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one of the uremic toxins Symptoms begin with difficulty in concentrating and can progress to lethargy, confusion, and coma Physical findings include nystagmus, weakness, asterixis, and hyperreflexia These symptoms and signs may improve after initiation of dialysis Neuropathy is found in 65% of patients who receive dialysis or who will need it soon but not until GFR is 10% of normal Peripheral neuropathies manifest themselves as sensorimotor polyneuropathies (stocking and glove distribution) and isolated or multiple isolated mononeuropathies Patients can have restless legs, loss of deep tendon reflexes, and distal pain The earlier initiation of dialysis may prevent peripheral neuropathies, and the response to dialysis is variable Other neuropathies result in impotence and autonomic dysfunction
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F Disorders of Mineral Metabolism
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The disorders of calcium, phosphorus, and bone are referred to as renal osteodystrophy The most common disorder is osteitis fibrosa cystica the bony changes of secondary hyperparathyroidism This affects ~ 50% of patients nearing ESRD As GFR decreases below 25% of normal, phosphorus excretion is impaired Hyperphosphatemia leads to hypocalcemia, stimulating secretion of PTH, which has a phosphaturic effect and normalizes serum phosphorus This continuous process leads to markedly elevated PTH levels and high bone turnover with osteoclastic bone resorption and subperiosteal lesions Metastatic calcifications, such as tumoral calcinosis, can occur Radiographically, lesions are most prominent in the phalanges and lateral ends of the clavicles Osteomalacia is a form of renal osteodystrophy with low bone turnover (affecting ~ 10% of patients nearing ESRD) With worsening renal function, there is decreased renal conversion of 25-hydroxycholecalciferol to the 1,25-dihydroxy form Gut absorption of calcium is diminished, leading to hypocalcemia and abnormal bone mineralization Deposition of aluminum in bone can also lead to osteomalacia Elevated aluminum levels are seen in patients after years of chronic aluminum hydroxide administration for phosphorus binding This entity is seen with decreasing frequency because aluminum-based binders are used less in the chronic setting and water used for hemodialysis is now cleared of aluminum Adynamic bone disease is a disorder of low bone turnover More than 25% of patients nearing ESRD show evidence of minimal osteoid and decreased or absent bone remodeling Its frequency is increasing because of increased use of active vitamin D analogs, which suppress PTH production All of the above entities can cause bony pain and proximal muscle weakness Spontaneous bone fractures can occur that are slow to heal When the calcium-phosphorus product (serum calcium [mg/dL] serum phosphate [mg/dL]) is above 60 70, metastatic calcifications are commonly seen in blood vessels, soft tissues, lungs, and myocardium Treatment should begin with dietary phosphorus restriction to 1000 mg/ d Oral phosphorus-binding agents, such as calcium carbonate or calcium acetate, act in the gut and are given in divided doses three or four times daily with meals These should be titrated to a serum calcium of less than 10 mg/dL (preventing hypercalcemia) and serum phosphorus of 27 46 mg/dL in patients with a GFR of 15 59 mL/min/173 m2 and serum
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Uremic encephalopathy does not occur until GFR falls below 10 15 mL/min Encephalopathy may be due to tertiary hyperparathyroidism, where an elevated PTH level or, rarely, hypercalcemia, can be the culprit PTH may be
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should not exceed 1 g/kg/d, and if protein restriction proves to be beneficial, the level of restriction may be increased to 06 08 g/kg/d 2 Salt and water restriction In advanced renal failure, the kidney is unable to adapt to large changes in sodium intake Intake greater than 3 4 g/d can lead to edema, hypertension, and congestive heart failure, whereas intake of less than 1 g/d can lead to volume depletion and hypotension For the nondialysis patient approaching ESRD, 2 g/d of sodium is an initial recommendation A daily intake of 1 2 L of fluid maintains water balance 3 Potassium restriction Restriction is needed once the GFR has fallen below 10 20 mL/min Patients should receive detailed lists concerning potassium content of foods and should limit their intake to less than 50 60 mEq/ d (2 g) Normal intake is about 100 mEq/d 4 Phosphorus restriction The phosphorus level should be kept below 46 mg/dL predialysis and below 55 mg/dL when on dialysis, with a dietary restriction of 800 1000 mg/ d Foods rich in phosphorus such as cola beverages, eggs, dairy products, and meat should be limited Below a GFR of 20 30 mL/min, phosphorus binders are usually required The treatment of hyperphosphatemia is discussed in the section on disorders of mineral metabolism 5 Magnesium restriction Magnesium is excreted primarily by the kidneys Dangerous hypermagnesemia is rare unless the patient ingests medications high in magnesium or receives it parenterally All magnesium-containing laxatives and antacids are relatively contraindicated in renal failure
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phosphorus of 35 55 mg/dL in patients with a GFR of less than 15 mL/min/173 m2 Sevelamer and lanthanum carbonate are other phosphorus-binding agents that do not contain calcium; they are particularly useful in patients with hypercalcemia, although long-term effects are unknown Aluminum hydroxide is an effective phosphorus binder but can cause osteomalacia and neurologic complications It can be used in the acute setting for serum phosphorus greater than 7 mg/dL, but long-term use should be avoided If aluminum levels are high, chelation with deferoxamine can be effective Vitamin D or vitamin D analogs should be given with secondary hyperparathyroidism (iPTH more than two to three times normal) if phosphorus levels are less than 55 mg/dL and calcium less than 10 mg/dL Vitamin D suppresses PTH and increases serum calcium and phosphorus levels; both need to be monitored closely to prevent hypercalcemia and hyperphosphatemia If calcitriol is used, the dosage should be 025 05 mcg daily or every other day initially Cinacalcet can be used if elevated serum phosphorus or calcium levels prohibit the use of vitamin D analogs Cinacalcet is a calcimimetic agent that targets the calcium-sensing receptor on the chief cells of the parathyroid gland
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