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.
Older people constitute an increasingly greater proportion of patients with advanced CKD, including those patients undergoing maintenance dialysis treatment. Frailty is a biologic syndrome of ...decreased reserve and resistance to stressors that results from cumulative declines across multiple physiologic systems and causes vulnerability to adverse outcomes. Frailty is common in elderly CKD patients, and it may be associated with protein-energy wasting (PEW), sarcopenia, dynapenia, and other complications of CKD. Causes of frailty with or without PEW in the elderly with CKD can be classified into three categories: causes primarily caused by aging per se, advanced CKD per se, or a combination of both conditions. Frailty and PEW in elderly CKD patients are associated with impaired physical performance, disability, poorer quality of life, and reduced survival. Prevention and treatment of these conditions in the elderly CKD patients often require a multifaceted approach. Here, we examine the causes and consequences of these conditions and examine the interplay between frailty and PEW in elderly CKD patients.
The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for nutrition in kidney diseases since 1999. Since the publication of the ...first KDOQI nutrition guideline, there has been a great accumulation of new evidence regarding the management of nutritional aspects of kidney disease and sophistication in the guidelines process. The 2020 update to the KDOQI Clinical Practice Guideline for Nutrition in CKD was developed as a joint effort with the Academy of Nutrition and Dietetics (Academy). It provides comprehensive up-to-date information on the understanding and care of patients with chronic kidney disease (CKD), especially in terms of their metabolic and nutritional milieu for the practicing clinician and allied health care workers. The guideline was expanded to include not only patients with end-stage kidney disease or advanced CKD, but also patients with stages 1-5 CKD who are not receiving dialysis and patients with a functional kidney transplant. The updated guideline statements focus on 6 primary areas: nutritional assessment, medical nutrition therapy (MNT), dietary protein and energy intake, nutritional supplementation, micronutrients, and electrolytes. The guidelines primarily cover dietary management rather than all possible nutritional interventions. The evidence data and guideline statements were evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.
The incidence and severity of hypertension are affected by nutritional status and intake of many nutrients. Excessive energy intake and obesity are major causes of hypertension. Obesity is associated ...with increased activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, possibly other mineralcorticoid activity, insulin resistance, salt-sensitive hypertension and excess salt intake, and reduced kidney function. High sodium chloride intake strongly predisposes to hypertension. Increased alcohol consumption may acutely elevate blood pressure. High intakes of potassium, polyunsaturated fatty acids, and protein, along with exercise and possibly vitamin D, may reduce blood pressure. Less-conclusive studies suggest that amino acids, tea, green coffee bean extract, dark chocolate, and foods high in nitrates may reduce blood pressure. Short-term studies indicate that specialized diets may prevent or ameliorate mild hypertension; most notable are the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits, vegetables, and low-fat dairy products, and the DASH low-sodium diet. Long-term compliance to these diets remains a major concern.
Patients with stages 4 and 5 chronic kidney disease (CKD), and particularly chronic dialysis patients, commonly are found to have substantially reduced daily physical activity in comparison to age- ...and sex-matched normal adults. This reduction in physical activity is associated with a major decrease in physical exercise capacity and physical performance. The CKD patients are often physically deconditioned, and protein energy wasting (PEW) and frailty are commonly present. These disorders are of major concern because physical dysfunction, muscle atrophy, and reduced muscle strength are associated with poor quality of life and increased morbidity and mortality in CKD and chronic dialysis patients. Many randomized controlled clinical trials indicate that when CKD and chronic dialysis are provided nutritional supplements or undergo exercise training their skeletal muscle mass and exercise capacity often increase. It is not known whether the rise in skeletal muscle mass and exercise capacity associated with nutritional support or exercise training will reduce morbidity or mortality rates. A limitation of these clinical trials is that the sample sizes of the different treatment groups were small. The aim of this review is to discuss the effects of nutrition and exercise on body composition, exercise capacity, and physical functioning in advanced CKD patients.
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Nutrition in Chronic Renal Failure was recently published in the American Journal of Kidney ...Diseases . This publication provides 27 clinical practice guidelines for adults and 10 clinical practice guidelines for children. The adult guidelines focus primarily on patients undergoing maintenance dialysis therapy, although there are several clinical practice guidelines on nutritional issues for patients with advanced chronic renal failure (CRF) not undergoing dialysis therapy. The pediatric guidelines focus entirely on children undergoing maintenance dialysis treatment. The present article discusses a number of the more prominent clinical practice guidelines for the adults. Among these is the recommendation that the protein-energy nutritional status in these patients should be assessed by a panel of measures rather than by any single measure. Also, non-dialyzed patients with advanced CRF (ie, glomerular filtration rate <25 mL/min) and those undergoing maintenance hemodialysis or chronic peritoneal dialysis should be prescribed a dietary energy intake of 35 kcal/kg/day for patients who are <60 years of age and 30 kcal/kg for patients ≥60 years of age. Maintenance hemodialysis patients should be prescribed 1.2 g protein/kg/d; chronic peritoneal dialysis patients should be prescribed 1.2 to 1.3 g protein/kg/d. For non-dialyzed patients with CRF (glomerular filtration rate <25 mL/min), 0.60 g protein/kg/d should be prescribed. For patients who will not accept such a diet or are unable to maintain an adequate energy intake on that diet, a protein intake of up to 0.75 g protein/kg/d may be prescribed. At least 50% of the protein intake for all of these patients should be of high biologic value. A guideline concerning indications for inaugurating maintenance dialysis treatment or renal transplantation on the basis of deteriorating nutritional status is also given.
Dietary treatment offers many benefits to patients with advanced chronic kidney disease (CKD) who are approaching the need for renal replacement therapy. A large number of these benefits are ...independent of whether diets slow the rate of progression of CKD. These diets are low in protein and many minerals, and provide adequate energy for the CKD patient. The diets can reduce accumulation of potentially toxic metabolic products derived from protein and amino acid degradation, maintain a healthier balance of body water, sodium, potassium, phosphorus, calcium and other minerals, and prevent or improve protein-energy wasting. Such diets may enable patients to safely delay the onset of chronic dialysis therapy or kidney transplantation. Dietary therapy may also augment the effectiveness of infrequent or incremental dialysis by maintaining healthier metabolic and clinical status and may enable some end-stage renal disease patients to avoid the need for temporary placement of hemodialysis catheters while their arterial venous fistulae or grafts mature. The anxiety that many advanced CKD patients commonly experience with regard to starting dialysis may incentivize them to accept and adhere to dietary therapy.
Background Serum albumin level predicts mortality in dialysis patients and is used to assess their health status and the quality of delivered care. Whether the threshold level of serum albumin at ...which mortality risk increases in peritoneal dialysis (PD) patients is the same as for hemodialysis (HD) patients has not been studied. Study Design Observational cohort study of dialysis patients undertaken to determine the survival-predictability of serum albumin level in PD patients and compare it with that in HD patients. Setting & Participants 130,052 dialysis patients (PD, 12,171; HD, 117,851) who received treatment in any of the 580 dialysis units owned by DaVita Inc between July 1, 2001, through June 30, 2006, followed up through June 30, 2007. Predictor Baseline and time-averaged serum albumin level (assayed using bromcresol green) and change in serum albumin level over 6 months. Outcome Measures All-cause, cardiovascular, and infection-related mortality. Results PD patients with baseline serum albumin level <3.0 g/dL had a more than 3-fold higher adjusted risk of all-cause and cardiovascular mortality and 3.4-fold higher risk of infection-related mortality (reference group: serum albumin, 4.00-4.19 g/dL). Adjusted all-cause mortality was significantly lower in PD patients with a ≥0.3-g/dL increase in serum albumin level over 6 months and significantly higher in those for whom it decreased by ≥0.2 g/dL (reference group: serum albumin change, +0.1 to −0.1 g/dL). A significant increase in death risk was evident for HD patients with serum albumin level <4.0 g/dL, but at <3.8 g/dL for PD patients. For each albumin category, overall death risk for PD patients was lower than for HD patients (reference group: HD patients with serum albumin of 4.00-4.19 g/dL). Limitations Study can identify associations only without attribution of causality and residual confounding cannot be excluded. Conclusions Serum albumin predicts all-cause, cardiovascular, and infection-related mortality in both PD and HD patients. However, the threshold at which risk of death increases varies by dialysis modality, and this difference should be considered by agencies or organizations that set quality standards.
In chronic kidney failure, there is impairment in the conversion of phenylalanine to tyrosine. As a result, tyrosine and the tyrosine/phenylalanine ratio are reduced in plasma and many tissues, and ...phenylalanine concentrations tend to be normal or slightly increased. Although animal studies indicate that the kidney is not a major contributor to the conversion of phenylalanine to tyrosine, human studies conducted in the postabsorptive state suggest that the kidney plays a major role in the uptake of phenylalanine and its hydroxylation and release as tyrosine. The human splanchnic bed in the postabsorptive state also displays net uptake of both phenylalanine and tyrosine and hydroxylation of substantial amounts of phenylalanine to form tyrosine. In chronic renal failure (CRF) patients, splanchnic uptake of tyrosine appears to be reduced in the postabsorptive state. After an amino acid meal, there is net release of phenylalanine from the splanchnic bed in normal subjects and to an even greater degree in CRF patients; tyrosine is released postprandially in both normal subjects and CRF patients. In the postabsorptive state, tyrosine release from the kidney is largely derived from the hydroxylation of phenylalanine. In CRF, the release of tyrosine from the kidney is reduced and this reduction may be marked with advanced CRF. These observations, as well as isotope studies indicating normal phenylalanine flux, reduced tyrosine flux and impaired conversion of phenylalanine to tyrosine in CRF patients, raise the possibility that tyrosine may be an essential amino acid in this condition. Further research will be necessary to answer this question. Oxidative stress, which often increases in CRF patients, may lead to increased formation of chlorotyrosine and nitrotyrosine in plasma proteins and of nitrotyrosine in the brain. Increased nitrotyrosine is also found in kidneys of patients with diabetic nephropathy or allograft nephropathy. Increased serum concentrations of oxidation products of phenylalanine have also been observed in patients with CRF. Impaired urinary excretion also may lead to accumulation of metabolic products of both phenylalanine and tyrosine in CRF. It is not known whether the elevated protein chlorotyrosine or nitrotyrosine or increased oxidative products of phenylalanine cause adverse metabolic or toxic effects in patients with CRF.
PDF
