Medical Nutrition Therapy for Renal Disorders

Pathophysiology

Kidney stone formation is a complex process that consists of saturation; supersaturation; nucleation; crystal growth or aggregation; crystal retention; and stone formation in the presence of promoters, inhibitors, and complexors in urine. A typical metabolic evaluation is described in Table 36-1.

Calcium stones are the most common: 60% of stones are calcium oxalate, 10% calcium oxalate and calcium phosphate, and 10% calcium phosphate. Other stones are 5% to 10% uric acid, 5% to 10% struvite, and 1% cystine.

Obese stone formers excrete increased amount of sodium, calcium, uric acid, and citrate, and have lower urine pH. Obesity is the strongest predictor of stone recurrence in first-time stone formers. As body weight increases, the excretion of calcium, oxalate, and uric acid also increases. Patients with higher body mass index (BMI) have a decrease in ammonia excretion and impaired hydrogen ion buffering (Li et al., 2009). With increasing BMI, uric acid stones become more dominant than calcium oxalate stones, especially in men (Eisner, 2010b).

Uric acid stones are common in the presence of type 2 diabetes. Hyperinsulinemia may also contribute to the development of calcium stones by increasing urinary calcium excretion (Maalouf et al., 2010b). Weight control may be considered one of the preventive modalities and in stone formers, a BMI of 18 to 25 kg/m² is recommended.

With malabsorptive bariatric procedures such as Roux-en-Y gastric bypass (RYGB), urolithiasis is higher than in obese controls, probably because of the increased prevalence of hyperoxaluria and hypocitraturia in RYGB patients (Maalouf et al., 2010a). However, restrictive gastric surgery (i.e., gastric banding or sleeve gastrectomy) is not associated with increased risk of kidney stones (Semins et al., 2010).

Agents added intentionally or unintentionally to food or drug products have led to the appearance of new types of stones containing melamine and indinavir (Zilberman, 2010). See Table 36-2.

Medical Management

Uric acid and struvite stones are the only type amenable to dissolution therapy in the form of ECSWL. Shockwave lithotripsy and endourologic techniques have almost replaced the open surgical procedures of stone removal of 20 years ago. Struvite stones are also treated with adjunctive culture-specific antimicrobial therapy that uses urease inhibitors. Management strategies are now aimed at kidney stone prevention (Asplin, 2008).

Medical Nutrition Therapy

After corrective treatment, nutrition assessment is needed to determine risk factors for stone recurrence. The risk in both men and women rises with increasing urine calcium and oxalate and decreases with increasing citrate and urine volume. There is a continuum of risk related to increasing urinary calcium and urinary oxalate. (Curhan and Taylor, 2008). Because urine chemistries change from day to day based on changes in the environment and diet, two 24-hour urine specimens are needed based on a usual diet, one during a week day and one on the weekend. Specific medical nutrition therapy (MNT) is then based on comprehensive metabolic evaluations. Nutrition counseling and metabolic monitoring can be quite effective (Table 36-4).

When a patient passes a stone, it should be determined if it is a new stone or a preexisting one and advisement given accordingly (Asplin, 2008). The effectiveness of any MNT should be monitored with evaluation of subsequent 24-hour urine collections. This gives the nutritionist and patient a measure of the effect of dietary changes. Once diet therapy is initiated, the goal is to prevent new stones from forming and preexisting stones from growing. See Pathophysiology and Care Management Algorithm: Kidney Stones.

Pathophysiology

Acute kidney injury (AKI), formerly acute renal failure (ARF), is characterized by a sudden reduction in glomerular filtration rate (GFR), the amount of filtrate per unit in the nephrons, and altered ability of the kidney to excrete the daily production of metabolic waste. AKI can occur in association with oliguria (decreased output of urine) or normal urine flow, but it typically occurs in previously healthy kidneys. Duration varies from a few days to several weeks. The causes of AKI are numerous, and can occur simultaneously (Table 36-5). These causes are generally classified into three categories: (1) Inadequate renal perfusion (prerenal), (2) diseases within the renal parenchyma (intrinsic), and (3) urinary tract obstruction (postrenal).

Medical Management

The ratio of blood urea nitrogen (BUN) to Cr can be used diagnostically to assess the location of damage to the kidney. Depending on where the insult occurs, BUN is increased because of poor filtration, and is more actively reabsorbed. In this situation, with a BUN/Cr ratio greater than 20 : 1, damage is prerenal (before the kidney). When damage is intrinsic (within the kidney), the BUN/Cr ratio decreases to less than 10 : 1. Generally, if careful attention is directed at diagnosing and correcting the prerenal or obstructive causes, AKI is short lived and requires no particular nutritional intervention.

Intrinsic AKI can result from causes listed in Table 36-5; of these, a prolonged episode of ischemia leading to ischemic acute tubular necrosis is the most devastating. Typically patients develop this illness as a complication of an overwhelming infection, severe trauma, surgical accident, or cardiogenic shock. The clinical course and outcome depends mainly on the underlying cause. Patients with AKI caused by drug toxicity generally recover fully after they stop taking the drug. On the other hand, the mortality rate associated with ischemic acute tubular necrosis caused by shock is approximately 70%. Typically these patients are highly catabolic, and extensive tissue destruction occurs in the early stages. Hemodialysis (HD) is used to reduce the acidosis, correct the uremia, and control hyperkalemia.

If recovery is to occur, it generally takes place within 2 to 3 weeks after the insult is corrected. The recovery (diuretic) phase is characterized first by an increase in urine output and later by a return of waste elimination. During this period dialysis may still be required, and careful attention must be paid to fluid and electrolyte balance and appropriate replacement.

Medical Nutrition Therapy

Nutritional care in AKI is particularly important because the patient not only has uremia, metabolic acidosis, and fluid and electrolyte imbalance, but also usually suffers from physiologic stress (e.g., infection or tissue destruction) that increases protein needs. The problem of balancing protein and energy needs with treatment of acidosis and excessive nitrogenous waste is complicated and delicate. In the early stages of AKI the patient is often unable to eat. Mortality in AKI is high, especially among those who are malnourished (Strejc, 2005). Early attention to nutritional support and early dialysis improves patient survival.

At the onset of AKI, depending on severity, some patients can be treated with medical management, other patients require renal replacement therapy (RRT) with standard HD or peritoneal dialysis (PD) to remove wastes and fluids until kidney function returns. In significant AKI, a patient in the intensive care unit (ICU) may require continuous treatments, rather than periodic dialysis. Continuous renal replacement therapy (CRRT) is the broad category term that includes a whole host of modalities. Most often used are continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), which use a small ultrafiltration membrane to produce an ultrafiltrate that can be replaced by parenteral nutrition (PN) fluids. This treatment allows parenteral feeding without fluid overload. Less often used are continuous arteriovenous hemofiltration, continuous arteriovenous hemodialysis, and continuous venovenous hemodiafiltration. These modalities differ in the type of blood access used, as well as type of filtration (diffuse versus convective, or both).

Pathophysiology

Once approximately one half to two thirds of kidney function has been lost, regardless of the underlying disease, progressive further loss of kidney function ensues. This is true even in diseases in which the underlying cause has been eliminated completely, such as in vesicoureteral reflux, cortical necrosis of pregnancy, or analgesic abuse. It is thought that, in response to a decreasing GFR, the kidney undergoes a series of adaptations to prevent this decline. Although in the short term this leads to improvement in filtration rate, in the long term it leads to an accelerated loss of nephrons and progressive renal insufficiency (Remuzzi et al., 2006). The nature of these adaptations involves a change in the hemodynamic characteristics of the remaining glomeruli, specifically leading to increased glomerular pressure. Factors that increase glomerular pressure tend to accelerate this process, whereas factors that decrease glomerular pressure tend to alleviate it.

Diabetes is the leading risk factor for CKD followed by hypertension. The National Kidney Foundation (NKF) divides CKD into five stages related to the estimated GFR (eGFR) (Table 36-7). Stages 1 and 2 are early stages with markers like proteinuria, hematuria, or anatomic issues. Stages 3 and 4 are considered advanced stages. Stage 5 results in death unless dialysis or transplantation is initiated.

Medical Management

The prevalence of CKD is now estimated at approximately one in nine adults in the United States, or 20 million Americans. This estimated prevalence of CKD is 11% of the population. Many states now urge clinical laboratories reporting serum Cr to also report the patient’s eGFR, the rate at which the kidneys are filtering wastes. The formula, which takes into account the patient’s sex, age, race, and Cr, is more accurate than the older Cockcroff-Gault formula sometimes used to calculate Cr clearance (Rigalleau et al., 2006). Patients having their eGFR calculated who have a low number do not necessarily have CKD. They must have repeated values over 3 months apart that are consistently low.

An online eGFR calculator can be found at the NKF site at http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. With screening tools like the calculated eGFR and a greater awareness of the progressive nature of CKD, more attention has focused on its social, medical, and financial effects. For example, CKD is strongly linked with cardiovascular disease; see Clinical Insight: Chronic Kidney Disease and Heart Disease—A Deadly Union.

Medical Nutrition Therapy

With each level of CKD, a different nutritional therapy may be proposed. The primary objectives of MNT are to manage the symptoms associated with the syndrome (edema, hypoalbuminemia, and hyperlipidemia), decrease the risk of progression to renal failure, and maintain nutritional stores. Patients are primarily treated with statins to correct hyperlipidemia, low-sodium diets, and diuretics (Appel, 2006). Patients with an established severe protein deficiency who continue to lose protein may require an extended time of carefully supervised nutritional care. The diet should attempt to provide sufficient protein and energy to maintain a positive nitrogen balance and to produce an increase in plasma albumin concentration and disappearance of edema. In most cases, sufficient intake from carbohydrate and fats are needed to spare protein for anabolism.

Some of the more common nutrition diagnoses in the CKD population include:

Depending on the nutrition diagnosis, MNT interventions are adjusted for various intakes of minerals, protein, and fluids.

Pathophysiology

Nephritic syndrome incorporates a group of diseases characterized by inflammation of the capillary loops of the glomerulus. These acute glomerulonephritides are sudden in onset, brief, and may proceed to complete recovery, development of chronic nephrotic syndrome, or ESRD. The primary manifestation of these diseases is hematuria (blood in the urine), a consequence of the capillary inflammation that damages the glomerular barrier to blood cells. The syndrome is also characterized by hypertension and mild loss of renal function. The most common presentation follows a streptococcal infection and is usually, although not always, self-limiting. Other causes include primary kidney diseases such as immunoglobulin A nephropathy (IgA); hereditary nephritis; and secondary diseases such as systemic lupus erythematosus (SLE), vasculitis, and glomerulonephritis (GN) associated with endocarditis, abscesses, or infected ventriculoperitoneal shunts.

Pathophysiology

Nephrotic syndrome comprises a group of diseases that derive from a loss of the glomerular barrier for protein. Large urinary protein losses lead to hypoalbuminemia with consequent edema, hypercholesterolemia, hypercoagulability, and abnormal bone metabolism. More than 95% of the cases of nephrotic syndrome stem from three systemic diseases: (1) diabetes mellitus, (2) SLE, and (3) amyloidosis; and from four diseases that are primarily of the kidney: (1) minimum change disease (seen only with electron microscopy), (2) membranous nephropathy, (3) focal glomerulosclerosis, and (4) membranoproliferative glomerulonephritis. Although renal function can deteriorate during the course of these diseases, it is not a consistent feature.

Dialysis

Patients may choose to dialyze in an outpatient dialysis facility or they may prefer HD at home using either conventional daily or nocturnal dialysis. They may choose PD and have a choice of continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD), or combinations of the two. Patients, families, and their physicians together evaluate the therapy that best meets the patient’s needs. Factors that come into account in this decision are availability of family or friends to assist with therapy, type of water supply to the home, capability of the patient or involved family (including eyesight and ability to perform sterile technique), previous abdominal surgeries, membrane characteristics of the individual’s peritoneal membrane, body size, cardiac status, presence of poor vascular access, desire to travel, and a host of other considerations.

HD requires permanent access to the bloodstream through a fistula created by surgery to connect an artery and a vein (Figure 36-2). If the patient’s blood vessels are fragile, an artificial vessel called a graft may be surgically implanted. Large needles are inserted into the fistula or graft before each dialysis and removed when dialysis is complete. Temporary access through subclavian catheters is common until the patient’s permanent access can be created or can mature; however, problems with infection make these catheters undesirable.

The hemodialysis (HD) fluid and electrolyte content is similar to that of normal plasma. Waste products and electrolytes move by diffusion, ultrafiltration, and osmosis from the blood into the dialysate and are removed (Figure 36-3) (Himmelfarb and Ikizler, 2010). Outpatient HD usually requires treatment of 3 to 5 hours three times per week in a dialysis unit (Figure 36-4). Newer therapies can shorten the duration of treatment by increasing its frequency. Patients on these more frequent dialysis therapies have lower mortality rates, approaching that of transplantation. Patients on daily dialysis at home typically have treatments lasting from 2 to 3.5 hours 5 to 6 days a week, whereas some home dialysis patients receive nocturnal dialysis 3 to 6 times a week for 8 hours, while they sleep.

Peritoneal dialysis (PD) makes use of the body’s own semipermeable membrane, the peritoneum. A catheter is surgically implanted in the abdomen and into the peritoneal cavity. Dialysate containing a high-dextrose concentration is instilled into the peritoneum, where diffusion carries waste products from the blood through the peritoneal membrane and into the dialysate; water moves by osmosis. This fluid is then withdrawn and discarded, and new solution is added.

Several types of PD exist. In CAPD, the dialysate is left in the peritoneum and exchanged manually, by gravity. Exchanges of dialysis fluid are done four to five times daily, making it a 24-hour treatment (Figure 36-5). In CCPD, patient treatments are done at night by a machine that does the exchanges. During the day these patients may keep a single dialysate exchange in the peritoneal cavity for extended periods (called a long dwell), perhaps the entire day. Several combinations of CAPD and CCPD are possible and are referred to here as PD.

Advantages of PD are avoidance of large fluctuations in blood chemistry, longer residual renal function, and the ability of the patient to achieve a more normal lifestyle. Complications include peritonitis, hypotension that requires fluid and sodium replacement, and weight gain. Tissue weight gain is experienced by most patients as a result of absorbing 400 to 800 calories per day from the glucose in the dialysate. This may be desirable in patients who are underweight, but eventually dietary intake or activity have to be modified to account for the energy absorbed from dialysate. Icodextrin (Extraneal, Baxter) is a long-chain, nonabsorbable sugar available for long dwell times. It offers superior fluid removal (ultrafiltration) without excess dextrose absorption. This can be useful for patients with diabetes and those with excessive tissue weight gain, but can cause other complications and is costly.

Evaluation of Dialysis Efficacy

Kinetic modeling is a method for evaluating the efficacy of dialysis that measures the removal of urea from the patient’s blood over a given period. This formula, often called Kt/V (where K is the urea clearance of the dialyzer, t is the length of time of dialysis, and V is the patient’s total body water volume), should ideally produce a result higher than 1.4 per HD, or 3.2 per week. These calculations are somewhat complex and are typically calculated using a computer program. A more accurate method for determining adequacy of HD is the eKt/V where e stands for equilibrated and takes into account the amount of time it takes for urea to equilibrate across cell membranes after dialysis has stopped. An acceptable eKt/V is 1.2 or greater.

Another method to determine effective dialysis treatment is the urea reduction ratio (URR), which looks at the reduction in urea before and after dialysis. The patient is considered well dialyzed when a 65% or greater reduction in the serum urea occurs during dialysis. Unlike Kt/V, this calculation can be done quickly at the patient’s bedside by the practitioner. The method for calculating the efficacy of PD is somewhat different, but a weekly Kt/V of 2 is the goal. The Kt/V can be altered by several patient- and dialysis-associated variables. The calculations for Kt/V can also be used to determine the patient’s protein-nitrogen appearance (PNA) rate, which is a simplified nitrogen balance test in the dialysis patient. The PNA values should be between 0.8 and 1.4. Patients on short daily HD and nocturnal HD require different calculations to estimate their Kt/V.

1. Prevent deficiency and maintain good nutrition status (and, in the case of children, growth) through adequate protein, energy, vitamin, and mineral intake (Table 36-8).

2. Control edema and electrolyte imbalance by controlling sodium, potassium, and fluid intake.

3. Prevent or retard the development of renal osteodystrophy by controlling calcium, phosphorus, vitamin D, and PTH.

4. Enable the patient to eat a palatable, attractive diet that fits his or her lifestyle as much as possible.

5. Coordinate patient care with families, dietitians, nurses, and physicians in acute care, outpatient, or skilled nursing facilities.

6. Provide initial nutrition education, periodic counseling and long-term monitoring of patients.

Protein

Dialysis is a drain on body protein, so protein intake must be increased accordingly. Protein losses of 20 to 30 g can occur during a 24-hour PD, with an average of 1 g/hour. Those receiving PD need 1.2 to 1.5 g/kg of body weight. At least 50% should be HBV protein. Patients who receive HD three times per week require a daily protein intake of 1.2 g/kg of body weight. Patients on dialysis who have low albumin levels have much higher mortality rates; thus emphasis is placed on adequate protein intake. Serum BUN and serum Cr levels, uremic symptoms, and weight should be monitored; and the diet should be adjusted accordingly.

In renal failure, prealbumin, which is metabolized by the kidney, is not a good nutritional marker, as values are routinely elevated. Albumin is a limited indicator of protein nutriture, but is routinely used in evaluating ESRD patients’ nutritional status. Federal mandates require intervention at levels below 4 g/dL. However, because of the complexity of either acute or chronic inflammation, albumin remains predictive of poor survival in ESRD. Hypoalbuminemia is multifactorial and may be related to poor nutrition, inflammation, or comorbid disease. When interpreting albumin values, it is important to know the laboratory’s methodology for measuring serum albumin, because different laboratory techniques give different results in renal failure (see Table 36-9).

Most patients find it challenging to consume adequate protein because uremia itself causes taste aberrations, notably to red meats. Some patients cannot even tolerate the smell of meat cooking. Often this protein aversion makes it difficult to achieve recommended high biological value protein intake. Patients may tolerate eggs, tofu, and “white” meats better. They can also use spices to hide the taste of meats, or serve animal proteins cold, to minimize the urea taste. Nutritional supplements may be helpful in some patients, and, occasionally, the phosphate restriction may need to be lifted to allow the consumption of dairy products to meet protein needs. As with all the nutritional parameters, meeting patient needs must be individualized.

Energy

Energy intake should be adequate to spare protein for tissue protein synthesis and to prevent its metabolism for energy (Byham-Gray, 2006). Depending on the patient’s nutrition status and degree of stress, between 25 and 40 kcal/kg of body weight should be provided, with the lower amount for transplantation and PD patients and the higher level for the nutritionally depleted patient. Tools have been developed to allow the renal dietitian to assess the quality of the patient’s nutrition status. The Subjective Global Assessment (Box 6-5) technique has been modified in this population to recognize the basic physiologic and immunologic changes in ESRD.

Fluid and Sodium Balance

The kidney’s ability to handle sodium and water in ESRD must be assessed frequently through measurement of blood pressure, edema, fluid weight gain, serum sodium level, and dietary intake. The vast majority of dialysis patients need to restrict sodium and fluid intakes. Excessive sodium intake is responsible for increased thirst, increased fluid gain, and resultant hypertension. Even those patients who do not experience these symptoms but produce minimal amounts of urine will benefit from a reduced sodium intake to limit their thirst and prevent large intradialytic fluid gains.

In the patient who is maintained on HD, sodium and fluid intake are regulated to allow for a weight gain of 4 to 5 lb (2 to 3 kg) from increased fluid in the vasculature between dialyses. The goal is a fluid gain of less than 4% of body weight. A sodium intake of 87 to 130 mEq (2 to 3 g) daily and a limit on fluid intake (usually about 750 mL/day plus the amount equal to the urine output) is usually sufficient to meet these guidelines. Only fluids that are liquid at room temperature are included in this calculation. The fluid contained in solid foods is not included in the 750 mL limit. Solid foods in the average diet contribute approximately 500 to 800 mL/day of fluid. This fluid in solid food is calculated to approximately replace the 500 mL/day net insensible water loss.

An 86- to 130-mEq (2- to 3-g) sodium diet requires no salt in cooking; no salt at the table; no salted, smoked, or cured meat or fish; and no salted snack foods, canned soups, or high-sodium convenience foods. In today’s increasing convenience food–oriented marketplace, it is estimated that 75% to 90% of sodium intake is consumed in convenience foods, with only 10% to 25% added to foods in cooking or at the table. It is important to remember that the most effective way to reduce the renal patient’s thirst and fluid intake is to decrease sodium intake. It is salt intake that drives fluid consumption. Appendix 37 gives the details of a low-sodium meal plan. Many physicians and dietitians believe it is unethical to restrict fluid in patients who are not on a restricted sodium diet, because feelings of thirst become overwhelming to the patient with a high sodium intake.

When educating about fluid balance, the health care provider must teach the patient how to deal with thirst without drinking. Sucking on a few ice chips, cold sliced fruit, or sour candies or using artificial saliva are all good suggestions. In approximately 15% to 20% of patients, hypertension is not alleviated even after meticulous attention to fluid and water balance. In these patients hypertension is usually perpetuated by a high level of renin secretion and requires medication for control.

Although most patients with ESRD retain sodium, a small number may lose it. Examples of conditions with a salt-losing tendency are polycystic disease of the kidney, medullary kidney disease, chronic obstructive uropathy, chronic pyelonephritis, and analgesic nephropathy. To prevent hypotension, hypovolemia, cramps, and further deterioration of renal function, extra sodium may be required. A diet for these types of patients may contain 130 mEq (3 g) or more of sodium per day, which is the amount in a normal diet without added salt. Adding salt or salty foods can satisfy the need for extra sodium. The number of patients who require this higher sodium intake is small, but these patients exemplify the need for individual consideration of the diet prescription and a thorough understanding of the patient’s underlying disease and present diet.

Patients receiving frequent dialysis treatments, either daily PD, short daily, or daily nocturnal dialysis may have higher allowance for sodium and fluid, based on an individual evaluation of their dry weight and laboratory values.

Potassium

Potassium usually requires restriction, depending on the serum potassium level, urine output, medications, and the frequency of HD. The daily intake of potassium for most Americans is 75 to 100 mEq (3 to 4 g). This is usually reduced in ESRD to 60 to 80 mEq (2.3 to 3.1 g) per day and is reduced for the anuric patient on dialysis to 51 mEq (2 g) per day. Some patients (i.e., those on high-flux dialysis or with increased dialysis times or frequencies such as PD, short daily or nocturnal) will be able to tolerate higher intakes. Again, a close monitoring of the patient’s laboratory values, K⁺ content of the dialysate, and dietary intake is essential.

The potassium content of foods is listed in Box 7-1 in Chapter 7, and in Appendixes 36 and 56. When counseling HD patients on a low-potassium diet, one should take care to point out that some low-sodium foods contain potassium chloride as a salt substitute rather than sodium chloride. Nutrition labels for products such as salt substitutes, LiteSalt, and low-sodium herb mixtures must all be checked carefully to be sure they do not contain dangerous levels of potassium. Low-sodium soy sauces, low-sodium soups, and other special dietary products may need particular review by a trained professional. Reviewing such practices not only with the patient but with other people who may be cooking for the patient, such as a church group or neighbors who may use salt substitutes is advisable.

When a thorough diet history does not reveal the reason for elevated serum potassium, other nondietetic sources of potassium should be researched. Examples include poor dialysis adequacy or missed dialysis treatments, too high a concentration of potassium in the dialysate bath, very elevated blood sugar in patients with diabetes, acidosis, constipation, significant GI bleeding, some medications, blood transfusions, major trauma, chemotherapy, or radiation therapy. Occasionally, blood samples are handled improperly, resulting in hemolysis and falsely elevated potassium levels.

Phosphorus

More than 99% of excess phosphate is excreted in the urine. However, as GFR decreases, phosphorus is retained in the plasma. Because of the large molecular weight of the phosphate molecule, it is not easily removed by dialysis and patients experience net “gain” of about one half of the phosphate they consume daily. Phosphate intake is lowered by restricting dietary sources to 1200 mg/day or less. The difficulty in implementing the phosphorus restriction comes from the necessity for a high-protein diet. High protein foods, such as meats, contain high levels of phosphorus in the form of ATP. Additionally, other sources of protein—dairy products, nuts, and legumes—are also high in phosphorus. Thus high phosphorus foods cannot be eliminated without restricting protein, creating a challenge to balance intake with dietary intervention alone.

The American diet, which contains highly processed foods, has resulted in increases in both the types and amounts of phosphorus available for absorption, making compliance with a phosphorus restriction more difficult. Naturally occurring phosphate in food is only approximately 60% absorbed. Commonly used phosphate additives such as trisodium phosphate, disodium phosphate, and dicalcium phosphate are nearly 100% absorbed, making the processed diet a likely contributor to elevated phosphorus levels. Dietary intervention should focus on a balance of limiting dairy, nuts, beans, and processed foods while still encouraging enough HBV proteins to meet dietary needs.

Because dietary restrictions alone are not adequate to control serum phosphorus, nearly all patients who undergo dialysis require phosphate-binding medications. Phosphate binders such as calcium carbonate, calcium acetate, sevelamer carbonate and lanthanum carbonate are routinely used with each meal or snack to bind to phosphorus in the gut. These medications bind excess dietary phosphate and transport it through the GI tract for elimination, thus preventing its absorption into the blood. Side effects of taking these medications over long periods are common. Some may cause GI distress, diarrhea, or gas. Severe constipation, leading to intestinal impaction is a potential risk of excessive use of some types of phosphate binders; occasionally this may lead to perforation of the intestine resulting in peritonitis or death. Common medications are listed in Table 36-10.

Calcium and Parathyroid Hormone

In ESRD, the body’s ability to maintain phosphorus-calcium balance is complicated by calcium and PTH controls. As GFR decreases, the serum calcium level declines for several reasons. First, decreased ability of the kidney to convert to inactive vitamin D to its active form, 1,25-(OH)₂D3 leads to poor GI absorption of calcium. Second, the need for serum calcium increases as serum phosphate levels increase. Both of these causes lead to hypertrophy of the parathyroid gland, which is responsible for calcium homeostasis. The resultant oversecretion of PTH increases resorption of bone to provide a calcium source.

The resulting metabolic bone disease, renal osteodystrophy, is essentially one of four types: (1) osteomalacia, (2) osteitis fibrosa cystica, (3) metastatic calcification, or (4) adynamic bone disease. With a deficit of calcium available from dietary absorption, the low calcium level triggers the release of PTH from the parathyroid glands. This acts to increase release of calcium from the bones by stimulating osteoclast activity. This can lead to osteomalacia or bone demineralization, as a result of lack of osteoblast stimulation to replace lost calcium in the bones.

Ongoing low calcium causes the parathyroid glands to continue producing PTH in an attempt to elevate serum calcium levels. In time this leads to secondary hyperparathyroidism, where even the baseline production of PTH by these enlarged glands is enough to cause severe bone demineralization (osteitis fibrosis cystica), which is characterized by dull, aching bone pain.

Even though the serum calcium level is elevated in response to PTH, serum phosphate concentration remains high as the GFR falls lower. If the product of serum calcium multiplied by the serum phosphate level is greater than 70, metastatic calcification is imminent. Metastatic calcification occurs when calcium phosphate, removed from bones, is deposited in nonbone cells. This extraskeletal calcification may develop in joints, soft tissue, and vessels.

Calciphylaxis occurs when calcium phosphate is deposited in wound tissues with resultant vascular calcification, thrombosis, nonhealing wounds, and gangrene. It is frequently fatal. Clinical management aims to keep the calcium × phosphorus product below 55 by preventing transient elevations in serum phosphate concentration (National Kidney Foundation, 2003). Phosphorus intake must be controlled to as great a degree as possible to avoid aggravation of the delicate situation posed by hyperparathyroidism, phosphate retention, vitamin D deficiency, and hypocalcemia in renal failure.

Many patients on dialysis suffer from hypocalcemia, despite calcium supplementation. Because of this, the routine drug of choice is active vitamin D, 1,25-(OH)₂D₃, available as calcitriol (Rocaltrol and Calcijex). Analogs such as doxercalciferol (Hectorol) and paricalcitol (Zemplar) are also effective in lowering PTH and raising calcium levels, but with less enhancement of gut absorption of calcium than the 1,25 forms. Other mechanisms for controlling PTH include the medication cinacalcet (Sensipar), a calcimimetic or calcium-imitating drug, which binds to sites on the parathyroid gland and gives the gland a false impression that calcium levels are elevated. The drug is effective in suppressing PTH production and may also lower calcium levels dramatically, with significant consequences. Overall, close monitoring is essential.

In more extreme cases of hyperparathyroidism, use of surgical excision of portions of the parathyroid glands can be used in an attempt to restore balance. This creates the risk of low PTH, and can lead to adynamic (low turnover) bone disease, characterized by decreased levels of bone turnover and suppression of both osteoclasts and osteoblasts. This condition is unique to ESRD, in which oversuppression of the parathyroid gland and too much active vitamin D lead to decreased bone formation and fragile bones with very little matrix. Usually diagnosed by a low PTH level, this disease results in a high risk of nonhealing fractures. Oversuppression of the parathyroid gland by use of vitamin D or its analogs can mimic this as well.

Overall the dietary balance of phosphorus, the use of phosphate binders and vitamin D analogs, the removal of phosphate by dialysis, and intense monitoring of laboratory values all contribute to bone management in ESRD.

Lipid

Atherosclerotic cardiovascular disease is the most common cause of death among patients maintained on long-term dialysis (Bennett et al., 2006). This appears to be a function of both underlying disease (e.g., diabetes mellitus, hypertension, nephrotic syndrome) and a lipid abnormality common among patients with ESRD. The patient with ESRD typically has an elevated triglyceride level with or without an increase in cholesterol. The lipid abnormality likely represents both increased synthesis of very-low-density lipoprotein and decreased clearance as well as increased reliance on animal-based proteins.

Treatment of hyperlipidemia with diet or pharmacologic agents remains controversial. Epidemiologic evidence demonstrating increased incidence of atherosclerotic coronary disease is balanced by studies that demonstrate that patients with clearly defined clinical evidence of atherosclerosis at the initiation of dialysis are at no increased risk for a cardiovascular event. Although routine treatment appears unwarranted, a good case can be made for dietary and pharmacologic treatment of patients with ESRD with underlying lipid disorders and evidence of atherosclerosis. Lipid-lowering drugs, including most statins, may have a significant effect on better management (see Chapter 34).

On the other hand, low cholesterol levels can be a significant predictor of mortality in ESRD. They can indicate poor oral intake, and may be a useful tool in diagnosing malnutrition. Use of lipid-lowering drugs should be monitored and cut back if needed in these patients, particularly if they are underweight or suffering from malnutrition.

Iron and Erythropoietin

The anemia of chronic renal disease is caused by an inability of the kidney to produce EPO, the hormone that stimulates the bone marrow to produce red blood cells, an increased destruction of red blood cells secondary to circulating uremic waste products; and blood loss with dialysis or blood sampling. A synthetic form of EPO, recombinant human EPO (rHuEPO), is used to treat this form of anemia. Clinical trials have demonstrated a dramatic improvement in correcting anemia and restoring a general sense of well being (Locatelli F, 2006).

Use of EPO increases red blood cell production 2.5-fold. Almost always accompanying the rise in hematocrit is an increased need for iron that requires IV supplementation. Oral iron alone is not effective in maintaining adequate iron stores in patients who take EPO. Unless a documented allergic reaction exists, almost all patients taking EPO require periodic IV or intramuscular iron. For patients who are allergic to IV iron, several better-tolerated forms are now available as iron dextran (Infed), iron gluconate (Ferrlecit), and iron sucrose (Venofer).

Serum ferritin is an accurate indicator of iron status in renal failure. Patients who have received several transfusions and who are storing extra iron may have high serum ferritin levels of 800 to 5000 ng/mL (a normal level is 68 ng/mL for women and 150 ng/mL for men; see Appendix 30). In patients who are receiving EPO, ferritin should be kept above 300 ng/mL but below 800 ng/mL. When ferritin values fall below 100 ng/mL, IV iron is usually given. The percent of transferrin saturation is another useful indicator of iron status in these patients and should be between 25% to 30%.

Vitamins

Water-soluble vitamins are rapidly lost during dialysis. In general, ascorbic acid and most B vitamins are lost through dialysate at approximately the same rate they would have been lost in the urine (depending on the type and duration of treatment), with the exception of folate, which is highly dialyzable. Patients who still produce urine may be at increased risk of loss of water-soluble vitamins. Folate is recommended to be supplemented at 1 mg/day based on extra losses. Because vitamin B₁₂ is protein-bound, losses of this B vitamin during dialysis are minimal. Altered metabolism and excretory function, as well as drug administration, also may alter vitamin levels. Little is known about GI absorption of vitamins in uremia, but it may be significantly decreased. Uremic toxins may interfere with the activity of some vitamins, such as inhibition of phosphorylation of pyridoxine and its analogs.

Another cause of decreased vitamin intake in uremia is the restriction of dietary phosphorus and potassium. Water-soluble vitamins are usually abundant in high-potassium foods such as citrus fruits and vegetables and high-phosphorus foods such as milk. Diets for patients on dialysis tend to be low in folate, niacin, riboflavin, and vitamin B₆. With frequent episodes of anorexia or illness, vitamin intake is decreased further. Whereas levels of water-soluble vitamins decrease as a result of dialysis, replacement of fat-soluble vitamins is not usually required in renal disease.

Several vitamin supplements that fit the needs of the uremic patient or the dialysis patient are now available by prescription: Nephrocaps, Nephplex, Dialyvite, and Renal Caps. An over-the-counter supplement containing the vitamin B complex and vitamin C is often used and can be less expensive than a prescription, but additional supplements of folic acid and pyridoxine may be needed.

Niacin has been found to be helpful in lowering phosphate levels in ESRD patients. It interferes with the sodium-phosphate pump in the GI lumen, causing decreased transport of phosphate, and thus works with a different mechanism than phosphate binders, (Cheng, S, 2006, 2008). It is usually dosed once daily, increasing compliance.

Enteral Tube Feeding

Patients with ESRD who require enteral tube feeding often do quite well on standard formulas used for most tube-fed patients (see Chapter 14). Patients should receive standard formulas before they try a “specialty” formula because the former are usually less expensive and typically have lower osmolality than the specific renal products. If electrolyte or fluid concerns arise, patients can be changed to one of the formulas now available that are specifically designed for renal patients: Nepro or Novasource Renal. If patients are receiving renal products only, they may develop problems with a low phosphorus or potassium levels as these products are often used in conjunction with oral intake.

Parenteral Nutrition

PN in ESRD is similar to PN used for other malnourished patients with respect to protein, carbohydrates, and fat, but differs in use of vitamins and minerals. Most researchers agree that vitamin needs for ESRD during PN differ from normal requirements; however, they do not agree on recommendations for individual nutrients. Folate, pyridoxine, and biotin should be supplemented. Vitamin A should not be provided parenterally unless retinol-binding protein is monitored because it is elevated in patients with ESRD. Because there is currently no parenteral vitamin that is specifically designed for patients with renal failure, a standard vitamin preparation is usually administered. Little information related to parenteral trace mineral supplementation is available. Because most trace minerals, including zinc, chromium, and magnesium, are excreted in the urine, a close monitoring of these minerals in the serum seems to be appropriate.

Intradialytic Parenteral Nutrition

Malnourished patients with chronic renal failure who are on HD have easy access to PN because of the direct blood access required by the dialysis therapy itself. Intradialytic PN (IDPN) can be administered if necessary without additional invasive procedures or need for a separate port. It is typically administered through a connection to the venous side of the extracorporeal circuit during dialysis. Because of the high blood flow rate achieved through use of the surgically created fistula and the high blood pump speeds that are attained, hypertonic glucose and protein can be administered without danger of phlebitis. Lipids may also be administered. Reimbursement issues are complex because IDPN is a supplemental feeding that requires the patient to have at least a functioning GI tract and only supplies an average of 1000 calories every HD treatment (Table 36-11).

Complications are similar to those encountered in usual PN, with the exception of postdialysis hypoglycemia caused by the abrupt ending of the glucose supply. To avoid this problem, glucose administration typically is tapered up and down during the first and last half hour of the 3- to 5-hour treatment. Insulin is given often, and can be given in the bag of the dextrose–amino acid solution, so that the patient does not become hypoglycemic if the infusion must be stopped. Blood sugar levels are typically monitored during the therapy. Some patients may benefit from a complex carbohydrate snack toward the end of the treatment to avoid posttreatment rebound hypoglycemia. Amino acid losses through the dialysate average approximately 10%.

Another method of nutrition support in PD patients is called intraperitoneal nutrition (IPN) using a peritoneal dialysate solution that contains amino acids instead of dextrose. Typically one bag of this solution is used per day. Some patients experience side effects from this treatment. Reimbursement issues are significant.