Risk Factors and Diagnosis

Chronic kidney disease is a progressive syndrome in which the kidneys lose their ability to filter blood, concentrate urine, excrete wastes, 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, patients with ESRD require renal replacement therapy via dialysis or kidney transplantation.

The term uremia refers to the constellation of ESRD sequelae that include shortness of breath, nausea, vomiting, anorexia, weight loss, lethargy, encephalopathy, asterixis, pruritis, pericarditis, seizures, and coma. Further, more than half of patients with ESRD are malnourished, which is associated with increased mortality.

Life expectancy for ESRD patients has improved since the advent of dialysis in the 1960s. Nonetheless, the 5-year survival is less than 50%.

Risk Factors

African Americans have a significantly higher prevalence of chronic kidney disease compared with other racial groups, due, in part, to higher rates of hypertension. Other risk factors for chronic kidney disease and ESRD include:

• Older age.
• Family history of chronic kidney disease (CKD).
• Urinary tract disorders: urolithiasis and urinary tract obstruction.
• Systemic medical disorders: diabetes mellitus, hypertension, autoimmune disorders (eg, systemic lupus erythematosus), and systemic infections.
• Nephrotoxic medications, for example NSAIDs and contrast dye.
• Tobacco use.

Diagnosis

ESRD is defined by a glomerular filtration rate that is less than 15 mL/min per 1.73 m2, and the need for replacement therapy.

Creatinine and blood urea nitrogen (BUN) are significantly elevated.

Testing to determine the underlying etiology may include urinalysis, renal imaging, such as ultrasound and CT scan, and renal biopsy.

Due to the kidneys' importance in regulating electrolyte and acid-base balance, ESRD leads to hyperkalemia, hyperphosphatemia, often hypocalcemia, and anion gap metabolic acidosis.

 Treatment

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

Early identification of kidney replacement candidates so that adequate preparation and planning can be done to ensure a smooth transition to dialysis may reduce morbidity and mortality. Referral to a nephrologist should occur as early as possible in order to plan for long-term therapy. Kidney transplantation is the treatment of choice for appropriate candidates.

There are 2 options for maintenance dialysis. Hemodialysis involves the creation of an arterovenous fistula and dialysis graft, usually in the arm, and treatment at a dialysis center, typically 3 times weekly. Continuous 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. Both methods have advantages and disadvantages, and outcomes are similar.

Complications

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

• Volume overload and hypertension (treated with a dietary sodium restriction).
• Hyperkalemia (treated with a low-potassium diet and, acutely, with kayexalate).
• Hypocalcemia (treated with calcitriol or other vitamin D analogues).
• Metabolic acidosis (treated with alkali therapy, such as sodium bicarbonate).
• Hyperphosphatemia (treated with dietary phosphate restriction and phosphate binders).
• Anemia (treated with erythropoietin).

Psychiatric Interventions

Psychiatric disorders are common and can interfere with treatment. Adherence to recommended diet and fluid restrictions increases life expectancy and can help to reduce medical complications, treatment side effects, and improve quality of life.¹ However, psychiatric disorders may interfere with treatment compliance, causing significantly higher interdialytic weight gain.² Depression is the most common psychiatric problem in ESRD patients and is associated with both mortality and morbidity.³ Antidepressant treatment (pharmacologic and psychotherapy combined) is not only effective in improving mood, but also improves biochemical indicators of nutritional status in hemodialysis patients.⁴ Psychological interventions have improved adherence to fluid restriction and related interdialytic weight gain.⁵

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.^6,7 Exercise also reduces depression in ESRD patients.⁸

 Nutritional Considerations

Nutrition-related concerns include maintenance of acceptable weight and serum proteins (eg, albumin), prevention of renal osteodystrophy, and reduction of cardiovascular risk.

Weight Maintenance and Protein Requirements
Protein needs are higher in patients with ESRD due to losses that occur during dialysis. The recommended dietary protein intake for clinically stable maintenance hemodialysis patients is 1.2 g/kg body weight/d, and 1.2 -1.3 g/kg body weight/d for individuals on peritoneal dialysis, 50% of which should come from sources high in biological value.⁹

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.¹⁰ The average energy intake of patients with ESRD is lower than the recommended 30 to 35 kcal/kg,¹¹ and 50% of patients reveal evidence of malnutrition.¹²

To prevent malnutrition-related morbidity and mortality, ESRD patients on dialysis should have periodic nutrition screening, consisting of laboratory measures (eg, albumin), comparison of initial weight with both usual body weight and percent of ideal body weight, subjective global assessment, 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.⁹

Sodium and Potassium Balance
ESRD patients should avoid high-sodium diets. Hypertension in dialysis patients is largely attributed to positive sodium balance and volume expansion.¹³ 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,¹⁴ current practice is such that almost 70% of dialysis patients require antihypertensive medications. 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.¹⁵

A high-potassium diet is normally desirable to control blood pressure and reduce risk for stroke; however, individuals with ESRD on hemodialysis cannot tolerate this diet because they are unable to excrete potassium. Therefore, ESRD patients may need to avoid such foods as bananas, melon, legumes, potatoes, tomatoes, pumpkin, winter squash, sweet potato, spinach, orange juice, milk, and bran cereal to prevent life-threatening hyperkalemia-induced arrhythmia. 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.¹⁶

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 pressure¹⁷ and risk congestive heart failure. The typical fluid allowance for patients on dialysis is 700 to 1000 mL/day, plus urine output.

Phosphorus
Elevated blood phosphorus concentrations are associated with increased mortality in ESRD patients,¹² and increase the risk for cardiovascular events, at least in part by contributing to vascular calcification.¹⁸ Excess phosphorus also causes secondary hyperparathyroidism, triggering the release of calcium from the bone matrix, and osteodystrophy.¹² Management of hyperphosphatemia and renal osteodystrophy has improved with phosphate binders, particularly sevelamer hydrochloride (Renagel), which also helps prevent hypercalcemia-related vascular calcification.¹⁹ However, certain factors continue to confound adequate control of phosphorus levels. These include covert phosphate intake from processed foods,²⁰ treatment with high doses of vitamin D analogues, and the high protein needs of ESRD patients. Protein intake over 50 grams/day causes positive phosphate balance, in spite of phosphate binder therapy.^12,21

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.²² The National Kidney Foundation clinical practice guidelines for nutrition in chronic renal failure suggest that patients achieve 100% of the Dietary Reference Intakes (DRI) for vitamins A, C, E, K, thiamin (B₁), riboflavin (B₂), pyridoxine (B₆), vitamin B₁₂, and folic acid, as well as 100% of the DRI for copper and zinc.⁹ 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.

Certain other dietary supplements may be helpful. Supplementation with L-carnitine has been approved by the U.S. Food and Drug Administration to treat carnitine depletion in dialysis patients. In small studies L-carnitine has also been found to improve lipid metabolism, protein nutrition, antioxidant status, and anemia.²³ However, some large studies have not confirmed these findings. Therefore, inadequate evidence exists to support the routine use of carnitine in patients who do not reveal signs of deficiency.²⁴ Both vitamin C (250 mg/d) and vitamin E (400 IU/d) have proven effective in some patients for treating painful muscle cramps, and they provide a less toxic alternative to quinine therapy.^25,26 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 considered the group at greatest risk for development of coronary artery disease. They often have increases in serum triglycerides and low high-density lipoprotein (HDL) cholesterol.²⁷ 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 Hyperlipidemia).

Orders

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

Nutrition Consultation: To assess calorie and protein requirements, and instruct patient in 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 the proper control of blood pressure, blood lipids, and blood glucose, in combination with appropriate medications. For patients who have progressed to the need for dialysis, morbidity and mortality can be reduced and quality of life enhanced through adherence to an appropriate dietary and medical regimen, along with regular physical activity.

 References

1. Durose CL, Holdsworth M, Watson V, et al. Knowledge of dietary restrictions and the medical consequences of noncompliance by patients on hemodialysis are not predictive of dietary compliance. J Am Diet Assoc. 2004;104:35-41.

2. Taskapan H, Ates F, Kaya B, et al. Psychiatric disorders and large interdialytic weight gain in patients on chronic haemodialysis. Nephrology (Carlton). 2005;10:15-20.

3. Wuerth D, Finkelstein SH, Kliger AS, et al. Chronic peritoneal dialysis patients diagnosed with clinical depression: results of pharmacologic therapy. Semin Dial. 2003;16:424-427.

4. Koo JR, Yoon JY, Joo MH, et al. Treatment of depression and effect of antidepression treatment on nutritional status in chronic hemodialysis patients. Am J Med Sci. 2005;329:1-5.

5. Sharp J, Wild MR, Gumley AI. A systematic review of psychological interventions for the treatment of nonadherence to fluid-intake restrictions in people receiving hemodialysis. Am J Kidney Dis. 2005;45:15-27.

6. Kouidi EJ. Central and peripheral adaptations to physical training in patients with end-stage renal disease. Sports Med. 2001;31:651-665.

7. Deligiannis A, Kouidi E, Tourkantonis A. Effects of physical training on heart rate variability in patients on hemodialysis. Am J Cardiol. 1999;84:197-202.

8. Levendoglu F, Altintepe L, Okudan N, et al. A twelve week exercise program improves the psychological status, quality of life and work capacity in hemodialysis patients. J Nephrol. 2004;17:826-832.

9. National Kidney Foundation. Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, National Kidney Foundation. Am J Kidney Dis. 2000;35(6 Suppl 2):S1-S140.

10. Mehrotra R, Kopple JD. Nutritional management of maintenance dialysis patients: why aren't we doing better? Annu Rev Nutr. 2001;21:343-379.

11. Cuppari L, Avesani CM. Energy requirements in patients with chronic kidney disease. J Ren Nutr. 2004;14:121-126.

12. Ritz E. The clinical management of hyperphosphatemia. J Nephrol. 2005;18:221-228.

13. Wang X, Axelsson J, Lindholm B, et al. Volume status and blood pressure in continuous ambulatory peritoneal dialysis patients. Blood Purif. 2005;23:373-378.

14. Krautzig S, Janssen U, Koch KM, Granolleras C, Shaldon S. Dietary salt restriction and reduction of dialysate sodium to control hypertension in maintenance hemodialysis patients. Nephrol Dial Transplant. 1998;13:552-553.

15. Ozkahaya M, Toz H, Ozerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002;15:655-660.

16. Newman LN, Weiss MF, Berger J, Priester A, Negrea LA, Cacho CP. The law of unintended consequences in action: increase in incidence of hypokalemia with improved adequacy of dialysis. Adv Perit Dial. 2000;16:134-137.

17. Rahman M, Fu P, Sehgal AR, et al. Interdialytic weight gain, compliance with dialysis regimen, and age are independent predictors of blood pressure in hemodialysis patients. Am J Kidney Dis. 2000;35:257-265.

18. Cozzolino M, Brancaccio D, Gallieni M, et al. Pathogenesis of vascular calcification in chronic kidney disease. Kidney Int. 2005;68:429-436.

19. Klemmer PJ. Calcium loading, calcium accumulation, and associated cardiovascular risks in dialysis patients. Blood Purif. 2005;23(suppl 1):12-19.

20. Uribarri J, Calvo MS. Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Semin Dial. 2003;16:186-188.

21. Rufino M, de Bonis E, Martin M, et al. Is it possible to control hyperphosphataemia with diet, without inducing protein malnutrition? Nephrol Dial Transplant. 1998;13(suppl 3):65-67.

22. Kalantar-Zadeh K, Kopple JD. Trace elements and vitamins in maintenance dialysis patients. Adv Ren Replace Ther. 2003;10:170-182.

23. Bellinghieri G, Santoro D, Calvani M, et al. Carnitine and hemodialysis. Am J Kidney Dis. 2003;41(3 Suppl 1):S116-S122.

24. Steinman TI, Nissenson AR, Glassock RJ, et al. L-carnitine use in dialysis patients: is national coverage for supplementation justified? What were CMS regulators thinking--or were they? Nephrol News Issues. 2003;17:28-30, 32-34, 36.

25. Khajehdehi P, Mojerlou M, Behzadi S, et al. A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps. Nephrol Dial Transplant. 2001;16:1448-1451.

26. Roca AO, Jarjoura D, Blend D, et al. Dialysis leg cramps. Efficacy of quinine versus vitamin E. ASAIO J. 1992;38:M481-M485.

27. Wanner C, Krane V, Metzger T, et al. Lipid changes and statins in chronic renal insufficiency and dialysis. J Nephrol. 2001;14(suppl 4):S76-S80.