ACUTE RENAL FAILURE CASE

Patient and Setting: CM is a 35-year-old African-American man; emergency

department

Chief Complaint: Nausea/vomiting, seizure

History of Present Illness: CM was discharged from the hospital 5 days earlier after a serious motor vehicle accident (MVA) that resulted in multiple injuries. During his 10-day hospitalization, a CT with contrast was performed to rule out intracranial bleeds (negative). He experienced an episode of rhabdomyolysis from bodily crush injuries and developed a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) cellulitis; all illnesses were treated appropriately. Since discharge from the hospital, CM reports that his feet are swelling, (+) fatigue, (+) nausea and vomiting, and (+) SOB. He has also noticed a decrease in urine output, although he reports he has not been eating or drinking much at home. Today, CM experienced a seizure and was subsequently brought to the emergency department.

Medical History: Hypertension (× 5 yrs), MVA, cellulitis (CA-MRSA),

contrast-induced nephropathy during recent hospitalization (serum creatinine returned to baseline prior to discharge)

Surgical History: N/A

Family History: Mother: ESRD, DM; Father: died at age 45 due to MI Social History: Ethanol intake: Nil; tobacco: once/month Medications: Lisinopril 40 mg PO BID for 5 years (restarted prior to

discharge after being withheld for 1 week during previous hospitalization)

Hydrochlorothiazide 25 mg PO QD for 5 years Amlodipine 10 mg PO QD for 2 years Septra DS 2 tabs PO BID for cellulitis Ibuprofen 800 mg PO TID for back pain Centrum One 1 tab PO QD Allergies: Morphine (tongue swelling, itching, rash, SOB)

Physical Examination: GEN: Well-developed, nourished African-American man VS: BP 190/100, HR 83, RR 26, T 37.3°C, Wt 80 kg, Ht 182 cm HEENT: WNL COR: RRR CHEST: Small crackles, rales, and wheezing ABD: WNL GU: Deferred RECT: Deferred EXT: Bilateral LE swollen with fluid, 3+ pitting edema NEURO: A & O × 2 (place, time)

Results of Pertinent Laboratory Tests, Serum Drug Concentrations, and Diagnostic Tests: Na 132 (132) HCO3 18 (18) Hct 0.39 (39) Plts 250 × 109 (250 × 103) K 5.9 (5.9) BUN 54 (150) Hgb 140 (14) Glucose 7 (126) Cl 100 (100) SCr 442 (5) Alb 31 (3.1) A1c 5% Lkcs 10 × 109 (10 × 103) Eosinophils 1% Blood Gas: pH 7.3 (7.3); pCO2 5.3 (40); HCO3 18 (18); pO2 12.9 (97) Blood Cultures: negative Urine Output: 300 mL/24 hr Urinalysis: WBC: 2+ Protein: 3+ RBC: 4+ Albumin: 2+ Color: cloudy LE: (−) Nitrite: (−) Blood: large Eosinophils: 0% Spec. Gravity: 1.011 Na: 65 Osmolality: 300 mOsm/kg Urine Cast: coarse granular pH: 8 FENA 3% PROBLEM LIST Identify principal problems from the scenario in priority order (see Answers for correct list of problems). SOAP NOTE To be completed by student (see Answers for correct SOAP Note)

CASE QUESTIONS

1. Identify agents in CM’s medication profile with the potential to cause acute renal failure and describe the mechanism for kidney damage.

2. List signs and symptoms of acute renal failure. 3. List the physical assessment and laboratory findings in CM consistent with

acute renal failure.

4. Identify the goals of therapy for treatment of acute renal failure in CM.

5. Describe pharmacologic and nonpharmacologic treatment options for acute

renal failure in CM including dosing regimens, route, dosing interval, and duration of therapy. Justify your choice.

6. Classify CM’s acute renal failure as prerenal, intrinsic, or postrenal and justify

your answer.

7. Which of the following radiographic examinations would be beneficial in determining whether CM’s acute renal failure is due to obstruction?

A) Computed tomography (CT) B) Ultrasound C) Magnetic resonance imaging D) Positron emission tomography (PET) scan

8. If oral furosemide is used, what is one reason a high dose may be required to

overcome diuretic resistance? A) Decreased conversion of furosemide to its active metabolite B) Decreased efficacy due to inactivation of furosemide by uremic toxins C) Decreased efficacy from altered regulation of sodium-potassium ATPase pump D) Decreased bioavailability of furosemide due to gastrointestinal edema

9. Discuss the limitations in using the Cockcroft-Gault method to assess kidney

function in patients with ARF.

10. What are potential therapies for CM’s hyperkalemia?

11. Interpret the clinical significance of a (+) urine eosinophilia?

12. Based on the available data on prevention of contrast-induced nephropathy, which of the following agents should not be recommended?

A) Fenoldopam B) Normal saline solutions C) Sodium bicarbonate solutions D) N-acetylcysteine

13. What is the mostly likely cause of CM’s recent seizure? 14. Summarize therapeutic, pathophysiologic, and disease management concepts

for acute renal failure using a key points format.

Model Answer

Problem List

1. Acute renal failure

2. Hyperkalemia

3. Hypertension

4. Metabolic Acidosis

5. Hypervolemia

6. Seizure

7. Cellulitis

SOAP Note

S: “I can’t pee, and when I do, my urine is a very dusty looking color. My ankles

and legs are swollen, and I have a lower back pain. My sister told me I had a

seizure.”

O: Lower back flank pain, decreased urine output with dingy colored urine;

crackles and rales on chest exam

Laboratory:

BP 190/100, K 5.9, BUN 54 (150), SCr 442 (5)

pH 7.3 (7.3), HCO3 18 (18)

Urine: WBC 2+, RBC 4+, Na 65, coarse granular casts

A: Problem 1: Acute renal failure, possibly drug-induced

Problem 2: Hyperkalemia due to acute renal failure

Problem 3: Hypertension secondary to acute renal failure and fluid

accumulation

Problem 4: Metabolic acidosis due to acute renal failure

Problem 5: Hypervolemia due to acute renal failure

Problem 6: Seizure secondary to uremia

Problem 7: Completion of therapy for CA-MRSA

P: Problem 1: Acute renal failure, possibly drug-induced

• Discontinue ACEI (lisinopril), NSAID (ibuprofen), diuretic (HCTZ),

and Septra, which are all potential drug-induced causes of acute renal

failure.

• Start a 500–1000 mL NS bolus. Repeat fluid boluses as patient can

tolerate.

• Start furosemide 80 mg IV over 30 minutes if no response to fluid

challenge, and increase dose if no response after 1 hour; if still no

response after 2 hours, consider adding thiazide diuretic (metolazone);

if no response, consider RRT based on indications for dialysis.

• Monitor urine output hourly.

• Monitor vital signs every shift.

• Monitor blood chemistries daily.

• Sepsis is a known cause of acute renal failure. Consider drawing blood

cultures to evaluate for infectious etiology.

Problem 2: Acute renal failure–induced hyperkalemia

• Address underlying causes of acute renal failure (decreased renal

perfusion, drug induced).

• Monitor EKG readings for hyperkalemia-induced dysrhythmia (peaked

T waves).

• Monitor serum potassium daily.

• Consider starting alternative antibiotic for treating CA-MRSA

(clindamycin, fluoroquinolone, pending susceptibilities) because

Septra can cause hyperkalemia.

Problem 3: Hypertension secondary to acute renal failure and fluid

accumulation

• Address underlying causes of ARF (decreased renal perfusion, drug

induced).

• The use of furosemide for fluid mobilization and renal perfusion may

decrease blood pressure as a result of normalizing blood volume.

• If blood pressure does not decrease with fluid removal, consider

starting antihypertensive therapy for hypertensive emergency (labetalol

20 mg by slow injection over 2 minutes with repeat injections of 40 or

80 mg given at 10-minute intervals) until the desired blood pressure is

achieved.

• Monitor blood pressure hourly for reduction in blood pressure and

prevention of hypotension.

• Monitor for end-organ damage from increased blood pressure.

• Educate patient on importance of blood pressure control, goals, and

blood pressure monitoring.

Problem 4: Metabolic acidosis due to acute renal failure

• Acidosis should correct with the improvements in renal function and

fluid administration.

• If acidosis is not corrected as renal function improves, consider

treatment with sodium bicarbonate.

• If RRT is initiated, the bicarbonate in the dialysate solution will treat

the metabolic acidosis.

Problem 5: Hypervolemia due to acute renal failure

• The use of furosemide for fluid mobilization should improve CM’s

symptoms of fluid overload (shortness of breath, edema).

• Monitor for improvement in breathing and edema.

• Perform chest exam after fluid mobilization to assess lung function.

• If fluid mobilization is not effective for edema, consider the use of

albumin to pull fluid from the interstitial space, if indicated.

Problem 6: Seizure secondary to uremia

• Address underlying causes of acute renal failure (decreased renal

perfusion, drug induced) to improve solute control and lower urea

concentration.

• Monitor blood urea nitrogen levels.

• Pharmacologic therapy with antiepileptic agents is not warranted at

this time.

• Monitor CM for further seizure activity.

• If renal function does not improve and urea levels do not decrease,

consider initiation of RRT for fluid and solute control.

Problem 7: Completion of therapy for CA-MRSA

• An alternative antibiotic to Septra should be chosen for the patient

based on sensitivities. (Septra is known to cause acute renal failure

from crystal formation and can cause allergic interstitial nephritis,

although this was ruled out in CM.)

• CM should receive the full course of treatment for CA-MRSA and be

scheduled for follow-up to evaluate for resolution of infection.

Answers to Case Questions

1. Agents in CM’s medication profile with the potential to cause ARF are as

follows:

a. Lisinopril (ACEI): Decreases glomerular filtration (GFR) rate by

preventing compensatory vasoconstriction of the efferent arteriole, an

angiotensin-mediated mechanism beneficial in conditions of decreased

renal perfusion (e.g., dehydration). Preventing constriction of the

efferent arteriole in these conditions decreases intraglomerular pressure

and, thus, GFR.

b. Ibuprofen (NSAID): Decreases glomerular perfusion by preventing the

dilation of the afferent artery, a prostaglandin-mediated mechanism

beneficial in conditions of decreased renal perfusion. This inhibition

results in decreased blood flow to the glomerulus and a decrease in

GFR.

c. Hydrochlorothiazide (diuretics): Diuretics may lead to a decrease in

circulating blood volume (and prerenal acute renal failure) if excessive

diuresis occurs. Overdiuresis is common in individuals with decreased

fluid intake or excessive losses and in the elderly.

Note: If the effects of ACEIs and NSAIDs and concomitant causes of

prerenal acute renal failure (e.g., conditions that decrease renal

perfusion) are not reversed, structural damage to the kidney or intrinsic

renal failure may result from prolonged ischemia.

d. Sulfamethoxazole-trimethoprim (Septra): May cause acute renal failure

by two mechanisms.

i. Formation of crystals in the urine (from the sulfamethoxazole

component) that may deposit in the tubules and cause

intratubular obstruction. Patients with a decrease in circulating

volume (e.g., dehydration, heart failure) and chronic kidney

disease are a greater risk for this type of drug-induced effect.

ii. Can cause interstitial nephritis and tubular necrosis, classified

as intrinsic renal failure. These types of acute renal failure have

been attributed, in part, to hypersensitivity to the

sulfamethoxazole component. (Note: Creatinine is primarily

filtrated by the glomerulus; however, as much as 10% is

secreted by the tubules. The trimethoprim component of Septra

inhibits the tubular secretion of creatinine, leading to a small

increase in serum creatinine, without a true change in kidney

function.)

2. Community patients that develop acute renal failure can present with

decreased urine output, weight gain, flank pain, edema, symptoms of uremia

(confusion, fatigue, bleeding, and decreased appetite), and cloudy or foamy

urine.

3. Physical findings consistent with fluid overload: Edematous ankles and legs

(3+ pitting edema), rales and crackles on lung exam; elevated BP 190/100

Laboratory tests: BUN 54 (150), SCr 442 (5), K 5.9, HCO3 18 (18)

Urine: Proteinuria, Na 65, coarse granular casts, RBC 4+, WBC 2+, osmolality

300 mOsm/kg

4. Goals for therapy include:

• Address underlying cause of acute renal failure

• Correct fluid and electrolyte disturbances

• Slow or reverse kidney damage

• Avoid further insults that would delay recovery (e.g., nephrotoxins)

• Provide supportive measures until kidney function returns

5. Pharmacologic and nonpharmacologic treatment options include the

following:

• Acute renal failure is commonly caused by medications. Removing

nephrotoxic drugs, specifically the ACEI (lisinopril), the NSAID

(ibuprofen), and Septra is the first step to treating acute renal failure in

CM.

• Fluid management is the mainstay of therapy in treating acute renal

failure. CM has signs of fluid overload and oliguric acute renal failure

(urine output < 400 mL/d); therefore, a cautious fluid challenge

regimen of 500–1000 mL intravenous bolus of normal saline over 30

minutes to an hour may be attempted to provide adequate extracellular

volume and maintain renal perfusion, yet minimize the risk of

worsening his volume status if urine output does not increase.

• Initiation of a loop diuretic such as furosemide should be considered if

CM fails to response to repeated fluid challenges. Furosemide 80 mg

intravenous should be initiated, and the dose should be adjusted based

on urine output. If no increase in urine output is observed in an hour,

the dose should be doubled. Consider adding metolazone, the thiazide-

like diuretic that retains its effect at GFRs of less than 30 mL/min, if a

loop diuretic alone does not increase urine output. Diuretic-resistant

acute renal failure may need to be treated by renal replacement therapy

(i.e., dialysis) depending on the patient’s clinical status and indications

for dialysis.

6. CM’s acute renal failure likely began as prerenal as a result of his poor intake

of fluids (decreasing effective circulating volume) in conjunction with use of

agents that prevent autoregulation by the kidney to maintain adequate

intraglomerular pressure (e.g., ACEI, NSAIDs). Although prerenal causes are

usually reversible, if not addressed, they lead to intrinsic renal failure as a

result of prolonged ischemic conditions. The structural damage associated

with intrinsic renal failure alters transport of solutes and water and urinary

concentrating ability. This damage may or may not be reversible. CM has

evidence of intrinsic renal failure: presence of granular casts in the urine, a

FENA >1%, urine sodium >40, urine + WBC and RBCs, and urine osmolality

<300 mOsm/kg. Postrenal ARF is not likely in CM because he does not have

evidence of obstruction.

7. B. Ultrasound

8. D. Decreased bioavailability of furosemide due to gastrointestinal edema

9. The Cockcroft-Gault (CG) equation is commonly used for estimating kidney

function in clinical practice; however, use of this equation is most appropriate

for patients with stable kidney function. This is not the case in acute renal

failure since serum creatinine values fluctuate in this patient population. For

example, CM’s serum creatinine could have been 3.5 yesterday, but today is 5.

Since CM’s kidney function may not be stable, the CG equation is not

recommended to assess his kidney function. Other methods that account for

changes in serum creatinine, such as the Jelliffe equation, are more appropriate

in acute renal failure. A measured creatinine clearance may also be calculated

using urine creatinine from a timed collection, along with the patient’s serum

creatinine.

10. Hyperkalemia is commonly associated with acute and chronic renal failure.

Once CM’s acute renal failure resolves, the potassium will likely correct. If a

loop diuretic such as furosemide is administered, it will assist in decreasing

serum potassium. If the potassium level is life threatening (>6.5, risk of

arrhythmias), agents that can rapidly lower serum potassium concentrations or

shift potassium intracellularly should be used (i.e., insulin/glucose, kayexalate)

in conjunction with a cardioprotective agent (e.g., 1 g IV calcium gluconate).

Treatment of CM’s metabolic acidosis will also address hyperkalemia.

11. A test that is positive for eosinophils in the urine is indicative of an allergic

process in the kidney, interstitial nephritis. A urine eosinophilia of >5% would

be significant for an acute allergic process. Urine eosinophilia is commonly

associated with a fever, arthralgia, and rash. Septra, NSAIDs, and diuretics

have been associated with allergic interstitial nephritis. The absence of

eosinophils in CM’s urine is a pertinent negative to help rule out allergic

interstitial nephritis.

12. A. Fenoldopam

13. Acute and severe elevations in serum urea nitrogen can have a neurotoxic

effect. Neurotoxicities include: depression, seizure, and psychosis.

14. Key Points

• Prevention is the best intervention for acute renal failure (ARF).

Conventional therapy offers little benefit to patients with established

ARF.

• Early recognition and management of prerenal ARF is important to

prevent intrinsic renal failure.

• Drug-induced causes of ARF should be evaluated in all cases of ARF.

• Patients with nonoliguric ARF have a significantly lower mortality rate

than anuric or oliguric patients; however, conversion from anuria or

oliguria to nonoliguria does not decrease mortality.

• Attempts to increase urine output may prevent complications of fluid

overload and facilitate patient management.

• In patients with ARF, a complete and regular review of drug therapy is

necessary to make appropriate dose adjustments for drugs that are

renally eliminated.

• Potential nephrotoxic agents should be avoided and alternative agents

should be used whenever possible. If potential nephrotoxins must be

administered, consider hydration to improve renal perfusion and

reduce tubular workload.

• RRT may be required to support the patient awaiting renal function

recovery based on the indications for dialysis.

• The potential for drug removal during dialysis must be considered

when designing drug regimens for patients with ARF.