Volume: 22 Issue: 1 January 2024 - Supplement - 1
FULL TEXT
Deviations of calcium, phosphate, parathyroid hormone, and vitamin D levels are the basis for the diagnosis of calcium-phosphate metabolism disorders. The plasma concentration of the biologically active form known as free calcium is regulated in a harmonious manner by its exchange in the bones and reabsorption by the kidneys. These steps take place under the control of parathyroid hormone and calcitriol. In the process of chronic kidney disease, the kidney cannot synthesize adequate calcitriol, and the resulting hypocalcemia and hyperphosphatemia cause the development of secondary hyperparathyroidism. Osteoporosis is a metabolic bone disease and is essentially the consequence of osteoclastogenesis-induced bone resorption that exceeds bone formation. Osteoporosis is common after kidney transplant. However, hypocalcemia following kidney transplant is rare. The hungry bone syndrome after parathyroidectomy is often responsible for this condition in the pretransplant period. Denosumab is a human monoclonal antibody developed against the receptor activator of nuclear factor kappa-B ligand (known as RANKL). Denosumab exerts an antiresorptive effect on bones by reducing differentiation into osteoclasts. It is an effective treatment option for osteoporosis in the general population. There is insufficient scientific data regarding the use of denosumab in kidney transplant patients. Here, we present the case of a kidney transplant recipient who developed severe hypocalcemia (serum calcium 4.7 mg/dL) after denosumab treatment for osteoporosis.
Key words : Calcitriol, Denosumab, Osteoclastogenesis, Osteogenesis, Osteoporosis
Case Report
A 58-year-old female patient with unknown primary diagnosis had received a kidney from a living donor (sibling) 21 years previously. She had presented with a history of hemodialysis for 5 months before transplant. The early posttransplant period had been uneventful. The patient had been receiving a maintenance immunosuppression therapy of prednisolone 5 mg/d, mycophenolate sodium 1080 mg/d, and cyclosporine 100 mg/d. The patient had experienced a progressive increase in intact parathyroid hormone (iPTH) levels in the past 5 years and developed secondary hyperparathyroidism. She was admitted to our clinic with weakness and fatigue, as well as spasm in her hands. On physical examination, the tests for Chvostek sign and Trousseau sign were positive. The laboratory analysis results at admission showed serum calcium 4.7 mg/dL, phosphorus 2.4 mg/dL, iPTH 1141 ng/L, albumin 41 g/L, urea 44 mg/dL, creatinine 1.8 mg/dL, glomerular filtration rate (GFR) 31 mL/min/1.72 m2, and calcifediol 13.6 μg/L (Table 1). A thorough investigation revealed that the patient had been treated with 2 consecutive doses of denosumab for osteoporosis (femoral neck T score 2.6) (Figure 1).
The results for biochemistry analysis before the induction of denosumab showed serum calcium 9.5 mg/dL, phosphorus 3.9 mg/dL, iPTH 282 ng/L, albumin 49 g/L, and GFR 30 mL/min/1.72 m2. She had not received simultaneous oral calcium and calcitriol therapy during denosumab treatment.
The patient immediately received intravenous calcium and vitamin D treatment, and serum calcium levels gradually increased to 8.5 mg/dL. After the calcium and phosphorus levels improved, the patient received only 0.5 μg calcitriol once daily as maintenance therapy. The outpatient biochemistry values at 6 months after treatment showed serum calcium 8.94 mg/dL, iPTH 211 ng/mL, phosphorus 3.6 mg/dL, and albumin 4.3 g/dL.
Discussion
Bone and mineral disorders are common in kidney transplant recipients. For this reason, such patients should be closely monitored for ongoing bone loss and regularly evaluated for bone mineral density. Osteoporosis treatment for organ recipients includes calcium and vitamin D supplementation and bisphosphonate administration. These options may be limited in patients with impaired allograft function. As an alternative treatment, the monoclonal antibody denosumab can be used.1-3 Denosumab is known to induce hypocalcemia in patients with severe chronic kidney disease (GFR <30 mL/min/1.72 m2, stages 4 and 5).4
Osteoporosis in the posttransplant period is an important risk factor for mortality and morbidity. There is no clear consensus on the treatment of osteoporosis in kidney recipients, and treatment is mostly based on experience with modalities applied to other patient groups. Renau and colleagues reported that osteoporosis is nearly 10 times more common in kidney transplant patients than otherwise healthy population.5 Spiechowicz and colleagues detected 20% osteoporosis and 50% osteopenia 4 years following renal transplant.6 Secondary hyperparathyroidism, vitamin D deficiency, and immunosuppressive drugs are often responsible for this condition.7
Denosumab may cause severe hypocalcemia in allograft recipients independent from GFR values.8 Also, denosumab treatment effectively increases bone mineral density and improves the T score of the lumbar spine and femoral neck. Our patient did not receive concomitant vitamin D and calcium replacement therapy during denosumab treatment; therefore, severe hypocalcemia developed. Intensive use of glucocorticoids in kidney transplant patients is associated with an increased risk of posttransplant osteoporosis. Glucocorticoids may exert this effect by reduction of osteoblast production or by induction of osteoblast apoptosis and promotion of osteoclastogenesis through the receptor activator of nuclear factor kappa-B ligand (known as RANKL) system. Denosumab can be preferred as an alternative treatment to bisphosphonates in patients with kidney disease, because bisphosphonates are eliminated via the kidneys and cannot be used in patients with GFR <30 mL/min/1.72 m2.9
In conclusion, clinicians should take great care when choosing denosumab. Especially, if they are planning to apply this treatment in kidney transplant patients, then they should consider concomitant vitamin D and calcium replacement therapy.10
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Volume : 22
Issue : 1
Pages : 342 - 344
DOI : 10.6002/ect.MESOT2023.P10
From the 1Department of Nephrology and Organ Transplantation Center, and the 2Department of General Surgery and Organ Transplantation Center, University of Health Sciences, Izmir Faculty of Medicine, Bozyaka Education and Research Hospital, Izmir-Turkey
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Murat Karatas, University of Health Sciences, Izmir Bozyaka Education and Research Hospital, Department of General Surgery and Transplantation, Karabaglar, Izmir 35100, Turkey
Phone: +90 2322505050
E-mail: drmuratkaratas@gmail.com
Table 1. The Patient’s Laboratory Results
Figure 1. The Patient’s Bone Mineral Density Results