Metabolic Abnormalities
Disorders of Potassium Balance
Disorders of potassium (K) homeostasis (both high and low potassium levels) may result in preventable morbidity and mortality. Potassium levels should be checked periodically in patients with renal disease. (See Appendix 3 in the original guideline document)
Hyperkalemia is a common disorder in patients with renal disease, especially when the glomerular filtration rate falls below 20 ml/min. Hyperkalemia may occur as a result of impaired tubular secretion of potassium (K) in patients with mild chronic kidney insufficiency. It is more prevalent among diabetics with type 4 Renal Tubular Acidosis and is frequently exacerbated by the use of certain drugs such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, NSAIDS, trimethoprim and non-selective beta blockers. Other contributing conditions include volume depletion leading to poor urine flow, severe hyperglycemia and starvation. Especially in diabetics, poor oral food intake (e.g. preoperative periods) resulting in low serum insulin levels may cause or exacerbate hyperkalemia. High intake of certain food items (see below) can also lead to hyperkalemia in patients with impaired renal function. Referral to a dietitian for a potassium-restricted diet is useful.
K > 6.5
Elevation of potassium (K) above 6.5 meq/L is a medical emergency and needs immediate attention to prevent life threatening cardiac arrhythmia.
K 5.5 - 6.5 mEq/L
A more conservative approach is generally acceptable if a rapidly reversible cause is identified (e.g. oral potassium supplementation) and the patient is symptomatic, without electrocardiogram (EKG) manifestations of hyperkalemia. Discontinuation of offending drugs, adequate nutrition, moderate potassium restriction and/or correction of prerenal azotemia or metabolic acidosis with sodium bicarbonate is frequently sufficient. Persistent hyperkalemia may require a more stringent dietary limitation although very low potassium diets (less than 40 meq/L/day) may lead to protein malnutrition. If the cause for hyperkalemia is not readily identifiable and the elevation in serum potassium is mild, other measures can be instituted in the outpatient setting. Liberalization of sodium intake, loop diuretics and thiazides may be used in selected patients although their side effects (volume depletion, hyperuricemia, etc.) must be taken into account. Another option includes the use of sodium polysterene sulfonate (SPS) or Kayexalate®. The usual dose for sodium polysterene sulfonate is 30 grams given with 100 mL of a 20% sorbitol solution. This can be repeated every 4 to 6 hours as needed. Lower doses (5 to 10 grams with meals) can be used to control chronic mild hyperkalemia. Fludrocortisone, a potent mineralocorticoid may be used in patients with type 4 renal tubular acidosis (RTA). Refractory hyperkalemia should prompt a referral to a nephrologist.
Potassium Content of Foods
- Highest content (>25 mEq/100 g) -- Dried
figs, molasses, seaweed
- Very high content (>12.5 mEq/100 g) --
Dried fruit (dates, prunes) nuts, avocados, bran cereals, wheat germ,
lima beans
- High content (>6.2 mEq/100 g)
- Vegetables: spinach, tomatoes, broccoli,
winter squash, beets, carrots, cauliflower, potatoes
- Fruits: bananas, cantaloupes, kiwi,
oranges, mango
- Meat: ground beef, steak, pork, veal, lamb
Since the cause of hyperkalemia may be multifactorial and may differ from patient to patient, the choice of treatment of mild-to-moderate hyperkalemia may require different combinations of the recommendations.
After therapy is instituted, a follow-up potassium level should be performed within one week to ensure effectiveness of therapy and identify any need for further modification of the treatment regimen.
Hypokalemia K < 3.5
Hypokalemia may occur as a result of diuretic therapy or renal disease and may cause cardiac arrhythmia and muscle weakness. A fall in serum potassium of 1 mEq/L reflects a loss of about 200-400 mEq in total body potassium. Replacement by foods high in potassium (see above) is usually less effective than administration of oral potassium chloride (KCl). Slow release tablets or capsules can be used, in the following dosage: (a) for prevention of hypokalemia, potassium chloride 8-20 mEq/day; (b) for treatment of potassium depletion, potassium chloride 40-100 mEq/day.
Severe hypokalemia, defined as serum potassium level below 3.0 mEq/L, may require intravenous potassium replacement, especially in patients on digoxin or if it is anticipated that potassium losses will continue (e.g. vomiting, diarrhea, etc.) In the patient with renal disease, replacement should be approached with caution. High potassium chloride doses must be used with more frequent measurements of the serum potassium. IV potassium chloride replacement should be given no faster than 10 mEq per hour. It is preferable to replace potassium as a chloride salt as opposed to potassium-citrate of potassium-bicarbonate; one exception to this may be renal tubular acidosis (the hypokalemic types) and chronic diarrheal states.
Disorders of Calcium Metabolism
The goal of therapy is to normalize serum calcium (Ca) to avoid development of renal osteodystrophy as well as neuromuscular and cardiovascular complications.
Calcium balance is altered in renal disease patients. Low serum calcium is a salient feature of renal disease and is a component of the syndrome of secondary hyperparathyroidism. Secondary hyperparathyroidism starts early in renal patients, when serum creatinine levels are between 1.5 to 2.0 mg/dL. Low calcium levels result primarily from deficiency of 1,25,dihydroxyvitamin D; however, not all patients with hypocalcemia should be started on vitamin D preparations. Normocalcemia can be obtained in many patients by using measures other than vitamin D administration (see below).
Ca < 8.0 mg/dL
Hypocalcemia is rare in patients with renal
disease unless the glomerular filtration rate falls below 30 ml/min. Calcium
may be low because of an associated hypoalbuminemia. A useful correction of
calcium concentration for hypoalbuminemia is corrected calcium (Ca) =
Measured Ca + (4- serum albumin) x 0.8. Hypocalcemia is frequently the result of associated hyperphosphatemia and decreased levels of 1,25,dihydroxyvitamin D3 levels. Along with hyperphosphatemia, hypocalcemia contributes to secondary hyperparathyroidism and renal osteodystrophy. Treatment of hypocalcemia should be modified in response to phosphate levels. In patients with a serum phosphate above 4.5 mg/dL, we recommend the use of calcium based phosphate binders. Calcium carbonate (1250 mg tablets containing 500 mg of elemental calcium) given as one to four tablets three times a day with meals is also effective. Calcium carbonate may also be administered as 420 mg tablets containing 168 mg of elemental calcium. Calcium acetate (667 mg tablets, two to four tablets a day with meals) is also effective, but is more expensive. This will frequently raise serum calcium (although not necessarily normalizing it) by lowering serum PO4. In hypocalcemic patients with normal serum phosphate, calcium-carbonate or calcium-acetate can be given between meals. The major side effect of these preparations is hypercalcemia.
Refractory hypocalcemia, especially in normophosphatemic patients, may require the use of calcitriol (1,25,dihydroxyvitamin D3). This form of therapy is better instituted in consultation with the nephrologist, given the possibility that the patient may be suffering from "adynamic bone disease", in which case vitamin D treatment may be counterproductive). Correction of hypocalcemia through nutritional means, such as the use of dairy products, frequently results in an elevation of serum phosphate that is obviously undesirable.
Ca > 11 mg/dL
Spontaneous hypercalcemia is infrequent in chronic renal failure patients, most often resulting from underlying conditions such as myeloma, sarcoidosis and neoplasms. More commonly, hypercalcemia in this population is iatrogenic, resulting from the use of calcium-containing binders, either alone or in combination Vitamin D analogues. In patients treated with calcium carbonate or calcium acetate, temporary discontinuation or reduction of calcium-based binders usually results in normalization of serum calcium. It is important to remember that patients may be taking calcium carbonate (Tums®) to alleviate dyspepsia without recognizing them as a source of calcium. In patients not on exogenous calcium or vitamin D, the development of hypercalcemia should prompt the work-up for an underlying condition.
When the Ca x PO4 product exceeds 70, there is a possibility of dangerous precipitation of Ca in non-osseous tissues. Use of Ca based PO4 binders may transiently exacerbate the problem. Use of aluminum hydroxide (300 to 600 mg p.o. tid with meals) for periods not to exceed 7-10 days (to avoid Al3+ toxicity) may be necessary. When the Ca x PO4 product falls below this dangerous level, calcium-carbonate or calcium-acetate may be started. RenaGel®, a new polymeric resin that does not contain calcium may be used, but its high cost and recent introduction will probably limit its use to the Nephrology Service.
Disorders of Phosphate Metabolism (Hyperphosphatemia is serum phosphate (PO4) >4.5 mg/dL)
Adequate control of serum phosphorus is important for preventing the development of secondary hyperparathyroidism and the occurrence of soft tissue calcifications. Hyperphosphatemia has been identified as an independent risk factor for mortality in hemodialysis patients.
Hyperphosphatemia is at the center of the pathogenesis of secondary hyperparathyroidism and renal osteodystrophy. As renal disease progresses, retention of PO4 leads to stimulation of parathyroid hormone (PTH) secretion resulting in high levels of osteoclastic and osteoblastic cell activity (high bone turnover), with increased deposition of extracellular bone matrix resulting in fibrosis. Measurement of serum phosphate level and serum calcium level four times per year is recommended.
Healthy individuals ingest about 1 to 1.8 grams of phosphorus a day. Patients with renal disease may require restriction to 0.8 to 1.2 grams of phosphorus a day. Use calcium carbonate or calcium acetate with meals (see treatment of hypocalcemia) when dietary restriction does not accomplish the target serum phosphate level of less than 4.5 mg/L.
Aluminum hydroxide should be used sparingly and for short duration to avoid aluminum loading and toxicity. Citrate based compounds should not be administered concurrently with aluminum based binders because they increase aluminum absorption in the gut, and may cause aluminum intoxication.
Hypoalbuminemia (Serum Albumin Less Than 3.5 g/dL)
Malnutrition in patients with renal failure is common. Mortality in dialysis patients correlates inversely with albumin levels. Early referral to a nutritionist is indicated in all patients with compromised renal function. Preferably patients should see a nutritionist at least twice a year and more frequently when they reach pre-end stage renal disease levels of glomerular filtration rate (< 20 ml/min). Protein intake may be assessed by 24-hour urinary urea nitrogen excretion (UN g/day).
Estimated Protein Intake (g) = [UN + (.031 x weight (Kg))] x 6.25
See the Annotation on Nutrition, below, for further information on the management of hypoalbuminemia.
Note: Rule out other coexisting disease e.g. liver disease, chronic infection, protein-losing enteropathy or occult malignancy.
Metabolic Acidosis (CO2 <20 mEq/L and serum pH <7.40)
Metabolic acidosis is common in renal insufficiency and results from the accumulation of organic acids in plasma as well as impairment of renal acidification mechanisms. It is important to maintain serum HCO3 (measured as plasma CO2) above 20 mEq/L. Correction of metabolic acidosis lessens renal osteodystrophy and improves protein metabolism.
Oral bicarbonate replacement in the form of NaHCO3 tablets is indicated when the serum carbon dioxide falls below 20 mEq/L. The recommended dose of bicarbonate is 0.5 mEq/Kg/day, in divided doses. We recommend using 650 mg tablets (containing 7.7 mEq Na/7.7 mEq HCO3-). The target is to titrate serum carbon dioxide to 20 mEq/L. Na citrate is not recommended because it facilitates aluminum absorption through the gut, resulting in possible severe and acute aluminum toxicity.
