Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy

Abstract

Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is ≥20-25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients' biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients with PEW, and highlights areas in need of further research.

FIGURE 1.

Schematic representation of the development of protein-energy wasting with advancing stages of chronic kidney disease. The appetite derangement component was reproduced with permission from reference . CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; ↑, increased; ↓, decreased.

FIGURE 2.

Probability (95% CI) of the presence of protein-energy wasting in patients with different eGFRs. Protein-energy wasting was defined as the presence of ≥2 of the following biochemical markers: serum albumin <3.7 g/dL, percentage of lymphocytes in white blood cells <22%, and white blood cell count >7500/mm³. Values are based on data from Kovesdy et al (3), assessed in 1220 patients with non-dialysis-dependent chronic kidney disease, obtained by using restricted splines. eGFR, estimated glomerular filtration rate.

FIGURE 3.

Mechanisms of action leading to the development of PEW in CKD. CKD, chronic kidney disease; GH, growth hormone; IGF-I, insulin-like growth factor-1; PEW, protein-energy wasting; ↑, increased; ↓, decreased.

FIGURE 4.

Suggested algorithm for clinical assessment and interventions aimed at assessing and treating PEW by manipulating protein intake in patients with chronic kidney disease. ¹Measured with bromcresol green method. ²Head-to-head comparisons of the different supplementation methods for the treatment of PEW are not available. Individual patient characteristics and tolerance of, adherence to, and affordability of specific supplementation methods should be considered. ³Efficacy and safety because treatment of PEW is not proven. ⁴Ideal amount of daily protein intake in PEW is unclear. Directed by specific clinical scenario. The efficacy and safety of PEW treatment in patients with non-dialysis-dependent chronic kidney disease is generally unproven. DEI, daily energy intake; DPI, dietary protein intake; EAA, essential amino acid; eDPI, estimated daily protein intake; KA, keto acid; LPD, low-protein diet; PEW, protein-energy wasting; RAAS, renin angiotensin aldosterone system.