MON-005 - Vancomycin-Associated Acute Tubular Injury Leading to Transient Arginine Vasopressin Resistance

Vancomycin-associated acute kidney injury (AKI) has been well described in the literature, including characterization of pathologic patterns such as acute tubular necrosis (ATN), acute interstitial nephritis and cast nephropathy. To our knowledge, there are no prior reports of vancomycin nephrotoxicity resulting in transient arginine vasopressin resistance (AVP-R), also known as nephrogenic diabetes insipidus.

We present a case of a 66-year-old woman with cerebral palsy, intellectual disability and deep venous thrombosis on apixaban who presented with sepsis. On presentation, she was hypotensive to 80/60 mm Hg and tachycardic to 150 beats/minute. Initial laboratory evaluation showed sodium 145 mmol/L (136-145), BUN 41 mg/dL (9-23), and creatinine (Cr) 0.88 mg/dL (0.5-0.8). Urinalysis was turbid with positive leukocyte esterase and specific gravity of 1.029 (1.001-1.030). She had urinary retention and gram-positive bacteremia consistent with urosepsis and was started on vancomycin and piperacillin-tazobactam. On hospital day 3, vancomycin trough level was supratherapeutic at 49.1 mcg/mL (10-40), followed by the development of AKI (Cr peaked at 3.1) and hypernatremia. Despite intravenous D5W at 150-200 ml/hr and oral free water, serum sodium continued to rise (up to 162 mmol/L). Concurrently, she developed polyuria with urine output of 2.5-3 L/day and inappropriately dilute urine (specific gravity 1.004 and urine osmolality 134 mOsm/kg). A desmopressin (IV 2 mcg) trial resulted in only 12% increase in urine osmolality (from 121 to 136 mOsm/kg). Serum copeptin was elevated at 84.2 pmol/L (1-13), consistent with AVP resistance. As patient’s renal function gradually improved, chlorthalidone was initiated and uptitrated with minimal effect on urine output. She was then transitioned to indomethacin 25mg once daily which resulted in marked improvement in urine output (decreased to ~1 L/day) and increase in urine specific gravity to 1.010 and osmolality to 339 mOsm/kg. The patient was diagnosed with acquired AVP-R secondary to vancomycin-induced acute tubular injury.

While acquired AVP-R is commonly associated with medications like aminoglycosides, lithium and demeclocycline, we report what we believe to be the first case of vancomycin induced AVP-R. This condition remains a diagnosis of exclusion and in our case, improvement in renal function supports a reversible tubular defect rather than permanent AVP-R. Serum copeptin is a valuable biomarker that can help in establishing the diagnosis when conventional testing is indeterminate. Thiazide diuretics alone may be insufficient for management, and indomethacin represents an effective therapeutic option that can improve polyuria by inhibiting renal prostaglandins, which otherwise antagonize AVP signaling in the collecting duct.

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