ACUTE RENAL FAILURE CASE

Patient and Setting:

CM is a 35-year-old African-American man; emergency department Nausea/vomiting, seizure

Chief Complaint:

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 (CAMRSA) 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) N/A Mother: ESRD, DM; Father: died at age 45 due to MI Ethanol intake: Nil; tobacco: once/month 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 Morphine (tongue swelling, itching, rash, SOB)

Surgical History: Family History: Social History: Medications:

Allergies:

Physical Examination: GEN: Well-developed, nourished African-American man VS: BP 190/100, HR 83, RR 26, T 37.3C, 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% 9 3 Lkcs 10 10 (10 10 ) 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+ 2+ Color: cloudy LE: () Blood: large Eosinophils: 0% Na: 65 Osmolality: 300 mOsm/kg Urine Cast: coarse granular FENA 3%

RBC: 4+ Nitrite: () Spec. Gravity: 1.011 pH: 8

Albumin:

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 CMs 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 CMs 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 CMs 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 CMs 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 CMs 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 cant 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: Problem 2: Problem 3:

Acute renal failure, possibly drug-induced Hyperkalemia due to acute renal failure Hypertension secondary to acute renal failure and fluid accumulation

Problem 4: Problem 5: Problem 6: Problem 7:

Metabolic acidosis due to acute renal failure Hypervolemia due to acute renal failure Seizure secondary to uremia 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 5001000 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 failureinduced 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 CMs 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 CMs 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 5001000 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 thiazidelike 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 patients clinical status and indications for dialysis.

6. CMs 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, CMs serum creatinine could have been 3.5 yesterday, but today is 5. Since CMs 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 patients serum creatinine.

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