14.2.1 Biomarkers of Nutritional Status

14.2.2 Clinical and Anthropometric Markers of Nutritional Status

14.2.3 Dietary Intake Information

There are many methods to estimate dietary intake; however, the accuracy of document is frequently fluctuating. In general, during a nutrition interview, the clinical dietitian may ask what the individual ate during the previous 24 h, beginning with the last item eaten prior to the interview. Alternatively, practitioners can also train individuals on completing a food record typically obtained for 3–7 days. The documentation should include portion sizes and how the food was prepared. However, documenting portion sizes is usually difficult, and requesting that every food be measured or weighed is usually very difficult to implement and time-consuming. Therefore, nutrition interviews are not commonly used in practice.

14.2.4 Other Methods to Assess Nutritional Status

14.3.1 Energy Intake

Designing a diet for the patients with CKD to receive enough calories is of most importance. However, in clinical practice, it is really a challenge to estimate accurate energy requirements in patients with CKD, since the daily energy requirements are influenced by many variable factors, such as resting energy expenditure, thermic effect of meals, physical activity level, and so on. Many previous studies have shown that the energy requirements of patients with CKD were similar to those of normal adults. Therefore, in CKD stages 1–3, the Kidney Disease Outcomes Quality Initiative (KDOQI) recommends that energy intake levels support a balanced diet and maintain desirable body weight but does not recommend specific energy intake amounts. However, in CKD stages 4 through 5 (GFR <30 mL/min/1.73 m²), specific energy intake amounts are recommended: 35 kcal/kg/day for those younger than 60 years and 30–35 kcal/kg/day for those older than 60 years. If the patients were overweight and obese, calories should be restricted because calories intake in excess of requirements might cause obesity, and obesity might in turn engender insulin resistance and impaired glucose disposal [1, 2, 4].

14.3.2 Protein Intake

Whether the quantity or quality of ingested protein is a risk factor for chronic kidney disease progression has been debated for nearly a century. Now, there are mounting evidences that the western-type diet, which contains exceeding 1.5 g per kilogram of ideal body weight per day, may cause glomerular hyperfiltration and proinflammatory gene expression, which are known risk factors for CKD progression. Experimental evidence in animal models has also shown that a high-protein diet dilates the glomerular afferent arterioles and increases glomerular filtration, whereas low protein intake constricts the afferent arterioles and lowers intraglomerular pressure. The current evidence has suggested that reducing protein intake could decrease proteinuria as efficiently as angiotensin-converting enzyme inhibitors, mainly because that a low-protein diet has a preglomerular effect that may enhance the postglomerular effect of angiotensin pathway modulators that dilate the efferent arterioles and consequently lower the intraglomerular pressure [1, 2, 4].

Besides, limiting protein intake also results in an instant reduction in urea generation. After protein breakdown, individual amino acids are deaminated by the removal of an α-amino group, leaving a carbon skeleton of ketoacids, which can be recycled to form other amino acids and proteins or can be used for energy generation through the tricarboxylic acid cycle, while urea is generated through the urea cycle. A persistently high blood urea level, termed azotemia, which is a commonly used marker for uremia, may enhance protein carbamylation and generate reactive oxygen species, leading to oxidative stress, inflammation, endothelial dysfunction, and ultimately, cardiovascular disease. Reducing protein intake could effectively decrease the production of wasted products and uremic toxins which in turn diminishes the uremic symptoms. Metabolic consequences of low protein diet have also been extensively researched in recent years: reduced oxidative stress, improved insulin sensitivity, better control of metabolic bone disorders in response to a reduced phosphate load, and improved anemia management.

For healthy persons, the recommended dietary allowance for protein is 0.8 g per kilogram per day, whereas the estimated average requirement for adults with CKD who are otherwise healthy is 0.66 g per kilogram per day. Hence, of the various ranges of low protein intakes, 0.6–0.8 g per kilogram of body weight per day is the most frequently recommended target for adults with moderate-to-advanced kidney disease (estimated GFR <45 mL/min/1.73 m²) and for the management of substantial proteinuria (urinary protein excretion, >0.3 g per day), especially if half of the protein is of “high biologic value” (e.g., dairy products). However, the so-called very-low-protein diet (<0.6 g of protein per kilogram per day), supplemented with essential amino acids or their ketoacids, is also used. People at increased risk for kidney disease, such as those who have undergone nephrectomy for kidney donation or for cancer treatment or who have diabetes mellitus, hypertension, or polycystic kidneys, may benefit from a modest protein intake (<1 g per kilogram per day) in order to maintain a moderately low intraglomerular pressure [1, 2, 4, 23, 24].

As mentioned previously, protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD); the safety and feasibility of long-term dietary modification are among the main concerns. From a basic point of view, the direct relationship between low protein intake and muscle wasting should be discovered. Unfortunately, this approach is not clinically relevant: muscle wasting in chronic kidney diseases seems to be caused by the imbalance toward a catabolic state (more protein degradation than synthesis) and is further deteriorated by the lack of physical activity. Additionally, metabolic acidosis closely related to inflammation and insulin resistance is also an important reason. Restrained protein intake has been proven to improve all these catabolic conditions. Therefore, the safety of and adherence to a low-protein diet might be improved by providing adequate energy (30–35 kcal per kilogram per day), ongoing nutritional education, and surveillance.

14.3.3 Sodium Intake

Patients with hypertension and CKD are usually salt-sensitive. The available evidence, detected as an increase in blood pressure of more than 10% when a low salt diet is switched to a high salt intake, demonstrated that a high-sodium diet (>4 g of sodium per day) in CKD has an influence on hypertension, cardiovascular risk factors, and outcomes. In patients with established CKD, dietary sodium restriction is invariably recommended to control fluid retention and hypertension and to improve the cardiovascular risk profile. However, the association between salt intake and renal outcome in subjects with preserved kidney function remains less well investigated and confounding. Several studies have demonstrated that a reduced sodium intake could enhance the effects of a low-protein diet and angiotensin-modulation therapy in decreasing intraglomerular pressure and might also decrease proteinuria and slow the progression of kidney disease. However, some other studies reported that strict sodium restriction might also activate the renin-angiotensin-aldosterone system, sympathetic nervous system, and insulin resistance.

As ingested sodium is primarily excreted via the kidneys, a 24-h urinary sodium excretion is a good indicator of sodium intake. Observational studies using urinary sodium excretion as a surrogate for sodium chloride intake have yielded inconsistent data, with some studies showing no association between dietary sodium intake and renal disease progression and others showing a positive association. A longitudinal study published in 2016, which involved serial 24-h urine collections from 3939 patients with CKD, suggested that the highest quartile of urinary sodium excretion (≥4.5 g per day), as compared with the lowest quartile (<2.7 g per day), was associated with a 45% higher mortality and a 54% higher risk of disease progression. Incrementally worse cardiovascular outcomes were observed when dietary sodium intake exceeded 4 g per day. Observations in the general population suggest a J-shaped association; dietary sodium intake that is higher than 5 g per day and intake that is lower than 3 g per day are each associated with an increased risk of cardiovascular disease and death. Although a daily dietary allowance of less than 2.3 g of sodium (<100 mmol) is often recommended for patients with cardiovascular disease, there is no evidence that patients with kidney disease will benefit from this sodium restriction. Therefore, a daily dietary sodium intake of less than 4 g (<174 mmol) is recommended for the overall management of CKD and its associated risks, with a sodium intake of less than 3 g (<131 mmol) for the specific management of symptomatic fluid retention or proteinuria. Evidence supporting a sodium intake of less than 1.5 g per day (<87 mmol per day) for patients with renal insufficiency is lacking, given the risk of hyponatremia and adverse outcomes. Once sodium excretion is excessive and blood pressure elevates, the nutrition consultation and repeating 24-h urine measurements of sodium are recommend to make dietary planning more easily [1, 2, 4, 23–25].

Whereas adequate fluid intake may mitigate the risk of kidney disease, patients with renal insufficiency generally have isosthenuria. This is the basis for the recommendation that patients with stage 3 CKD limit fluid intake to less than 1.5 L per day in order to avoid hyponatremia; adjustment of that limit for a hot climate and other conditions associated with high insensible fluid losses is imperative. Adjunctive therapy with loop diuretics is often prescribed, particularly for patients who tend to have symptomatic fluid retention or hyponatremia, given the association of such conditions with poor outcomes in CKD. It should also be noted that diuretics alone might fail because an unrestricted salt intake will overcome the effectiveness of diuretic.

14.3.4 Potassium Intake

Substantial evidence has supported that potassium-rich foods could reduce the possibility of developing chronic diseases, such as hypertension, diabetes, and coronary heart disease. Thus, given the well-established association of higher dietary potassium with lower sodium intake and lower incidences of hypertension, stroke, and kidney disease, a relatively high daily intake of potassium of 4.7 g (120 mmol) was recommended in the general population by guidelines from the Institute of Medicine. However, the causal relationship between dietary potassium and hypertension in patients with CKD was less studied in the previous researches.

Accompanied by renal insufficiency, the kidneys’ ability to excrete excess potassium might be impaired. Besides, the impairment in the action of protective hormones (e.g., aldosterone) or use of ACEIs, ARBs, or nonsteroidal anti-inflammatory drugs may also result in the impaired potassium excretion. Therefore, a careful search for other causes of hyperkalemia should be undertaken before restricting dietary potassium. Particularly, drugs that reduce potassium excretion should be eliminated, acidosis should be corrected, and constipation should be relieved. Undoubtedly, more studies are further needed to investigate the advantage and dangers of increasing (or limiting) dietary potassium in patients with CKD.

A higher dietary potassium intake may be associated with a higher risk of kidney disease progression. Among patients with very advanced CKD, the highest quartile of dietary potassium intake, as compared with the lowest quartile, is associated with an increase in the risk of death by a factor of 2.4; the association is independent of the plasma potassium level and other nutritional measures. Therefore, the National Kidney Foundation’s expert panel recommended potassium restriction for individuals with advanced CKD (e.g., stage 4 CKD and an estimated GFR <30 mL/min/1.73 m²). In other epidemiologic studies, both moderately low (<4.0 mmol per liter) and high plasma potassium levels (>5.5 mmol per liter) are associated with more rapid kidney disease progression. Dietary potassium restriction is often recommended in patients with hyperkalemia, especially those with more advanced stages of kidney disease. However, excessive dietary restrictions can expose patients to less heart-healthy and more atherogenic diets and worsen constipation, which may actually result in higher gut potassium absorption. Despite the higher risk of hyperkalemia with the progression of kidney disease, few studies have examined the effects of dietary potassium restriction or methods of extracting potassium during food preparation and cooking. It is not clear whether potassium-binding agents can allow the liberalization of dietary potassium intake with the inclusion of healthier potassium-rich foods. In patients with a tendency toward hyperkalemia (>5.5 mmol of potassium per liter), a dietary potassium intake of less than 3 g per day (<77 mmol per day) is recommended, with the stipulation that the balanced intake of fresh fruits and vegetables with high fiber should not be compromised [1, 2, 4, 23, 24, 26, 27].

14.3.5 Phosphorus Intake

Numerous studies have determined positive phosphate balance and hyperphosphatemia to be the risk factors for vascular calcification, cardiovascular mortality, and left ventricular hypertrophym in chronic kidney disease. Daily dietary phosphorus intake is approximately 1000–1200 mg, of which approximately 950 mg is absorbed. Phosphorus could be removed by two systems, the gastrointestinal tract (150 mg/day) and the urine (800 mg/day). However, as kidney function declines, renal phosphorus excretion might be progressively impaired. Decreased glomerular filtration of phosphorus is initially compensated by decreased tubular reabsorption regulated by parathyroid hormone and fibroblast growth factor 23 (FGF-23). Elevated parathyroid hormone and FGF-23 levels can cause renal bone disease, left ventricular hypertrophy, vascular calcification, and accelerated progression of kidney disease from vascular and tubulointerstitial injury, highlighting the importance of dietary phosphorus management, even in patients without apparent hyperphosphatemia. There is a close relationship between protein and phosphorus intake: 1 g protein brings 13–15 mg phosphate, of which 30–70% is absorbed through the intestinal lumen. High-protein diet may aggravate uremic symptoms and hyperphosphatemia; however, although a low-protein diet also decreases phosphorus intake, the quantity and bioavailability of phosphorus differ according to the type of protein. For example, the phosphorus-to-protein ratios of egg whites and egg yolks (which have 3.6 and 2.7 g of protein per egg, respectively) are 1–2 mg per gram and 20–30 mg per gram, respectively. The gastrointestinal absorption of phosphorus, mostly in the form of phytates, is lower from plants (along with fibers) than that from meat (30–50% vs. 50–70%). Since food additives include readily absorbable inorganic phosphorus, ingestion of processed foods results in an even higher phosphorus burden. Restricting dietary phosphorus intake to less than 800 mg per day (26 mmol per day) is recommended for patients with moderate-to-advanced kidney disease, and the consumption of processed foods with a high phosphorus-to-protein ratio should be minimized. However, in patients with stage 5 CKD who receive dialysis therapy or who are at increased risk for PEW, excessively stringent restriction of protein intake to control hyperphosphatemia may be associated with poor outcomes. Thus, an individualized dietary approach that incorporates ample use of phosphorus binders is optimal [1, 2, 4, 23, 24, 28].

14.3.6 Calcium and Vitamin D

Vitamin D insufficiency and deficiency is widely prevalent in the patients with CKD, which is further exacerbated by the reduced ability to convert 25-(OH) vitamin D into the active form, 1,25 dihydroxy-vitamin D. The associated decline in 1,25-dihydroxy vitamin D may further diminish gastrointestinal absorption of calcium; however, passive diffusion of ionized calcium continues and may lead to a positive calcium balance, which is aggravated by diminished urinary calcium excretion due to secondary hyperparathyroidism. Increased calcium release from bone in hyperactive renal bone disease (increased bone resorption because of secondary hyperparathyroidism) enhances the positive calcium balance and may worsen vascular calcification. Gut calcium absorption varies because of differences in dissociation and bioavailability from one type of elemental calcium to another; for instance, calcium citrate is more readily absorbable than calcium acetate. Two studies suggested that an intake of 800–1000 mg of elemental calcium per day (20–25 mmol per day) can result in a stable calcium balance in people with stage 3 or 4 CKD. Hence, whereas the suggested calcium intake for persons without kidney disease is 1000–1300 mg per day (25–32 mmol per day), 800–1000 mg of elemental calcium from all sources per day should suffice in patients with moderate-to-advanced CKD [1, 2, 4, 23].

Native vitamin D supplementation (cholecalciferol or ergocalciferol) may be offered to patients with CKD and low levels of circulating vitamin D. In some studies, vitamin D analogs have been associated with decreased proteinuria in addition to the healing of renal osteodystrophy. Notwithstanding inconsistent data on the requirement for and the effect of vitamin D in certain subpopulations of patients with CKD, including black Americans, who have lower total vitamin D levels and higher parathyroid hormone levels than those in white Americans, hydroxylated vitamin D agents may be needed in addition to native vitamin D to control progressive secondary hyperparathyroidism.

14.3.7 Vegetarian Diet, Fiber, and the Microbiome

Plant-based diets, despite containing low amounts of protein, are also rich in potassium and phosphorus, and therefore vegetarianism is believed to be unsuitable for CKD patients. However, numerous clinical studies have recently demonstrated that such a plant-based diet could be beneficial for the patients when they learn how to use it wisely. Plant-based foods are recommended as part of many strategies for the prevention and management of kidney disease because these foods contain smaller amounts of saturated fatty acids, protein, and absorbable phosphorus than meat; they also generate less acid and are rich in fibers, polyunsaturated and monounsaturated fatty acids, magnesium, potassium, and iron. Besides, according to several studies, a plant-based diet was found to delay the progression of CKD, help to control high blood pressure, and decrease proteinuria, while others indicated that high plant protein intake is likely to accelerate CKD progression when compared to animal proteins. Therefore, the National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients.

Besides, constipation can lead to higher retention of uremic toxins and hyperkalemia, whereas loosening stools may enhance fluid loss and removal of nitrogenous products. The protein in a vegetarian diet is less fermentable, and has high fiber content, increasing peristalsis, and the number of bowel movements, and is associated with less uremic toxin production, exposure, and absorption.

Uremia itself, as well as dietary restrictions and pharmacotherapy, including antibiotics, may alter the gut microbiome; this change may affect the symptoms and progression of kidney disease. Gut dysbiosis, which is manifested by qualitative and quantitative changes in host microbiome profile and disruption of gut barrier function, was commonly seen in patients with CKD. Endotoxin derived from gut bacteria can incite a powerful chronic inflammation in the host organism. Furthermore, disruption of gut barrier function in CKD may allow translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Therefore, targeted microbiome modulation through nutritional interventions, such as consumption of probiotics, may help to control the production, degradation, and absorption of certain uremic toxins that are fermentation by-products of gut microbial activities, including indoxyl sulfate, p-cresol, and trimethylamine [1, 2, 4, 23, 29]. For example, in a study involving 40 patients with moderate-to-advanced CKD, a lower ratio of dietary fiber to protein was associated with higher blood levels of indoxyl sulfate and p-cresol. Nutritional and pharmacologic interventions, including the use of absorbent ingestible agents and high-fiber or vegetarian diets, are being tested as a means of reducing gut absorption of uremic toxins to control uremic symptoms and slow disease progression.

14.3.8 Carbohydrate and Fat Intake

National dietary recommendations have promoted high-carbohydrate, low-fat diets to reduce cardiovascular disease risk. These recommendations were based on observational studies in which low fat intake was associated with a low risk for cardiovascular disease, presumably by lowering LDL cholesterol levels. Unrefined carbohydrates account for half the usual daily energy intake, and the proportion may be even higher in a low-protein diet. In patients with kidney disease, carbohydrates should be complexed with high fiber content (e.g., whole-wheat breads, multigrain cereal, oatmeal, and mixed fruits and vegetables) to help reduce dietary phosphorus and protein as well as urea and creatinine generation. Such a diet may promote a more favorable microbiome with less constipation.

Reducing fat as part of a low-calorie diet is a practical way to reduce energy intake. However, clinical trials of diet therapy to reduce lipids and slow progression of CKD have not been conducted. Dietary fat recommendations for obese patients with CKD should be in accordance with the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) guidelines (2001) developed for cardiovascular risk reduction. In CKD stages 1 through 4, the KDOQI recommends that 25–35% of the total energy intake comes from fat, with 10% of the total from saturated fat. The recommended cholesterol intake is 200 mg/day. The objective of these guidelines is to control blood lipid levels, minimizing elevated blood glucose and triglyceride levels. Because diets for patients with CKD are sometimes mildly restricted in protein, it may be difficult to provide sufficient energy without resorting to a large intake of high-glycemic index carbohydrates that may increase triglyceride production. Another challenge when addressing fat intake is maintaining recommended macronutrient balances when lowering saturated fat in the diet. When saturated fat is reduced in the diet, it can be replaced with unsaturated fat, protein, or carbohydrates. The optimal means of replacement of saturated fats is not known. Data from dietary intervention trials suggest that a diet low in saturated fat that uses either protein or unsaturated fats to replace carbohydrates can have favorable effects on lipids. Unsaturated fat is the preferred lipid in the diet. Replacement of butter with flaxseed, canola, or olive oil, all of which are rich in unsaturated fatty acids, may be worthwhile. For example, a recent study suggested that dietary unsaturated fatty acid supplementation in patients with diabetes and hypertriglyceridemia may reduce albuminuria and preserve renal function. There is currently no evidence that low-fat diets, recommended by some guidelines, improve kidney disease outcomes. In a low-protein diet, fat and carbohydrates should together account for more than 90% of the daily energy intake requirement of 30–35 kcal per kilogram to avoid PEW. Obviously, in patients with diabetic kidney disease, proper glycemic control should be maintained, but adequate energy intake is needed to mitigate the risk of PEW and hypoglycemia, which increases with worsening kidney function [1, 2, 4, 23].

14.3.9 Dietary Management of Acidosis in Chronic Kidney Disease

Daily acid production results from bicarbonate losses in the gut (20–30 mmol of bicarbonate per day), breakdown of amino and nucleic acids from proteins (20–30 mmol per day), and oxidation of carbohydrates and fats to lactic acid and ketoacids (10–20 mmol per day). The kidney plays an important role in regulating of the acid–base balance. The kidneys regenerate the bicarbonate used for buffering by the excretion of both net acid and acid buffers, including phosphate, and by ammoniagenesis through the deamination of glutamine in the proximal tubule and its synthetization to ammonium in the collecting ducts, with subsequent urinary excretion. Hence, chronic kidney disease and reduced glomerular filtration rate may contribute to the development of chronic metabolic acidosis. Kidney disorders, including renal tubular defects, are often associated with chronic metabolic acidosis. Metabolic acidosis is a relatively common complication in patients with renal failure, particularly in those with GFR falls below 30 mL/min/1.73 m². Also, a large amount of evidence identifies acidosis not only as a consequence of, but as a contributor to, kidney disease progression.

Diet plays an important role in acid–base balance. The modern high-protein diets may yield about 1 mmol/kg body weight/day of net endogenous H+ production, while the fruits and vegetables may generate base from the metabolism of organic anions such as citrate and malate. The 24-h urinary excretion of ammonium and titratable acid minus bicarbonate could be used as an indicator of total net acid excretion (NAE). A well-controlled clinical trial in healthy adults consuming various diets has revealed that pH value in 24-h urine was closely related to the total renal NAE. Moreover, the total urinary NAE can be reasonably estimated from dietary intake, intestinal absorption, and the metabolism of most important inorganic anions and cations in urine. On the basis of these factors, the potential renal acid load (PRAL) can be calculated directly from dietary intakes. While protein-rich foods such as meat, fish, and cheese are the food groups with the highest acid loads, fruits, vegetables, salads, and fruit juices have a high alkalizing potential. An increase in the dietary acid load may be associated with glomerular hyperfiltration. Metabolic acidosis is associated with more rapid kidney disease progression and an increase in the overall risk of death. Hyperparathyroidism, along with chronic buffering of acid by bone, leads to progressive loss of bone minerals and worsening renal osteodystrophy. Hence, reduced protein intake with a greater proportion of diet from plant-based foods to correct acidosis improves bone mineralization and may slow protein breakdown and disease progression. Adjunctive alkali therapy can also be considered to mitigate acidosis in patients with CKD [1, 2, 4, 30].

14.3.10 Trace Elements and Vitamins

PEW has the potential to impact not only macronutrient metabolism but also vitamin and trace element status in patients with CKD. Inadequate food intake may result in an insufficient ingestion of antioxidant vitamins, including vitamins C and E and carotenoids; in addition, patients with advanced renal disease often become deficient in folate, vitamin K, and calcitriol. A micronutrient imbalance in patients with kidney disease may contribute to a higher burden of oxidative stress, inflammation, and cardiovascular disease. Among the trace elements, iron deficiency is most problematic given the high frequency of gastrointestinal blood loss in patients with CKD. Deficiencies of zinc, copper, and selenium may occur, whereas aluminum and magnesium levels may increase. A recent study showed that 800 μg of folic acid per day, when added to enalapril, led to slower disease progression than that with enalapril alone. Experimental models of CKD suggest that vitamin K supplementation may blunt the development of vascular calcification. Daily intake of other vitamins and trace elements at conventional doses is often recommended both for persons at high risk for kidney disease and for those with established renal insufficiency [1, 2, 4].

14.3.11 Practice Strategies

Dietary protein, energy, and micronutrient intakes should be assessed regularly. In addition, 24-h urine collection should be performed to estimate the dietary intakes of protein (based on urinary urea nitrogen), sodium, and potassium; to measure creatinine clearance and proteinuria; and to evaluate adherence to dietary recommendations, with suggestions for improving adherence if necessary. Excessive restrictions may be harmful and should be avoided [4].