Diet in Chronic Kidney Disease

Abstract

With the increasing incidence of CKD worldwide due to the causes involving multiple comorbidities such as hypertension, diabetes mellitus etc., CKD becomes a common disease throughout the world where nutrition plays an important role in the management of disease. Also, diet modification becomes necessary to control the intake of energy, proteins, fats, vitamins & minerals (Na⁺, K⁺, Ca⁺² & phosphorus) in daily food ration which is quite a burdensome. Lack of adherence to dietetic recommendation contributes to low consumption of nutrients including energy, vitamins and minerals which can further lead to protein energy wasting (PEW) known as protein energy malnutrition (PEM) of CKD. Additionally, usage of patient-centred & cost-effective nutritional modifications and disease specific dietary changes may help in enhancing longevity and delaying the need of hemodialysis in millions of people across the world.

1. Introduction

Chronic kidney disease is defined as evidence of structural or functional renal impairment for three or more months which is generally progressive and irreversibly affecting multiple metabolic pathways [1]. In CKD, alteration in protein & energy homeostasis, increase in protein catabolism, acid-base derangements and hormonal dysfunction occur which hinder normal growth and development of the patient. Chronic kidney disease can be categorized in stages according to GFR as described in Figure 1.

Figure 1.

Stages of chronic kidney disease (GFR in ml/min/1.73 m²).

As chronic kidney disease progresses, accumulation of nitrogen containing products from dietary & intrinsic protein catabolism may blunt appetite. There are tendencies for negative nitrogen balance and loss of muscle mass which in consequence can lead to cachexia, exacerbated by coexisting conditions & fraility, particularly in adult patients. Hence, nutritional status of many patients often becomes disordered and protein energy wasting shows up ending with dietary adjustement requirements in CKD patients.

Nutritional therapy helps in managing various complications of CKD likewise uremia, electrolyte imbalance, acid-base imbalance, water & salt retention, mineral & bone disorders and failure to thrive. Again, it also helps in delaying or avoiding dialysis therapy. However, possible yet not proved, dietary therapy can also slow down the disease progression independent of uremia management. The symptoms of CKD vary according to the respective stages given in Table 1.

Level of severity or risk	Normal kidney function (eGFR >60) and no proteinuria, but have CKD risk factors (diabetes, hypertension, or solitary kidney)	Mild to moderate CKD (eGFR 30–<60) without significant proteinuria (<0.3 g/day)	Advanced CKD (eGFR < 30) or any CKD with significant proteinuria (>0.3 g/day)	Transitioning to dialysis therapy with good reserve kidney functions including incremental dialysis preparation	Prevalent dialysis therapy, or any CKD stage with existing or imminent PEW
CKD stage	No CKD, or CKD stage 1 (eGFR >90) or stage 2 (eGFR 60–<90)	CKD Stage 3a (eGFR 45–<60) or 3b (eGFR 30–<45)	CKD stage 4 (eGFR 15–<30) or 5 (eGFR < 15)	Usually CKD Stage 5, although dialysis transition but it may happen at higher eGFR also	CKD stage 5, or any stage with PEW
Symptoms	At this stage, usually there are no symptoms related to kidney disease but patient may have symptoms related to the underlying conditions such as diabetes mellitus, polycystic kidneys or uncontrolled hypertension. Solitary kidney usually is not associated with any symptom unless ESRD develops.	Patient may have no symptom, but some may report fluid retention, e.g., oedema of dependent extremities upon upright position or facial oedema in the morning and shortness of breath. Urination changes such as nocturia (due to isosthenuria) may occur. Secondary hypertension may arise and result in symptoms if uncontrolled.	Worsening symptoms are often observed including more severe peripheral oedema and pulmonary symptoms due to fluid overload. Other symptoms include foamy urine, fatigue, pruritus, muscle cramps, restless extremities, altered mental status, sleep wake cycle disturbance, memory & concentration disorders, decreased taste & smell, diminished appetite, nausea & vomiting, growth retardation may occur in children.	Symptomatically deterioration and uremic complications may prompt transition to dialysis including decompensated heart failure, refractory hiccups, peripheral neuropathy, uremic encephalopathy, uremic bleed like gum bleeding or GI bleeding (due to platelet dysfunction), pericarditis, sexual dysfunction, amenorrhea, skeletal deformities. Weight loss, muscle wasting and symptoms related to electrolyte & mineral derangements such as hypocalcemia.	Additional symptoms related to dialysis treatment include post-dialysis light headedness & fatigue, worsening muscle wasting & weight loss, worsening cramps during dialysis treatment or with ultrafiltration and worsening cardiovascular symptoms such as palpitations or chest pain.

Table 1.

Clinical symptoms in different stages of chronic kidney disease (CKD).

2. General approach to dietary management

The widespread nutritional & metabolic alterations, high incidence of malnutrition and current evidence that dietary therapy retards the progression of CKD, indicates the critical aspect of nutritional therapy in CKD patients. There are mainly five goals of dietary management:

1. To maintain good nutritional status

2. To prevent or decrease uremic toxicity

3. To prevent or decrease metabolic disorders of renal failure

4. To reduce the risk of cardiovascular, cereberovascular and peripheral vascular diseases

5. To arrest or retard the progression of renal failure

Adherence to special diets is often difficult and frustating for patients & their families. This requires a team approach with support of family, doctor, dietician, nursing staff and whenever available social worker or psychiatrist, who can also help in improving the adherence capacity of patient to specific dietary changes.

3. Intrarenal hemodynamics

Dietary protein intake does not influence the level of systemic arterial blood pressure but intrarenal hemodynamics regularly respond to the changes in dietary protein intake and in return, protect against renal injury. Due to progressive loss of nephron in CKD, protein intake is a primary determinant of the degree of functional & structural growth in remaining nephrons of remnant kidney. High protein intake stimulates the growth of cells (hypertrophy), exacerbate proteinuria and increases the weight of kidney while restricting protein intake prevents an increase in kidney size [2]. Likewise, both GFR and renal blood flow can be improved following an acute or chronic increase in dietary proteins. There is also an evidence, indicating a low protein diet lowers intraglomerular pressure by constricting the afferent arterioles and enhance the post glomerular effect of angiotensin pathway modulators that dilate efferent arterioles which further diminishes progressive renal injury (Figure 2) [3].

Figure 2.

Effects of low protein, low salt diet on afferent arteriole [3].

There are also various studies, stating the risks of toxicity from high protein diet which potentiates proteinuria and had both direct and indirect toxic effects on proximal tubular epithelial cells. Proteins also catabolize into some toxic intermediates (Indoxyl sulfate, phenylacetic acid) which contribute further in renal injury [4].

4. Assesment of nutritional status

Routine nutritional screening of CKD patients should be done at least biannually with the intent of identifying patients at risk of developing protein-energy wasting (PEW). Physical examination, body composition, anthropometric measurements and biochemical determinants are the components of nutritional assessment in CKD patients. Anthropometric measurements include practical, economical & non-invasive techniques that describe body mass, size & shape which is the most basic and an indirect method of assessing body composition. Likely, direct methods are bioelectrical impedance analysis (BIA), creatinine kinetics, near infrared and dual-energy X-ray absorptiometry (DEXA). These can be used in assessing body composition but they are expensive and cannot be used easily in different scenarios. DEXA is considered as a gold standard in assessing the body composition in patients of CKD but it is labour intensive, costly & an invasive method which can be easily altered by a number of factors such as hydration status in CKD (Table 2) [5].

Area	Assessments
Physical examination	Diet history, appetite assesement questionnaires, food diaries
Anthropometric measurements	Body weight, height, BMI; Percentage weight change; Skin fold thickness; Midarm muscle circumference
Body composition	Neutron activation; Near infrared reactance; Bioelectrical impedence; DEXA
Biochemical determinants	Serum electrolytes; Serum proteins (albumin); Lipid profile (cholesterol); Creatinine index
Nutritional scoring systems	Subjective global assessment
Immunological assays	Hemogram (Lymphocyte counts); Delayed cutaneous hypersensitivity test
Functional test	Grip strength

Table 2.

Assessment tools for nutrition in CKD [5].

There are limited evidences regarding the use of any one method over other for identifying patients who are at risk of protein-energy wasting (PEW).

4.1 Protein energy wasting (PEW)

Protein energy wasting is a syndrome consists of metabolic & nutritional abnormalities which often occur in CKD also called as PEM of CKD. It is associated with increased mortality and morbidity in CKD patients. There are various reasons for protein energy wasting like poor food intake, poor appetite, dietary restrictions, uremia induced alteration, chronic inflammation, metabolic acidosis & endocrine abnormalities which lead to hypermetabolism resulting in excess muscle & fat catabolism. Furthermore, contribution by low physical activity, fraility and hemodialysis precipitate in the development of PEW (Figure 3).

Figure 3.

Pathogenesis of PEW in CKD patients.

Serial assessment of CKD patients are done by using several scoring tools including Subjective Global Assesment (SGA), Malnutrition Inflammation Score (MIS), Geriartic Nutritional Risk Index (GNRI) and PEW Diagnostic Criteria.

PEW diagnostic criteria is used in making diagnosis of PEW, published by ISRNM, 2013, which is described in Figure 4.

Figure 4.

PEW diagnostic criteria [6].

From the above listed categories, at least three out of the four (3/4) (and at least one in each of the selected category) must be present in order to make the diagnosis of CKD related PEW. Each criteria should be fulfilled on at least three occasions, preferably 2–4 weeks apart [6].

The sequelae of PEW include malaise, fatigue, impaired wound healing, increased susceptibility to infections, increased cardiovascular disease risk and increased hospitalization & mortality rates (Figure 5).

Figure 5.

Pathophysiology of PEW in CKD.

4.2 Tools for nutritional assessment

See Figure 6.

Figure 6.

Tools for nutritional assessment and management.

4.2.1 Patient interview and physical examination

Detailed history and physical examination have to be done in order to find out the risks of PEW. History has to be taken to find out the symptoms of nausea, vomiting, decreased appetite and recent changes in body weight. It is important to take history regarding uremic or non uremic causes and regarding the cause of CKD and PEW.

4.2.2 Assessment of food intake

24 hour food recall method can be used to know about the food intake on both dialysis and nondialysis days which should be performed twice in a year. Generally, food intake on dialysis days is about 20% lower as compared to non dialysis days. Assessment of food intake can also be done by using food frequency questionnaires.

4.2.3 Nutritional screening tools

Various tools can be used in screening of nutritional status of a CKD patient. The important ones are Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA), Malnutrition Screening Tool (MST). The MST includes two questions; one regarding weight loss and other regarding appetite. If the score of these questions, when added together, comes out to be more than 2 then there is a high risk of developing malnutrition and PEW.

4.2.4 Nutritional assessment tools

When patient is screened positive for malnutrition then, further assessments have to be done by using various tools & methods to make the confirmed diagnosis of PEW. These assessments may include;

4.2.4.1 Body composition

4.2.4.1.1 Body weight and body mass index

Ideal or median standard weight should be measured and compared with the actual body weight. It is also important to compare ideal or median standard weight to the prior body weight. BMI should be used cautiously as it gives a poor estimate of fat mass and its distribution within the body, especially in patients with CKD.

4.2.4.1.2 Anthropometry

There are multiple anthropometric measurements which are used in assessing the patient nutrition, each with some advantages and disadvantages of their own. Waist to Hip Ratio (WHR) & Skinfold Thickness are used for classification of obesity in CKD patients which combinely show better results than BMI in various cross-sectional studies.

Skinfold thickness should be measured at the midpoint of biceps or triceps and can be related to mid-arm muscle circumference from the equation given below;

$$\begin{array}{l}Mid-arm\text{muscle circumference}\left(\text{MAMC}\right)\\ =mid-arm\text{circumference}\left(cm\right)-\left\{3.14\times \text{triceps skinfold}\left(cm\right)\right\}\end{array}$$E1

Skinfold thickness provides an estimate of body fat whereas midarm circumference is useful in estimating muscle mass. If the values of either mid-arm circumference or triceps skinfold thickness is below the 25th percentile, patient is likely to be malnourished. In obese patients, skinfold thickness may not be accurate as most of the calipers have their upper limits that cannot accommodate high levels of adiposity.

4.2.4.1.3 Bioimpedance

When a constant alternating current is applied to the human body, there comes resistance & reactance by the body against the alternating current which is measured and termed as bioimpedance. The values of resistance & reactance are used in emperical equations which predict total-body water using resistance and total-body mass from the ratio of resistance to reactance or from the graph plotted between resistance & reactance as its geometrical derivative, the phase angle. In non-dialysed CKD patients or patients on peritoneal dialysis, there are insufficient studies & evidences suggesting the use of bioelectrical impedance in assessment of body composition but in CKD patients on MHD, bioimpedance preferably multi-frequency bioelectrical impedance (MF-BIA) can be used to assess body composition. It should be ideally performed after 30 minutes or more likely at the end of the hemodialysis session to allow redistribution of body fluids throughout the body [5].

4.2.4.1.4 Dual energy X-ray absorptiometry (DEXA)

In the beginning, DEXA used to measure the bone density but later it was adapted to quantify soft tissue composition of the body including muscle mass & fat. Now, DEXA is mainly used for research purposes as it is costlier than other methods. There is also no data relating DEXA that results in the outcomes of patients with advanced CKD but whenever feasible DEXA should be used in patients of CKD 1 to 5D and post-transplant patients because it is not easily influenced by hydration status of the patient and still remains the gold standard method for measuring body composition.

4.2.4.2 Biochemical parameters

4.2.4.2.1 Albumin

Albumin is a major circulating protein in the body that maintains the osmotic pressure and helps in transporting a variety of molecules. Serum albumin may be used as one of the best predicter of hospitalization & mortality in patients of CKD. Campbell et al. found that low albumin concentrations (<3.8 g/dL) were significantly associated with higher morbidity & mortality [5]. It also correlates with other nutritional assessment tools like bioimpedance and can be influenced easily by other inflammatory conditions & comorbidities.

4.2.4.2.2 24 hour urinary collection

It is performed to estimate dietary intake of proteins (urinary urea nitrogen), electrolytes (Na⁺, K⁺), creatinine clearance and proteinuria. It is also helpful in evaluating the adherence of patient to dietary recommendations which further, can be used in improving lack of adherence by suggesting the required changes in the diet. Excretion of protein end product as urea is easily measured and is often used to estimate adequacy of dialysis.

4.2.4.2.3 Acute phase reactants

There are various molecules & proteins that are related to the inflammation in CKD which may be increased or decreased according to the disease activity.

Serum prealbumin levels may be elevated because of interaction of prealbumin with retinol binding protein and decreased renal clearance. In hemodialysis patients, S. prealbumin <20 mg/dl are associated with increased risk of mortality, even in patients with normal albumin level. Also, fall in serum prealbumin over 6 months is independently associated with increase in mortality [7].

C-reactive protein (CRP) is a positive acute phase reactant which correlates negatively with Albumin and other proteins concentration in the body. When Albumin and Prealbumin levels are low, it is apt to check CRP levels which can help in revealing potential covert inflammation but its level is highly variable in ESRD patients.

In CKD patients there are also decreased cholesterol and increased IL-6 levels which can also be used in assessment of nutritional status of the patient.

5. Nutritional guidelines

5.1 Macronutrients

5.1.1 Proteins

See Figure 7.

Figure 7.

Foods containing high amount of protein.

Proteins are responsible for adequate growth & development of children and maintenance of body structure in adults. Proteins are catabolized into urea and many other known & unknown compounds in the body. These compounds are cleared by the kidneys and get excreted in urine normally. When GFR starts to decline, these by-products get accumulated in the blood & different organs that progressively start getting affected leading to impaired organ functions as a consequence. Catabolized products of proteins are also responsible for a major fraction of kidney workload. Various studies and researches have confirmed the detrimental role of the renal hyperfiltration response associated with high protein intake in the kidneys causing further fall in GFR [8]. Therefore, in patients of CKD, reducing protein intake (0.55–0.6 g/kg/d) will reduce hyperfiltration which will have many beneficial effects like reduction in clinical symptoms, postpone the need of maintenance hemodialysis and decrease in mortality but on the other hand, reducing protein intake may also impair nutritional status in individuals who are at risk for PEW.

The quality of protein intake also matters. The rationale behind the use of proteins having branched chain amino acid is that during protein metabolism, these amino acids are deaminated by removal of an α-amino group leaving behind a carbon skeleton which can be recycled to form other amino acids and proteins or can be used in energy generation through the tricarboxylic acid cycle [9]. During protein catabolism, there is also generation of urea through the urea cycle. Hence, restricting dietary protein results in a proportional reduction in urea generation and use of ketoacids decreases the need of protein intake by providing the essential amino acids.

Protein intake can be classified according to relevant kidney disease conditions as suggested by MDRD study (Table 3) [3].

Dietary protein intake range	Daily protein intake grams per kg ideal body weight (g/kg/day)	Comment
Protein free diet	<0.30 g/kg/day	Not recommended in any person including CKD patients
Very low protein diet	0.3–0.6 g/kg/day	Have to be supplemented with essential amino acids, keto-acids or hydroxy-acids
Low-protein diet	0.6–0.8 g/kg/day	Recommended for advanced CKD (≥stage 3b or in patients having substantial proteinuria), usually no supplementation is needed until the diet contains at least 50% high biologic value proteins
Moderately low protein intake	0.8–1.0 g/kg/day	Recommended range for adults without CKD but have risk factors of CKD including diabetes mellitus, hypertension, solitary kidney (following nephrectomy), and polycystic kidneys
Moderate protein intake	1–1.2 g/kg/day	Recommended range for healthy adults without CKD or known risks of CKD, although most Americans eat higher DPI
Moderately high protein diet	1.2–1.5 g/kg/day	Recommended range for maintenance dialysis patients on conventional treatment, e.g. thrice weekly HD or daily PD, with minimal residual kidney function (urine urea clearance < 2 ml/min)
High to very high protein diet	>1.5 g/kg/day	Can be used for acute conditions such as hypercatabolic AKI, high grade burns, and severe PEW but over limited period of time

Table 3.

Ranges of dietary protein intake (DPI) according to kidney diseases [3].

Protein intake in CKD can be determined according to CKD stages as described in Figure 8.

Figure 8.

Daily dietary protein intake in CKD patient (g/kg/day) [10, 11].

Factors such as providing adequate energy (30–35 kcal/kg/day), nutritional education and surveillance, may improve adherence to a low-protein diet [12].

5.1.2 Energy

Adequate amount of energy is required in a diet of CKD patient in order to maintain desirable body mass, to limit gluconeogenesis and to prevent protein catabolism. Number of factors are required to determine the energy intake in adults diagnosed with CKD. These include the age of patient, gender, weight, overall health status, level of physical activity, metabolic stressors and treatment goals.

According to KDOQI classification the energy requirement in CKD patients is defined as Figure 9.

Figure 9.

Daily energy requirement of CKD patients [13].

Patients should be monitored routinely to assess the energy requirements and further, changes should be made in nutritional status if energy requirements are not met satisfactorily. Various conditions in which energy intake requires changes are described in Figure 10.

Figure 10.

Conditions requiring change in energy intake.

Protein and energy balance are the most important tasks in the prevention of PEW. In case of low protein diet, one should increase energy intake by using other sources of energy like carbohydrates and fats.

5.1.3 Fats

Unsaturated fatty acids are the preferred lipid in the diet of a CKD patient. A recent study suggested that dietary n − 3 fatty acid supplementation (flaxseed, canola, or olive oil) in patients with diabetes and hypertriglyceridemia may reduce albuminuria and preserve renal function thus, slowing down the progression of CKD [14]. In a low-protein diet, combined fats & carbohydrates should account for more than 90% of the required daily energy intake in order to avoid protein–energy wasting [15]. Total 25–35% of calories should come from fat. High intake of saturated fatty acid causes atherosclerotic changes in vessels of kidneys and other organs which in turn increase the risk of Malnutrition-Inflammation-Atherosclerosis (MIA) syndrome, leading to increased risk of cardiovascular deaths in CKD patients. Long-chain n − 3 PUFA helps both in reducing triglycerides & LDL cholesterol levels as well as in raising HDL levels.

The therapeutic goal in patients with CKD is to maintain the lipid levels in the range of;

• Low density lipid (LDL) < 100 mg/dl

• Fasting triglyceride levels < 500 mg/dl

  With regards to diet composition, the usual recommendation is <7% saturated fat in diet, <10% of total calories should be derived from polyunsaturated fatty acids and <20% of total calories should come from monounsaturated fatty acids. Also, cholesterol should be <300 mg/day according to latest recommendations [14].

5.1.4 Carbohydrates and fibers

Carbohydrates are generally used in unrefined form and they make half of the usual daily energy intake which may be even higher in those having low protein diet. In patients with CKD, carbohydrate resources should also consist of fibers in higher amount (e.g., whole-wheat breads, multigrain cereal, oatmeal, mixed fruits & vegetables) which help in reducing absorption of dietary phosphorus and decrease generation of urea and creatinine as well [16]. Recommended intake of carbohydrates is no lower than 130 g. This ensures proper functioning of central nervous system & RBCs. Insufficient amount of carbohydrates in a diet can cause disruption in metabolism of fatty acids leading to accumulation of ketones and development of metabolic acidosis. Moreover, acidosis increases anorexia, promotes release of cortisol which enhances protein catabolism and also reduces the synthesis of albumin thus, intensifying malnutrition & loss of muscle mass. Hence, increased risks of PEW [17]. The right quality of sugar intake is also necessary as fructose increases obesity and risks of diabetes which further promote kidney damage. It is recommended that 50–60% of diet should contain carbohydrates that means 1000 kcal or 250 g of carbohydrates for a 2000 kcal diet. Fibers are another entity which is an important part of diet in patients of CKD. Diet of a vegetarian contains a good amount of fiber which helps in reducing dyslipidaemia by decreasing absorption of fat, K⁺, uremic toxins etc. from GIT as they reduce gastrointestinal transit time. Fibers also generate favorable microbiome which helps in controlling uremic symptoms and slows down the disease progression. An amount of 20–30 g of fiber per day should be consumed which can help in reducing dyslipidaemia. In general, high fiber diets are also associated with lower cardiovascular mortality [18].

5.2 Micronutrients

Micronutrients in our daily food ration play an essential role in maintaining many metabolic functions and therefore should be present in adequate amount for which Daily Reference Intakes (DRIs) is made for each micronutrient. However, there is lack of evidence regarding appropriate intake of various micronutrients for people with CKD. The common reasons for deficiency of various micronutrients include insufficient dietary intake, dietary prescriptions which may limit vitamin-rich foods (particularly water-soluble vitamins), dialysis procedure, improper absorption of vitamins and certain medications & illnesses.

5.2.1 Sodium and fluids

Sodium is an extracellular cation responsible for fluid homeostasis in the body. In CKD patients, dietary sodium restriction is invariably recommended to control fluid retention and hypertension and to improve the cardiovascular risk profile. Patients with high sodium intake (>4 g/day) exhibit a strong relationship with hypertension while reduced sodium intake along with low protein and angiotensin modulation therapy result in decreased intraglomerular pressure which reduces proteinuria and slows down the disease progression. In CKD patients, the excretion of sodium is disturbed which can cause sodium retention and contribute in formation of oedema due to accumulation of water in tissues.

It is recommended that CKD patient should restrict sodium intake of <4 g/day while CKD patients with fluid retention and oedema should restrict sodium intake to <3 g/day. Excessive restriction of sodium of less than 1.5 g/day in CKD patients can cause hyponatremia and other adverse outcomes (Figure 11) [19].

Figure 11.

Daily requirement of Na⁺ intake in CKD patients [3].

$$\left[1\text{g}\text{salt}=0.4\text{g}Na=17meqN{a}^{+}\right]$$E2

CKD patients should limit fluid intake to less than 1.5 L/day due to isosthenuria, as excess of fluid intake can cause hyponatremia [19]. Additional fluid intake can be done if patient has residual renal function which is based on daily urine output & insensible fluid loss (Figure 12).

Figure 12.

Foods to be avoided due to high sodium intake.

5.2.2 Potassium

Potassium is the main intracellular cation which plays an important role in mediating cellular electrophysiology, vascular functions, BP and neuromuscular functions. Abnormal potassium levels can cause muscular weakness, hypertension, ventricular arrhythmias and deaths. In CKD patients, the various mechanisms involved in the homeostasis of potassium (i.e. adrenergic system, insulin, aldosterone & urinary clearance) are impaired and hyperkalaemia can also be found in CKD patients on hemodialysis. There is a well-established association that states, high potassium with low sodium in diet can lower down the incidences of hypertension, stroke, nephrolithiasis and kidney diseases. In healthy adults and those at risk of kidney disease, a relatively high daily potassium intake of 4.7 g (120 mmol) is recommended [20]. Although, in patients with kidney diseases, a higher dietary potassium intake may be associated with a higher risk of poor kidney disease progression. According to various epidemiologic studies, both moderately low plasma potassium levels (<4.0 mmol/liter) and high levels (>5.5 mmol/liter) are associated with rapid kidney disease progression. In patients of advanced kidney disease and hyperkalaemia, it is advised to restrict dietary potassium intake to less than 3 g/day (<77 mmol/day) but excessive dietary restrictions can expose the patient to more atherogenic diets and worsen constipation which may actually result in higher gut potassium absorption [21]. A reduction in the consumption of potassium is usually achieved by limiting or excluding potassium rich fruits and vegetables from daily food ration (DFR) (Figure 13).

Figure 13.

Potassium containing foods.

During restriction of potassium intake, intake of fresh fruits & vegetables with high fiber should not be compromised. Potassium content in vegetables & fruits can be lowered by soaking them in water for 2–4 hours, a process called leaching and also boiling can be used otherwise. Both the techniques are associated with reduced food taste and palatability which can be improved by using aromatic herbs (Figures 14 and 15).

Figure 14.

Conditions associated with increased level of K⁺.

Figure 15.

Daily requirement of K⁺ intake in CKD patients [3].

5.2.3 Phosphorus

Phosphorus is an essential nutrient required for bone growth & mineralization as well as for regulation of acid-base homeostasis. Phosphorus is present in most foods both as a natural component and added as an approved ingredient during food processing. It is necessary to control dietary levels of phosphorus in order to avoid hyperphosphatemia. In CKD patients, there is an abnormal renal function which causes excess phosphorus in the body resulting in hyperphosphatemia leading to disorders of bone and mineral metabolism. Hyperphosphatemia which can cause complications is infrequently seen in early stages of CKD (stage 1–3) as there are high levels of both parathyroid hormone as well as fibroblast growth factor 23 (FGF-23) in blood and tissues, promoting urinary phosphorus excretion. Patients at stage 5 of chronic kidney disease, receiving dialysis therapy or who are at increased risk for protein–energy wasting, there are low levels of vit D₃ & calcium which cause elevated parathyroid hormone and FGF-23 but due to poor renal function phosphorus is not excreted therefore, it gets accumulated in body and causes vascular calcification, renal bone diseases, left ventricular hypertrophy and accelerated progression of kidney disease from vascular & tubulointerstitial injury [22].

Phosphate binders can be used in patients with S. Phosphate level of >5.5 mg/dl but still the basic means of controlling phosphate levels in the body is dietary restrictions. As the quantity and bioavailability of phosphorus differ according to the type of protein (generally 1 g protein contains 13 mg of phosphorus), a low protein diet can easily decrease phosphorus intake but stringent restriction of phosphate by restricting protein intake should not be done as it is associated with poor outcomes. Use of veg diet (fibers) over meat causes low absorption of phosphorus (30–50% vs. 50–70%) as phosphorus is absorbed mostly in the form of phytates [23]. Processed food also contains readily absorbable inorganic phosphorus and this phosphorus is not mentioned on the Nutrition Facts label of processed food results in an even higher phosphorus burden. It is recommended to restrict the intake of dietary phosphorus to less than 800 mg/day (26 mmol/day) from all sources for patients with moderate to advanced kidney diseases (Figures 16 and 17).

Figure 16.

Daily requirement of phosphorus in CKD patients [11].

Figure 17.

High phosphorus containing foods.

5.2.4 Calcium

Calcium plays an important role in maintenance of bone health, nerve impulse conduction, muscle contraction, blood coagulation, hormone secretion and intercellular adhesions. Approximately all of total body calcium is found in the bones and a small proportion is present in the extracellular and intracellular spaces. Calcium balance is tightly regulated by calciotropic hormones (vitD₃ and PTH) at multiple levels in the body such as absorption from the intestine, reabsorption from kidneys and exchange from bones. Calcium balance in CKD is poorly understood, its concentration is maintained in normal ranges until very late in CKD where it decreases but slightly. It is due to decrease in vitD₃ in CKD patients which causes decrease in gut absorption of calcium and causes secondary hyperparathyroidism resulting in decreased calcium excretion in urine and increased calcium release from bone in the form of ionized calcium and may cause positive calcium balance responsible for extraosseous calcium deposition like in blood vessels which can increase risks of cardiovascular mortality in CKD patients [24].

According to many studies, calcium intake in normal adults without kidney disease is 1000–1300 mg/day (25–32 mmol/day) while in CKD stage 3 or 4, 800–1000 mg of elemental calcium per day (20–25 mmol/day) in the diet will result in a stable calcium balance in the body. In patients with ongoing dialysis or any stage with existing PEW, <800 mg of elemental calcium per day from all sources should suffice and prevents extraosseous complications (Figure 18) [25].

Figure 18.

Daily calcium requirements in CKD [3].

The total intake of elemental calcium (including both dietary and elemental calcium) should not exceed more than 2000 mg/day.

5.2.5 Other minerals

5.2.5.1 Iron

Iron deficiency is common among CKD patients due to various reasons which can further result in iron deficiency anemia. People with advanced kidney disease and those on hemodialysis lose iron from digestive tract due to frequent bleeding episodes caused by uraemia, frequent blood investigations and hemodialysis itself. In CKD patients, iron deficiency can be absolute iron deficiency, in which patients have severely reduced or absent iron stores or functional iron deficiency, in which patients have adequate iron stores but iron cannot be incorporated into erythroid precursors due to increased levels of hepcidin leading to anemia of chronic disease. Iron deficiency criteria is different among CKD patients as compared to normal people. Among CKD patients, absolute iron deficiency is defined as transferrin saturation (TSAT) ≤20% and serum ferritin concentration ≤100 ng/mL (in pre dialysis and peritoneal dialysis patients) or ≤200 ng/mL (in hemodialysis patients). Serum ferritin is an acute phase reactant and is generally higher in CKD patients due to diffuse inflammation which characterizes advanced kidney disease and hemodialysis [25]. Intravenous iron supplementation is the preferred method for advanced CKD patients while both Intravenous or oral iron is recommended for patients with moderate CKD. Oral iron has generally poor efficacy in hemodialysis patients but in Peritoneal Dialysis it is much more convenient to use (Figure 19).

Figure 19.

Goals for iron stores in CKD patients [5].

Iron can be administered via different routes and doses as described in Figure 20 [26].

Figure 20.

Different routes and doses of iron administration.

5.2.5.2 Magnesium

The main source of magnesium in daily food ration are grain products, milk & milk products and potatoes. As these also contain phosphorus and potassium, patients with chronic kidney disease are often seen not taking these diets. Hypomagnesemia is also caused by tubular dysfunction and interstitial fibrosis which impair tubular magnesium reabsorption. Deficiency of magnesium is related to early tubular cell death and inflammation induced by phosphate load thus, increase the risk of end-stage kidney disease along with high-serum phosphate levels. It also has a capacity to inhibit the calcification of vascular smooth muscle cells induced by phosphate thus, retarding the progression of coronary artery calcification among non-dialysis CKD patients. Patients on hemodialysis with mild hypermagnesemia exhibit low mortality rate. Approximately, 200–300 mg/day of magnesium intake should be there.

5.2.5.3 Zinc

Zinc is an essential micronutrient which has multiple important functions like antioxidant, anti-inflammatory effects, forms a component of bio-membranes and glucose homeostasis. Zinc deficiency impairs insulin formation & secretion, decreased leptin levels and present as loss of appetite, taste disturbances, growth inhibition & slower wound healing. Deficiency is attributed to low intake of the bio element with the diet and increasing renal failure. Intake should be based on recommendations for the general population that is 8 mg/day for women and 11 mg/day for men [5]. There are no specific changes recommended as no such strong relation has been found in between zinc and CKD.

5.2.5.4 Selenium

Selenium is a trace element that has known antioxidant properties and acts as a cofactor for various antioxidant enzymes like glutathione peroxidase. CKD patients have low levels of selenium which can result in increased oxidative injury and inflammation. There are also some studies which suggest that low levels of selenium may be associated with increased risk of mortality in advanced kidney diseases and patients on MHD, especially, from infections [27]. There is not enough evidence to make recommendation of selenium supplementation for malnutrition-inflammation syndrome in MHD patients. The current Recommended Dietary Allowance (RDA) for selenium is 55 mcg/d for women and men [5].

5.2.5.5 Copper

Copper is also a micronutrient which is mainly found in vegetables, cereals, meat, fish, poultry, & legumes. The recommended daily intake of copper for adults is 900 mcg/day but the average daily intake is between 1 mg and 1.6 mg. Absorption of copper from the gut and the amount present in the diet are responsible for maintaining adequate levels of copper in the body both of these which are reduced in patients on hemodialysis causing deficiency of copper.

5.3 Vitamins

5.3.1 Fat soluble vitamin

Proper level of fat-soluble vitamins (A, E, D and K) in a diet is important due to their antioxidative role in the body. Fat soluble vitamins are not removed by dialysis and therefore should not be supplemented unless their deficiency is noted.

5.3.1.1 Vitamin D

Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are recognized as a pro hormones. There are two sources of vitamin D as it can be absorbed from gut and can also be synthesized by the human skin through the action of sunlight [28].

The functions of vitamin D include regulation of calcium & phosphorus in the body and various other potential pleiotropic effects like on immune, cardiovascular & neurological systems. Some studies also suggests that vitamin D has some antineoplastic activity. A number of factors and conditions contribute to decreased vitamin D levels in patients with CKD like dietary restrictions, loss of vitamin D binding protein (DBP) during hemodialysis, reduced sun light exposure, aging, diabetes mellitus and obesity. In some studies, vitamin D analogues have been associated with decreased proteinuria along with reversal of renal osteodystrophy [29]. Again, many studies suggest that there is a significant decline in PTH levels via supplementation of cholecalciferol or ergocalciferol in CKD patients including renal transplant recipients. Hydroxylated vitamin D agents may be needed in addition to native vitamin D to control progressive secondary hyperparathyroidism. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) have to be given in patients according to vit. D levels in blood. Vitamin D supplementation (cholecalciferol or ergocalciferol) may be given to the CKD patients with low serum vitamin D levels (<30 ng/ml) (Figure 21).

Figure 21.

Daily requirement of Vit. D in CKD patients [5].

5.3.1.2 Vitamin A and E

It is reasonable to not routinely supplement vitamin A or E because of the potential for vitamin toxicity. Optimal serum levels of vitamin E are not defined for CKD patients. There is an increased risk of impaired platelet aggregation and haemorrhagic stroke in cases of high doses of vitamin E supplementation because vitamin E interacts with both anticoagulant & antiplatelet drugs. Therefore, its supplementation has to be avoided in CKD patients who are already receiving these medications [30]. High levels of vitamin A can cause anemia and lipid abnormalities. Oral doses ≥400 IU of vitamin E is not recommended without at least intermittent monitoring of serum vitamin E levels [5].

5.3.1.3 Vitamin K

Vitamin K acts as a cofactor for enzyme gamma-glutamyl carboxylase which is needed for carboxylation of various proteins like coagulation factors (II, VII, IX and X). Deficiency of these factors can lead to impaired blood clotting and increased risk of bleeding. Vitamin K also participates in normal bone formation and structure by helping in the carboxylation of proteins which control calcium deposition in bones (e.g., osteocalcin). Matrix G1a protein (MGP) is a vitamin K-dependent protein produced by vascular smooth muscle cells which inhibits vascular calcification and atherosclerotic plaque calcification in vessels [5].

There are two classes of vitamin K, phylloquinone (vitamin K1) from plant products and menaquinones (vitamin K2) from animal/dairy products both of which are responsible for vitamin K activity. In CKD patients on antibiotics, vitamin K deficiency can be aggravated by multiple factors and can lead to elevated prothrombin time due to increasing age, thrombocytopenia & platelet dysfunction, high serum urea & creatinine and low serum albumin concentrations [31]. Vitamin K supplementation may return prothrombin time to normal in such patients. The recommended dietary vitamin K intake for CKD patients is not defined, it is similar to general population. Vitamin K supplementation is needed in hemodialysis patients on antibiotics or those who are not eating as they have low serum vitamin K.

5.3.2 Water soluble vitamins

Water soluble vitamins like vitamin B complex, folate and vitamin C are removed by dialysis and should be supplemented in diet. High flux dialysis removes greater quantity of water-soluble vitamins. Despite water solubility of thiamine (B1), riboflavin (B2), pantothenic acid (B5) and biotin (B7) plasma concentrations of these vitamins are not usually decreased in patients undergoing MHD. It can be due to counterbalance of loss of these vitamins in hemodialysis and no excretion in urine.

Niacin (B3) concentrations have been reported to be low in patients undergoing MHD and therefore supplemented in dose of 7.5 mg/day.

Pyridoxine (B6) many studies show the deficiency of vit. B6 concentration in many patients undergoing hemodialysis. B6 supplements improve various parameters of immune function in MHD patients including lymphoblast formation. Treatment with pyridoxine decreases plasma homocysteine levels and plasma oxalate concentrations. 5 mg of pyridoxine HCl is supplemented in non-dialysed patients of CKD 1 to 5 and 10 mg in patients undergoing MHD.

Folic acid is also decreased in patients undergoing MHD which along with B12 deficiency can also causes anemia and hyperhomocysteinemia. Dietary folic acid requirements are increased in CKD 4 and 5 during the time when they commence erythropoietin therapy. Supplementation of folic acid 1 mg/day is adequate in patients of CKD and if hyperhomocysteinemia is present it is given in the doses of 5–15 mg/day.

Vitamin B12 deficiency is uncommon in patients of CKD because its daily requirement is less (3 μg/day) and it is also protein bound in plasma hence, poorly dialysed. Therefore, no extra supplementation is needed in patients of CKD.

Ascorbic acid (vitamin C) acts as an antioxidant but in patients with high iron stores or transferrin, it releases catalytic iron from ferritin and drives cycle of repetitive reduction of ferric to ferrous forms which causes free radical injury [31]. Vitamin C is also decreased in patients undergoing MHD as foods rich in vitamin C also contains good amount of potassium such as citrus fruits and juices and are restricted for these patients. Clinical signs suggestive of mild scurvy has been found in many patients undergoing MHD. Kang et al. [32] reports that intravenous vitamin C (500 mg IV in each hemodialysis session for 3 months) is effective in erythropoietin resistant normoferritinemic anemia thus, helps in reducing cost, risk of exposure and adverse effects of erythropoietin & iron [33]. CKD patients at any stage and post-transplant are at risk of Vitamin C deficiency. For these patients, vitamin C is supplemented at a dose of 90 mg/day for men and 75 mg/day for women. Higher doses of Vitamin C supplementation (500 mg daily) also require caution as they have been shown to increase serum oxalate levels and can deposit in tissues in the form of oxalate crystals. Therefore, it should be supplemented in short term to avoid oxalosis [32, 34].

6. Discussion

As enlightened in this chapter, significance of putting forward the need for daily food requirements of various nutrients to control the progression of CKD. Also as discussed, the importance of sticking to those requisites which as a consequence prevent the development of malnutrition via rapid fall in GFR and delay the need for MHD. Therefore, is it of utmost priority that patients must comply to follow the specific diet as recommended. Except for, such high magnitude of changes in the diet for a patient, especially CKD stage 3–5 & patient on MHD is so overwhelming that if presented at once, the patient could become demoralized and lose his motivation. So, the goal is to prioritize the dietary modifications which mainly address the control of protein, energy, sodium, potassium, phosphorus & magnesium with a need to supplement calcium & vitamins along the diet. Patients with lipid disorders have higher risks of developing cardiovascular adverse events. It is better to use statins & fibrates initially to overcome the challenge so that, the patient can focus on other aspects of necessary alternations in diet. If the patient complies well with former dietary modifications, latter nutrients can be explored more intensively with the patient. A good compliance to low protein diet can be regularly assessed by using urinary nitrogen excretion. It is recommended that patients with CKD should be more careful while considering their food preferences. They must opt for consultation from a registered dietician to work on diet plans specific to the patient provided his resources. One can also find a registered dietician specialized in kidney diseases through ‘Academy of Nutrition and Dietetics’. Here, the dietician counsels the patient regarding the required changes in diet according to medical & health goals. Another approach is ‘Medical Nutrition Therapy’ (MNT) in which management of kidney diseases is done through a tailored nutritional plan. Dietician plays an important role in providing the right diet plan & maintaining the compliance of patient to the dietary modifications. Patient can improve their dietary intake by discussing with their dietician about the food they prefer. As a result, a better & healthy diet plan can be made with patient preferences which will help to overcome challenges. In order to maximize the compliance to the diet, patient should visit the dietician regularly to make a 7-day meal plan & modifications in their diet monthly. A patient should never consider to make any change in the recommended diet without consulting their dietician. While attending both physician & dietician, it will consume patient’s great amount of time from their daily routine which can hinder the process & patient’s compliance. Thereby, it is needed that a specialized physician dedicated to both treat & suggest dietetic programs in a single setting made possible. It will ultimately help to improve the clinical outcomes & quality of life of patients with CKD. There are certain government organizations & limited private insurance companies that pay for certain number of visits to dietician and one can also opt for MNT with dietician under his insurance. Many research publications such as Modification of Diet in Renal Disease (MDRD), National Kidney Foundation, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) and KDOQI Clinical Practice Guideline for Nutrition in CKD show the importance of dietary modifications in the management of CKD. These guidelines help both physician and dietician to modify diet of patients with CKD in accordance to their stage of disease. Further researches can be done to discover the importance of dietary modification in the management of CKD that in future will help us to improve the quality of life and clinical outcomes in CKD patients.

7. Conclusion

Approximately 10% of the adult population worldwide has chronic kidney disease. Given the high incidence & prevalence of chronic kidney disease and considering the exceptionally high costs and burden of maintenance dialysis therapy & kidney transplantation, an urgent need for patient-centred and cost-effective alternative disease management strategies such as nutritional interventions with disease-specific dietary ranges may help in increasing longevity and can prolong the dialysis-free interval for millions of people.

Acknowledgments

I’d like to express my gratitude to Almighty and everyone who helped me completing this chapter. Furthermore, I would also like to thank my guide and teacher (Prof. Mohd. Aslam) who helped me throughout the chapter with his valuable guidance and ideas. I would like to give my special thanks to my parents & my friends because without their special suggestions and support, it would not have been easy to complete this project.

Glossary

BIA	bioelectrical impedance analysis
Ca^+2	calcium
CKD	chronic kidney disease
DXA	dual-energy X-ray absorptiometry
ESRD	end stage renal disease
EAA	essential amino acids
MHD	maintenance hemodialysis
PD	peritoneal dialysis
HBV	high biological value
KA	keto acids
K^+	potassium
Na^+	sodium
PEM	protein energy malnutrition
PEW	protein energy wasting
FGF-23	fibroblast growth factor 23