Hyperkalemia in Animals with Renal Disease
ACVIM 2008
Larry D. Cowgill, DVM, PhD, DACVIM
Davis and San Diego, CA, USA


Urinary excretion is the major route for the elimination of dietary and endogenous potassium which can be disrupted with renal impairment. Potassium balance is typically preserved in patients with chronic kidney disease, but hyperkalemia can develop in response to acute decompensation of stable I.R.I.S. Stage III and Stage IV chronic kidney disease. As chronic kidney disease progresses to an advanced state (less than 5% to 10% of normal renal function) compensatory adjustments for potassium homeostasis become ineffective and potassium retention and hyperkalemia may develop. Hyperkalemia is the most common electrolyte imbalance encountered in animals with acute uremia and can cause severe cardiovascular instability and death. The severity of the hyperkalemia generally is proportionate to the degree of azotemia and decrement of urine formation. The toxicity associated with hyperkalemia is intensified by acidosis, hypocalcemia, and hyponatremia that can coexist with either acute or chronic uremia.

The development and severity of hyperkalemia can be aggravated further by inappropriate administration of potassium in enteral or parenteral fluids, metabolic acidosis, and the use of angiotensin converting enzyme inhibitors (ACEi). The recognition of hyperkalemia in dogs with chronic kidney disease has increased recently with the advent of more aggressive management. Hyperkalemia may be associated with the increasing use of ACEi for the management of hypertension and proteinuria now recognized as risk factors for progression of chronic kidney disease. Hyperkalemia is a known complication of ACEi usage in human patients with kidney disease; a similar effect in animal patients may restrict or preclude their use. More importantly, we now recognize hyperkalemia as a serious complication in dogs with I.R.I.S Stage II, III, and IV chronic kidney disease when they are fed commercial renal diets to supply daily energy and nutrient requirements (Figure 1). Currently formulated commercial renal diets likely provide excessive dietary loads of potassium (when consumed to meet daily nutrient requirements) that cannot be excreted effectively in animals with moderate/severe renal dysfunction. Hyperkalemia is a more prevalent and serious feature of acute uremia in cats with the increasing prevalence of acute ureteral obstruction over the past 10 years. Hyperkalemia has become recognized in animals undergoing extended hemodialysis. Predialysis serum potassium concentrations between 6 and 10 mmol/L are seen in approximately 75% of dogs maintained on chronic intermittent hemodialysis for longer than 2 weeks. It is associated with varying degrees of hyponatremia and metabolic acidosis, and its prevalence is associated with the duration of dialytic support, degree of azotemia, ultrafiltration requirements, and the intensity of dialysis. In this setting, hyperkalemia often is difficult to manage and can represent a persistent life-threatening risk. The cause remains unknown but could involve dialysis induced disruptions of cellular potassium or volume regulation, excessive dietary potassium load, or altered potassium regulation associated with severe chronic uremia.

Figure 1.
Figure 1.

Development of hyperkalemia in a hemodialysis dependent dog with chronic kidney disease in response to feeding a commercial renal diet via an esophageal feeding tube (dashed insert) and its resolution with a potassium restricted formulated diet.

Hyperkalemia decreases the transmembrane potassium gradient, depolarizes cell membranes, and impairs excitation and conduction. When expressed at the sinus node and on myocardial cells these perturbations cause classic electrocardiographic abnormalities associated with the severity of hyperkalemia. The cardiac effects lead progressively to bradycardia, atrial standstill, and cardiac arrest as the hyperkalemia worsens. These same electrophysiological disturbances affecting skeletal muscle, smooth muscle, and peripheral nerves produce profound weakness, flaccid paralysis, respiratory failure, GI hypomotility, paresthesia, and hyporeflexia.


The severity of the hyperkalemia and associated cardiac and neuromuscular disturbances dictate the therapeutic approach for this disorder. Options for the acute management of hyperkalemia are to antagonize the increased resting membrane potential in cardiac myocytes, redistribute potassium from the extracellular to the intracellular fluid compartments, and to eliminate the potassium load from the body.

Severe hyperkalemia (> 8 mmol/L) is associated with life-threatening cardiac arrhythmias and conduction disturbances which are accentuated by the rate of increases in serum potassium and the degree of hyponatremia. To immediately resolve these threats, calcium gluconate (10% solution) is administered at 0.5-1.0 ml/kg as a slow intravenous bolus over 10-15 minutes to increase the threshold potential for cardiac excitation. Calcium chloride is not appropriate because of its potency, acidifying tendency, and irritation if injected extravascularly. Rapid injection of calcium solutions may cause hypotension and cardiac arrhythmias; therefore, arterial blood pressure and ECG monitoring should be established during calcium administration. The infusion should be halted temporarily if S-T segment elevation, Q-T interval shortening, progressive bradycardia, or hypotension is observed. The effects of calcium infusion on the myocardium are rapid in onset but short in duration (approximately 30 to 60 minutes), and calcium administration has no direct effect to lower the serum potassium concentration. Calcium infusion should be regarded as a "stop-gap" to counteract the conduction disturbances until longer-lasting controls can be initiated. Once the cardiotoxicity has been controlled, transient lowering of serum potassium can be achieved by promoting its translocation from the extracellular to the intracellular fluid compartment with sodium bicarbonate or insulin and glucose administration. During these temporary reprieves from the hyperkalemia, additional measures must be initiated to provide long-term regulation of serum potassium. If conventional therapy fails to provide an immediate or lasting resolution for the hyperkalemia, peritoneal or hemodialysis is indicated as alternative therapies.

Moderate hyperkalemia (6.0-8.0 mmol/L) may resolve spontaneously with the onset or induction of a diuresis. If a diuresis cannot be established or serum potassium cannot be controlled with fluid or diuretic administration, all potassium containing fluid should be replaced with solutions devoid of potassium, and sodium bicarbonate given to correct any existing bicarbonate deficit. Sodium bicarbonate can be administered empirically at 1-2 mmol/kg intravenously over 20 minutes in the absence of serum bicarbonate measurements. Therapeutic effects begin within 10 minutes and may persist for 1 to 2 hours. Bicarbonate administration increases extracellular pH which translocates potassium into cells in exchange for hydrogen ions. Sodium bicarbonate is contraindicated in animals with metabolic alkalosis and potentially is risky in overhydrated animals. Sodium bicarbonate administration may lower serum calcium concentration and induce a hypocalcemic crisis in animals with preexisting hypocalcemia. Recent studies have shown equal efficacy for hypertonic sodium chloride and sodium bicarbonate to reduce serum potassium and to counteract its cardiac toxicity in experimental dogs with induced hyperkalemia and may be useful in dogs with concurrent hyperkalemia and metabolic alkalosis. Hypertonic (20%) glucose can be administered at 0.5 to 1.5 g/kg intravenously as an alternative to sodium bicarbonate. Glucose stimulates insulin release and promotes the transcellular uptake of potassium. Alternatively, regular insulin can be given at 0.25-1.0 units/kg IV in combination with intravenous glucose at 1-2 g/unit of administered insulin. The effects of bicarbonate and glucose/insulin are more sustained then calcium gluconate but must be repeated as clinical circumstances dictate until the potassium load is alleviated.

Mild hyperkalemia (< 6.0 mmol/L) is rarely problematic but should be monitored at 8 to 12 hour intervals. Mild hyperkalemia generally resolves with initial (potassium free) replacement fluids and administration of furosemide and/or sodium bicarbonate.

In contrast to medical treatments for hyperkalemia which merely shift extracellular potassium to intracellular pools or antagonize its neuromuscular toxicity, long-term control is directed to elimination of the existing and ongoing potassium load. Contributing factors including the use of potassium containing enteral or parenteral solutions, ACEi, and potassium containing medications should be modified. Sodium polystyrene sulfonate resin (Kayexalate) may be given orally at 2 g/kg in 3 to 4 divided doses daily as a suspension in 20% sorbitol (to prevent constipation). The resin exchanges sodium for potassium secreted into the intestinal lumen to promote increased intestinal potassium clearance. Exchange resins may be effective to control mild hyperkalemia, but have little efficacy or indications in the management of potassium associated cardiotoxicity. The acceptability of these preparations is low due to persistent side effects including nausea, constipation, gastrointestinal ulceration and necrosis. Hemodialysis eliminates potassium from both extracellular and intracellular pools and provides the most effective way to alleviate excessive potassium loads. Interesting, within minutes of starting hemodialysis the electrocardiographic abnormalities, conduction disturbances, and bradycardia associated with severe hyperkalemia resolve in animals with either acute or chronic uremia. The mechanism of these effects is not known, but they occur before there is any measurable improvement in serum potassium concentration. Thus, hemodialysis is an effective treatment for both the acute and prolonged management of hyperkalemia. For animals manifesting hyperkalemia associated with oral or enteral feeding of commercial renal diets, it is necessary to have a home-cooked diet formulated by a veterinary clinical nutritionist that contains a reduced potassium content. Compared to the typical potassium content of commercial renal diets of approximately1.6 mg per 1000 kcal of metabolizable energy, a home formulated diet containing <0.9 mg per 1000 kcal metaabolizable energy will generally control persisting hyperkalemia.

Speaker Information
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Larry Cowgill, DVM, PhD, DACVIM
Sacramento, CA

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