ARF (Acute

Renal Failure)
Clinical Pharmacy II and Pharmacotherapeutics
(PHP006)
Department of Pharmacy Practice
Definitions and
Background

1. AKI is defined as an
acute decrease in kidney
function or GFR over
hours, days, or even
weeks and is associated
with an accumulation of
waste products and
(usually) volume.
 2. Criteria and classification of AKI
a. Definition of AKI according to KDIGO
i. Increase in SCr of 0.3 mg/dL
or more within 48 hours; or

ii. Increase in SCr to 1.5 times baseline or more

(baseline known or presumed within prior 7 days); or

iii. Urinary volume less than 0.5

mL/kg/hour for at least 6 hours.
 b. Urinary output classification

i. Anuric: Less than 50 mL/24 hours; associated with

worse outcomes

ii. Oliguric: Less than 0.5 mL/kg/hour for 12 hours or

more

iii. Nonoliguric: More than 500 mL/24 hours;

associated with better patient outcomes and easier
to manage because of fewer problems with volume
overload.
 Risk factors for ARF:
Being hospitalized,
especially for a
Peripheral
serious condition Advanced age
artery disease
that requires
intensive care

Kidney
Diabetes Hypertension Heart failure
diseases

Liver diseases
 Diagnosis
Patient History Medication History

Clinical Presentation (symptoms, signs)

physical examination, laboratory values,

diagnostic procedures (signs)
 Diagnosis and Work up
1- Signs and Symptoms of AKI
• Peripheral edema signs
• Weight gain
• Nausea, vomiting, diarrhea, anorexia
• Mental status changes
• Fatigue
• Shortness of breath
• Pruritus
• Volume depletion (prerenal AKI) signs
• Weight loss (prerenal AKI)
• Anuria alternating with polyuria (postrenal AKI)
• Colicky abdominal pain radiating from flank to groin (postrenal AKI)
 Diagnosis (Cont.)
2- Physical Examination Findings (Signs)
• Increased blood pressure
• Jugular venous distention (JVD)
• Pulmonary edema
• Rales
• Asterixis
• Pericardial or pleural friction rub
• Hypotension or orthostatic hypotension (prerenal AKI)
• Rash (intrinsic AKI due to acute interstitial nephritis)
• Bladder distention (postrenal bladder outlet obstruction)
• Prostatic enlargement (postrenal AKI)
 Diagnosis (Cont.)
3- Laboratory Tests (Signs)
• Elevated SCr (reference range approximately 0.6–1.2 mg/dL)
• Elevated BUN (reference range approximately 8 to 25 mg/dL)
• BUN-to-creatinine ratio greater than 20:1 for units of mg/dL
(prerenal AKI); less than 20:1 for units of mg/dL (intrinsic or
postrenal AKI)
• Hyperkalemia
• Metabolic acidosis
 Diagnosis (Cont.)
4- Urinalysis (Sediment) (Signs)
• Scant or bland (prerenal or postrenal AKI)
• Brown, muddy granular casts (intrinsic ATN)
• Proteinuria (glomerulonephritis or allergic interstitial nephritis)
• Eosinophiluria (acute interstitial nephritis)
• Hematuria or red blood cell casts (glomerular disease or bleeding in
urinary tract)
• WBCs or casts (acute interstitial nephritis or severe pyelonephritis)
 Treatment
Treatment Goals
maintain a state of euvolemia with good
urine output (at least 1 mL/kg/hour),

return SCr to baseline,

correct electrolyte and acid-base

abnormalities.
appropriate drug dosages based on kidney
function and avoidance of nephrotoxic drugs.
 Treatment (Cont.)
Pharmacologic Therapy
»» Loop Diuretics
• Most studies evaluating loop diuretics (furosemide, bumetanide,
torsemide, and ethacrynic acid) for prevention or treatment of AKI
demonstrate improved urine output but no effect on survival or need
for dialysis.
• There are some reports that loop diuretics may worsen kidney
function and may be due in part to preload reduction that results in
renal vasoconstriction.
• Thus, loop diuretics should be reserved for the treatment of volume
overload and should not be given to prevent AKI or hasten recovery
of kidney function in euvolemic or hypovolemic individuals.
 Treatment (Cont.)
● Several adaptive mechanisms by
the kidney limit effectiveness of
loop diuretic therapy. As the
concentration of diuretic in the
loop of Henle decreases,
postdiuretic sodium retention
can occur. This effect can be
minimized by decreasing the
dosage interval (ie, dosing more
frequently) or by administering a
continuous infusion.
 Treatment (Cont.)
How to Avoid?
● Precautions regarding loop diuretic use:
Avoidance could
1- Prolonged administration of loop diuretics can lead to be achieved
a second type of diuretic resistance. through
2- Hypertrophy of distal convoluted tubule cells can administration of
the distal
occur secondary to enhanced delivery of sodium to the convoluted tubule
distal tubule. Subsequently, increased sodium chloride diuretic 30 to 60
absorption occurs in the distal tubule, which diminishes minutes prior to
the effect of the loop diuretic on overall sodium the loop diuretic in
an attempt to
excretion. inhibit sodium
3- Addition of a distal convoluted tubule diuretic, such as reabsorption at
metolazone or hydrochlorothiazide, to a loop diuretic the distal
can result in a synergistic increase in urine output. convoluted tubule.
 Treatment (Cont.)
• Thiazide diuretics, when used as single agents, are generally not
effective for fluid removal.
• Mannitol is also not recommended for treating volume overload
associated with AKI. In patients with renal dysfunction, mannitol
excretion is decreased, resulting in expanded blood volume and
hyperosmolality.
• Potassium sparing diuretics, which inhibit sodium reabsorption in the
distal nephron and collecting duct, are not sufficiently effective in
removing fluid. In addition, they increase the risk of hyperkalemia in
patients already at risk.
• Thus loop diuretics are the diuretics of choice for managing volume
overload in AKI.
 Treatment (Cont.)
• Based on the lack of conclusive evidence, there is no indication for use
of low dose dopamine in treating the AKI.
• Fenoldopam, a selective dopamine-1 receptor agonist approved for
short-term management of severe hypertension, has also been
studied for prevention and treatment of AKI. No data conclusively
support its use, and the risk of hypotension further limits routine
administration.
• Studies are underway to investigate the utility of atrial natriuretic
peptide, a hormone secreted by the heart that generates sodium
loss, in prevention or early treatment of AKI.
 Treatment (Cont.)
We recommend not using diuretics to prevent AKI (Grade 1B).

We suggest not using diuretics to treat AKI, except in the

management of volume overload (Grade 2C).
We recommend not using low-dose dopamine to prevent or treat AKI
(Grade 1A).

We suggest not using fenoldopam to prevent or treat AKI (Grade 2C).

We suggest not using ANP to prevent (Grade 2C) or treat (Grade 2B)
AKI.
 Treatment (Cont.)

We suggest achieving a total energy intake of 20 to 30 kcal/kg/day in

patients with any stage of AKI (Grade 2C).

We suggest avoiding restriction of protein intake with the aim of

preventing or delaying initiation of RRT (Grade 2D).

We suggest administering 0.8 to 1.0 g/kg/day protein in noncatabolic AKI

patients without need for dialysis (Grade 2D), 1.0 to 1.5 g/kg/day in
patients with AKI on RRT (Grade 2D).
 Treatment (Cont.)
• Nonpharmacologic Treatment:
»» Renal Replacement Therapy
• RRT in the form of dialysis may be necessary in patients with
established AKI to treat volume overload that is unresponsive to
diuretics, to minimize accumulation of nitrogenous waste products,
and to correct electrolyte and acid–base abnormalities while renal
function recovers. There is wide variation in practice on indications
for RRT, timing of initiation and discontinuation of RRT, intensity of
treatment, and optimal type of RRT.
• Absolute indications for dialysis usually include:
• BUN greater than 100 mg/dL (35.7 mmol/L)
• Potassium greater than 6 mEq/L (6 mmol/L)
• Magnesium greater than 9.7 mg/dL (4.0 mmol/L)
• Metabolic acidosis with a pH less than 7.15
• Diuretic-resistant fluid overload
• Supportive Therapy
• Supportive therapy in AKI includes adequate
nutrition, correction of electrolyte and acid–
base abnormalities (particularly
hyperkalemia and metabolic acidosis), fluid
management, and correction of any
hematologic abnormalities.
• Because AKI can be associated with
multiorgan failure, treatment may include
the medical management of infections,
cardiovascular and GI conditions, and
respiratory failure.
Management of complications
Management Complication

•Calcium gluconate (10-20 ml of 10% sol) Hyperkalemia

•Insulin + glucose 10 U + 50 ML 50% GLUCOSE
•Beta 2 agonist(salbutamol) 10-20 MG NEUBILIZER
•ion exchange resin
•hemodialysis

❖IV or oral sodium bicarbonate Acidosis

❖Hemodialysis if severe acidosis < 7.15
 Treatment (Cont.)
1. Prerenal azotemia: Correct primary hemodynamics.
a. Intravenous normal saline, lactated Ringer solution or other
balanced crystalloid, if volume depleted.
b. Blood pressure management, if needed
c. Blood products, if needed
d. Hold or discontinue medications that affect renal hemodynamics
(i.e., ACEIs, ARBs, NSAIDs).
 Treatment (Cont.)
Intrinsic: No specific therapy universally effective
a. Eliminate the causative hemodynamic abnormality or toxin.
b. Avoid additional insults.
c. Manage fluid and electrolytes to prevent volume depletion or overload
and electrolyte imbalances.
d. Nutrition support is important, but no specific recommendations are
widely accepted.
e. Medical therapy recommendations according to the KDIGO guidelines
i. Loop diuretics: Recommend not using to prevent AKI (grade 1B) and
suggest not using to treat AKI, except to manage hypervolemia (grade
2C)
ii. Therapeutic agents (e.g., dopamine, nesiritide, fenoldopam, mannitol)
are not indicated in AKI management and may be harmful for the patient.
 Case (1)
A 75-year-old man (height 73 inches, weight 92.5 kg) presents at your institution
with abdominal pain and dizziness. He has a brief history of gastroenteritis and
has had nothing to eat or drink (NPO) for 24 hours. His blood pressure reading
while sitting is 120/80 mm Hg, which drops to 90/60 mm Hg when standing. His
heart rate is 90 beats/minute. His basic metabolic panel shows sodium (Na) 135
mEq/L, chloride (Cl) 108 mEq/L, potassium (K) 4.7 mEq/L, carbon dioxide (CO2)
26 mEq/L, blood urea nitrogen (BUN) 40 mg/dL, serum creatinine (SCr) 1.5
mg/dL, and glucose 188 mg/dL. He has no known drug allergies.
Which is the best approach for treating this patient?
a) Administer furosemide 40 mg intravenously × 1 dose.
b) Insert Foley catheter to check for residual urine.
c) Administer fluid bolus (500 mL of normal saline solution).
d) Administer insulin lispro 3 units subcutaneously.
 Answer
Administer fluid bolus (500 mL of normal saline solution).
Initial treatment of AKI requires identifying and reversing (if possible) the
insult to the kidney. This patient’s symptoms and presentation are
consistent with prerenal azotemia because of volume depletion, making
fluid administration the best choice in this case (Answer C is correct). The
patient has no suggestion of obstruction (e.g., distended abdomen,
history of benign prostatic hypertrophy) (Answer B is incorrect). Diuretic
administration would be inappropriate because it would worsen his
volume depletion and probably further impair his kidney function (Answer
A is incorrect). Fluid management is critical to managing AKI, necessitating
a careful assessment of the patient. Although his glucose concentration is
elevated, insulin is not necessary at this time (Answer D is incorrect)
 Case (2)
A 48-year-old African American man (weight 70 kg) with a history of
type 2 diabetes, hypertension, and osteoarthritis
is admitted to the intensive care unit after an acute myocardial
infarction. He was initially hypotensive, requiring
3 L of intravenous fluid. His blood pressure is now 100/65 mm Hg.
Medications before admission include nicotine patch, metformin 500 mg
orally twice daily, lisinopril 20 mg/day, acetaminophen 650 mg every 6
hours for joint pain, and aspirin 81 mg/daily. Before admission, his
kidney function was normal (SCr 1.0 mg/dL); however, during the past
24 hours, his kidney function has declined (BUN 20 mg/dL, SCr 2.1
mg/dL). Serum sodium is 140 mEq/L and serum potassium is 4.4 mEq/L.
Urinary volume has been 300 mL over the past 12 hours through urinary
catheter.
His urine shows muddy casts. His urinary sodium is 45 mEq/L and
urinary creatinine is 20 mg/dL. He has edema
and pulmonary congestion.
1) Which is the best assessment of this patient’s
AKI? Answer
1. Answer: B
This patient has AKI on the basis of either the increase in SCr of greater than 0.3
mg/dL in the past 24 hours or the decrease in urinary output of less than 0.5
mL/kg/ hour (Answer D is incorrect). The patient’s SCr concentration has
increased by more than 1.9 times baseline, so it is not stage 1 (Answer A is
incorrect). The SCr concentration has not increased more than 3 times
baseline or achieved a concentration of greater than 4 mg/ dL, and the
patient has not required RRT, so it should not be classified as stage 3 (Answer
C is incorrect). His urinary output of greater than 0.3 mL/kg/hour is also not
consistent with stage 3 AKI. The increase in SCr of 2.0–2.9 times baseline and
the patient’s urinary output of less than 0.5 mL/kg/hour for more than 12
hours are both consistent with stage 2 AKI (Answer B is correct).
B. KDIGO stage 2 AKI.
2) Which best depicts this patient’s FENa?
Answer
2. Answer: D
Fractional excretion of sodium can help distinguish prerenal AKI from
intrinsic AKI. This calculation requires both urinary and serum
concentrations of sodium and creatinine from a spot urine sample:
FENa = [(urinary sodium/serum sodium)/(urinary Cr/SCr)] × 100 =
[(45/140)/(20/2.1)] × 100 = 3.4% (Answer D is correct; Answers A–C
are incorrect). This is greater than 2% and is consistent with
decreased sodium reabsorption and increased renal sodium
excretion.
 3) Which is the best classification of this patient’s AKI?
B. Intrinsic renal disease. Answer
3. Answer: B
This patient has AKI, probably because of ATN, a type of intrinsic renal failure
(Answer B is correct). Hypotension despite rapid fluid resuscitation can
cause ATN. The rapid rise in SCr, the BUN/SCr ratio of about 10:1, and the
presence of muddy casts on urinalysis all suggest ATN. The FENa greater
than 2% is also consistent with intrinsic AKI. There is no evidence of
prerenal causes (volume depletion). The absence of an elevated BUN/SCr
ratio greater than 20:1 and absence of low urinary sodium and low FENa
are all suggest it is not prerenal AKI (Answer A is incorrect). Although azotemia
lisinopril can cause a functional AKI, this usually occurs with initiation of
therapy and presents similarly to prerenal AKI (Answer D is incorrect).
Answer C is incorrect because there is no evidence of obstruction in this
patient with urinary output present through the urinary catheter.
 4) Which medication should be discontinued because of its
risk for worsening kidney function in this patient?
A. Lisinopril.
B. Nicotine patch.
C. Acetaminophen.
D. Aspirin.
 Answer
4. Answer: A
One strategy in managing AKI is to remove potentially nephrotoxic drugs, either direct
toxins or medications
that alter intrarenal hemodynamics. The following orders are common for patients in
AKI: no ACEIs, ARBs, NSAIDs, or intravenous contrast. However, low-dose aspirin
can be continued without adversely affecting kidney function (Answer D is
incorrect). It is also important to remove (or reduce the dose of) agents that are
cleared renally. Metformin, which accumulates in decreased kidney function,
should temporarily be discontinued at this time because of an increased risk of
lactic acidosis, not because of an adverse effect on kidney function (Answer C is
incorrect). In this case, lisinopril is most likely to affect kidney function, so it should
be discontinued (Answer A is correct). Unlike NSAIDs, acetaminophen does not
interfere with prostaglandin synthesis peripherally; thus, it does not cause
hemodynamically mediated AKI (Answer B is incorrect).
5) Which is most appropriate to add at this time?
A. Intravenous 0.9% sodium chloride.
B. Hydrochlorothiazide.
C. Furosemide.
D. Fluid restriction.
 Answer
5. Answer: C
This patient presents with ATN, anuria, and volume overload. Although loop
diuretics have not been shown to improve clinical outcomes in patients
with AKI, they may increase urinary output, which will help with fluid and
electrolyte balance. In addition, this patient is hypervolemic, so a trial of
intravenous loop diuretics would be appropriate (Answer C is correct).
Adding 0.9% sodium chloride (Answer A) would worsen fluid overload.
Hydrochlorothiazide (Answer B) would not be appropriate because thiazide
diuretics are unlikely to be effective with such poor kidney function. Fluid
restriction (Answer D) may be necessary if furosemide fails to increase
urinary output, but it would not be the first-line approach.
 Case (3)
A 44-year-old man is admitted with gram-negative
bacteremia. He receives 4 days of parenteral
aminoglycoside
therapy and develops acute tubular necrosis (ATN).
Antibiotic therapy is adjusted on the basis of culture and
sensitivity results.
Which laboratory value is most consistent with this
presentation?

A. BUN/SCr ratio greater than 20:1.

B. Urinalysis with no casts visible.
C. Fractional excretion of sodium (FENa) more than 2%.
D. Urinary sodium less than 20 mEq/L.
 Answer
Answer: C
The patient has intrinsic AKI (i.e., ATN). Aminoglycosides can cause direct
damage to the tubules. In ATN, the BUN/SCr ratio would be normal (10–15:1),
whereas an elevated BUN/SCr ratio (greater than 20:1) reflecting
hypovolemia is common in prerenal azotemia (Answer A is incorrect). Urinary
sodium of less than 20 mEq/L is also a marker of hypovolemia and would be
consistent with prerenal azotemia AKI (Answer D is incorrect). Fractional
excretion of sodium also distinguishes prerenal and intrinsic renal damage. A
low FENa (less than 1%) in an oliguric patient suggests that tubular function is
still intact, whereas a FENa greater than 2% is common in intrinsic renal
failure (Answer C is correct). Cellular debris is often present in intrinsic renal
failure because of renal tubular cell death or damage, whereas a normal
urinalysis would be more consistent with prerenal AKI (Answer B is incorrect).
 Case (4)
A 60-year-old patient (weight 72 kg) with a history of diabetes and hypertension is in
the intensive care unit after having a myocardial infarction about 1 week ago with
secondary heart failure. He now has pneumonia. He has been hypotensive for the
past 5 days. Before his admission 1 week ago, his SCr was 1.0 mg/dL. His urinary
output has steadily been declining for the past 3 days, despite adequate hydration,
with 700 mL of urinary output in the past 24 hours. His medications include
intravenous dobutamine, nitroglycerin, and cefazolin. Yesterday, his BUN and SCr
were 32 and 3.1 mg/dL, respectively; today, they are 41 and 3.9 mg/dL. His urinary
osmolality is 290 mOsm/kg. His urinary sodium is 45 mEq/L, and there are tubular
cellular casts in his urine. Which type of AKI is this patient most likely experiencing?
A. Prerenal azotemia.
B. ATN.
C. Acute interstitial nephritis (AIN).
D. Hemodynamic/functional-mediated AKI.
 Answer
Answer: B

The presence of hypotension despite adequate hydration, a normal

BUN/SCr ratio (10–15:1), urinary osmolality, and presence of urinary
casts all point to ATN (Answer B is correct). Prerenal AKI is unlikely,
considering adequate hydration, high urinary sodium (greater than 40
mEq/L), and lack of high urinary osmolality (Answer A is incorrect).
Functional AKI would look similar to prerenal AKI on urinalysis with
low urinary sodium and no tubular casts (Answer D is incorrect).
Classically, AIN would present with eosinophils in the urine (Answer C
is incorrect).