Pharmacy Clinic
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ARF is defined as a precipitous decline in renal function over a relatively short period (ranging from several hours to
several weeks).
ARF is a failure of the kidneys to excrete nitrogenous wastes, and to maintain fluid, electrolytes and acid base
homeostasis
ARF is marked by a significant, rapid rise in serum creatinine (Scr) and urea nitrogen (BUN).
Oliguria (urine output <20 mL/hr)) often occurs in ARF
Non-oliguric ARF is not infrequent 50 – 60 % of the cases
ARF which develops during hospitalization is associated with a high mortality rate (~35%).
Cardiac complications, bleeding, and infections are the leading causes of death associated with ARF.
Conditions which precipitate ARF are usually classified as pre renal, renal (intrinsic), or post-renal
A pre-renal condition is characterized by a marked reduction in renal blood flow (renal hypoperfusion, decreased RBF)
which may be brought about by true ECF volume depletion (eg, severe diarrhea), hypotension, congestive heart
failure, or by a significant reduction in the effective circulating volume as in cirrhosis
Acute renal failure can present in all medical settings but is predominantly acquired in hospitals. The condition
develops in 5 percent of hospitalized patients, and approximately 0.5 percent of hospitalized patients require dialysis
In most cases of prerenal disease, re-hydration or plasma expansion leads to a relatively rapid improvement in renal
function (urine flow and Scr).
Prerenal ARF is characterized by;
oliguria
a BUN and Scr are high
a normal or nearly normal urinalysis
a relatively concentrated urine (Uosm > 500 mOsm/L)
and a low fractional Na excretion (<1% ) with UNa< 25 mEq/L.
a bland urine sediment
and a BUNtoserum creatinine ratio of greater than 20:1
Overview of blood urea nitrogen (BUN) and serum creatinine. Given the central role of BUN and serum creatinine in
determining the presence of renal failure, an understanding of the metabolism of these substances is needed. Urea
nitrogen derives from the breakdown of proteins that are delivered to the liver. Thus, the urea nitrogen production
rate can vary with exogenous protein intake and endogenous protein catabolism. Urea nitrogen is a small, uncharged
molecule that is not protein bound, and as such, it is readily filtered at the renal glomerulus. Urea nitrogen
undergoes renal tubular reabsorption by specific transporters. This tubular reabsorption limits the value of BUN as a
marker for glomerular filtration. However, the BUN usually correlates with the symptoms of uremia. By contrast, the
production of creatinine is usually more constant unless there has been a marked reduction of skeletal muscle mass
(eg, loss of a limb, prolonged starvation) or diffuse muscle injury.
Although creatinine undergoes secretion into renal tubular fluid, this is very modest
in degree. Thus, a steady-stable serum creatinine concentration is usually a relatively
good marker of glomerular filtration rate
The blood urea nitrogen (BUN)-creatinine ratio often deviates from the usual value of about 10:1. These deviations
may have modest diagnostic implications. As an example, for reasons as yet unclear, tubular reabsorption of urea
nitrogen is enhanced in low-urine flow states. Thus, a high BUN-creatinine ratio often occurs in prerenal and postrenal
forms of renal failure. Similarly, enhanced delivery of amino acids to the liver (as with catabolism, corticosteroids,
etc.) can enhance urea nitrogen formation and increase the BUN-creatinine ratio.
A BUN-creatinine ratio lower than 10:1 can occur because of decreased urea nitrogen formation (eg, in protein
malnutrition, advanced liver disease), enhanced creatinine formation (eg, with rhabdomyolysis), impaired tubular
secretion of creatinine (eg, secondary to trimethoprim, cimetidine), or relatively enhanced removal of the small
substance urea nitrogen by dialysis.
In patients with prerenal acute renal failure, the parenchyma is undamaged, and the kidneys respond as if volume
depletion has occurred. Thus, the kidneys avidly reabsorb sodium in order to reabsorb water.
Specific causes of a fractional excretion of sodium of less than 1 percent that are not the result of prerenal acute
renal failure include contrast nephropathy and pigment nephropathy.
Two instances of prerenal acute renal failure with a fractional excretion of sodium greater than 1 percent deserve
mention
First, patients receiving diuretics may truly have prerenal acute renal failure, but the fractional excretion of sodium
may be increased by diuretic-induced sodium excretion.
Second, patients with chronic renal insufficiency have impaired sodium reabsorption. Therefore, if they develop
prerenal acute renal failure, they may be unable to reabsorb enough sodium to have a less than 1 percent fractional
excretion of sodium.
Not all BUN and serum creatinine elevations result from acute renal failure. Cephalosporins and trimethoprim-
sulfamethoxazole (Bactrim, Septra) may cause acute renal failure as a result of interstitial disease, but these agents
sometimes cause elevated serum creatinine levels simply by inhibiting the tubular secretion of creatinine without
causing real damage to the kidneys. The BUN can be elevated in patients who are receiving corticosteroids, those with
increased catabolism or those with gastrointestinal tract bleeding.
Acute renal failure in patients with congestive heart failure occurs because of decreased renal blood flow. This
decrease is due to hypovolemia from overdiuresis or hypervolemia that causes elevated filling pressures of the left
ventricle and leads to decreased cardiac output.
Patients in the former group may respond to the discontinuation of diuretics and gentle hydration.
Patients in the latter group are treated with diuretics and may need inotropes and vasodilators. Invasive
hemodynamic monitoring may be required for fluid management.
The primary agents that cause prerenal acute renal failure are angiotensin-converting enzyme (ACE) inhibitors and
nonsteroidal anti-inflammatory drugs (NSAIDs).
The inhibition of ACE prevents the conversion of angiotensin I to angiotensin II, leading to decreased levels of
angiotensin II. Angiotensin II increases the glomerular filtration rate by causing constriction of the efferent arteriole;
its absence decreases the glomerular filtration rate because of dilatation of the efferent arteriole.
In certain patients (e.g., those with hypovolemia or bilateral renal artery stenosis), the glomerular filtration rate is
particularly dependent on the effects of angiotensin II. If these patients take an ACE inhibitor, their glomerular
filtration rate decreases, and prerenal acute renal failure can develop. Potassium, BUN and creatinine levels should
be obtained soon after patients start taking an ACE inhibitor. NSAIDs cause prerenal acute renal failure by blocking
prostaglandin production, which also alters local glomerular arteriolar perfusion.
Diminished renal blood flow causes ischemia in the renal parenchyma. If the ischemia is prolonged, acute tubular
necrosis may develop. Early restoration of renal blood flow should shorten the ischemic time and prevent
parenchymal injury. A response to the restoration of renal blood flow should occur in 24 to 48 hours. The keys to
therapy are treating the underlying disorder, maintaining euvolemia and eliminating offending agents.
several weeks).
ARF is a failure of the kidneys to excrete nitrogenous wastes, and to maintain fluid, electrolytes and acid base
homeostasis
ARF is marked by a significant, rapid rise in serum creatinine (Scr) and urea nitrogen (BUN).
Oliguria (urine output <20 mL/hr)) often occurs in ARF
Non-oliguric ARF is not infrequent 50 – 60 % of the cases
ARF which develops during hospitalization is associated with a high mortality rate (~35%).
Cardiac complications, bleeding, and infections are the leading causes of death associated with ARF.
Conditions which precipitate ARF are usually classified as pre renal, renal (intrinsic), or post-renal
A pre-renal condition is characterized by a marked reduction in renal blood flow (renal hypoperfusion, decreased RBF)
which may be brought about by true ECF volume depletion (eg, severe diarrhea), hypotension, congestive heart
failure, or by a significant reduction in the effective circulating volume as in cirrhosis
Acute renal failure can present in all medical settings but is predominantly acquired in hospitals. The condition
develops in 5 percent of hospitalized patients, and approximately 0.5 percent of hospitalized patients require dialysis
In most cases of prerenal disease, re-hydration or plasma expansion leads to a relatively rapid improvement in renal
function (urine flow and Scr).
Prerenal ARF is characterized by;
oliguria
a BUN and Scr are high
a normal or nearly normal urinalysis
a relatively concentrated urine (Uosm > 500 mOsm/L)
and a low fractional Na excretion (<1% ) with UNa< 25 mEq/L.
a bland urine sediment
and a BUNtoserum creatinine ratio of greater than 20:1
Overview of blood urea nitrogen (BUN) and serum creatinine. Given the central role of BUN and serum creatinine in
determining the presence of renal failure, an understanding of the metabolism of these substances is needed. Urea
nitrogen derives from the breakdown of proteins that are delivered to the liver. Thus, the urea nitrogen production
rate can vary with exogenous protein intake and endogenous protein catabolism. Urea nitrogen is a small, uncharged
molecule that is not protein bound, and as such, it is readily filtered at the renal glomerulus. Urea nitrogen
undergoes renal tubular reabsorption by specific transporters. This tubular reabsorption limits the value of BUN as a
marker for glomerular filtration. However, the BUN usually correlates with the symptoms of uremia. By contrast, the
production of creatinine is usually more constant unless there has been a marked reduction of skeletal muscle mass
(eg, loss of a limb, prolonged starvation) or diffuse muscle injury.
Although creatinine undergoes secretion into renal tubular fluid, this is very modest
in degree. Thus, a steady-stable serum creatinine concentration is usually a relatively
good marker of glomerular filtration rate
The blood urea nitrogen (BUN)-creatinine ratio often deviates from the usual value of about 10:1. These deviations
may have modest diagnostic implications. As an example, for reasons as yet unclear, tubular reabsorption of urea
nitrogen is enhanced in low-urine flow states. Thus, a high BUN-creatinine ratio often occurs in prerenal and postrenal
forms of renal failure. Similarly, enhanced delivery of amino acids to the liver (as with catabolism, corticosteroids,
etc.) can enhance urea nitrogen formation and increase the BUN-creatinine ratio.
A BUN-creatinine ratio lower than 10:1 can occur because of decreased urea nitrogen formation (eg, in protein
malnutrition, advanced liver disease), enhanced creatinine formation (eg, with rhabdomyolysis), impaired tubular
secretion of creatinine (eg, secondary to trimethoprim, cimetidine), or relatively enhanced removal of the small
substance urea nitrogen by dialysis.
In patients with prerenal acute renal failure, the parenchyma is undamaged, and the kidneys respond as if volume
depletion has occurred. Thus, the kidneys avidly reabsorb sodium in order to reabsorb water.
Specific causes of a fractional excretion of sodium of less than 1 percent that are not the result of prerenal acute
renal failure include contrast nephropathy and pigment nephropathy.
Two instances of prerenal acute renal failure with a fractional excretion of sodium greater than 1 percent deserve
mention
First, patients receiving diuretics may truly have prerenal acute renal failure, but the fractional excretion of sodium
may be increased by diuretic-induced sodium excretion.
Second, patients with chronic renal insufficiency have impaired sodium reabsorption. Therefore, if they develop
prerenal acute renal failure, they may be unable to reabsorb enough sodium to have a less than 1 percent fractional
excretion of sodium.
Not all BUN and serum creatinine elevations result from acute renal failure. Cephalosporins and trimethoprim-
sulfamethoxazole (Bactrim, Septra) may cause acute renal failure as a result of interstitial disease, but these agents
sometimes cause elevated serum creatinine levels simply by inhibiting the tubular secretion of creatinine without
causing real damage to the kidneys. The BUN can be elevated in patients who are receiving corticosteroids, those with
increased catabolism or those with gastrointestinal tract bleeding.
Acute renal failure in patients with congestive heart failure occurs because of decreased renal blood flow. This
decrease is due to hypovolemia from overdiuresis or hypervolemia that causes elevated filling pressures of the left
ventricle and leads to decreased cardiac output.
Patients in the former group may respond to the discontinuation of diuretics and gentle hydration.
Patients in the latter group are treated with diuretics and may need inotropes and vasodilators. Invasive
hemodynamic monitoring may be required for fluid management.
The primary agents that cause prerenal acute renal failure are angiotensin-converting enzyme (ACE) inhibitors and
nonsteroidal anti-inflammatory drugs (NSAIDs).
The inhibition of ACE prevents the conversion of angiotensin I to angiotensin II, leading to decreased levels of
angiotensin II. Angiotensin II increases the glomerular filtration rate by causing constriction of the efferent arteriole;
its absence decreases the glomerular filtration rate because of dilatation of the efferent arteriole.
In certain patients (e.g., those with hypovolemia or bilateral renal artery stenosis), the glomerular filtration rate is
particularly dependent on the effects of angiotensin II. If these patients take an ACE inhibitor, their glomerular
filtration rate decreases, and prerenal acute renal failure can develop. Potassium, BUN and creatinine levels should
be obtained soon after patients start taking an ACE inhibitor. NSAIDs cause prerenal acute renal failure by blocking
prostaglandin production, which also alters local glomerular arteriolar perfusion.
Diminished renal blood flow causes ischemia in the renal parenchyma. If the ischemia is prolonged, acute tubular
necrosis may develop. Early restoration of renal blood flow should shorten the ischemic time and prevent
parenchymal injury. A response to the restoration of renal blood flow should occur in 24 to 48 hours. The keys to
therapy are treating the underlying disorder, maintaining euvolemia and eliminating offending agents.
Acute Renal Failure
Go to Chronic Renal Failure
Go to Drug Dosing in Renal Failure
Go to Dialysis
Lab values
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Go to Drug Dosing in Renal Failure
Go to Dialysis
Lab values
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