Vancomycin Nephrotoxicity in an ICU patient usually occurs with other potential risk factors for acute kidney injury (AKI). Proper diagnosis of the patient requires a high index of suspicion for vancomycin nephrotoxicity.

A 38-year-old male is evaluated in the ICU by nephrology for AKI. The patient has a history of diabetes mellitus type II with recurrent cellulitis and has been treated with vancomycin and piperacillin‐tazobactam. The patient became septic and required IV fluids and pressors. He has a history of hypertension. However, given the hypotension and AKI, his losartan and empaglifozin were held. The patient was hypotensive for a short period.

The patient has CKD G4 with a baseline cr of 2.2 mg/dL. Two days later, his creatinine is 3.5 mg/dL.

His vancomycin trough was 30 mg/L.

Urinalysis revealed protein but no blood and granular casts. Renal tubular epithelial cells are also noted.

Vancomycin Nephrotoxicity

Requires a high index of suspicion in the ICU

Please answer the following questions:

What is the most likely cause of the patient’s acute kidney injury?
* shock
* vancomycin
* piperacillin-tazobactam
* losartan
* empaglifozin

vancomycin nephrotoxicity is the cause.

What is the most common cause of hospital-acquired acute kidney injury (AKI)?
A
Acute interstitial nephritis (AIN)
B
Acute tubular necrosis (ATN)
C
Chronic kidney disease
D
Prolonged therapy

B. ATN

Which of the following is a risk factor for vancomycin nephrotoxicity?
A
Vancomycin doses ≥4 g/d
B
Low serum creatinine levels
C
Short-term therapy
D
Use of non-loop diuretics

A Vancomycin doses ≥4 g/d

What laboratory finding is indicative of acute tubular necrosis (ATN)?
A
Low urine output
B
High blood pressure
C
Fractional excretion of sodium higher than 2%
D
Increased potassium levels

C Fractional excretion of sodium higher than 2%

What is a common cause of damage to renal tubular epithelial cells in acute tubular necrosis (ATN)?
A
Ischemia
B
Infection
C
Dehydration
D
Hypertension

A Ischemia

What is essential for renal recovery when a patient has vancomycin nephrotoxicity?
A
Administering additional antibiotics
B
Early recognition and prompt discontinuation of the drug
C
Increasing fluid intake
D
Monitoring blood pressure regularly

B
Early recognition and prompt discontinuation of the drug

Discussion:

Acute Kidney Injury and Vancomycin Nephrotoxicity

Overview of Acute Kidney Injury (AKI)

Acute kidney injury (AKI) is a sudden decrease in kidney function, which can be caused by various factors. In hospital settings, the most common cause of AKI is acute tubular necrosis (ATN), characterized by damage to renal tubular epithelial cells. This damage is often because of ischemia or exposure to nephrotoxins.

Causes of Acute Tubular Necrosis (ATN)

ATN can be identified through careful evaluation of:
* Hemodynamics, volume status, and medications

Vancomycin can cause of AKI in patients, with most reported cases linked to acute interstitial nephritis (AIN). However, ATN has also been documented in patients receiving vancomycin.

Indicators of ATN

Diagnosis of ATN is supported by:
* Rapid rise in serum creatinine levels
* Fractional excretion of sodium greater than 2%
* Urine microscopy demonstrating numerous renal tubular epithelial cells and granular casts

Risk Factors for Vancomycin Nephrotoxicity

* Several risk factors increase the likelihood of vancomycin nephrotoxicity, including:
* Chronic kidney disease
* Prolonged therapy with vancomycin
* Doses of vancomycin ≥ 4 grams per day
* Trough concentrations of vancomycin > 15 mg/L
Concurrent use of loop diuretics or other nephrotoxins, such as concomitant use of piperacillin-tazobactam
* Early recognition and prompt discontinuation of vancomycin is crucial for kidney recovery.
* Concurrent Nephrotoxin Exposure in vancomycin nephrotoxicity

Patients receiving vancomycin, particularly in ICU settings, may also be exposed to other nephrotoxic agents, which can further compromise kidney function. These include:
* Proton pump inhibitors, other antibiotics such as piperacillin-tazobactam, Acyclovir, calcineurin inhibitors, chemotherapy agents, intravenous contrast, vasopressors, loop diuretics, Renin-angiotensin system blockers

Acute Interstitial Nephritis (AIN)

AIN can be caused by certain antibiotics, such as piperacillin-tazobactam, and proton pump inhibitors like omeprazole.

AIN may also be associated with:
* Drugs, infections, autoimmune diseases, and malignancy

Only 10% to 30% of patients with AIN exhibit the classic triad of symptoms, which includes fever, rash, and eosinophilia. Urine chemistries may show variable fractional excretion of sodium, while urinalysis may reveal:
* Hematuria, pyuria, leukocyte casts, and possibly eosinophiluria (not a reliable diagnostic marker). Nephrologists no longer suggest ordering this study to evaluate for acute interstitial nephritis.

Drug-induced AIN typically presents with a gradual increase in serum creatinine levels 7 to 10 days post-exposure, but can occur within 1 day if there has been prior exposure. It may also manifest months after exposure, particularly with NSAIDs and proton pump inhibitors. Here, the patient’s urinalysis findings do not support AIN.

Contrast-Induced Nephropathy (CIN)

Contrast-induced nephropathy (CIN) leads to ATN, with serum creatinine levels rising within 48 hours of contrast exposure. However, the patient in question did not receive any contrast, ruling out CIN as a cause of AKI.