Background The safety of Denosumab, a fully human monoclonal antibody against RANKL, which was developed for treatment of osteoporosis and prevention of fractures, remains unclear in kidney transplanted patients.
Objectives Our aim was to assess its clinical and biological tolerance in this specific population.
Methods Design: Prospective observational monocentric cohort. Inclusion criteria: kidney transplant recipient who received at least one subcutaneous injections of 60 mg denosumab; age ≥18 years.
Safety assessment: the following variables were collected every 6 months: infection, reaction at the injection site, plasmatic parameters of renal function and mineral metabolism (estimated glomerular filtration rate, serum creatinine, calcium, 1–25 [OH] vitamin D, PTH).
Results Patients were recruited from April 2014 to September 2015. All patients received immunosuppression therapy including prednisolone ≥5 mg/d. The main baseline characteristics of the 37 kidney transplant recipients were the following [mean]: male: 41%, age: 60.5 years, BMI: 24,1, transplantation duration: 7.1 years, osteopenic patients: 36%, osteoporosis patients: 64%, total lumbar spine T-score: -2.04 SD, total hip T-score: -2.7 SD, T-score femoral neck: 0.676 g/cm2, serum creatinine: 132.8 mmol/L, calcium: 2.33 mmol/L, 1–25 [OH] vitamin D: 93.5 nmol/L, PTH 95: ng/l. All patients were prescribed vitamin D and calcium supplementation.
During the mean 12-month follow-up period, there were no unexpected adverse event [AE] or severe adverse event, no graft failure and no deaths. No patient experienced fracture. Only one patient presented an infectious AE with recurrent cutaneous abscess. Renal function remained stable with no difference in serum creatinine between baseline and 12 months for the majority of the kidney transplant recipients. However, 9 recipients experienced a decrease in renal function with a mean increased in serum creatinine of 32.5micromol/L between baseline and 12 months. Serum calcium was stable, no hypocalcaemia was observed. Among patients with normal baseline PTH, two presented hyperparathyroidism during the follow-up period. Among the 11 patients with baseline hyperparathyroidism, 7 had an increased PTH level between baseline and 12 months. None were initiated on cinacalcet.
Conclusions Our results suggest that denosumab is safe in kidney transplant recipients. We did not observe an increase in the infection rates, nor hypocalcemia. However, several patients experienced a decrease in their renal function or an increased hyperparathyroidism.
Disclosure of Interest None declared