ORF34-01 - Low Dose Denosumab in the Management of Post-Transplant Tertiary Hyperparathyroidism

Denosumab is used in hypercalcemia management, most typically hypercalcemia of malignancy refractory to bisphosphonates. It is not formally recommended for tertiary hyperparathyroidism, and its use in patients with chronic kidney disease carries increased risk of hypocalcemia. Evidence for denosumab use in kidney transplant recipients with hypercalcemia remains limited.

We present the case of a 56-year-old male with a history of end-stage renal disease due to hypertensive nephrosclerosis, previously on dialysis, status post bilateral nephrectomy due to renal cell carcinoma and status post living unrelated kidney transplant, admitted with acute kidney injury and hypercalcemia approximately 1 month post-transplant.

Post-transplant days 2-3, he developed hypercalcemia (albumin-adjusted calcium 11.3 mg/dL-13.1 mg/dL, reference range (RR) 8.5-10.5 mg/dL) which resolved with intravenous fluids (IVF) and cinacalcet. Post-op day 22 he had recurrent hypercalcemia (10.9 mg/dL), elevated creatinine (2.9 mg/dL, RR 0.70-1.30 mg/dL), and elevated intact parathyroid hormone (PTH) (448 pg/mL, RR 10-65 pg/mL).

Renal biopsy showed patchy acute tubular injury with scattered calcifications. Imaging showed transplanted kidney calcinosis and renal calculi. Transplanted kidney ureter stent removal was difficult due to calcium encrustation.

Given persistent hypercalcemia despite IVF and cinacalcet, acute kidney injury, multiple kidney stones, and nephrocalcinosis, low dose denosumab 30 mg was administered subcutaneously. Serum calcium peaked at 12.7 mg/dL the following day and decreased to 11.0 mg/dL by day two.

During this time, he underwent successful removal of the encrusted ureteral stent, transplant percutaneous nephrolithotomy and transplant nephrostomy tube placement. Calcium normalized 3 days after denosumab. He did not become hypocalcemic (nadir 8.8 mg/dL at 7 days). 26 days after denosumab, calcium remained normal (9.7 mg/dL), creatinine improved (nadir 1.36 mg/dL), and phosphorus was low (1.3 mg/dL, RR 2.4-4.7 mg/dL).

49 days after denosumab, he underwent 3.5 gland parathyroidectomy with forearm reimplantation. Hypocalcemia was prevented with calcium carbonate and calcitriol pre- and post-operatively. Transient post-operative hypercalcemia (11.6 mg/dL on post-op day 6), resolved by day 23 (calcium 8.4 mg/dL) with PTH 235 pg/mL, now suggestive of secondary hyperparathyroidism.

In conclusion, low dose denosumab 30 mg may be an effective and safe option for treating post-transplant tertiary hyperparathyroidism with hypercalcemia refractory to cinacalcet, particularly when rapid calcium reduction is clinically necessary.