Background/Purpose:

Safety of denosumab, a fully human monoclonal antibody against RANKL developed for osteoporosis and prevention of fracture remains unclear in kidney transplanted patients.

A recent placebo-controlled trial has demonstrated its efficacy on bone mineral density (BMD) and bone turnover biomarkers (Bonani et al. Am J Transplant. 2016). Patients in the denosumab group experienced more episodes of cystitis and asymptomatic hypocalcemia than patients in the placebo group.

Our aim was to assess the clinical and biological tolerance of denosumab in this specific population.

Methods:

Prospective observational monocentric cohort.

Inclusion criteria: kidney transplant recipient who received at least one subcutaneous injections of 60 mg denosumab; age ≥ 18 years.

Safety outcomes: 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, osteopenia: 36%, osteoporosis: 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 32.5 micromol/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. None of them experienced severe hypercalcemia, nor hypocalcemia.

Conclusion:

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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-denosumab-in-a-monocentric-cohort-of-kidney-transplant-recipients/