All patients undergoing long-term renal replacement therapy (RRT) develop accompanying metabolic and other disorders. These disorders require appropriate attention and adjunctive treatment. Approach varies by patient but typically includes nutritional modifications and management of multiple metabolic abnormalities (see also Nutrition Nutrition Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more ).
(See also Overview of Renal Replacement Therapy Overview of Renal Replacement Therapy Renal replacement therapy (RRT) replaces nonendocrine kidney function in patients with renal failure and is occasionally used for some forms of poisoning. Techniques include continuous hemofiltration... read more .)
Diet should be carefully controlled. Generally, hemodialysis patients tend to be anorexic and should be encouraged to eat a daily diet of 35 kcal/kg ideal body weight (in children, 40 to 70 kcal/kg/day depending on age and activity). Daily sodium intake should be limited to 2 g (88 mEq [88 mmol]), potassium to 2.3 g (60 mEq [60 mmol]), and phosphate to 800 to 1000 mg. Fluid intake, inclusive of the fluids contained in food, is limited to 1000 to 1500 mL/day and monitored by measuring weight gain between dialysis treatments. Patients undergoing peritoneal dialysis need a protein intake of 1.25 to 1.5 g/kg/day (compared with 1.0 to 1.2 g/kg/day in hemodialysis patients) to replace peritoneal losses (8.4 +/- 2.2 g/day). Survival is best among patients (both hemodialysis and peritoneal dialysis) who maintain a serum albumin > 3.5 g/dL (35 g/L); serum albumin is the best predictor of survival in these patients.
Anemia of renal failure
The anemia that occurs in renal failure should be treated with recombinant human erythropoietin and iron supplementation (see Anemia and coagulation disorders Anemia and coagulation disorders Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more ). Because the absorption of oral iron is limited, many patients require IV iron during hemodialysis. (Ferric carboxymaltose, sodium ferric gluconate, and iron sucrose are preferred to iron dextran, which has a higher incidence of anaphylaxis.) Iron stores are assessed using serum iron, total iron-binding capacity, and serum ferritin. Typically, iron stores are assessed before the start of erythropoietin therapy and thereafter every other month. Iron deficiency Iron Deficiency Iron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body. Heme iron is contained mainly in animal products. It is absorbed much better than nonheme iron (eg, in plants... read more is the most common reason for erythropoietin resistance. However, some dialysis patients who have received multiple blood transfusions have iron overload Overview of Iron Overload Typical adults lose about 1 mg iron (Fe) per day in shed epidermal and gastrointestinal cells; menstruating females lose on average an additional 0.5 to 1 mg/day from menses. This iron loss... read more and should not be given iron supplements.
Coronary artery disease
Risk factors for coronary artery disease Risk Factors Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more must be managed aggressively because many patients who require RRT have hypertension, dyslipidemia, or diabetes; smoke cigarettes; and ultimately die of cardiovascular disease. Continuous peritoneal dialysis Peritoneal Dialysis Peritoneal dialysis uses the peritoneum as a natural permeable membrane through which water and solutes can equilibrate. Compared to hemodialysis, peritoneal dialysis is Less physiologically... read more is more effective than hemodialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more in removing fluid. As a result, hypertensive patients require fewer antihypertensive drugs. Hypertension can also be controlled in about 80% of hemodialysis patients by filtration alone. Antihypertensive drugs Drugs for Hypertension A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers... read more are required in the remaining 20%. Treatment of dyslipidemia Treatment Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol (HDL-C) level that contributes to the development of atherosclerosis... read more , diabetes management Treatment Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , and smoking cessation Smoking Cessation Most smokers want to quit and have tried doing so with limited success. Effective interventions include cessation counseling and drug treatment, such as varenicline, bupropion, or a nicotine... read more are very important.
Hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more , a consequence of phosphate retention due to low glomerular filtration rate (GFR), increases risk of soft-tissue calcification, especially in coronary arteries and heart valves, when calcium (Ca) × phosphate (PO4) > 50 to 55. It also stimulates development of secondary hyperparathyroidism. Initial treatment is calcium-based antacids (eg, calcium carbonate 1.25 g orally 3 times a day, calcium acetate 667 to 2001 mg orally 3 times a day with meals), which function as phosphate binders and reduce phosphate levels. Constipation and abdominal bloating are complications of chronic use. Patients should be monitored for hypercalcemia.
Sevelamer carbonate 800 to 3200 mg or lanthanum carbonate 500 to 1000 mg, sucroferric oxyhydroxide 500 to 1000 mg, or ferric citrate 2 to 3 grams with each meal is an option for patients who develop hypercalcemia while taking calcium-containing phosphate binders. Some patients (eg, those hospitalized with acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more and very high serum phosphate concentrations) require addition of aluminum-based phosphate binders, but these drugs should be used short-term only (eg, 1 to 2 weeks as needed) to prevent aluminum toxicity.
Hypocalcemia and secondary hyperparathyroidism
These complications often coexist as a result of impaired renal production of vitamin D and hypophosphatemia. Treatment of hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more is with calcitriol either orally (0.25 to 1.0 mcg orally once a day) or IV (1 to 3 mcg in adults and 0.01 to 0.05 mcg/kg in children per dialysis treatment). Treatment can increase serum phosphate level and should be withheld until the level is normalized to avoid soft-tissue calcification. Doses are titrated to suppress parathyroid hormone (PTH) levels, usually to 150 to 300 pg/mL ([150 ng/L]; PTH reflects bone turnover better than serum calcium). Oversuppression decreases bone turnover and leads to adynamic bone disease, which carries a high risk of fracture. The vitamin D analogs doxercalciferol and paricalcitol have less effect on calcium and phosphate absorption from the gut but suppress PTH equally well. Early hints that these drugs may reduce mortality compared with calcitriol require confirmation.
Cinacalcet, a calcimimetic drug, increases sensitivity of parathyroid calcium-sensing receptors to calcium and may also be indicated for hyperparathyroidism, but its role in routine practice has yet to be defined. Its ability to decrease PTH levels by as much as 75% may decrease the need for parathyroidectomy in these patients.
Toxicity is a risk in hemodialysis patients who are exposed to aluminum-contaminated dialysate (now uncommon) and aluminum-based phosphate binders. Manifestations are osteomalacia, microcytic anemia (iron-resistant), and probably dialysis dementia (a constellation of memory loss, dyspraxia, hallucinations, facial grimaces, myoclonus, seizures, and a characteristic electroencephalogram [EEG]).
Aluminum toxicity should be considered in patients receiving RRT who develop osteomalacia, iron-resistant microcytic anemia, or neurologic manifestations such as memory loss, dyspraxia, hallucinations, facial grimaces, myoclonus, or seizures. Diagnosis is by measurement of plasma aluminum before and 2 days after IV infusion of deferoxamine 5 mg/kg. Deferoxamine chelates aluminum, releasing it from tissues and increasing the blood level among patients with aluminum toxicity. A rise in aluminum level of ≥ 50 mcg/L suggests toxicity. Aluminum-related osteomalacia can also be diagnosed by needle biopsy of bone (requires special stains for aluminum).
Treatment is avoidance of aluminum-based binders plus IV or intraperitoneal deferoxamine.
Pearls & Pitfalls
Renal osteodystrophy is abnormal bone mineralization. It has multiple causes, including vitamin D deficiency Vitamin D Deficiency and Dependency Inadequate exposure to sunlight predisposes to vitamin D deficiency. Deficiency impairs bone mineralization, causing rickets in children and osteomalacia in adults and possibly contributing... read more , elevated serum phosphate Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more , secondary hyperparathyroidism, chronic metabolic acidosis Metabolic Acidosis Metabolic acidosis is primary reduction in bicarbonate (HCO3−), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly... read more , and aluminum toxicity. Treatment is of the cause.
Vitamin deficiencies result from dialysis-related loss of water-soluble vitamins (eg, B, C, folate) and can be replenished with daily renal multivitamin supplements (eg, containing thiamine, riboflavin, niacin/niacinamide, vitamin B6, vitamin B12, folic acid, and pantothenic acid).
Calciphylaxis is a rare disorder of systemic arterial calcification causing ischemia and necrosis in localized areas of the fat and skin of the trunk, buttocks, and lower extremities. Cause is unknown, though hyperparathyroidism, vitamin D supplementation, and elevated calcium (Ca) and phosphate (PO4) levels are thought to contribute. It manifests as painful, violaceous, purpuric plaques and nodules that ulcerate, form eschars, and become infected. It is often fatal. Treatment is usually supportive. Several cases have been reported in which sodium thiosulfate given IV at the end of dialysis 3 times a week along with aggressive efforts to reduce the serum Ca × PO4 product has resulted in considerable improvement.
Constipation Constipation Constipation is difficult or infrequent passage of stool, hardness of stool, or a feeling of incomplete evacuation. (See also Constipation in Children.) No bodily function is more variable and... read more is a minor but troubling aspect of long-term RRT and, because of resulting bowel distention, may interfere with catheter drainage in peritoneal dialysis. Many patients require osmotic (eg, sorbitol) or bulk (eg, psyllium) laxatives. Laxatives containing magnesium (eg, magnesium hydroxide) or phosphate (eg, Fleet enema) should be avoided.