General therapeutic considerations in patients with acute renal failure

American Journal of Pharmaceutical Education,  Summer 1999  by Erstad, Brian L

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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 medications 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.

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) 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 elimination 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

PREVENTION OF ACUTE RENAL FAILURE

A number of commercially-available agents have shown promise in experimental studies of renal failure in animal models including vasoactive agents such as clonidine, diuretic agents such as furosemide, oxygen free radical scavengers such as dimethyl sulfoxide, and rheologic drugs such as pentoxifylline. Other vasoactive medications (dopamine, calcium channel blockers, and more recently fenoldopam) that act through a variety of mechanisms have been used in patients in the early stages of renal dysfunction in the clinical setting. While such agents may increase urine output, glomerular filtration, or renal blood flow, they have not been shown in controlled trials to prevent acute renal failure from occurring. Investigational therapies that have shown promise include growth factors, and agents used to enhance cell energetics(6). Whether these positive findings will be confirmed in patients presenting in various stages of acute renal failure has yet to be determined for most of the products under study. The majority of agents demonstrating benefits were given before or shortly after the induction of renal failure in tightly-controlled experimental settings. This is not possible in many patients with more advanced disease. Never-the-less, medications such as the loop diuretics (e.g., furosemide, ethacrynic acid, bumetanide) are commonly used, once plasma volume has been optimized, to convert a patient with oliguric to nonoliguric renal insufficiency. The nonoliguric form of renal insufficiency is associated with an improved prognosis. However, it is important to realize once a patient has established renal failure, there is no pharmacologic agent that has been shown to reverse the course of the disease(7).