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Kidney and Urinary Tract Function

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Heart Disease. The spectrum of heart diseases that occur with CKD include left ventricular hypertrophy, ischemic heart disease, and congestive heart failure. 23,26 People with CKD tend to have an increased prevalence of left ventricular dysfunction, with both depressed left ventricular ejection fraction, as in systolic dysfunction, and impaired ventricular filling, as in diastolic failure (see Chapter 19). Multiple factors lead to develop- ment of left ventricular dysfunction, including extra- cellular fluid overload, shunting of blood through an arteriovenous fistula for dialysis, and anemia. Anemia, in particular, has been correlated with the presence of left ventricular hypertrophy. These abnormalities, cou- pled with the hypertension that often is present, cause increased myocardial work and oxygen demand, with eventual development of heart failure. Gastrointestinal Disorders Most people with CKD have gastrointestinal symptoms. Anorexia, nausea, and vomiting are common in persons with uremia, along with a metallic taste in the mouth that further depresses the appetite. 13,24 Early-morning nausea is common. Ulceration and bleeding of the gas- trointestinal mucosa may develop, and hiccups are com- mon. A possible cause of nausea and vomiting is the decomposition of urea by intestinal flora, resulting in a high concentration of ammonia. Nausea and vomit- ing often improve with restriction of dietary protein and after initiation of dialysis, and disappear after kidney transplantation. Disorders of Mineral Metabolism Disorders of mineral and bone metabolism begin early in the course of CKD, and include a complex interac- tion between disturbances in calcium and phosphorous metabolism, parathyroid hormone (PTH), active vita- min D, bone abnormalities, and vascular or other soft tissue calcifications. Calcium, Phosphorous, PTH, and Vitamin D Levels. The typical pattern of progression includes hyperphos- phatemia, hypocalcemia, a decrease in active vitamin D levels, and secondary hyperparathyroidism. 13,24,27–29 Regulation of serum phosphate levels requires a daily urinary excretion of phosphate equal to the amount that was ingested in the diet. With deteriorating renal func- tion, phosphate excretion is impaired, causing serum phosphate levels to rise. As a result, serum calcium lev- els, which are inversely regulated in relation to serum phosphate levels, fall. The drop in serum calcium, in turn, stimulates parathyroid hormone (PTH) release, with a resultant increase in calcium resorption from bone. Although serum calcium levels are maintained through increased PTH function, this adjustment is accomplished at the expense of the skeletal system and other body organs. The kidneys regulate vitamin D activity by convert- ing the inactive form of vitamin D (25[OH] vitamin D 3 ) to calcitriol (1,25[OH] vitamin D 3 ), the active form of

kidney function is severely compromised. 13,24 Because of this adaptive mechanism, it usually is not necessary to restrict potassium intake until the GFR has dropped below 5 to 10 mL/min/1.73 m 2 . 13 In persons with kid- ney failure, hyperkalemia often results from failure to follow dietary potassium restrictions; constipation; acute acidosis that causes the release of intracellular potassium into the extracellular fluid; trauma or infec- tion that causes release of potassium from body tissues; or exposure to medications that contain potassium, prevent its entry into cells, or block its secretion in dis- tal nephrons. Acid–base Balance. The kidneys also regulate the pH of the blood by eliminating hydrogen ions produced in metabolic processes and regenerating bicarbon- ate. 13 This is achieved through hydrogen ion secre- tion, sodium and bicarbonate reabsorption, and the production of ammonia, which acts as a buffer for titratable acids (see Chapter 8). With a decline in kidney function, these mechanisms become impaired and metabolic acidosis may occur when the person is challenged with an excessive acid load or loses exces- sive alkali, as in diarrhea. The acidosis that occurs in persons with kidney failure seems to stabilize as the disease progresses, probably as a result of the tremen- dous buffering capacity of bone. However, this buffer- ing action is thought to increase bone resorption and contribute to the skeletal disorders that occur in per- sons with CKD. Cardiovascular Complications Cardiovascular disease continues to be a major cause of death in persons with CKD. In fact, persons with CKD are more likely to die of cardiovascular disease than kidney failure. 22–24 Coexisting conditions that have been identified as contributing to the burden of cardiovascular disease include hypertension, diabetes mellitus, anemia, endothelial dysfunction, and vascular calcifications. Dyslipidemia is often an additional risk factor for cardiovascular disease in persons with CKD. The most common lipid abnormalities are hypertriglyc- eridemia, reduced high-density lipoprotein (HDL) lev- els, and increased concentrations of lipoprotein (a) (see Chapter 18). 25 Hypertension. Hypertension commonly is an early manifestation 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 vasodila- tor prostaglandins, and increased activity of the renin- angiotensin-aldosterone system. Early identification and aggressive treatment of hypertension has been shown to slow the progression of renal impairment in many types of kidney disease. 23,24 Treatment involves salt and water restriction and the use of antihypertensive medi- cations to control blood pressure. Many persons with CKD need to take several antihypertensive medications to control their blood pressure (see Chapter 18).