CKD – high protein intake or not?

12th September 2024, A/Prof Chee L Khoo

Protein

Inadequate protein intake in older adults may cause impairments of muscle mass and muscle function as well as impairment in immune function. Higher protein intake has been associated with increased muscle mass and strength, slower rate of bone loss, higher bone mineral density, lower risk of frailty, and improved cardiovascular function and recovery from illness (including wound healing) (1,2).  However, if you have chronic kidney disease (CKD), the recommendations can be a bit tricky. We were always taught that high protein intake can put a strain on the kidneys and can lead to reduction in eGFR especially in patients with CKD. However, there is evidence to suggest that sarcopenia in patients with CKD is associated with increased mortality.

Thus, the landscape out there about protein intake in patients with CKD is actually quite conflicting. Rat studies showed that high protein diet leads to glomerular hyperfiltration which is the prelude to early renal damage (3). Theoretically, high protein intake comes with high phosphate and high phosphate causes renal damage (4). In the PREVEND trial, all-cause mortality and non-cardiovascular mortality were associated with protein intake but those with low protein intake had the highest event rates (5). In the Gubbio Study, 1 g/day higher protein intake was related to more negative eGFR change (6). In the Singapore Chinese Health Study, red meat intake was strongly associated with end stage renal disease (ESRD) but other poultry, eggs and fish intake was not. But the red meat eaters ate less fruits and vegetables (7).

However, there are studies that says the opposite. In the Nurses’ Health Study: dietary intake was NOT associated with eGFR change but in women with eGFR 55-80, there was a reduction of eGFR of -1.6 per 10 g increase in protein intake (8). In the ONTARGET trial, patients in the highest tertile of total and animal protein intake had better renal outcomes compared with participants in the lowest tertile (9). In exercise-trained men and women without known kidney disease, protein intakes ranging from 3.2-4.4 g/kg/day (4-5.5× greater than the current RDA of 0.8 g/kg/day) are well-tolerated with no significant changes in clinical safety markers (10).

Whether high protein is good or bad for kidney disease becomes even more confusing in older patients. In older patients, there are multiple organ system changes that affects protein synthesis and degradation. Protein synthesis is reduced because of a shortage of available nutrients due to loss of appetite, sedentary behaviour, and insulin and protein anabolic resistance. On the other hand, protein degradation, increased oxidative modification of proteins, and accumulation of inflammatory diseases lead to an increased need for protein.

We are also unsure about which type of protein is good and which type is bad. Plant protein is supposed to have a lower impact on remaining nephrons, mitigate glomerular hyperfiltration, reduce proteinuria, preserve kidney function, and protect from metabolic derangements. On the other hand, animal-based  protein can have higher biological value and anabolic potential, so higher animal based protein intake may improve nutritional status.

To explore the whole issue in relation to whether high protein intake is good or bad for older patients with CKD, Carballo-Casla et al explored the connections between higher protein intake in older patients with CKD and mortality rate (11). They analyse data from three cohort of patients – randomly sampled community dwelling individuals in Spain 60-65 years and >65 years old (Seniors-ENRICA 1 and Seniors-ENRICA 2) and randomly sampled community dwelling individuals >60 years or older living in Stockholm (Swedish National Study on Aging and Care in Kungsholmen (SNAC-K)). Data from habitual food consumption over the previous year over multiple years were analysed. Food consumption were converted into nutrients using food composition tables. Proteins were deemed to have plant or animal origin according to the foods from which they came. Cereal, legume, nut, and other vegetable proteins were considered plant proteins, while dairy, meat, egg, fish, and other animal proteins were considered of animal origin. Participants with CKD were grouped into stages 1 to 5 from the Kidney Disease: Improving Global Outcomes guidelines.5 Participants with CKD 4 and 5, those undergoing kidney replacement therapy and kidney transplant recipients were excluded. Mortality data were obtained from national registries.

Results

There were 14 399 participants of which 4789 had CKD. The maximum follow up was 10 years. The mean age of the participants were 78 years old. After a maximum follow-up of 10 years, 1468 participants died. Amongst participants with CKD, higher protein intake is associated with lower mortality. Compared with those on 0.8g protein/kg/day, those on 1.0g/kg/day was associated with a 12% reduction in mortality. For those on 1.20g/kg/day, there was a 21% reduction, for those on 1.4g/kg/day there was a 27% reduction and for those on 1.6g/kg/day there was a 33% reduction in mortality.

The mortality improvement was seen irrespective of the age of the participants. The associations were comparable whether it was plant or animal protein. When they looked at participants without CKD, the mortality improvement with increasing protein was even stronger.

This study by Carballo-Casla et al is in line with similar studies suggesting that increased protein intake is either neutral or positively beneficial for mortality. In a Korean study, higher total protein intake showed a null association with 11-year all-cause mortality (12). A French study looked at patients with CKD over 60 years, higher total protein intake was not associated with increased mortality after 3 years (13). In a Japanese study of adults with CKD and older than 65 years, higher total protein intake was associated with lower risk of all-cause death over 4 years, although participants had been advised to limit protein intake depending on their CKD stage (14).

It would seem that high protein intake in people with normal kidneys is probably beneficial whereas high protein intake in people with renal impairment may or may not cause further deterioration of renal function. The jury is still out. We will need to balance the potential harm of increased protein intake on kidney function with the harm of sarcopenia. Current Kidney Disease: Improving Global Outcomes (CKDIGO) guideline recommends that patients with mild CKD (stages 1 & 2) not consume more than 1.3 g/kg/day of protein. In stages 3-5 (without dialysis) of CKD, protein intake should be limited to 0.6-0.8 g/kg/day (15).

References:

  1. Lonnie M, Hooker E, Brunstrom JM, et al. Protein for life: review of optimal protein intake, sustainable dietary sources and the effect on appetite in ageing adults. Nutrients. 2018;10(3):360
  2. Bauer J, Biolo G, Cederholm T, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J AmMed Dir Assoc. 2013;14(8):542-559.
  3. Brenner B et al. N Engl J Med 1982;307
  4. Goraya N et al. Kidney Int 81:86–93
  5. Halbesma N et al. J. Am. Soc. Nephrol. 20
  6. Cirillo M et al. Nephrol. Dial. Transplant. 29
  7. Lew Q-LJ et al. J. Am. Soc. Nephrol. 28
  8. Knight EL et al. Ann. Int. Med. 138
  9. Dunkler D. et al. JAMA 173
  10. Antonio J et al. J Nutr Metab. 2016
  11. Adrián Carballo-Casla, Carla Maria Avesani, Giorgi Beridze, et al. Protein Intake and Mortality in Older Adults With Chronic Kidney Disease. JAMA Network Open. 20
  12. Kwon YJ, Lee HS, Park GE, et al. The association between total protein intake and all-cause mortality in middle aged and older korean adults with chronic kidney disease. Front Nutr. 2022;9:850109.24;7(8):e2426577
  13. Torreggiani M, Fois A, Moio MR, et al. Spontaneously low protein intake in elderly CKD patients:myth or reality? analysis of baseline protein intake in a large cohort of patients with advanced CKD. Nutrients. 2021;13 (12)
  14. Watanabe D, Machida S, Matsumoto N, Shibagaki Y, Sakurada T. Age modifies the association of dietary protein intake with all-cause mortality in patients with chronic kidney disease. Nutrients. 2018;10(11):1744.
  15. Stevens PE, Ahmed SB, Carrero JJ, et al; Kidney Disease: Improving Global Outcomes (KDIGO) CKDWork Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314.