Acute Renal Failure – Pre-Renal Causes
Pre-renal acute renal failure (ARF) is the result of decreased filtration through the glomerulus, leading to an elevation in the patient’s creatinine and, if severe enough, dysregulation of electrolyte and fluid homeostasis. Approximately 20% of hospitalized patients will experience some type of ARF, and 20% of those cases will be pre-renal. Other causes of ARF are post-renal/obstructive and intrinsic renal disease.
II. Diagnostic Approach.
A. What is the differential diagnosis for this problem?
A number of conditions lead to decreased renal perfusion and subsequent pre-renal ARF, including intravascular volume depletion, decreased cardiac output, systemic vasodilation, and macrovascular and microvascular kidney-level alterations in blood flow.
Intravascular volume depletion is the most common cause of pre-renal failure. Intravascular volume depletion can be the result of poor oral intake or excessive fluid loss. Causes of fluid loss include diarrhea, vomiting, excessive sweating, excessive urination (possibly caused by diuretics), hemorrhage, and pancreatitis; these patients usually appear to be generally volume depleted. In other cases of intravascular volume depletion patients may appear clinically volume overloaded while still suffering from ineffective circulating volume. Disease states that result in ineffective circulating volume include cirrhosis, congestive heart failure, and hypoalbuminemia.
Congestive heart failure also contributes to decreased glomerular filtration because of its associated decreased cardiac output. Similarly, other conditions that cause decreased cardiac output can also cause pre-renal ARF. These conditions include acute myocardial infarction, valvular heart disease, pulmonary embolism, abdominal compartment syndrome, and renal artery obstruction.
Pre-renal ARF can also be caused by systemic vasodilation, as in cases of hypotension and shock. This includes medication-induced hypotension, distributive shock from sepsis or anaphylaxis, hemorrhagic shock from trauma, severe gastrointestinal bleeding or internal hemorrhage, neurogenic shock, obstructive shock from cardiac tamponade, and tension pneumothorax.
Obstruction to flow through the kidney can occur at a more local level. Macrovascular obstruction of flow occurs in renal artery stenosis from atherosclerosis, fibromuscular dysplasia, and vasculitis. Obstruction at the microvascular level is almost exclusively medication-induced. Medications that induce afferent arteriolar vasoconstriction include non-steroidal anti-inflammatory drugs, calcineurin inhibitors (cyclosporine, tacrolimus, sirolimus), amphotericin B, aminoglycosides, norepinephrine, and radiocontrast agents. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers can also lead to pre-renal ARF by causing blood flow to bypass the glomerulus through efferent arteriolar vasodilation.
B. Describe a diagnostic approach/method to the patient with this problem.
Acute renal failure regardless of the etiology is categorized by the RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease) and is determined by change in the patient’s baseline creatinine and urine output (See Figure 1). A reasonable diagnostic approach is to first rule out pre-renal or post-renal causes of ARF before performing a more complex evaluation for intrarenal causes.
1. Historical information important in the diagnosis of this problem.
Mild AKI can be asymptomatic, though patients more often will present with non-specific complaints including nausea, anorexia, and weakness.
Assess for signs of volume depletion from decreased oral intake, diarrhea, vomiting, excessive sweating, or excessive urination. Causes of distributive shock such as sepsis and anaphylaxis should be assessed with other causes of shock such as neurogenic, obstructive, and hemorrhagic usually clinically evident.
A thorough review of the patient’s medical history and medication list should be done, particularly with regard to the presence of congestive heart failure, cirrhosis, or hypoalbuminemia and looking specifically for the medications listed above.
2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
Vital signs may show hypotension and tachycardia. Orthostatics may be positive. Dry mucus membranes and decreased skin turgor on the forehead or back of the hand may be seen, although these signs are not sensitive except in elderly patients.
Diseases that result ineffective circulating volume, such as congestive heart failure and cirrhosis, will result in dependent edema in the decompensated state.
Macrovascular obstruction of the renal arteries can result in audible abdominal bruits ausculated just inferior to the costal margin and 5cm lateral to the midline. These patients may also have hypertension resistant to multiple medications.
3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
All patients with concern for ARF should have a basic metabolic panel performed, including measurement of magnesium and phosphorus, as well as a complete blood count with differential to assess for signs of sepsis. A urinalysis should be ordered as this will help distinguish between pre-renal or post-renal/obstructive ARF and intrinsic causes; a normal urinalysis suggests a pre-renal or post-renal etiology.
Urine electrolytes (specifically sodium and creatinine) should be measured to allow for the calculation of the fractional excretion of sodium (FENa). Since it was initially studied in the mid-1970s, the FENa has been the standard method to evaluate whether ARF is due to a pre-renal or intrinsic renal cause. The FENa is a simple calculation (See Figure 2). A FENa of <1% suggests a pre-renal cause, while >3% suggests an intrinsic renal cause. It is important to note that, strictly speaking, this rule only applies to patients with oliguric renal failure (urine output < 400 ml/day) where obstruction has been ruled out (usually by ultrasound or bladder scan), as that is how it was originally studied.
The FENa test is confounded by certain disease states and medications (See Figure 3) with the most common being medications that affect natriuresis including diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone agonist or antagonists. When there are confounders to the fractional excretions of sodium, the fractional excretion of urea can be used as a surrogate since it is also reflective of water conservation by the body. This calculation uses the same formula as FENa but substitutes urea values in serum and urine in place of sodium. Values below 35% suggest pre-renal cause of renal failure and those above 55% suggest an intrinsic renal cause.
C. Criteria for Diagnosing Each Diagnosis in the Method Above.
The RIFLE criteria should be applied to a patient with suspected of acute renal failure to determine the degree of acute kidney injury and whether or not the patient is oliguric or not. The next step should be take a good history and determine if the patient is at risk for potential causes of pre-renal failure and if their physical exam supports one of these potential diagnosis. If the history and physical are suggestive of one of the low circulating volume states, empiric treatment with volume repletion can be initiated without further diagnostic tests.
D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.
When a patient’s clinical picture suggests pre-renal ARF and the renal function improves with fluid resuscitation, further diagnostic testing, including renal imaging and renal biopsy, is unnecessary.
III. Management while the Diagnostic Process is Proceeding.
A. Management of Clinical Problem Pre-renal Acute Renal Failure.
Pre-renal failure is never in itself life-threatening, and as an isolated condition it can usually be easily corrected with the administration isotonic intravenous fluids. Administration of one liter of normal saline should improve the patient’s renal function if the cause if partially pre-renal, although more than one liter is often necessary.
The one exception to the immediate administration of fluids is the ineffective circulating volume state of right sided or left sided congestive heart failure where volume resuscitation could exacerbate the patient’s clinical condition. In these cases the goal should be optimization of cardiac output over fluid resuscitation.
In all cases of ARF, potentially offending medications should be held until the kidney function begins to show improvement.
B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.
There are a few common pitfalls in the evaluation and management of pre-renal failure. Since the patient’s volume status is not always clinically clear in ineffective circulating volume states, there may be times where the decision between diuresis and volume resuscitation is difficult. If a patient has received more than a liter of isotonic intravenous fluids and the creatinine has not decreased, you can probably conclude that this is not isolated pre-renal failure due to a low circulating volume, although this has not been well studied. Reliance on the FENa should also not supersede good clinical judgement given its poor specificity and many potential confounders.
IV. What's the evidence?
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Molitoris,, B.A., Lee, Goldman and, Andrew, I., Schafer,. “Acute Kidney Injury.”. 2016. pp. 778-783.
Shah,, S.R.,, Tunio,, S.A.,, Arshad,, M.H.,, Moazzam,, Z.,, Noorani,, K.,, Feroze,, A.M.,, Shafquat,, M.,, Hussain,, H.S.,, Jeoffrey, S.A.H.. “Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence.”. . vol. 8,. 2016. pp. 120-124.
Singri, N,, Ahya, SN,, Levin, ML.. “Acute renal failure.”. JAMA.. vol. 289. 2003. pp. 747-51.
Ostermann, M,, Chang, R.. “Challenges of defining acute kidney injury.”. Q J Med. vol. 104. 2011. pp. 237e43
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- Acute Renal Failure - Pre-Renal Causes
- I. Problem/Condition.
- II. Diagnostic Approach.
- A. What is the differential diagnosis for this problem?
- B. Describe a diagnostic approach/method to the patient with this problem.
- 1. Historical information important in the diagnosis of this problem.
- 2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
- 3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
- C. Criteria for Diagnosing Each Diagnosis in the Method Above.
- D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.
- III. Management while the Diagnostic Process is Proceeding.
- A. Management of Clinical Problem Pre-renal Acute Renal Failure.
- B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.