Dietary Protein as Kidney Protection: Quality or Quantity?

Abstract

CKD is a global health challenge, and diet is the largest CKDrelated risk factor for death and disability. 1 Dietary protein restriction has been identified as a possible kidney-protective intervention, and some small-scale studies support its efficacy to slow nephropathy progression. 2 Nevertheless, the largest study to examine the effect of dietary protein restriction on nephropathy progression, the Modification of Diet in Renal Disease (MDRD) study, showed that GFR decline at 3 years was no different between patients given a low-protein diet (0.58 g/kg per day) and a usual-protein diet (1.3 g/kg per day). 3 Because this landmark study failed to show benefit from reduction of the quantity of protein typical of diets ingested in developed societies, investigators began examining whether changing the quality of ingested protein might slow nephropathy progression.The two changes in dietary protein quality currently receiving the most attention are substituting non-nitrogen ketoanalogue proteins and substituting plant-sourced for animal-sourced protein. Naturally occurring amino acids contain nitrogen, which when metabolized yield nitrogenous wastes that increase BUN and possibly other untoward effects on kidney function. 4 Furthermore, diets in developed societies are largely acid producing because of the proportionately greater amount of animal-source proteins (which are acid producing) than plant-source proteins (which are largely base producing). Small-scale studies support that addition of plantsourced protein, such as fruits and vegetables, improves metabolic acidosis, reduces kidney injury, and slows nephropathy progression. [5][6][7] The mechanisms by which changes in the quality of ingested protein might slow nephropathy progression are incompletely understood. Substituting non-nitrogen ketoanalogues might allow patients to realize the benefit of dietary protein while avoiding possible untoward effects of nitrogenous wastes. 4 Furthermore, adding base-producing plant proteins might lower kidney levels of substances, which in the short term facilitate kidney acid excretion but in the long term induce interstitial fibrosis that mediates nephropathy progression. 8 On the other hand, substituting plant-based for animal-based dietary protein promotes gut flora, which produce metabolites considered less nephrotoxic than flora promoted by animalsourced protein, 9 improves bone mineral parameters, 10,11 and reduces BP and body weight. [5][6][7]12 In this issue of the Journal of the American Society of Nephrology, Garneata et al. 13 explored the potential contributions of ketoanalogues and plant-based diets to nephropathy progression by comparing effects of a very-low-vegetarian protein diet (0.3 g/kg per day) supplemented with ketoanalogues (VKD) with a usual mixed-source low-protein diet (0.6 g/kg per day) (LPD) on CKD progression to the end points of need for RRT or a 50% decline in baseline kidney function, measured as eGFR. This 18-month, prospective, randomized controlled trial of 207 patients involved a 3-m...

Dietary Phosphorus Intake and the Kidney

“…Serum phosphorus decreased from 5.9 to 4.4 mg/dL in the KD group compared with an increase from 5.8 to 6.2 mg/dL in the LPD group ( P < 0.01 for all comparisons). Whether the beneficial effect was driven primarily by differences in amino acids, dietary acid load, or phosphorus is unclear in this study and other protein restriction studies (62). …”

Dietary Protein Sources and Risk for Incident Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study

“…Given the hypothesized effect of specific types of protein on renal vasodilation, renal blood flow, and GFR, analyses of food groups instead of total total protein intake may be a more appropriate method. 19 This approach follows early observations that showed renal blood flow increases in dogs as a consequence to meat feeding. 5 Controlled short-term feeding studies in humans support that an increase in the GFR can be induced by animal protein, specifically protein from meat.…”

“…9, 10 Such investigations are warranted as these provide a more adequate assessment of the complexities of diet-disease associations. 19 …”

Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

“…In 2010, Menon showed in a post-hoc analysis of MDRD study that low plasma bicarbonate levels increased the risk of outcomes such as renal death and mortality [ 30 ]. Wesson et al showed the paramount role of a diet rich in fruit and vegetables, not only from the nutritional point of view, but also in the nephrology field, because it ensures an amount of alkali that are needed in CKD [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”