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Evaluation of estimated glomerular function (eGFR) versus creatinine clearance (CrCl) to predict acute kidney injury when using zoledronate for the treatment of osteoporosis



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.


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.


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.


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.


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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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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The authors confirm that the manuscript is original and has not been submitted elsewhere. Each author acknowledges that he/she has contributed in a substantial way to the work described in the manuscript and its preparation.

Corresponding author

Correspondence to M. Schini.

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Not applicable (service evaluation).

Conflict of interest

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 (2021).

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  • Acute kidney injury
  • Bisphosphonate
  • Kidney
  • Osteoporosis
  • Zoledronate
  • Zoledronic acid