Vancomycin (VAN) has been associated with acute kidney injury (AKI) since it has been put into clinical use in the 1950's. Early reports of AKI were likely linked to the impurities of the VAN preparation. With the advent of the more purified forms of VAN, the incidence of AKI related to VAN were limited to acute interstitial nephritis (AIN) or as a potentiating agent to other nephrotoxins such as Aminoglycosides. VAN as the sole etiologic factor for nephrotoxic acute tubular necrosis (ATN) has not been described. Here, we report a case of biopsy-proven ATN resulting from VAN.
R. H. is a 23-year-old male with a history of childhood acute lymphocytic leukemia in remission, neuroectodermal tumor status postresection, and gamma knife therapy, who presented to our Emergency Department (ED) with complaints of fever and chills. He also noticed yellowish drainage around the site of a peripherally inserted central catheter (PICC). In the ED, patient was febrile to 101.7° Fahrenheit with a blood pressure of 113/83 mm Hg and pulse of 134 bpm. The PICC line was removed, and antibiotic therapy initiated with piperacillin-tazobactam and VAN. RH received 1 gm IV of VAN in the ED, and upon admission to the floor, received another 2 gm IV. Piperacillin-tazobactam was discontinued. Eight hours later, another 2 grams of VAN were given, with cumulative dose of 5 gm in 24 hrs (50 mg/kg in 24 hours). Patient’s admission creatinine was 0.97 mg/dL. The patient was 103 kg and 72′′ tall. Attempting to use a loading dose of 15 mg/kg based on total body weight [
The following day, the serum creatinine was 3.62 mg/dL. He became oligo-anuric with a urine output of 50 cc in 24 hours. Urinalysis revealed a bland urine sediment and a urine sodium of 75 meq/L and a fractional excretion of sodium of 2.77%. He had not been exposed to IV contrast, received an aminoglycoside or exposed to any other potential nephrotoxins.
Blood cultures were negative, and the PICC line tip cultures were positive for
Laboratory and clinical parameters.
Day | Scr mg/dl | UO 24 hrs | VAN dose | VAN S. Conc. | HD |
---|---|---|---|---|---|
0 | .97 | NR | 5 gm | ND | No |
1 | 3.62–4.26 | 50 cc | ND | No | |
2 | 6.25 | <50 cc | ND | No | |
3 | 8.41 | <50 cc | ND | No | |
4 | 9.96 | <50 cc | 64.7 | Yes | |
5 | 9.36 | 1000 cc | Yes | ||
9 | 9.21 | 2000 cc | ND | Yes | |
10 | 5.88 | 2500 cc | ND | No | |
30 | 1.24 | NR | ND | No |
Scr—serum creatinine; UO—urine output; VAN—Vancomycin; S. Conc—Serum concentration; HD—hemodialysis; ND—not done; NR—not recorded.
Representative photographs of the renal biopsy showing tubular damage secondary to drug toxicity. In both panels (a) and (b) a number of tubules show moderate degree of acute tubular necrosis (asterisks). Some of tubules contain hyaline or epithelial casts in their lumina (green arrows), while several tubules show vacuolization of their cytoplasm (green arrowheads). One of the glomerular afferent arteriole shows swollen endothelia and occlusive change (black arrow).
VAN, a parenteral glycopeptide antibiotic, has been used clinically since 1956. The original preparation contained a number of impurities and was brown in color, hence, the nickname “Mississippi Mud”. It is these impurities that were thought to be responsible for certain toxicities such as anaphylaxis, toxic epidermal necrolysis, erythema multiforme, ototoxicity, and nephrotoxicity [
In 1983, Farber andMoelleringreported the incidence of nephrotoxicity with VAN to be 5% [
Other risk factors associated with nephrotoxicity include prolonged therapy for >21 days, [
As VAN safety profile improved and with the emerging prevalence of methicillin-resistant
The potential mechanism of action of VAN-associated nephropathy has been studied in both humans and animals. The energy-dependent transport mechanisms found in the proximal tubular epithelium render the kidneys highly susceptible to toxicant-induced renal injury. VAN exposure in renal proximal tubule epithelial cells results in increased cell proliferation as evidenced by increased number of cells, total protein, and DNA synthesis. VAN enhances cellular ATP concentration and stimulates oxygen consumption, supporting its role as a stimulant of oxidative phosphorylation [
While it is unclear if VAN-associated acute tubular necrosis is preventable, these data argue for prompt serum VAN monitoring given the rapid functional decline of patient nephrologic function even before the patient was scheduled to receive the 4th dose of therapeutically dosed VAN. Additionally, these data may support previously published literature suggesting that VAN doses >4 g per day, and patient body weights in excess of 101.4 kg may predispose to nephrotoxicity, [
The most common VAN-associated nephrotoxicity is AIN [