Part II-Nutrition in Kidney Disease: Core Curriculum 2022

Dietary Nutrient Intake

Protein Intake

Case 4: Mr. Y is a 65-year-old man with CKD secondary to hypertension. His eGFR is 24 mL/min/1.73 m2. He is very adherent to office visits and medications.

Question 4: Which of the following is the recommended level of dietary protein intake for this patient?

a) 0.28-0.43 g/kg body weight per day

b) 0.55-0.60 g/kg body weight per day

c) 0.80-0.90 g/kg body weight per day

d) 1.00-1.20 g/kg body weight per day

For the answer to the question, see the following text.

The rationale for reducing dietary protein intake in CKD is that a lower protein load reduces hyperfiltration and lowers the production of uremic toxins, including p-cresyl sulfate, indoxyl sulfate, trimethyl aminoxide, and fibroblast growth factor 23 (FGF-23). Protein intake recommendations in stages 3-5 CKD, without diabetes, ranging from 0.55 to 0.6 g/kg per day to reduce the risk of kidney failure or death (odds ratio, 0.621 [95% CI, 0.391-0.985]), although a reduction in protein intake to 0.55-0.6 g/kg per day had no clear effect on decline in eGFR.However, another review comparing normal protein intakes of 0.8 to >1.0g/kg per day to protein intakes of0.5-0.6 g/kg per day in stage 3 CKD found little or no difference in rates of death or kidney failure. For those with diabetes, protein intakes of 0.6-0.8 g/kg per day are recommended. Both animal and plant protein sources can be encouraged, with no nutritional advantage of animal protein over plant-based sources. Protein intake of 0.55-0.6 g/kg per day is only sustainable in a stable, neutral metabolic state and should only be undertaken under close clinical supervision with the intent to reduce clinical symptoms and delay the initiation of dialysis. Protein intakes of 0.55-0.6 g/kg per day are not recommended during hospitalization, during infection or treatment with immunosuppressive medications, or during or after the short-term loss of body weight. Furthermore, whether actual body weight, ideal body weight, or adjusted body weight is used to calculate protein may be determined using clinical judgment and personalized to individuals.

Beyond examining protein restriction alone, several studies have looked at the effects of keto acid– or amino acid–supplemented low-protein diets (LPDs) or very-low protein diets (VLPDs) on certain metabolic and kidney outcomes parameters. Because the supplemental keto acids are primarily given to substitute for dietary protein intake, most of these studies are with VLPDs. Accordingly, several meta-analyses indicate that VLPDs supplemented with keto acids delay the initiation of maintenance dialysis and significantly reduce urea production, along with having potentially beneficial effects on insulin resistance and oxidative stress. From a safety perspective, well-designed diets planned by skilled dietitians and implemented by motivated and adherent patients are effective and do not harm the nutritional condition. The recommended level forVLPD is 0.28-0.43 g dietary protein per kilogram of body weight per day with additional keto acid/amino acid analogs to meet protein requirements (0.55-0.60 g/kg per day).

In HD and PD, there is an absence of randomized controlled trials for protein intake and outcomes. Based on observational studies, the recommended protein intake is 1.0-1.2 g/kg per day when in a stable metabolic state and with adequate energy intake. With diabetes, higher protein intake may be required to achieve glycemic control. Therefore, the correct answer to the question4 is (b).

Energy Intake

To maintain normal nutritional status, the 2020 KDOQI nutrition guideline recommends prescribing an energy intake of 25-35 kcal per kilogram of body weight per day based on age, sex, physical activity level, body composition, weight status goals, CKD stage, and concurrent illness or presence of inflflammation. These considerations are required when estimating energy requirements for individuals because they determine overall energy balance. The ratio of carbohydrate, fat, and protein for individuals with CKD depends on the CKD stage and coexisting comorbidities such as diabetes, cardiovascular disease, and obesity. Generally, carbohydrates make up around 50% of energy intake, with the remainder from protein and fat.

Carbohydrate Intake

When protein intake is limited, such as when using a lowprotein diet to prevent the buildup of uremic toxins, carbohydrate intake will need to increase to meet energy requirements. Carbohydrates include starches and sugars, with a preference for starchy foods that are less processed such as whole grains, including brown rice, whole wheat bread or pasta, oats, barley, and spelling. Whole grain carbohydrate sources contain more B vitamins and dietary fiber than refined carbohydrates. Fiber is important for reducing gut transit time, which reduces intestinal potassium absorption and reduces cholesterol, decreasing gut toxins and supporting a healthy gut microbiota. Whole-grain foods are now encouraged in Chronic Kidney Disease because in less refined starches the phosphorus is present as phytate, which is not digestible in the human gut and so does not contribute to dietary phosphorus.

Potatoes and other starchy vegetables are often dietary staples and can be included in the diets of those with CKD. Potatoes, sweet potatoes, and yams all contain potassium, which can be reduced in cooking by cutting the tubers into small pieces then soaking and boiling them in water before eating or by further cooking via roasting or baking, or mashing. Cutting, soaking, and heating destroy some of the cellular structure, releasing the potassium from the food.

Naturally occurring sugars in fruit, vegetables, milk, and plain yogurt do not contribute to the health risks associated with free sugars, so they can be eaten in moderation as part of a healthy diet for Chronic Kidney Disease. The free sugars found in soda, cordials, sugar-sweetened beverages, cookies, and cakes are associated with heart disease and becoming overweight or obese, and they have low nutritional value. These types of sugars should be avoided unless overall energy intake is poor.

Fat Intake

CKD patients commonly have dyslipidemia, with abnormalities in lipid profiles detectable as kidney function starts to decline. Nephrotic syndrome or other comorbid conditions such as diabetes mellitus and liver disease as well as the use of drugs that affect lipid metabolism (eg, thiazide diuretics, β-blockers) contribute further to dyslipidemia evident in this population.

In patients receiving maintenance HD, increased serum triglycerides and very-low-density lipoproteins and decreased LDL and high-density lipoproteins (HDL)are the most common abnormalities. The elevation in triglycerides is believed to be linked to elevated levels of apolipoprotein CIII (Apo-CIII), which inhibits lipoprotein lipase. Increased lipoprotein (a) (Lp[a]) levels are also seen in a substantial percentage of maintenance HD patients. Patients treated with PD have higher levels of serum cholesterol, triglyceride, LDL cholesterol, and apo-B than those seen in patients on maintenance HD, even though the mechanisms altering lipid metabolism are shared between the 2 groups. This may be due to increased protein losses through the peritoneum, perhaps by mechanisms related to the nephrotic syndrome, and by the glucose load of the dialysate leading to higher triglyceride synthesis and hyperinsulinemia. PD patients also have higher levels of Lp(a).

The dietary management of dyslipidemia in the setting of kidney disease is not well-established, except in kidney transplantation. In general, CKD patients are recommended to follow the general advice for heart health, including saturated fat less than 7% of total energy and unsaturated fat, such as olive oil, to substitute for saturated fats including butter and animal fats.

Micronutrient Intake

Micronutrients include vitamins, trace elements, and electrolytes and are essential for optimal biological function. The main concern in patients with CKD is that as a result of reduced dietary intake or dietary restrictions, comorbid conditions, and/or losses through the dialysis procedure deficiencies in certain vitamins and trace elements may develop. However, excess intake of certain micronutrients may also occur, leading to vitamin toxicity (eg, vitamin C, vitamin D) or clinical complications (eg, sodium, potassium, phosphorus). Because the delicate balance between underconsumption and overconsumption is also influenced by the stage of CKD and each person’s unique needs and risk factors, developing an optimal dietary strategy for a person with CKD can be challenging.

Vitamins.

Studies have suggested that patients with CKD are at risk for deficiencies in vitamin B1 (thiamine), B2 (riboflavin), and B3 (niacin), vitamin C, vitamin K, and vitamin D. However, the studies were nearly all performed in persons on maintenance dialysis and from varying geographic regions and time periods, making it difficult to apply these conclusions to individual patients. Moreover, dietary reference intakes for individual vitamins (and other micronutrients) are not available for the CKD population as they are in the general population.

Due to concern beginning decades ago over possible micronutrient deficiencies, particularly with water-soluble B vitamins, vitamin supplements tailored to patients with CKD were developed. Presently 70% of maintenance HD patients in the United States are prescribed such supplements. Yet the evidence for routine supplementation is thin. A reasonable alternative strategy would be to supplement only those individuals who by history or examination exhibit impaired dietary intake and/or nutrient loss for sustained periods of time.

Electrolytes.

Although electrolyte intake in patients with CKD should always be tailored to individual needs, a few general suggestions can be offered. Sodium consumption should be limited to less than 100 mmol/ d (2.3 g) to help control blood pressure and limit extracellular volume expansion. Replacing bread, processed meats, and cheese with fresh meats, fish, brown rice, legumes, and whole wheat pasta can reduce sodium intake. Because major sources of dietary potassium are fruits, vegetables, legumes, and nuts, all of which contain high levels of fiber and other micronutrients that offer potential health benefits, efforts should be made to avoid automatically restricting these foods unless the individual’s serum potassium is elevated and other non-dietary causes of hyperkalemia have been considered and addressed.

Similarly, the consumption of fruits and vegetables, which contain natural alkali, should be encouraged if possible because they can help reduce the complications of kidney disease-related systemic acidosis such as bone damage, muscle loss, and a possible decline in residual kidney function. Dietary phosphorus intake should be adjusted to maintain serum phosphorus levels in the normal range. Phosphorus should ideally be obtained from plant-based foods, such as whole grains, legumes, and pulses because the phosphorus is typically less well absorbed and whole-grain foods have a higher nutritional value compared with processed foods that contain phosphate additives.

The intake of dietary calcium in patients with CKD stages 3-4 should be achieved at 800 to 1,000 mg daily to maintain a neutral calcium balance. The intake goals in more advanced diseases may be complicated by concurrent use of vitamin D analogs and calcimimetics.

Trace Elements.

Information on trace elements such as zinc, selenium, or a number of other metals found in minute concentrations in the body in persons with CKD is sparse. Therefore, routine supplementation of trace elements is not recommended.

Nutritional Supplementation

Case 5: A 74-year-old woman who has had type 2 diabetes mellitus and has been on maintenance HD for 5 months is noted to have had a gradual weight loss from premorbid 68 kg to the current 59 kg. For the last 3 months, she has had problems with eating. She states that she does not tolerate meals well (usually less than half consumed), and she had a very poor appetite. She especially feels weak the afternoons after dialysis and has had no energy to cook a full meal on those days. Her dialysis time is at 11:00 AM, which interferes with her lunch. She was offered nutritional supplements, which she has tried to drink once in the morning and once at supper. She has had trouble tolerating supplements due to fullness and some bloating.

Question 5: Which step(s) would you take to address her signs and symptoms of early satiety, gastrointestinal disturbances, fatigue, weight loss, and reduced nutritional intake?

a) Review her medications, the adequacy of her dialysis, and her acid-base balance.

b) Request (or complete) a nutritional assessment (eg, SGA) of her body stores, gastrointestinal symptoms, functional capacity, and food intake to determine factors contributing to her poor nutritional state.

c) Review the timing and type of her nutritional supplement (or request a dietitian to review the timing and type of her nutritional supplement).

d) All of the above.

For the answer to the question, see the following text.

When intake from food alone is inadequate, supplementation with nutrition formulations can be used to meet nutritional requirements to prevent or treat malnutrition. In CKD, undernutrition is associated with poorer outcomes, and using nutritional interventions is warranted in these patients. Oral nutritional supplements (ONS), enteral tube feeding, and parenteral nutrition may be used when clinically indicated (Box 1). In reference to case 5, all the options are appropriate and should be completed to provide the most suitable nutritional care for the patient. Thus, the best answer to question 5 is (d).

ONS are suitable when oral intake is possible and safe. Enteral tube feeding using a nasogastric tube or gastrostomy tube is suitable when it is unsafe to swallow or when adequate nutrition cannot be consumed orally. Box 2 provides a list of several important considerations when prescribing oral nutritional supplementation.

If there is no requirement for fluid restriction or electrolyte modification, standard ONS and enteral feeds may be used with ongoing monitoring. Special considerations with CKD include providing adequate energy and protein within a reduced volume as well as electrolyte modification, depending on the eGFR and serum electrolyte levels. If fluid restrictions and/or electrolyte modification are required, nutrient-dense, lower-volume, or kidney-specific products should be considered. In many cases, a high-energy oral nutrition supplement or enteral nutrition formula with fiber is an appropriate first-line choice.

Parenteral nutrition is used when the digestive tract is inaccessible or nonfunctioning, and it is usually managed by a multidisciplinary team. Intradialytic parenteral nutrition (IDPN) is a form of supplemental nutrition support that may be useful in a narrow therapeutic range. Bydefifinition, it is parenteral nutrition supplied during HD and can therefore be given only as often as dialysis. Generally, IDPN can assist to meet nutritional requirements if patients are achieving 20 kcal/kg per day but are unable to meet their full energy requirements. The frequency of usage of IDPN in the United States has not been reported but it is likely to be uncommon. Nephrologists typically order the IDPN, sometimes with expert support from the company providing the IDPN. Financial barriers may exist because the estimated cost of IDPN is ~$300 per day compared with a few dollars for oral supplements. Many insurers cover IDPN only if specific eligibility criteria are fulfilled (including failure to respond to oral or enteral nutrition). IDPN therapy has the potential for complications that include electrolyte and lipid disorders.

Dietary Supplements Dietary supplements used to prevent or treat disease, also known as nutraceuticals, are quite popular in the general populace and have also been studied to some extent in patients with CKD. For example, fish oil–derived long-chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid [EPA], docosahexaenoic [DHA]) are known to mediate cell membrane physiology, eicosanoid production, signal transduction, and the inflflammatory cascade. Several modestly sized studies in patients on maintenance HD found no benefit of fish oil supplementation on sudden cardiac death, cardiovascular disease, or HD access thrombosis. However, it does lower triglyceride and LDL levels and raises HDL levels. Antioxidant therapy in the forms of vitamin E, coenzyme Q, acetylcysteine, bardoxolone methyl, or human recombinant superoxide dismutase has not been shown to improve cardiovascular outcomes or overall mortality, but better-powered studies are needed to confirm these results.

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Pharmacological Interventions

Anabolic Hormones

Men receiving maintenance HD very commonly have testosterone defificiency, which is associated with increased mortality risk and decreased muscle function. A number of clinical trials showed significant benefits for HD patients with nandrolone decanoate treatment in terms of anthropometric (eg, body weight, BMI, skinfold measurements) and biochemical parameters as well as serum concentrations of total protein, albumin, and transferrin.

Anti-inflflammatory Agents

Given that systemic inflflammation causes an exaggerated protein catabolic response, treatment with specific and nonspecific anti-inflflammatory agents has been suggested as a novel strategy to prevent the development or worsening of PEW in patients with CKD. The preliminary data using anticytokine therapies and high-dose omega-3 administration are intriguing; however, long-term studies are needed to determine whether there are reproducible effects of anti-inflflammatory strategies in patients with advanced CKD.

Appetite Stimulants

In experimental animal studies, ghrelin, a stomach-derived growth hormone-releasing hormone able to stimulate appetite via the central nervous system, has been found to increase muscle mass. There is a long history of using appetite stimulants such as megestrol acetate, melatonin, cyproheptadine, and dronabinol to improve appetite in maintenance dialysis patients, but there has been no systematic examination of their effificacy.

Acute Kidney Injury

Nutritional requirements in hospitalized patients with AKI are variable and largely depend on the severity of AKI, the setting, the underlying disease process, and the treatment provided. The nutritional hallmark of AKI, especially in the setting of critical illness, is excessive catabolism. Factors that have been postulated as the underlying mechanism for this high rate of protein and energy catabolism include concurrent illnesses leading to exaggerated proinflammatory cytokine release, inability to feed patients because of surgical and other reasons, and metabolic derangements predisposing patients to diminished utilization and incorporation of available nutrients. Whether uremic toxin accumulation further exacerbates these abnormalities is questionable because aggressive dialytic clearance does not substantially improve mortality in stage 3 AKI patients.

The nutritional markers that correlate best with effificacy of nutritional therapy and patient outcomes are considerably different in AKI patients than in CKD patients. Blood levels of biochemical markers such as serum albumin and pre albumin are influenced by volume status and concurrent inflflammatory state. Similarly, the use of traditional measures of body composition such as anthropometry has limited application in AKI patients owing to major shifts in body water.

The aim of nutritional care in patients with AKI is to support their nutritional needs safely to minimize further metabolic imbalance. In patients deemed to be non catabolic, standard nutritional modifications may only be required if there is an identifified electrolyte imbalance or modified fluid requirement. The Society of Critical care medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines recommend that for critically ill patients the energy requirements be determined using indirect calorimetry or estimated as25-30 kcal/kg per day with ongoing monitoring and adjustment, as clinically indicated. Protein requirements in these patients range from 1.2 to 2.0 g/kg per day and may increase up to a maximum of 2.5 g/kg per day for those requiring frequent or continuous kidney replacement therapy. In critically ill patients, standard enteral nutrition formulations are appropriate unless significant electrolyte abnormalities are evident, in which case specific nutritional formulations with a modified electrolyte profile may be considered. Provision of large quantities of nutrients, especially intravenously, may result in more fluid administration and predispose patients to fluid overload, resulting in earlier initiation of dialytic support.

Hospitalized Patient With Underlying Kidney Disease

It is important to note that nutritional guidelines for use in CKD apply when the individuals with CKD are otherwise reasonably well and living in the community. The nutritional requirements for hospital patients with CKD as an underlying condition will be modified by the metabolic state and comorbid conditions present in the acute hospitalization period. In situations where patients are in an acute catabolic state, protein and energy intake should be increased to meet acute requirements. Modifications to dietary patterns should occur when the patient is metabolically stable.

Obesity

The global obesity problem has profound implications for nephrology due to its wide and growing prevalence and its substantial impact on CKD. Obesity is a mediator of kidney disease, predominating through the development of proteinuria, AKI, CKD, and kidney failure. The mechanisms include a variety of direct (intraglomerular shear-related damage, podocyte stress, fat infiltration, lipotoxicity, and upregulated renin-aldosterone and sympathetic systems) and indirect (development of type 2 diabetes, hypertension, and cardiopulmonary disease) causes (Fig 2). Obesity also impedes optimal care of patients with CKD by, for example, precluding many obese patients from undergoing kidney transplantation and limiting the success of dialysis access placement and function. Finally, obesity greatly increases the burden of disease and disability in people with CKD.

Treatment options for obesity in patients with CKDinclude dietary and lifestyle interventions, pharmacotherapy, and bariatric (now also known as metabolic)surgery. Accumulating evidence demonstrates that weight loss may ameliorate or even prevent the development of CKD, though the exact amount of weight loss needed to accrue these benefits and the precise benefits are still being elucidated. In most people with obesity, the body “defends” against weight loss through upregulation of hormonal and other mechanisms. This explains why for the majority of the population weight loss is best achieved and maintained through medications or metabolic surgery that help to reset these mechanisms.

Of the 4 antiobesity drugs approved by the US Food and drug administration, only the glucagon-like peptide 1 (GLP-1) agonist liraglutide, which lowers weight by as much as8 kg on average, can safely be used in all stages of CKD. Newer and even more powerful GLP-1 agonists alone or in combination with other drugs are expected to soon enter the market that may induce an average of 16%-20% or greater weight loss. They would constitute major advances in anti-obesity treatments for patients with CKD if found to be safe in that population.

Metabolic surgery offers the largest and most sustained weight reduction of any treatment option. In randomized trials, metabolic surgery showed much greater benefits in improving or remitting major CKD risk factors like type 2 diabetes and hypertension compared with nonsurgical weight-loss strategies. A growing body of observational studies has found that metabolic surgery may slow the development and progression of CKD and may even reduce mortality in people with preexisting CKD. Though increasing severity of CKD is associated with more complications after metabolic surgery, even for individuals with advanced CKD the perioperative and mortality risks are only modestly higher than in the general population. Thus, metabolic surgery should be considered safe and effective for patients with CKD. However, no evidence-based guidelines currently exist to help determine which individuals with CKD would most benefit from such surgery.

Article Information Authors' Full Names and Academic Degrees:

Helen L. MacLaughlin, RD, Ph.D., Allon N. Friedman, MD, and T. Alp Ikizler, MD.

Authors' Affiliations: School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane, and Royal Brisbane and Women’s Hospital, Herston, Australia (HLM); Division of Nephrology, Indiana University, Indianapolis, Indiana (ANF); and Division of Nephrology and Hypertension and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee (TAI).

Address for Correspondence:

T. Alp Ikizler, MD, Vanderbilt University Medical Center, 1161 21st Ave South & Garland, Division of Nephrology, S-3223 MCN, Nashville, TN 37232-2372.

Support:

None.

Financial Disclosure:

Dr. MacLaughlin reports consulting fees from Abbott Nutrition and Nestle. Dr. Friedman reports consultant fees from GI Dynamics and Goldfinch Bio. Dr. Ikizler reports personal fees from Fresenius Kabi, Abbott Renal Care, and Nestle.

Peer Review:

Received January 14, 2021, in response to an invitation from the journal. Evaluated by 2 external peer reviewers and a member of the Feature Advisory Board, with direct editorial input from the Feature Editor and a Deputy Editor. Accepted in revised form May 21, 2021.

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