Chronic kidney disease (CKD) is a progressive syndrome in which the kidneys lose their ability to filter blood, concentrate urine, excrete waste products, and maintain electrolyte balance. End-stage renal disease (ESRD) is the end result of many forms of CKD. It is characterized by severely limited kidney function that is insufficient to maintain life. Thus, most patients with ESRD require renal replacement therapy via hemodialysis, peritoneal dialysis, or kidney transplantation.

The term uremia refers to an increased blood urea concentration leading to a constellation of ESRD sequelae that include shortness of breath, nausea, vomiting, anorexia, weight loss, lethargy, encephalopathy, asterixis, pruritis, pericarditis, seizures, and coma.

Life expectancy for ESRD patients has improved since the advent of dialysis in the 1960s, especially with the introduction of renal transplantation. Five-year survival ranges from 25-98%, depending on risk factors.[1]

Risk Factors

Black Americans have a significantly higher prevalence of CKD compared with other racial groups in the United States due, in part, to higher rates of hypertension and diabetes. Non-Hispanic White individuals generally have the lowest risk. Other risk factors for CKD and ESRD include the following:

Age. There is a normal age-related decline in glomerular filtration rate (GFR). Therefore, in very old persons, signs of kidney damage such as abnormal proteinuria must be sought in addition to the decline in GFR to avoid a misdiagnosis of CKD.

Family history of CKD.

Urinary tract disorders. Urolithiasis and urinary tract obstruction.

Systemic medical disorders. Diabetes mellitus, hypertension, autoimmune disorders (e.g., systemic lupus erythematosus), overweight and obesity, excessive alcohol use, and systemic infections.

Nephrotoxic medications such as nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics, and radiocontrast dye.

Tobacco use.

APOL1 genetic variant.[2]

Diagnosis

ESRD is defined by a GFR that is less than 15 mL/min/1.73 m².

Creatinine and blood urea nitrogen are significantly elevated.

Testing to determine the underlying etiology may include urinalysis and renal imaging such as ultrasound and CT scan. Rarely, a renal biopsy may be required if other testing is inconclusive.

Due to the kidneys’ importance in regulating electrolyte and acid-base balance, ESRD leads to hyperkalemia, hyperphosphatemia, often hypocalcemia, and anion gap metabolic acidosis. Vitamin D deficiency is also common.

Treatment

In general, once CKD has degenerated to ESRD, it is irreversible. Treatment is aimed at treating complications and replacing renal function via dialysis or transplantation.

Referral to a nephrologist should occur prior to stage IV (GFR of 15-30 mL/min/1.73 m²) in progressive CKD, and otherwise as early as possible in order to plan for long-term therapy. Kidney transplantation is the treatment of choice for appropriate candidates, and it requires considerable preparation and planning. Avoiding dialysis prior to transplant may reduce morbidity and mortality. In patients who require dialysis prior to transplant, or those ineligible for transplant, there are 2 options for maintenance dialysis.

Hemodialysis typically involves the surgical creation of an arteriovenous fistula (a connection between an artery and vein), usually in the forearm. It can take several weeks to mature, but it is the preferred method of hemodialysis since it consists entirely of the patient’s own (native) tissue. Sometimes, a dialysis graft may be placed instead. This is similar to the fistula but involves placement of a prosthetic tube between the artery and vein. A dialysis graft may be used immediately, but it typically does not last as long as a native fistula and has a higher rate of complications. If access is needed emergently, a temporary dialysis catheter may be placed, typically in the subclavian vein. Hemodialysis is usually done at a dialysis center 3 times weekly or at home, which allows for longer and more frequent hemodialysis sessions.[3]

Peritoneal dialysis involves inserting the dialysate into the patient’s abdomen and allowing dialysis to occur continuously or intermittently without requiring the patient to travel regularly to a dialysis center. It may be done at night, while the patient is sleeping.

Both methods have advantages and disadvantages, and outcomes are similar. Initiation of peritoneal dialysis, compared with hemodialysis, tends to be associated with somewhat better survival outcomes, but patients are often younger and have fewer comorbidities. Patients who have a worse prognosis at the onset of renal failure tend to do better with hemodialysis.[4] Pretransplant peritoneal dialysis is associated with better posttransplant survival than pretransplant hemodialysis.[5]

Elderly patients with ESRD, often with other comorbidities, may fare better with conservative management compared with initiation of dialysis. Median life expectancy in these patients can range from 6-23 months in the absence of renal replacement therapy.[6]

Complications

It is essential to treat ESRD complications that may arise. When remaining kidney function is markedly reduced, the following complications are often seen in conjunction with dialysis therapy:

Volume overload with coexistent hypertension is typically treated with dietary sodium and fluid restriction as well as loop diuretics.[7]

Hyperkalemia is commonly treated with a low-potassium diet and, acutely, with beta-2 agonists, dextrose, and insulin. Kayexalate should be used with caution; its effect can often be delayed by many hours. This medication was put into use prior to initiation of the modern US Food and Drug Administration testing and approval process, and some studies have questioned its true degree of effectiveness.[8]

Hypocalcemia is treated with oral calcium, calcitriol, or other vitamin D analogues.

Metabolic acidosis is treated with alkali therapy. Both hemodialysis and peritoneal dialysis use a base in the dialysate to correct metabolic acidosis by replenishing serum bicarbonate.[9]

Hyperphosphatemia is treated with dietary phosphate restriction and phosphate binders.

Anemia may be due to iron deficiency, chronic inflammation, decreased production of erythropoietin by the kidneys, or a combination of these. Hemoglobin levels should be checked at least every 3 months but are often checked more frequently for dialysis patients. Erythropoietin-stimulating agents have been shown to improve morbidity and mortality due to the decreased need for transfusions and therefore decreased risk of adverse events related to transfusion. These medications should only be used once iron deficiency has been treated or ruled out. Overcorrection of hemoglobin levels should be avoided. There is an increased risk of stroke and malignancy associated with therapeutic doses of erythropoietin-stimulating agents.[10] The target hemoglobin level should be one in which the symptoms of anemia can be relieved. Often, the goal is for a hemoglobin level between 9 and 11 g/dL.[11],[12]

Psychiatric Interventions

Psychiatric disorders are common in the context of kidney disease and can interfere with treatment. Adherence to recommended diet and fluid restrictions increases life expectancy and can reduce the risk of medical complications and treatment side effects, as well as improve quality of life.[13] However, psychiatric disorders may interfere with treatment compliance, causing significantly higher interdialytic weight gain.[14] Depression is the most common psychiatric problem in ESRD patients and is associated with both mortality and morbidity.[15] Antidepressant treatment (combined with psychotherapy) not only is effective in improving mood but also improves biochemical indicators of nutritional status in hemodialysis patients.[16] Psychological interventions have improved adherence to fluid restriction and related interdialytic weight gain.[17]

Exercise

Exercise should be encouraged in ESRD patients. Exercise training in patients with ESRD and hypertension reduces blood pressure and has other cardiovascular benefits, such as reducing the incidence of cardiac arrhythmias and improving left ventricular function and heart rate variability.[18],[19] Exercise also reduces depression in ESRD patients.[20]

Goals of Care and Advanced Planning

Compared with the general population, patients with ESRD have significantly worse outcomes after cardiac arrest. When cardiopulmonary resuscitation is initiated, survival to hospital discharge can be as low as 8%, with a 6-month survival rate of 3%.[21] Physicians should discuss quality of life as well as goals of care as they relate to end-of-life care. This discussion should take place with patients in an office setting, preferably while the patient and the patient’s family are not dealing with any acute illness or stressors. ESRD patients may be overly optimistic regarding major illness. The likelihood of return to baseline function after a cardiac arrest is very low in patients with ESRD, and clinicians can do a great deal to provide education, answer questions, and arrange do-not-resuscitate orders if desired by the patient.[22]

Nutritional Considerations

Nutrition-related concerns include prevention of protein energy wasting and renal osteodystrophy, maintenance of acceptable serum proteins (e.g., albumin) and blood glucose control, and reduction of cardiovascular risk.

Many ESRD patients are malnourished, putting them at increased mortality risk. Appetite loss, when present, is often multifactorial and may be due to accumulation of toxins, chronic inflammation, comorbid conditions, gastrointestinal dysfunction, acidotic state, as well as the actual dialysis procedure. Socioeconomic factors can also play a role, as patients may be depressed, unable to purchase their own food, unable to obtain good-quality food, or lacking in social support.[23]

Weight Maintenance and Protein Requirements

Protein needs are higher in patients with ESRD due to losses that occur during dialysis. The daily recommended dietary protein intake for clinically stable maintenance hemodialysis patients is 1.2 g/kg body weight, and 1.2-1.3 g/kg body weight for individuals on peritoneal dialysis, 50% of which should come from sources high in biological value.[24]

Nutritional status should be assessed, and every patient with ESRD should receive a diet plan. ESRD patients on dialysis may spontaneously reduce protein and calorie intake as a result of uremic toxins, elevations in leptin and other cytokines, and delayed gastric emptying.[25] The average daily energy intake of patients with ESRD is lower than the recommended 30-35 kcal/kg, and 50% of patients reveal evidence of malnutrition.[26],[27]

To prevent malnutrition-related morbidity and mortality, ESRD patients on dialysis should have individualized, frequent nutrition assessments and counseling, consisting of laboratory measures (e.g., albumin), comparison of initial weight with both usual body weight and percent of ideal body weight and body mass index, as well as subjective global assessments and dietary interviews with review of food diaries. Nutrition counseling should be intensive initially and provided every 1 or 2 months thereafter. If nutrient intake appears inadequate, malnutrition is apparent, or adverse events or illnesses threaten nutritional status, counseling should be increased. If protein-calorie needs cannot be met with the usual diet, patients should be offered dietary supplements or, if necessary, tube feeding or parenteral nutrition to approximate protein and calorie requirements.[24]

Sodium and Potassium Balance

ESRD patients should avoid high-sodium foods. Hypertension in dialysis patients is largely attributed to positive sodium balance and volume expansion.[28] While many patients on dialysis can effectively control blood pressure without drugs on a low-sodium (2 g) diet and a low-sodium (130 mmol) dialysate, current practice is such that a significant percentage of dialysis patients require the addition of antihypertensive medications.[29] Although many patients may not achieve a therapeutic degree of sodium restriction, those who do can effectively control blood pressure and reverse left ventricular hypertrophy.[30]

For most people, a high-potassium diet is desirable to control blood pressure and reduce risk for stroke. However, individuals with ESRD on hemodialysis cannot excrete potassium. Therefore, ESRD patients should be educated regarding high-potassium foods, which include many “heart healthy” fruits, vegetables, legumes, and grains and given guidelines to include moderate amounts of these foods while avoiding other sources of dietary potassium.[31] Evidence indicates that the vast majority of patients comply with potassium restriction.[1] In patients on peritoneal dialysis, hyperkalemia is significantly less likely, and hypokalemia has been reported in some patients, at times requiring an increase in potassium-containing foods and even potassium supplementation.[32]

Fluid Restriction

It is essential that ESRD patients restrict their fluid intake. Without adherence to a specified fluid allowance, patients are more likely to have poorly controlled blood pressure and risk congestive heart failure.[33] The typical fluid allowance for patients on dialysis is 700-1000 mL/day, plus urine output.

Phosphorus

Elevated blood phosphorus concentrations are associated with increased mortality in ESRD patients and increase the risk for cardiovascular events, at least in part by contributing to vascular calcification.[18],[34] Excess phosphorus also causes secondary hyperparathyroidism, triggering the release of calcium from the bone matrix, and osteodystrophy.[18]

Management of hyperphosphatemia and renal osteodystrophy has improved with phosphate binders, particularly sevelamer hydrochloride (Renagel), which also helps prevent hypercalcemia-related vascular calcification.[35] Long-acting nicotinic acid or niacin is also effective in lowering serum phosphorus while increasing plasma high-density lipoprotein (HDL) concentrations. However, certain factors continue to confound adequate control of phosphorus levels. These include covert phosphate intake from processed foods, treatment with high doses of vitamin D analogues, and the high protein needs of ESRD patients.[36] Protein intake over 50 g/day causes positive phosphate balance, in spite of phosphate binder therapy.[18],[37] Phosphorus in foods of plant origin is less readily absorbed by the gastrointestinal tract compared with phosphorus in processed foods and foods of animal origin. Therefore, patients on hemodialysis should include an abundance of foods of plant origin and avoid processed foods.[38]

Micronutrient Supplements

Micronutrient supplements are essential for ESRD patients. Individuals on dialysis commonly suffer from deficiencies of vitamin C, folate, vitamin B6, calcium, vitamin D, iron, zinc, and possibly selenium, which can contribute to an antioxidant-deficient state.[28] The National Kidney Foundation clinical practice guidelines for nutrition in chronic renal failure suggest that patients achieve 100% of the dietary reference intake for vitamins A, C, E, K, B1, B2, B6, B12, and folic acid, as well as 100% of the dietary reference intake for copper and zinc.[15] As a result of restricted intake of many foods and losses of water-soluble vitamins during dialysis, patients are usually given specially formulated vitamins. Intravenous forms of vitamin D analogues and iron are typically given to patients. While oral iron supplements may not be needed, oral vitamin D (ergocalciferol) may be beneficial. A deficiency of this vitamin may be a risk factor for early mortality in ESRD patients, and vitamin D supplementation may improve survival.[39]

Certain other dietary supplements may be helpful. Supplementation with L-carnitine has been approved by the US Food and Drug Administration to treat carnitine depletion in dialysis patients. In small studies, L-carnitine has been shown to improve lipid metabolism, protein nutrition, antioxidant status, and anemia.[40] However, these benefits have not been confirmed by any large randomized controlled trial, and the differences in study protocol, i.e., carnitine dosage, sample size, administration route, etc., make it difficult to confirm benefits of carnitine supplementation. Therefore, evidence remains inadequate to support the routine use of carnitine in patients who do not have signs of deficiency.[41] Both vitamin C (250 mg/day) and vitamin E (400 IU/day) have proven effective in some patients for treating painful muscle cramps, and they provide a less toxic alternative to quinine therapy.[42],[43] However, additional clinical trials are required before these can be used as standard therapy.

Saturated Fat and Cholesterol

Dialysis patients should follow a diet low in saturated fat and cholesterol. These patients are at very high risk for coronary artery disease. They often have increases in serum triglycerides and low HDL cholesterol.[44] Although they must eat a relatively high-calorie diet to spare protein, patients on dialysis should avoid foods that raise triglycerides and cholesterol concentrations. (See Dyslipidemias chapter.)

The relationship between total cholesterol and cardiovascular mortality is clearly evident in ESRD patients, although this relationship may be obscured in those with elevated markers of inflammation or malnutrition, preexisting cardiovascular disease, diabetes, or advanced age.[45]

Fiber

The intestinal microbiota plays a role in the chronic inflammatory status of ESRD patients because the kidneys are not able to excrete uremic toxins produced by certain bacterial species in the gut.[31] Dietary fiber provides the fuel for healthful gut bacteria, which results in a decreased production of inflammatory mediators.[46]

Orders

See Basic Diet Orders chapter.

A 2-g sodium, 2-g potassium, phosphate-restricted diet low in saturated fat and cholesterol.

Nutrition consultation to assess calorie and protein requirements and individualized instruction in the above dietary recommendations.

B-complex with small doses of vitamin C, 1 tablet daily by mouth. Consider supplemental ergocalciferol or cholecalciferol.

What to Tell the Family

End-stage renal disease is often preventable with proper control of blood pressure, blood lipids, and blood glucose, in combination with appropriate medications. Family members can help ESRD patients maintain a healthful diet, regular physical activity, and appropriate medication regimens.

References