Porth's Pathophysiology, 9e

1122

UNIT X Disorders of Renal Function and Fluids and Electrolytes

parathyroid gland with medication such as the calcimimetic agent cinacalcet. 28 However, because adynamic bone disease is often a consequence of overzealous treatment of secondary hyperthyroidism, these agents require careful use. Hematologic Disorders Anemia.  Chronic anemia (hemoglobin levels <13.5 g/dL in adult men and <12 g/dL in adult women) is the most profound hematologic alteration that accompanies CKD. 21 African Americans and people with diabetes have even higher rates of anemia for each advanced stage of CKD. 28 The NKF guidelines recommend that those people with a GFR less than 60mL/min/1.73m 2 should be evaluated for anemia.Assessment for anemia and its causes includes measures of hemoglobin, hematocrit, and iron stores. The anemia of CKD is due to several factors, includ- ing chronic blood loss, hemolysis, bone marrow suppres- sion due to retained uremic factors, and decreased red cell production due to impaired production of erythropoietin and iron deficiency. The kidneys are the primary site for the pro- duction of the hormone erythropoietin, which controls red blood cell production. 21 In renal failure, erythropoietin pro- duction usually is insufficient to stimulate adequate red blood cell production by the bone marrow. Among the causes of iron deficiency in people with CKD are anorexia and dietary restrictions that limit intake, and the blood loss that occurs during dialysis. 21 When untreated, anemia causes or contributes to weak- ness, fatigue, depression, insomnia, and decreased cognitive function. There also is an increasing concern regarding the physiologic effects of anemia on cardiovascular function. 2 The anemia of renal failure produces a decrease in blood viscos- ity and a compensatory increase in heart rate. The decreased blood viscosity also exacerbates peripheral vasodilation and contributes to decreased vascular resistance. Cardiac output increases in a compensatory fashion to maintain tissue perfu- sion. Anemia also limits myocardial oxygen supply, particu- larly in people with coronary heart disease, leading to angina pectoris and other ischemic events. 29 Mr. Reterez has severe fatigue probably due to a low hematocrit and hemoglobin secondary to his CKD, which occurred due to his polycystic kidney disease. This is anemia of chronic disease. Most likely, Mr. Reterez will be put on an erythropoietin supple- ment to assist in triggering his bone marrow to reproduce more red blood cells. He will also be carefully checked by his primary care provider for signs of cardiovascular dis- ease and also managed for hypertension since his blood pressure is 145/92 and his pulse is 92. A significant advance in medical management of CKD was realized when recombinant human erythropoietin (rhEPO) became available in 1989 to help maintain hematocrit levels in people with kidney failure. 2 One erythropoiesis-stimulating protein with a prolonged half-life was introduced for ­treatment

of anemia in CKD about 3 years ago. It is ­darbepoetin alfa, a hyperglycosylated analog of rhEPO. 30 However, evidence sug- gests it is no more effective, but is more expensive for people with CKD on dialysis than epoetin alfa. 31 Secondary benefits of treating anemia with rhEPO, previously attributed to the correction of uremia, include improvement in appetite, energy level, sexual function, skin color, and hair and nail growth, and reduced cold intolerance. Because worsening of hyper- tension and seizures have occurred when the hematocrit was raised too suddenly, frequent measurements of hematocrit are necessary. Additionally, currently researchers are question- ing if erythropoietin-stimulating agents are as effective as once thought or if they are actually toxic. 32 More evidence is needed to validate whether the erythropoietin-stimulating agents should be used or not. 32 Coagulopathies.  Bleeding disorders are manifested by epi- staxis, menorrhagia, gastrointestinal bleeding, and bruising of the skin and subcutaneous tissues. Although platelet produc- tion often is normal in CKD, platelet function is impaired. 6,17 Coagulative function improves with dialysis but does not completely normalize, suggesting that uremia contributes to the problem. People with CKD also have greater susceptibility to thrombotic disorders. Cardiovascular Disorders The overall mortality rate from cardiovascular disease in peo- ple with CKD is many times that of the general population. 29 Even after stratification for age, the incidence of cardiovascu- lar disease remains 10 to 20 times higher in people with CKD than in the general population. 29 Hypertension.  Hypertension commonly is an early manifes- tation of CKD. The mechanisms that produce hypertension in CKD are multifactorial. They include an increased vascular volume, elevation of peripheral vascular resistance, decreased levels of renal vasodilator prostaglandins, and increased activ- ity of the renin–angiotensin system. Early identification and aggressive treatment of hyper- tension has been shown to slow the progression of renal impairment in many types of kidney disease. 2,32 Treatment involves salt and water restriction and the use of antihyper- tensive medications to control blood pressure. Many people with CKD need to take several antihypertensive medications to control blood pressure. There is a new class of hyperten- sion drugs called endothelin blockers. These drugs are being trialed in people with difficult-to-manage hypertension. 33 Heart Disease.  The spectrum of cardiovascular disease due to CKD includes left ventricular hypertrophy and ischemic heart disease. People with CKD tend to have an increased preva- lence of left ventricular dysfunction, with both depressed left ventricular ejection fraction, as in systolic dysfunction, and impaired ventricular filling, as in diastolic failure. 2 Multiple factors lead to development of left ventricular dysfunction, including extracellular fluid overload, shunting of blood