EP04 Hypercalcaemia of sarcoidosis in a patient with severe renal impairment successfully treated with denosumab

Abstract

Background: Denosumab has been used for the management of hypercalcaemia of malignancy where bisphosphonates are contraindicated (e.g. due to severe renal impairment). Unlike bisphosphonates, denosumab is not cleared by the kidneys. In one case report of a patient with multiple myeloma and severe renal impairment, denosumab therapy was associated with improvement in renal function. There are limited data for its use in the management of resorption related hypercalcaemia due to other causes including sarcoidosis. Method(s): We present the case of a 60 year old female with background chronic kidney disease (CKD), diabetes mellitus with severe retinopathy, non-alcoholic fatty liver disease, hypertension, and previous stroke. She was diagnosed with biopsy-proven sarcoidosis after she was admitted with hypercalcaemia of 3.7mmol/L. Her parathyroid hormone (PTH) was suppressed and total 25 vitamin D was low at 35 nmol/L. CT scan showed splenomegaly and multiple enlarged lymph nodes in the chest and abdomen. Lungs were clear. A CT guided para-aortic lymph node biopsy revealed non-caseating epithelioid granulomas with multinucleated giant cells. Her hypercalcaemia initially responded to intravenous hydration, high doses of oral and intravenous glucocorticoids, and pamidronate. Azathioprine was later started and the dose gradually titrated. However on reducing the dose of oral prednisolone, serum calcium started to rise reaching 2.9mmol/L in February 2019. Her eGFR was 22mL/min. Using FRAX, her 10 year probability of major osteoporotic and hip fracture was 13% and 1.1% respectively. Result(s): The patient was given denosumab 60mg via subcutaneous route in March 2019 and her calcium has been normal since (see table). This is associated with improvement in renal function. Her PTH which was suppressed at presentation (0.7) was raised at 21.3 (normal range 1.3 - 9.3) pmol/L when last checked in September 2019, as would be expected in CKD. She is currently on 7mg of prednisolone and gradually weaning off. She remains on azathioprine 100mg BD. Conclusion(s): We conclude that denosumab could be an option for the management of hypercalcaemia of sarcoidosis if bisphosphonates are contraindicated. More data are required to establish safety at variable degrees of renal impairment and to identify an optimal dose for this indication.