Acute Kidney Injury Case File

Acute Kidney Injury Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 23

A 57-year-old woman with a history of Type 2 diabetes mellitus and hypertension  has been admitted to the ICU for management of acute urinary tract infection sepsis, today being ICU day 3. The patient weighs 63 kg. The patient's laboratory studies  demonstrated an increase in serum creatinine from 1.0 mg/dL to 2.1 mg/dL.  Her serum electrolytes are within normal limits. Her total  urine output for the  most recent 24 hours (day 2) is only 650 mL, which is significantly less than the  output from the 24 hours before (day 1), recorded as 1100 mL.

⯈What is the most likely diagnosis?

⯈What are the best next steps in evaluating and managing this patient?

ANSWER TO CASE 23:

Acute Kidney Injury

Summary: A 57-year-old woman is being managed in the ICU with a new diagnosis of acute urinary tract infection sepsis. On hospital day 3 her urine output drops significantly and her serum creatinine increases from 1.0 mg/dL to 2.1 mg/dL.

• • Most likely diagnosis: Acute kidney injury with the serum creatinine increasing twofold and associated with decreased urine output.
• • Next step: Initiate immediate supportive treatment (fluid management, antibiotics directed at source control, vasopressors, and diuretics) and obtain CBC, serum chemistry, urinalysis, and blood and urine cultures if new infection is suspected. Initiate consultation with the renal service for possible renal replacement therapy.

ANALYSIS

Objectives

1. To become familiar with the diagnosis, staging, and treatment of acute kidney injury.
2. To list the causes of acute kidney injury in ICU patients.
3. To understand the indications for emergent renal replacement therapy.

Considerations

The patient's history indicates a known diagnosis of acute urinary tract infection sepsis, which in itself is a potentially life-threatening condition. On her third day of hospitalization, she develops a significant increase in the serum markers of her kidney function, a decrease in urine output, and an abrupt rise in serum creatinine. These markers indicate that her kidney function is compromised and investigation into the cause and initiation of treatment should begin. The initial decline of kidney function may be reversible with treatment; however, the underlying cause of the kidney dysfunction will need to be addressed so that ultimately the urological system can regain normal homeostasis. It is likely that with adequate management, the kidneys' functional status may normalize; however, the possibility of further decompensation may occur, leading to the requirement of renal replacement therapy for patient survival.

Approach To:

Acute Kidney Injury

DEFINITIONS

OLIGURIA: Decrease from the normal level of urine output (<0.5 mL/kg/h).

ANURIA: No urine output in >24 hours, usually irreversible.

RENAL REPLACEMENT THERAPY: Dialysis/hemofiltration, the only FDA approved therapy for AKI.

CHRONIC KIDNEY DISEASE: An irreversible failure in the homeostasis of the renal filtration system.

SIRS: Systemic inflammatory response syndrome that comprises abnormal body temperature (higher than 38°C or <36°C ), heart rate >90 beats/minute, respiration >20 breaths/minute, or arterial partial pressure of CO2 <32 mm Hg, and deranged white blood cell counts ( >12 X 10³/mm³, <4 X 103/mm³, or >10% bands).

SEPSIS: SIRS and an identifiable source of infection (or high level of suspicion of an identifiable source of infection).

SEPTIC SHOCK: Meeting the criteria for sepsis with low blood pressure (SBP <90 mm Hg).

UROSEPSIS: Sepsis caused by infection of the urinary tract and/or male genital organs (eg, prostate).

CLINICAL APPROACH

Acute kidney injury (AKI) has now replaced the term acute renal failure. It is now widely agreed that there is a spectrum of the disease extending from less severe forms of injury to that of more advanced injury. The significance of this disease is great, with up to 200,000 people each year in the United States affected and a hospital-acquired prevalence of 7.1 %. There is a strong evidence that sepsis and septic shock are the most important causes of AKI in critically ill patients, accounting for 50% or more of cases of AKI in ICU patients. It is now recognized that AKI is an independent risk factor for mortality, with experimental models suggesting that AKI is associated with an up-regulation of systemic inflammatory mediator release.

AKI is a clinical diagnosis characterized by rapid reduction in function resulting in inability to maintain electrolyte, fluid and acid-base homeostasis. The mainstay for diagnosis of AKI has been the measurement of urine output over a given time period, as well as a rise in specific biological markers of kidney function, with the most common being serum creatinine (SCr). Specifically, AKI is defined when 1 of the following criteria is met:

• SCr rises by >26 μmol/L within 48 h
• SCr acutely rises >1.5 fold from the reference value (Note: Reference SCr should be the lowest creatinine value recorded within 3 months of the event.)
• Urine output is <0.5 mL/kg/h for >6 consecutive hours.

Staging of AKI is useful at the bedside, as AKI is considered a spectrum of severity, and the recognition of disease severity is helpful in the selection of treatments (Table 23-1).

Although urine output and SCr are presently the best biomarkers for AKI, they are not ideal, since kidney injury has already occurred before these values become abnormal; therefore, reliance on these markers may result in delays in disease recognition. This has led to the search for biomarkers enabling early diagnosis of

kidney insult and earlier treatment. At present, several novel biomarkers are being investigated, and these include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM- 1), interleukin-18 (IL-18), and cystatin C. These biomarkers show early promise for tools for the early detection of AKI.

Management

The first step in the management of AKI is to be aware of patients at highest risk for the development of AKI. These include age > 75 years, chronic kidney disease (CKD, eGFR <60 mL/min/1.73 m²), cardiac failure, peripheral vascular disease, diabetes mellitus, and those taking nephrotoxic medications. Acute medical conditions that increase the risk of AKI include reduced fluid intake or increased fluid losses (dehydration), urinary tract obstruction or infections, sepsis, myoglobinuria, and recent drug ingestion.

The urinalysis can provide useful information in determining the cause of AKI. Significant proteinuria ( + 3 or + 4 ) suggests intrinsic glomerular disease. Hematuria in association with proteinuria may indicate a diagnosis of glomerular disease. Hematuria may also indicate the presence of a tumor in the lower urinary tract. Myoglobinuria produces a positive reagent strip reaction (dipstick) without traces of RBC in the urine. The presence of > 5 WBC per high-power field in a patient with AKI suggests the presence of infection, acute interstitial nephritis, or glomerulonephritis. Urine microscopy can also provide useful information regarding AKI causes. Urinary crystals are identified in patients with glycol poisoning, tumor lysis syndrome, or drug exposures (sulfonamides, acyclovir, and triameterene). Other diagnostic tests for patients with AKI include urine osmolality, urine/plasma creatinine and urea ratios, urinary sodium, fractional excretion of sodium (FENa), fractional excretion of urea, free water clearance, and creatinine clearance. Patients who are prerenal may have increased urinary sodium reabsorption and increased urinary urea reabsorption; therefore, they would exhibit low FENA and FEUrea Patients with AKI caused by hepatorenal syndrome have extremely low urinary sodium (<10 mmol/L).

Ultrasound i s the most useful diagnostic modality to assess for the possibility of upper urinary tract obstruction. It is important to recognize that hydronephrosis may not be present in patients with urinary tract obstruction and hypovolemia; therefore, patients suspected of obstructive uropathy should undergo a repeat study after repletion of intravascular volumes.

Acute kidney injury can be a potentially reversible disorder if treated in a timely and appropriate manner. Early recognition is important and may improve the chances for full recovery of kidney functions. A patient's supportive measures must be optimized to include appropriate fluid therapy, administration of vasopressor and/or inotropic medicines, and treatment of the underlying illness, particularly sepsis. Accurate measurements of all intake including oral, intravenous rates, and boluses as well as all output (urine, emesis, etc) must be accurately recorded to give the clinician the most complete and accurate assessment of the patient's volume status. This may require the use of an indwelling urine catheter for precise urine output measurement. All medications administered should be interrogated for potential nephrotoxic effects and stopped accordingly. Avoidance of intravenous radiographic contrast will help avoid further injury to the kidneys.

Generally accepted indications for renal replacement therapy (RRT) include profound acidemia, electrolyte imbalances (eg, hyperkalemia), ingestion or idiopathic overload of toxins/metabolites, symptomatic fluid overload, and symptomatic uremia (eg, increased bleeding from platelet dysfunction, pericardia! tamponade, and severe mental status change). Ideally, RRT should be initiated once the diagnosis of AKI is certain and unavoidable, yet prior to terminal organ complications.

Venous access for RRT requires planning that takes into consideration the level of irreversible kidney damage and the anticipated duration of therapy. When short term (temporary) dialysis is anticipated, venovenous access is the preferred route. Venovenous access is established with ultrasound-guided placement of a double lumen catheter into a large central vein (preferably internal jugular or femoral veins). This access may be used for weeks until the patient's physiologic homeostasis will be determined to become normal or if prolonged RRT is required. For patients in whom long-term dialysis is anticipated, planning should be initiated for the placement of arteriovenous access. In comparison to intermittent dialysis, continuous renal replacement therapy may have the advantage of achieving better control of uremia, prevention of hypotension during dialysis, and improved clearance of inflammatory mediators; however, there is no convincing evidence to indicate that continuous RRT provides additional advantages over intermittent RRT. Similarly, clinical evidence does not support the use of high-dose RRT over standard-dose RRT.

All patients who survive AKI but whose kidney function does not return to normal will need planning for CKD management, including but not limited to longterm RRT access. A center for RRT will need to accept the patient and subsequently into the practice of a renal physician. Kidney transplantation is the definitive treatment for those with failed kidneys.

Long-term Prognosis

Despite advances in the supportive care of patient with AKI in the ICU, prognostication of renal recovery continues to be a difficult challenge. Several urinary biomarkers are being investigated for their prognostication value for AKI recovery. These include urinary neutrophil gelatinase-associated lipocalin (uN-GAL) , urinary hepatocyte growth factor (uHGF), urinary cystatin C (uCystatin C) , and IL-18. Recent clinical studies suggest that patterns of change in these urinary markers may be valuable in predicting recovery in AKI patients.

CLINICAL CASE CORRELATION

• See also Cases 24 and 25 (Acid-Base Abnormalities I and II), Case 26 (Fluid and Electrolyte Abnormalities), and Case 33 (Multiorgan Dysfunction). 

COMPREHENSION QUESTIONS

23.1  A 5 8-year-old man with diabetes mellitus presents to hospital with left lower quadrant pain for 2 days. He has had nausea and vomiting with subjective fevers and anorexia. His vital signs are temperature of 100.4°F, pulse of 112 beats/minute, BP of 100/68 mm Hg, respiratory rate of 20 breaths/minute, and oxygen saturation of 99% on room air. His eyes are sunken and abdomen is tender in the left lower quadrant. Laboratory studies are significant for WBC of 15,000 and SCr of 1.68 mg/dL (reference value is 0.95). What is the initial best treatment to prevent further kidney injury?

A. Obtain immediate blood and urine cultures then start empiric antibiotics.

B. Admit to hospital and keep NPO.

C. Obtain CT scan to rule out intraabdominal abscess.

D. Insert 2 large-bore IVs then bolus with 1 to 2 L crystalloid.

E. Insert Foley catheter to measure urine output.

23.2  A 24-year-old man weighing 80 kg is admitted to the intensive care unit following an exploratory laparotomy after a GSW to his lower right hemithorax and abdomen. Intraoperative exploration showed a 1 cm laceration on the dome of the liver, a right diaphragmatic injury, and a transverse colon injury requiring partial colectomy with primary anastomosis. He was also found to have laceration of the left kidney. During the night, his urine output is measured at 60 mL/h for the first 3 hours, 50 mL/h for the fourth hour, and 20 mL/h for the fifth and sixth hours, and the urine appears dark. His heart rate and blood pressure have not changed. What is the next step in his management ?

A. Place a central venous catheter for CVP monitoring.

B. Bring the patient back into the operating room for reexploration.

C. Obtain CT imaging of the abdomen and pelvis.

D. Transfuse packed red blood cells.

E. Bolus the patient intravenous fluids.

23.3  You are managing patients in the intensive care unit, and you are concerned that one of your patients with sepsis due to a lung infection has developed fluid overload secondary to stage 3 AKI and may not recover her normal kidney function. What is the best plan for instituting appropriate care for this patient?

A. Obtain urinary electrolyte measurement.

B. Obtain measurement of the patient's platelet count.

C. Insert a venovenous access catheter for RRT.

D. Refer patient for renal transplantation consideration.

E. Increase the dose of her loop diuretic medication.

23.4  A 43-year-old man with AKI had a venovenous catheter placed for urgent RRT. He is now in his hospital bed and his wound bandages are saturated with blood. You notice that he is also bleeding from his peripheral IV sites. What is the definitive treatment?

A. Transfusion of red blood cells.

B. Transfusion of platelets.

C. Initiate RRT.

D. Administer DDAVP.

E. Give intravenous calcium.

ANSWERS TO QUESTIONS

23.1  D. This patient is presenting with signs and symptoms concerning for the diagnosis of acute diverticulitis and septic shock. His presenting SCr of 1.68 is >1.5 that of his baseline and thus meets the criteria of AKI . This patient has intravascular volume depletion from his illness. Fluid resuscitation is the first step in early goal-directed therapy of sepsis and will subsequently yield benefit for the hypoperfusion state of his kidneys. Oxygen therapy should be given along with fluid resuscitation, followed with blood cultures and the appropriate antibiotic initiated for his presumed intraabdominal sepsis. Imaging may be helpful to guide therapy but only after the patient is hemodynamically stable. A Foley catheter should be placed to determine fluid volume status and guide the clinician on management of fluid therapy.

23.2  A. This patient does not meet the definitions of AKI but is in danger of its development. One criteria for AKI is urine output (UOP) <0.5 mL/kg/h for >6 hours. This patient would be of concern for AKI if his UOP is <40 mL/h, which he has had for the last 2 hours. Given his injuries and recent operation, his low urine output is likely secondary to intravascular volume depletion. The next step in management would therefore be to confirm this diagnosis with the placement of a CVP line, and then to replete his volume as necessary.

23.3  C. Studies have demonstrated that for acute RRT, venovenous access is the modality of choice, especially given that this patient is fluid overloaded at this time. Urinary electrolytes are not helpful at this time to further define the patient's kidney functions. Referral for renal transplantation is premature, as the patient's renal functions may eventually recover from her stage 3 AKI. Increasing the dose of her loop diuretics is an option; however, given the patient's fluid status and ongoing pulmonary problem, dialysis may be the more effective strategy for this patient at this time.

23.4  C. This patient has platelet dysfunction due to uremia from kidney failure. The definitive treatment is RRT. Administering blood products will not achieve the desired hemostasis that is required. Calcium is often needed as a replacement for patients receiving red blood cell transfusions, as calcium is sequestered by the high amounts of citrate in the fluid. DDAVP, also known as vasopressin arginine, can improve the binding of platelets in clot formation. It can be used as temporizing first-line treatment for uremic bleeding if there is a delay before the patient can receive RRT.

CLINICAL PEARLS

⯈ Urine output and serum creatinine are the best biomarkers for acute kidney injury. 

⯈ AKI is potentially reversible with the appropriate measures if performed early; however, some patients may evolve to develop CKD. 

⯈ RRT may be needed for  both short-and long-term therapy with kidney injury. 

References

Chuasuwan A, Kellum JA. Acute kidney injury and its management. Contrib Nephrol. 2011; 1 71:218-225. 

Florian ME, Pilatz A, Weidner W. Optimal management of urosepsis from the urological perspective. International] Antimicrob Agents. 2007:390-397. 

Lewington A, Kanagasundaram S. Renal association clinical practice guidelines on acute kidney injury. Nephron Clin Pract. 2011;118(suppll):c349-c3 90. 

Srisawat N, Wen X, Lee M, eta!. Urinary biomarkers predict renal recovery in critically ill patients with renal support. Clin] Am Soc Nephrol. 2011;6: 1815-1823. 

Zarjou A, Agarwal A. Sepsis and acute kidney injury.] Am Soc Nephrol. 2011;22(6):999-1006. 

Liu KD, Brakeman PR. Renal repair and recovery. Crit Care Med. 2008;36(4 suppl):S1 87-S192.

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