Abstract
Summary
Zoledronate could be contributing to the development of acute kidney injury in a small number of patients. Since estimated glomerular function (eGFR) is simpler to obtain and at least as good a predictor as creatinine clearance (CrCl), it should be used in everyday practice.
Introduction
Zoledronate is widely used for the treatment of osteoporosis. A potential side effect is acute kidney injury (AKI). Advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) in 2019 stated that CrCl and not estimated glomerular filtration rate (eGFR) should be used and that treatment should not be given if CrCl < 35 ml/min. The objective of this study was to compare our current method of assessing renal function (eGFR) with the method proposed by the MHRA (CrCl) for predicting AKI after zoledronate infusions.
Methods
The evaluation was performed at the Metabolic Bone Centre in Sheffield Teaching Hospitals, UK. Data on all the patients who had zoledronate from 1/09/2015 to 1/10/2020 were included.
Results
Data on 4405 patients were retrieved (total number of infusions 7660). Creatinine in the 14 days post-infusion was available for a total of 969 infusions and AKI was observed within 14 days following 45 infusions (4.6%). One patient died due to pneumonia. One patient needed continued haemodialysis. Severe AKI (threefold in creatinine and/or eGFR < 15 ml/min/173 m2) was observed within 1 year following 24 infusions. If the MHRA recommendations had been followed, 996 infusions with baseline CrCl < 35 ml/min would not have been given. Of these, follow-up data on serum creatinine within 14 days were available for 142 infusions, showing AKI in only four (2.8%). Logistic regression showed that both CrCl and eGFR were significant factors in predicting AKI within 14 days, but that the current recommended cut-off of CrCl 35 ml/min had poor sensitivity.
Conclusion
Since eGFR is at least as good a predictor of AKI as CrCl, and permits the treatment of more patients at high fracture risk, we recommend that eGFR is used to determine renal function for zoledronate treatment. We suggest that the infusion is given over 30 min in patients with eGFR < 50 ml/min/1.73 m2.
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References
Perazella MA, Markowitz GS (2008) Bisphosphonate nephrotoxicity. Kidney Int 74:1385–1393
EMC Zoledronic acid 5 mg solution for infusion. https://www.medicines.org.uk/emc/medicine/28527#gref. Accessed 15 October 2021
MHRA (2019) Prescribing medicines in renal impairment: using the appropriate estimate of renal function to avoid the risk of adverse drug reactions. https://www.gov.uk/drug-safety-update/prescribing-medicines-in-renal-impairment-using-the-appropriate-estimate-of-renal-function-to-avoid-the-risk-of-adverse-drug-reactions. Accessed 15 October 2021
KDIGO (2012) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf. Accessed 15 October 2021
Kellum JA, Lameire N, Group KAGW (2013) Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 17:204
Levey AS, Stevens LA (2010) Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 55:622–627
Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822
Boonen S, Sellmeyer DE, Lippuner K, Orlov-Morozov A, Abrams K, Mesenbrink P, Eriksen EF, Miller PD (2008) Renal safety of annual zoledronic acid infusions in osteoporotic postmenopausal women. Kidney Int 74:641–648
Miller PD, Jamal SA, Evenepoel P, Eastell R, Boonen S (2013) Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 28:2049
Miller PD, Ragi-Eis S, Mautalen C, Ramirez F, Jonkanski I (2011) Effects of intravenous ibandronate injection on renal function in women with postmenopausal osteoporosis at high risk for renal disease–the DIVINE study. Bone 49:1317–1322
Lyles KW, Colón-Emeric CS, Magaziner JS et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809
Reid DM (2009) Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 373:1253
Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Bastin S, Gamble GD (2020) Effects of zoledronate on cancer, cardiac events, and mortality in osteopenic older women. J Bone Miner Res 35:20–27
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
Grey A, Bolland MJ, Horne A, Mihov B, Gamble G, Reid IR (2017) Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial. CMAJ 189:E1130–E1136
Abrahamsen B, Ernst MT, Smith CD, Nybo M, Rubin KH, Prieto-Alhambra D, Hermann AP (2020) The association between renal function and BMD response to bisphosphonate treatment: real-world cohort study using linked national registers. Bone 137:115371
Jiang HX, Majumdar SR, Dick DA, Moreau M, Raso J, Otto DD, Johnston DW (2005) Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res 20:494–500
Acknowledgements
The authors would like to thank all the medical staff at the Metabolic Bone Centre for their contribution to the work.
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MS receives consultancy from Kyowa Kirin International and grant funding from Roche Diagnostics. SS received research funding from IDS. RE receives consultancy funding from IDS, Sandoz, Nittobo, Samsung, Haoma Medica, CL Bio, Biocon, Amgen, Hindustan Unilever, Pharmacosmos, Takeda and Viking and grant funding from Nittobo, Roche, Pharmacosmos and Alexion. JSW Speaker's honoraria from Eli Lilly and Sandoz, grant funding from Alexion, donation of drug from Eli Lilly and Consilient for clinical studies, consulting fees from Mereo Biopharma. NP, LTU, ET and AK declare they have no conflict of interest.
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Schini, M., Peel, N., Toronjo-Urquiza, L. et al. Evaluation of estimated glomerular function (eGFR) versus creatinine clearance (CrCl) to predict acute kidney injury when using zoledronate for the treatment of osteoporosis. Osteoporos Int 33, 737–744 (2022). https://doi.org/10.1007/s00198-021-06160-6
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DOI: https://doi.org/10.1007/s00198-021-06160-6