General Therapeutic Considerations in Patients with Acute Renal Failure Brian L. Erstad1 College of Pharmacy, The University of Arizona, P.O. Box 210207, Tucson AZ 85721-0207

PROLOGUE The purpose of this review is to provide the pharmacy student with an overview of the therapeutic considerations in patients with acute renal failure that has not responded to preliminary interventions (e.g., fluid therapy for restoration of plasma volume in patients with hypovolemia-induced renal dysfunction). A taxonomical listing of goals and objectives is provided to direct the student towards desired learning outcomes. The definition, causes, consequences, and prevention of acute renal failure are briefly discussed followed by a delineation of associated problems and treatment options. The problems discussed in this review fall into five general categories: fluid and electrolyte disturbances, acid/base imbalance, infectious complications, coagulopathies, and alterations in macronutrient

metabolism and elimination. INTRODUCTION In addition to adjusting renally eliminated medications in patients with acute renal failure, which is beyond the scope of this discussion, pharmacists may be asked for recommendations concerning other problems associated with this disease. After providing introductory material about the definition, causes, consequences, and prevention of acute renal failure, the remainder of this review is intended to provide the pharmacy student with an overview of the problems and therapeutic strategies associated with established renal failure. Until med1

Associate Professor, Department of Pharmacy Practice and Science

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Table I. Goals and objectives of discussion of acute renal failure Goal 1.

Goal 2.

Goal 3.

Goal 4.

Goal 5.

Goal 6.

Goal 7.

To understand the definition and causes acute renal failure. TO 1.1 (Comprehension-definitions): Discuss the problems with the definition of acute renal failure as used in different published studies. EO 1.1.1 (Knowledge-definitions): List the amount of change in mg/dL between successive serum creatinine concentrations that is commonly used to define acute renal failure. TO 1.2 (Comprehension-causes): Compare the major causes of acute renal failure. EO 1.2.1 (Knowledge-causes): List the three major categories of acute renal failure as used in this discussion. EO 1.2.2 (Knowledge-causes): List one example of a specific cause for each of the three major categories listed above. To understand the lack of efficacy of medications for reversing established renal failure. TO 2.1 (Knowledge-medications): List at least three classes of medications that have been studied for reversing established renal failure. TO 2.2 (Knowledge-medications): Cite the efficacy of medications for reversing established renal failure. To understand common fluid and electrolyte disturbances associated with acute renal failure. TO 3.1 (Comprehension-fluids): Explain how fluid intake or administration may vary substantially depending on the type of acute renal failure. EO 3.1.1 (Knowledge-fluids): Define the following terms: oliguria, anuria, and nonoliguric renal failure. TO 3.2 (Comprehension-electrolytes): Explain the usual patterns of electrolyte changes in acute renal failure. EO 3.2.1 (Knowledge-electrolytes): List at least one common cause and one common treatment for hyponatremia in patients with acute renal failure. EO 3.2.2 (Knowledge-electrolytes): List at least five causes of hyperkalemia in patients with acute renal failure. EO 3.2.3 (Comprehension-electrolytes): Explain when hyperphosphatemia is most likely to be clinically important. To understand the most common acid/base disorder associated with acute renal failure. TO 4.1 (Knowledge-acid/base): List the most common acid/base disorder associated with acute renal failure. TO 4.2 (Comprehension-acid/base): Explain the effect on potassium of a rapid correction of the metabolic acidosis associated with acute renal failure. To understand the that infections are a common complication of acute renal failure and understand some of the potential therapeutic options for treating these infections. TO 5.1 (Comprehension-infections): Discuss the incidence and mortality of infectious complications associated with acute renal failure. TO 5.1. (Comprehension-infections): Explain three major steps in identifying and treating infections associated with acute renal failure. To understand the coagulopathy associated with acute renal failure and potential therapies. TO 6.1 (Knowledge-coagulopathy): Identify the most likely blood cell line accounting for the coagulopathy associated with acute renal failure. TO 6.1 (Knowledge-coagulopathy): List at least three medications that can be used to treat the coagulopathy associated with acute renal failure. To understand the nutritional considerations in the patient with acute renal failure. TO 7.1 (Comprehension-evaluating): Explain at least two of the problems which are likely to account for the lack of outcome be fits of nutritional support in published studies. TO 7.2 (Comprehension-pathophysiology): Describe how the nutritional support of acute renal failure varies between hospitalize patients with concomitant disease states and outpatients with stable renal failure. EO 3.5.1 (-monitoring): List the major parameters used to monitor adequacy of calorie and protein intake via parenteral nutrition. EO 3.5.2 (Knowledge-monitoring): List at least three electrolytes that should be routinely monitored when initiating nutritio in a patient with acute renal failure.

ications are developed that reverse established renal failure, the primary management issues relate to prevention and early treatment of established complications. The potential problems associated with acute renal failure that may be amenable to therapeutic interventions can be divided into five major areas: fluid and electrolyte disturbances, acid/base imbalance, infectious complications, coagulopathies, and alterations in macronutrient metabolism and elimination. There is a good deal of overlap between these categories. Additionally, this is not a comprehensive list of all possible problems associated with renal failure. However, many of the other problems associated with renal failure arise from inadequate attention paid to these basic disturbances. For example, inappropriate fluid management may lead to volume overload with resultant cardiovascular and pulmonary complications (e.g., hypertension and pulmonary edema). Similarly, neurologic complications may result from inadequate monitoring and adjustments of fluids, electrolytes, or protein. Although this is intended to be introductory material, references are provided for students interested in obtaining more detailed information. See Table I for a taxonomical-based listing of goals and objectives. 210

DEFINITION AND CAUSES OF ACUTE RENAL FAILURE There is no universally-accepted definition of acute renal failure. Depending on the study, investigators have defined it as an increase in the serum creatinine at least 0.5 mg/dL or 50 percent above baseline values, a 50 percent decrease in creatinine clearance, or the development of complications necessitating the institution of dialysis(1) Similarly, a specific time-frame for defining acute renal failure has not been universally accepted, but the term acute implies an onset of hours to days, not months or years. The causes of acute renal failure are usually considered under three general categories: prerenal, intrinsic, and postrenal events. There are a variety of specific causes of renal failure in each of these categories. For example, hypovolemia due to inadequate circulating blood volume is the most common cause of so-called prerenal azotemia. The term prerenal refers to the origin of the pathogenic process (i.e., before the kidney), since it is the decreased circulating blood volume that leads to inadequate perfusion of the kidneys and resultant kidney failure. The term azotemia refers to nitrogenous substances in the blood that accumulate due to impaired elimina

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Table II. Causes of hyperkalemia Category Diet Diseases Drugs

Major examples Intake of fluids or foods containing potassium, salt substitutes Acidosis, adrenal insufficiency, renal dysfunction, rhabdomyolysis ACE inhibitors, cyclosporine, NSAIDS, potassiumsparing diuretics, potassium supplements, trimethoprim

tion by the kidneys. Nephrotoxic medications such as aminoglycoside antimicrobials and radiocontrast agents are common causes of intrinsic renal failure, while obstructive processes (e.g., prostate cancer or hypertrophy) are the most common postrenal causes. While a complete delineation of the causes and diagnosis of acute renal failure is beyond the scope of this discussion, this information can be found in published literature(2). CONSEQUENCES OF ACUTE RENAL FAILURE Regardless of the cause, the disruption of normal renal function is responsible for a progressive set of events that can ultimately affect every major organ system in the body, particularly if it converts into chronic renal insufficiency followed by endstage renal failure(3). In one study, the mortality rate for hospitalized patients was much higher in patients with acute renal failure compared to matched patients without this problem (34 versus seven percent, respectively, P