Abstract
Initial management of acute kidney injury (AKI) includes timely recognition of the problem and correction of the underlying cause. Once established, management focuses on preventing extension of kidney injury and providing supportive care. Several modes of renal replacement therapy are used in severe AKI, including peritoneal dialysis, continuous renal replacement therapy, intermittent hemodialysis (IHD) prescribed in a conventional manner, and prolonged IHD or hemodiafiltration.
Keywords
acute kidney injury, creatinine, dialysis, diuretics, intravenous fluids, nephrotoxicity, renal replacement therapy, volume status
Acute kidney injury (AKI) is defined by a decline in kidney function or reduction in urine output occurring over hours to days. It is associated with prolonged hospitalization, substantial resource utilization, high mortality, and progressive chronic kidney disease (CKD) and end-stage renal disease (ESRD) in survivors. The principles of management of AKI include timely recognition of the problem, identification and correction of the underlying cause, and steps to avoid further kidney injury. After AKI is established, current therapeutic options are limited, and mortality remains high despite recent technologic advancements. Nonetheless, regional and temporal variations in mortality among patients hospitalized for AKI suggest that several elements of management, including supportive care, management of complications, and use of renal replacement therapy (RRT), may influence outcomes. This chapter focuses on the management of early or established AKI resulting from prerenal causes or acute tubular necrosis (ATN), which contribute to the majority of cases encountered in hospitalized patients. Readers are referred elsewhere in the Primer for a review of specific aspects of treatment for acute interstitial nephritis, glomerulonephritis, urinary obstruction, and systemic diseases involving the kidney.
Initial Recognition and Early Management
Timely detection and recognition of AKI is desirable because it can allow for prompt implementation of interventions to abort kidney damage and to avoid the development of severe kidney injury and its complications ( Box 34.1 ). AKI is usually identified based on an increase in serum creatinine; however, creatinine is an insensitive early marker of changes in kidney function, and AKI may develop before such changes become apparent. Furthermore, small changes in serum creatinine early in the course of AKI may not be readily appreciated, even though they can represent large changes in the glomerular filtration rate (GFR). Oliguria or anuria is an important sign that can identify AKI before changes in serum creatinine become apparent. Several novel biomarkers for AKI have been identified in recent years, including kidney injury molecule-1 (KIM-1), neutrophil gelatinase–associated lipocalin (NGAL), interleukin-18 (IL-18), and cystatin C, which may identify a decline in GFR or kidney damage earlier, and be more sensitive than changes in serum creatinine or urine output. However, these tests are not yet widely used in clinical practice, and their appropriate role in guiding management of patients with or at risk for AKI remains to be defined. Automated alerts for AKI based on serum creatinine or urine output changes are becoming increasingly common in electronic laboratory and medical record systems; however, whether these alerting systems improve processes of care and outcomes of AKI remains controversial.
- •
Timely recognition of changes in urine output or kidney function
- •
Identification and reversal of underlying cause (guided by urinalysis)
- •
Correction of prerenal states and maintenance of hemodynamic stability
- •
Exclusion of postrenal causes (risk factors include history of hydronephrosis, recurrent UTIs, diagnoses consistent with obstruction, and absence of other identifiable causes such as prerenal states, heart failure, or exposure to nephrotoxic medications)
- •
Avoidance of nephrotoxic agents, if possible, and adjustment of medications to doses appropriate for level of kidney function
- •
Provision of supportive care, including nutrition and medical interventions to maintain fluid, electrolyte, and acid-base balance
- •
Initiation of renal replacement therapy when needed
- •
Assessment for recovery of kidney function, and follow-up to assess for development or progression of chronic kidney disease
UTI, Urinary tract infection.
After AKI has been identified, further clinical assessment, investigation, and intervention typically proceed simultaneously. A thorough history and examination are required to identify potential causes of AKI. Ischemia, sepsis, and exposure to nephrotoxic agents are the most common causes of AKI in hospitalized patients. A search for prerenal and postrenal causes should be performed because their correction can lead to rapid recovery of kidney function. A number of urine studies have been described to distinguish prerenal AKI from ATN, including the urine sodium concentration, fractional excretion of sodium, and fractional excretion of urea. Unfortunately, all of these tests have limitations in their diagnostic performance, and interpretation is dependent on the clinical context. Clinical examination to assess volume status remains an important aspect of early management. AKI due to hypovolemia may be rapidly reversed by the administration of intravenous fluids. Volume status should be frequently reassessed to determine the response to intravenous fluids and to avoid volume overload. Stopping medications that impair glomerular filtration, including nonsteroidal antiinflammatory drugs (NSAIDs), diuretics (when there is volume depletion), and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), when appropriate, can help reverse kidney dysfunction, especially in the setting of low effective arterial blood volume. Drugs that cause direct nephrotoxicity, such as aminoglycosides and intravenous radiocontrast, should be used cautiously or avoided, if possible. Selected use of kidney ultrasound is useful for identifying hydroureter and/or hydronephrosis, indicative of a postrenal cause. Lower urinary tract obstruction can be identified and treated by bladder catheterization showing a large postvoid residual urine volume, whereas nephrostomy tubes or ureteric stents can be used to treat upper urinary tract obstruction.
Urinalysis and urine microscopy provide important information about intrinsic kidney causes of AKI. Hematuria and proteinuria should prompt further investigations for causes of glomerulonephritis, whereas white bloods cell casts should prompt a careful assessment for causes of interstitial nephritis, including a review of medication exposures. The findings of granular casts and/or renal tubular epithelial cells are associated with an increased likelihood of ATN and help predict patients at highest risk for worsening kidney function, the requirement for RRT, or death.
Supportive Care and Medical Management of Complications
After AKI is established, management focuses on preventing extension of kidney injury and providing supportive care while awaiting kidney recovery. Attempts are usually made to avoid further exposure to nephrotoxic agents to the greatest extent possible, without compromising management of other comorbidities. Doses of medications cleared by the kidney should be adjusted for the level of kidney function. This can be particularly important for antimicrobial agents so as to maintain appropriate therapeutic levels in patients with sepsis, while avoiding drug toxicity. The involvement of a clinical pharmacist may be helpful. Some observational reports suggest that computerized decision support tools in medication order entry systems may reduce adverse drug safety events in patients with AKI.
Supportive care in patients with AKI requires maintenance of fluid, electrolyte, and acid-base balance. Disorders of sodium and water handling, metabolic acidosis, and hyperkalemia are common complications of AKI. Hyponatremia may result from impaired free water excretion, whereas hypernatremia is common in patients with inadequate free water intake, hypotonic fluid losses, or large-volume intravenous saline infusions for resuscitation. These abnormalities may be corrected by modifying free water intake or the composition of intravenous fluids. Acid generation can be reduced by dietary protein restriction, although this may be undesirable in hypercatabolic patients. Alkaline intravenous fluids, such as sodium bicarbonate, may be provided to correct metabolic acidosis, although volume overload and pulmonary edema may limit this intervention. Hyperkalemia should be treated by discontinuing exogenous sources of potassium. In the presence of electrocardiogram (EKG) changes, calcium gluconate may be administered. Beta-agonists, insulin, and sodium bicarbonate can shift potassium out of the plasma and into cells. Attempts to eliminate potassium through the gastrointestinal tract with ion exchange resins may be used; however, these agents are slow to take effect, have limited efficacy, have been associated with bowel necrosis or perforation, and are unlikely to be adequate in patients with severe hyperkalemia. When medical management of these abnormalities is unsuccessful, or medical interventions cannot be tolerated by the patient, RRT is usually necessary unless recovery of kidney function is imminent.
Intravenous Fluids and Hemodynamic Support
Hypotension is a common contributor to AKI, and after AKI is established, kidney perfusion may be further diminished through disruption of renal autoregulation. Early correction of hypovolemia and hypotension not only reverses most prerenal causes of AKI but also likely prevents extension and allows recovery from ATN. Strategies to maintain hemodynamic stability include the use of intravenous fluids, vasopressors/inotropic medications, and protocols for hemodynamic monitoring to guide the use of these therapies. Although more aggressive use of intravenous fluids in the initial phase of illness may be beneficial when AKI is volume responsive, excessive fluid repletion in oliguric patients with established ATN can have adverse effects. A positive fluid balance has been associated with increased mortality in observational studies. A restrictive fluid strategy may be more appropriate in some patients, particularly those with concomitant lung injury.
Isotonic crystalloids are the principal intravenous fluid for intravascular volume expansion of AKI patients. Normal (0.9%) saline is considered the standard crystalloid for most patients. Results from some observational studies have introduced concerns that the high chloride concentration of normal saline could itself confer a risk of AKI. However, a recent cluster randomized crossover trial comparing buffered crystalloid solution to normal saline did not detect a difference in AKI incidence in critically ill patients requiring crystalloid therapy. Colloid solutions such as albumin and starches are theoretically attractive alternatives for intravenous volume expansion, given their oncotic properties, but their appropriate use remains controversial. No differences in the incidence or duration of RRT were observed in a randomized trial of critically ill patients, comparing treatment with 4% albumin in 0.9% saline with isotonic saline alone. However, a systematic review of randomized trials suggested that the use of hyperoncotic albumin solutions may reduce the risk of AKI and be appropriate for some patients, including those with ascites, spontaneous bacterial peritonitis, or burns, or following surgery. Hydroxyethyl starch is an alternative colloid solution; however, when compared with crystalloids, hyperoncotic hydroxyethyl starch has been associated with a higher incidence of AKI, dialysis, and features of renal tubular injury (termed osmotic nephrosis ) on kidney biopsy, suggesting these solutions may be harmful. Because colloids do not consistently reduce mortality when compared with crystalloids across all populations who are at high risk of AKI, these solutions are usually reserved for selected indications and avoided in patients with traumatic brain injury, where use has been associated with increased mortality.
Shock is a common contributor to AKI in patients with sepsis, anaphylaxis, liver failure, and burns. Appropriate fluid resuscitation remains of paramount importance in patients with AKI accompanied by these conditions, as well as those undergoing major surgical procedures. Vasopressors such as norepinephrine, dopamine, or vasopressin may be required when hypotension persists despite intravascular fluid resuscitation. Several early randomized trials using management strategies that focused on achieving specific hemodynamic and oxygenation parameters (e.g., early provision of intravenous fluids, blood transfusion, vasopressors, or inotropes based on specific goals for blood pressure, central venous pressure, serum lactate, central venous oxygen saturation, and urine output) reported improved outcomes in high-risk surgical patients or patients with septic shock. However, more recent trials of goal-directed therapeutic interventions have not replicated these findings. The need for administration of additional therapies such as blood transfusions and inotropes is typically individualized to a patient’s conditions when shock is refractory to initial management with intravenous fluids and vasopressors.
Diuretics
Oliguria has long been recognized as an important prognostic sign in AKI. The diuretic response to furosemide was recently formalized as a prognostic test for AKI, coined the “furosemide stress test,” a procedure involving the administration of 1 to 1.5 mg/kg of furosemide. Failure to produce a urine output greater than 200 mL over the subsequent 2 hours outperformed several laboratory biomarkers for predicting progressive AKI. Diuretics can induce hypovolemia, leading to prerenal AKI, and their use has been associated with increased mortality and delays in kidney recovery in observational studies. However, when volume overload is present, diuretics are often prescribed to control fluid balance. Systematic review of trials that included patients with or at risk for AKI found no significant effects of furosemide on the risks of death, requirement for RRT, or number of dialysis sessions. Although furosemide facilitates diuresis, use of diuretics does not appear to improve kidney recovery among patients with AKI requiring dialysis. Nonetheless, diuretics can be used effectively to achieve fluid balance and may facilitate mechanical ventilation and improved outcomes in patients with lung injury.
Vasodilators and Other Pharmacologic Agents
Several pharmacologic agents with renal vasodilatory properties have been studied, with the aim of increasing renal blood flow and ameliorating ischemic damage in AKI. However, none of these agents are proven to improve the clinical outcomes of AKI. Low-dose dopamine is associated with increased renal blood flow, increased urine output, and small improvements in creatinine clearance. However, a systematic review of trials, including patients with or at risk for AKI, showed that low-dose dopamine had no significant effect on survival, need for dialysis, or adverse clinical events. Dopamine is associated with arrhythmias and intestinal ischemia and is not currently recommended to prevent or treat AKI. Fenoldopam is a dopamine type 1 receptor agonist that also increases renal blood flow, although it decreases systemic vascular resistance. A meta-analysis suggested promising results with the use of fenoldopam in critically ill patients, including reductions in AKI, need for RRT, and in-hospital mortality. However, given its risk of hypotension, along with limitations of the existing published trials, further trials are necessary to support the use of fenoldopam for this indication. Atrial natriuretic peptide (ANP) has favorable renovascular effects that increase the GFR in animals. However, large trials of ANP (0.2 µg/kg per minute) in critically ill patients with AKI showed no effects on mortality or dialysis-free survival but did show a higher incidence of hypotension. One systematic review has suggested that low-dose ANP (0.1 µg/kg per minute) is not associated with hypotension and may lead to a reduction in the requirement for RRT. Yet again, further large trials of low-dose ANP will be required before this agent can be recommended for AKI prevention or treatment.
There is inadequate efficacy and safety data to support the use of growth factors for AKI. Although insulin-like growth factor-1 showed promising results on recovery of kidney function in animals, small trials have failed to demonstrate beneficial results in humans. A small trial of erythropoietin for the prevention of AKI following cardiac surgery reported a reduction in incidence of AKI in treated patients; however, a subsequent trial in the intensive care unit (ICU) detected no effect.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
