Dietary protein supplementation
PEW is common, and is one of the most powerful predictors of poor outcomes in CKD and ESRD. While its etiology is complex, one of the recognized causes of PEW is a decrease in protein and energy intake.18 There is broad agreement about the need for dietary interventions in patients with CKD with protein intake <0.6- 0.8 g/kg/day, or in patients with ESRD with protein intake <1.1-1.2 g/kg/day. Such interventions usually start with dietary counseling aimed at assuring that a proper amount and quality of proteins, energy and other nutrients is ingested (Figure 1).
In cases where counseling is unsuccessful, nutritional supplementation with high biological value proteins or their equivalents in the form of essential amino acids and ketoacids can be considered. PEW can be improved by using various methods of protein supplementation.19 Whether or not there is a longer term clinical benefit of such strategies remains unproven; improvement in mortality rates can be inferred from observational studies,20 but randomized controlled trials to test this hypothesis have not yet been completed.
There is considerably more controversy about protein supplementation to goals above the stated 0.6-0.8 g/kg/day (or 1.1-1.2 g/kg/day in ESRD). Higher protein intake may be necessitated in acutely hypercatabolic patients (such as patients with sepsis), but the added value of increased protein intake in patients with features of PEW who are not acutely catabolic or in those at risk of PEW is much less clear. Increasing protein intake in such patients could promote anabolism and faster re-building of body protein and muscle stores, or it could better prevent their catabolism.
However, the added anabolic value of supplemental proteins or protein equivalents diminishes with increasing baseline levels of intake,21 hence, it is unclear to what extent supplementation to achieve intakes above the 0.6-0.8 g/kg/day (or 1.1-1.2 g/kg/day in ESRD) level would be useful. It is also largely unknown what total amount of daily protein intake one should aim for in such patients. Protein intake as high as 1.5 g/kg/day has been suggested in elderly patients,22 and one of approximately 1.5-2.5 g/kg/day in patients with acute kidney injury (AKI), the actual value depending on the severity of AKI, the presence of underlying catabolic diseases, and the presence or absence of renal replacement therapy.23
However, the amount of protein intake in CKD or ESRD patients with PEW that provides the ideal balance between improving nutrition and preventing toxic effects of excess protein remains unclear.
Whatever the ideal amount of excess protein intake may be in patients with PEW, the potential toxicities associated with higher protein intake necessitate a cautious and controlled approach to these strategies, especially in patients with CKD. Glomerular filtration rate is increased by high protein intake through afferent arteriolar dilatation and through effects on the glomerular basement membrane; thus, high protein intake can result in glomerular hyperfiltration, worsening proteinuria, and accelerated progression of CKD.24
Furthermore, the accumulation of various protein breakdown products as a result of decreasing kidney function can result in uremic toxicity, the uremic syndrome, and metabolic effects such as oxidative stress, altered endothelial function, nitric oxide production, and insulin resistance.25
As mentioned above, the deleterious effects of excess protein intake can be controlled by adding various prescription supplements containing protein equivalents such as essential amino acids or ketoacids. It is possible that protein sources rich in branched-chain amino acids (especially leucine and isoleucine) or their keto-analogues could be more beneficial in patients with PEW by virtue of their anabolic effects.26
However, these questions will need to be clarified in properly designed and conducted clinical trials before their mainstream application can be advocated. Until then, an individualized approach to these decisions is suggested based on a patient’s catabolic status and other clinical and financial considerations.