a follow-up of 41 months, the authors found a strong linear association between protein intake and annual kidney function decline. Annual change in eGFR-cysC was double in patients with protein intake >1.20 compared with those taking proteins <0.80 g/kg for ideal body weight: -1.60 vs -0.84 mL/min/1.73 m². These was also an inverse association between intake of animal protein and eGFR-cysC and a similar but non-significant association for plant protein intake. This study showed that higher protein intake was associated with a more rapid kidney function decline in post-MI patients.
In their editorial comment , the authors write that a high-protein diet (HPD) is not a emerging food culture but rather a prevailing dogma in society. ‘It has even gone so far that we feel pressured to eat more proteins and less carbohydrates’, the authors state. They explain how overnutrition has resulted in the acceptance of benefits of a HPD. But, they question: ‘is HPD safe for kidney health or not?’ and list some of the evidence and recommendations against a HPD. Low-protein diet (LPD) is recommended for those with CKD or at risk for CKD, such as diabetes patients and obese subjects with microalbuminuria, and those with reduced kidney reserve (solitary kidney or earlier stages of CKD). The Recommended Dietary Allowance (RDA) for protein is 0.8 g/kg/day and the estimated requirement is likely even lower, around 0.6 g/kg/day. An LPD for CKD management is defined as daily protein in the range of 0.6–0.8 g/kg/day and for persons with a solitary kidney or at high risk of CKD, high protein intake >1.0 g/kg/day should be avoided. They end by writing: ‘It is time to unleash the taboo and make it loud and clear that a high-protein diet is not as safe as claimed, as it may compromise kidney health and result in a more rapid kidney function decline in individuals or populations at high risk of CKD. It is prudent to avoid recommending high-protein intake for weight loss in obese or diabetic patients or those with prior cardiovascular events or a solitary kidney if kidney health cannot be adequately protected.’
Would you advice patients against a high-protein diet?
- Yes, all patients
- Yes, but only CKD patients or those with increased risk of renal failure