ODP130 Zoledronate-Induced Acute Tubular Necrosis With Baseline Normal Renal Function: A Rare Phenomenon
Authors: Khawaja Umar Sharif , Shah Nirali , Wang Ally 
Published: November 2022

Abstract

Introduction
Zoledronate is an intravenous bisphosphonate that is commonly used to decrease bone resorption in patients with osteoporosis. The incidence of acute tubular necrosis (ATN) using zoledronate in patients with normal renal function is rare. Herein, we report the occurrence of severe ATN following treatment with a single zoledronate infusion in a patient with osteoporosis and normal renal function.

Case Presentation
A 51-year-old female with hypertension, well-controlled type 2 diabetes c/b gastroparesis without nephropathy(HbA1c6.8%), status-post hysterectomy, and bilateral oophorectomy, who was recently diagnosed with osteoporosis. Bone densitometry with Hologic revealed T scores of -2.8 at the spine and a T score of - 0.9 at the left hip. Her medications included lisinopril, metformin, and empagliflozin. Due to a history of gastroparesis, zoledronate was chosen as the preferred treatment. Pre-infusion blood work showed: a creatinine of 0.92 (0.5-1.1 mg/dl), 25-hydroxyvitamin-D 37.8 (30-100 NG/ml), calcium 8.9 (8.5-10.5mg/dl) and urine microalbumin 14 (&lt;30 mg/g). Two days after the infusion, the patient developed emesis, diarrhea, oliguria, and fevers. She was evaluated in the emergency room and found to have acute renal failure (creatinine 10 mg/dL). She was given three liters of intravenous fluids with no improvement in urine output. Microscopic evaluation of spun urine revealed non-dysmorphic RBCs and numerous muddy brown granular casts consistent with ATN. Despite treatment with intravenous fluids, her creatinine did not improve and peaked on hospital days 11 to 11.65mg/dl. A 24-hour urine collection revealed proteinuria of 3 grams/24 hours. The patient was then empirically started on methylprednisolone 500mg for suspected glomerulonephritis. A renal biopsy was subsequently performed, which confirmed ATN. The patient's creatinine improved steadily to 5.49mg/dl by discharge. A subsequent creatinine one-month post-discharge was 1.36mg/dL.

Discussion
Zoledronate is widely used at low doses in the treatment of osteoporosis. ATN due to zoledronate infusion has been described in patients with pre-existing renal dysfunction and those receiving large and frequent doses for malignancy but rarely reported with the lower doses used to treat patients with osteoporosis and normal renal function. Zoledronate is believed to cause ATN by internalization in the renal tubular cells via the process of fluid-phase endocytosis. The intracellular accumulation of zoledronate may act as an epithelial toxin inducing tubular cytotoxicity. Interestingly, our patient had normal renal function without diabetic nephropathy and did not use nephrotoxic medications prior to the infusion.

Conclusion
We report a case of severe ATN due to a single dose of zoledronate in a patient with osteoporosis and previously normal renal function. This case highlights the need to be aware of the potential nephrotoxicity of zoledronate even in patients with normal renal function at baseline.
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