Acute tubular necrosis (ATN) due to bisphosphonates has been reported with Zoledronic acid but the time to recovery (if any) has been usually less than 4 months. Possible recovery time from ATN of any cause is usually less than 6 months. In this paper, we present the case of a 59-year-old Caucasian female with metastatic breast cancer who had received 16 monthly injections of Zoledronic acid for treatment of tumor induced hypercalcemia and developed several episodes of mild acute kidney injury which resolved by withholding treatment. Unfortunately, after the sixteenth injection, the patient experienced severe acute kidney injury, with a peak serum creatinine of 8.0？mg/dL. Although urinalysis showed muddy brown casts, because of atypical recovery time and presence of eosinophiluria and subnephrotic range proteinuria, a kidney biopsy was performed. Diagnosis of typical acute tubular necrosis was confirmed without any other concomitant findings. The course was remarkable for an unusually slow recovery of renal function over 15 months without need for renal replacement therapy until the patient expired from her metastatic cancer two years later. We reviewed all the published cases of acute kidney injury due to Zoledronic acid and suggest recommendations for clinicians and researchers. 1. Introduction The use of Zoledronic acid has been reported to cause acute tubular necrosis, but little is known about the particular features of this type of toxic tubular necrosis. 2. Case Report A 59-year-old Caucasian female with history of type II diabetes mellitus and hypertension was referred to the Emory Renal Clinic for evaluation of increased serum creatinine (SCr). The patient had hypertension for 7 years, type II diabetes mellitus known for 5 years without any documented complications, mild anemia, dyslipidemia, and a baseline SCr of 1.0？mg/dL about 6 months prior to referral. There was no recorded quantification of proteinuria or microalbuminuria since she had been diagnosed with diabetes. Her surgical history was only significant for tonsillectomy. She was single and had never been pregnant. Her medication list included stable doses of Lisinopril, Atenolol, and Pioglitazone. She denied any NSAID use. Her family history was negative for cancers, hypertension, diabetes, or chronic kidney disease. Social history was negative for alcohol, tobacco, or illicit drug abuse. She was a college graduate who worked as a microbiologist. The patient had been well until 2 years earlier, when she presented with posttraumatic bruising of her right breast. After resolution of the
References
[1]
C. Ramazzina, Y. Z. Aschmann, O. Kummer, A. E. R. Bravo, and M. Bodmer, “Zoledronate-associated end stage renal failure and hypocalcaemia,” Praxis, vol. 96, no. 17, pp. 673–678, 2007.
[2]
G. S. Markowitz, P. L. Fine, J. I. Stack et al., “Toxic acute tubular necrosis following treatment with zoledronate (Zometa),” Kidney International, vol. 64, no. 1, pp. 281–289, 2003.
[3]
K. Koike, K. Fukami, S. Morishige et al., “A case of acute kidney injury related to intravenous zoledronic acid in a patient with multiple myeloma,” Japanese Journal of Nephrology, vol. 51, no. 5, pp. 557–562, 2009.
[4]
T. K. Joensuu, “Renal toxicity following zoledronic acid reversed with ibandronate in a prostate cancer patient with bone metastases,” Urologia Internationalis, vol. 80, no. 4, pp. 448–450, 2008.
[5]
P. Conte and V. Guarneri, “Safety of intravenous and oral bisphosphonates and compliance with dosing regimens,” Oncologist, vol. 9, supplement 4, pp. 28–37, 2004.
[6]
V. Guarneri, S. Donati, M. Nicolini, S. Giovannelli, R. D'Amico, and P. F. Conte, “Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 years,” Oncologist, vol. 10, no. 10, pp. 842–848, 2005.
[7]
D. Banerjee, A. Asif, L. Striker, R. A. Preston, J. J. Bourgoignie, and D. Roth, “Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity,” American Journal of Kidney Diseases, vol. 41, article E18, 2003.
[8]
J. H. Lin, “Bisphosphonates: a review of their pharmacokinetic properties,” Bone, vol. 18, no. 2, pp. 75–85, 1996.
[9]
A. Lühe, K. Künkele, M. Haiker et al., “Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety,” Toxicology in Vitro, vol. 22, no. 4, pp. 899–909, 2008.
[10]
G. S. Markowitz, G. B. Appel, P. L. Fine et al., “Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate,” Journal of the American Society of Nephrology, vol. 12, no. 6, pp. 1164–1172, 2001.
[11]
J. R. Green, Y. Seltenmeyer, K. A. Jaeggi, and L. Widler, “Renal tolerability profile of novel, potent bisphosphonates in two short-term rat models,” Pharmacology and Toxicology, vol. 80, no. 5, pp. 225–230, 1997.
[12]
J. Body, T. Pfister, and F. Bauss, “Preclinical perspectives on bisphosphonate renal safety,” Oncologist, vol. 10, supplement 1, pp. 3–7, 2005.
[13]
N. Zojer, A. V. Keck, and M. Pecherstorfer, “Comparative tolerability of drug therapies for hypercalcaemia of malignancy,” Drug Safety, vol. 21, no. 5, pp. 389–406, 1999.
[14]
Zometa (Package Insert), Novartis Pharmaceuticals, Hanover, NJ, USA, 2005.
[15]
L. S. Rosen, D. Gordon, M. Kaminski et al., “Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial,” Cancer, vol. 98, no. 8, pp. 1735–1744, 2003.
[16]
T. Pfister, E. Atzpodien, and F. Bauss, “The renal effects of minimally nephrotoxic doses of ibandronate and zoledronate following single and intermittent intravenous administration in rats,” Toxicology, vol. 191, no. 2-3, pp. 159–167, 2003.
[17]
R. Bell, “Efficacy of ibandronate in metastatic bone disease: review of clinical data,” Oncologist, vol. 10, supplement 1, pp. 8–13, 2005.
[18]
A. Heidenreich, C. Ohlmann, P. Olbert, and A. Hegele, “High-dose ibandronate is effective and well tolerated in the treatment of pain and hypercalcemia due to metastatic urologic cancer,” European Journal of Cancer, vol. 1, supplement 5, article S70, 2003.
[19]
C. Ohlmann and A. Heidenreich, “Efficacy of ibandronate in the management of painful osseous metastases due to hormone refractory prostate cancer,” Supportive Care Cancer, vol. 11, p. 396, 2003.
[20]
J. T. Chang, L. Green, J. Beitz, P. Tarassoff, Y. Hei, and D. Maladorno, “Renal failure with the use of zoledronic acid,” The New England Journal of Medicine, vol. 349, no. 17, pp. 1676–1679, 2003.
[21]
A. Munier, V. Gras, M. Andrejak et al., “Zoledronic acid and renal toxicity: data from French adverse effect reporting database,” Annals of Pharmacotherapy, vol. 39, no. 7-8, pp. 1194–1197, 2005.
[22]
I. J. Diel, R. Weide, H. K？ppler et al., “Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review,” Supportive Care in Cancer, vol. 17, no. 6, pp. 719–725, 2009.
