Porth's Essentials of Pathophysiology, 4e

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Acute Kidney Injury and Chronic Kidney Disease

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coarse fibrous bone. 13,28 Cortical bone is affected more severely than cancellous bone. Low–bone-turnover osteodystrophy or lack of bone mineralization leads to rickets in children and osteoma- lacia in adults. Osteomalacia is characterized by a slow rate of bone formation and defects in bone mineral- ization, which may be caused by vitamin D deficiency, excess aluminum deposition, or metabolic acidosis. 13,28 Metabolic acidosis is thought to have a direct effect on both osteoblastic and osteoclastic activity, as well as on the mineralization process, by decreasing the availabil- ity of trivalent phosphate. Another type of low–bone- turnover osteodystrophy, adynamic osteodystrophy, which is almost as common as high–bone-turnover osteodystrophy and is especially common among per- sons with diabetes. It is characterized by a low number of osteoblasts, a normal or reduced number of osteo- clasts, and reduced bone volume and mineralization that may result, in part, from excessive suppression of PTH production with calcitriol. Early treatment of hyperphosphatemia and hypocal- cemia is important to prevent or slow the development of skeletal complications. 28 Phosphate-binding antacids (aluminum salts, calcium carbonate, or calcium acetate) may be prescribed to decrease absorption of phosphate from the gastrointestinal tract. Aluminum-containing antacids can contribute to the development of osteodys- trophy, whereas calcium-containing phosphate binders can lead to hypercalcemia, thus worsening soft tissue calcification, especially in persons receiving vitamin D therapy. Phosphate-binding agents that do not contain calcium or aluminum (e.g., sevelamer, lanthanum) are now available. 24 Pharmacologic forms of activated vita- min D often are used to increase serum calcium levels and, at least partially, reverse the secondary hyper- parathyroidism and osteitis fiborosa that occur with CKD. 31,32 Secondary hyperparathyroidism may also be treated by activating the calcium-sensing receptor on the parathyroid gland (see Chapter 8). The calcimimetic agent cinacalcet, the first representative of a new class of drugs that act through the calcium-sensing receptor, has been approved for treatment of secondary hyperpara- thyroidism in CKD. 24 Hematologic Complications Anemia. Anemia tends to develop early in the course of CKD, often interfering with the quality of life. 32–34 The anemia of CKD is due to several factors, including chronic blood loss, hemolysis, bone marrow suppres- sion due to retained uremic factors, and decreased red cell production due to impaired production of erythro- poietin and iron deficiency. The kidneys are the primary site for the production of the hormone erythropoietin, which controls red blood cell production. 32–34 In renal failure, erythropoietin production usually is insufficient to stimulate adequate red blood cell production by the bone marrow. Among the causes of iron deficiency in persons with CKD are anorexia and dietary restrictions that limit intake, as well as the blood loss that occurs during dialysis.

vitamin D. 30,31 Reduced levels of 1,25[OH] vitamin D 3 impair the absorption of calcium from the intestine. Calcitriol also has a direct suppressive effect on PTH production; therefore, reduced levels of calcitriol pro- duce an increase in PTH levels. Most persons with CKD develop secondary hyperparathyroidism, the result of chronic stimulation of the parathyroid glands. Vitamin D also regulates osteoblast differentiation, thereby affecting bone replacement. Metastatic Calcifications. When the calcium–phos- phate product (serum calcium [mg/dL] × serum phos- phate [mg/dL]) rises above 60 to 70, metastatic calcifications are commonly seen in arteries, visceral organs, and joints. Alkalemia, which often persists after hemodialysis and may even persist between dialysis treatments, may predispose to precipitation of calcium salts in soft tissues. 28 Vascular calcifications may affect almost any of the medium-sized arteries, and has been seen in arter- ies of the forearm, wrist, eyes, feet, abdominal cavity, and brain. 13,28 They are seen more frequently in people older than 40 years of age and in persons on hemo- dialysis. Visceral calcifications may be found in the myocardium, lungs, and stomach. 13,28 In cardiac calci- fication, the deposits usually develop in the conduction system and may result in serious cardiac arrhyth- mias. When calcification occurs in the lungs, it causes a fibrotic response in the small arteries and alveolar septa, leading to restrictive and diffusion abnormali- ties. Periarticular calcification in the shoulders, wrists, phalangeal joints, hips, and ankles is common in people on dialysis. 13,28 The major symptom associated with these deposits is limitations in joint movement because of the deposits. Bone Disease. A hallmark of CKD is renal osteodys- trophy or bone disease, which is typically accompanied by reductions in bone mass, alterations in bone micro- structure, bone pain, and skeletal fracture. 13,24,27–29 There are changes in bone turnover, mineralization, and bone volume, accompanied by bone pain and muscle weak- ness, risk of fractures, and other skeletal complications. Two major types of bone disease are commonly encoun- tered in CKD: high-bone turnover due to enhanced bone resorption, and low-bone turnover due to impaired bone mineralization. 24,28 Mild forms of defective bone metabolism may be observed in early stages of CKD (stage 2), and they become more severe as kidney func- tion deteriorates. All of the bone disorders can cause bone pain, proximal muscle weakness, and increased risk of fractures. High-bone turnover osteodystrophy or osteitis fibrosa, the most common type of disease, is the result of secondary hyperparathyroidism and the osteoclast stimulation effects of PTH. 28 Because bone resorption and formation are coupled processes, osteoblast activity is also increased (see Chapter 42, Understanding Bone Remodeling). Although the osteoblasts produce exces- sive amounts of bone, mineralization fails to keep pace, and there is a decrease in bone density and formation of