Bisphosphonates may be effective in treating calciphylaxis in kidney transplant recipients with persistent secondary hyperparathyroidism (SHPT) who cannot tolerate or respond poorly to sodium thiosulphate (STS), according to investigators.

Ho-Kwan Sin, MD, and colleagues from Kwong Wah Hospital in Hong Kong reported on 2 calciphylaxis cases treated with bisphosphonates in Transplantation Reports.

The first patient, a 62-year-old man, developed a painful left calf ulcer 8 cm x 5 cm over 2 months. The ulcer persisted despite antibiotics and surgical debridement. Biopsy showed extensive epidermal ulceration, subcutaneous fat necrosis, and granulation tissue formation. Mural calcification was noted in medium-sized deep dermis vessels which harbor intravascular thrombi, consistent with a diagnosis of calciphylaxis.

His medical history included diabetes mellitus, hypertension, atrial fibrillation, gout, end-stage kidney disease due to diabetic nephropathy, and deceased donor kidney transplant.


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At presentation, the man’s estimated glomerular filtration rate (eGFR) was stable at 23mL/min/1.73 m2. However, he displayed persistent SHPT with intact parathyroid hormone (iPTH) of 12pmol/L despite previous parathyroidectomy. Serum calcium and phosphate were normal, but serum alkaline phosphatase (ALP) was elevated to 234IU/L.

Clinicians halted warfarin (2.5mg daily) and alfacalcidol (0.25µg) and administered oral vitamin K1 (10 mg daily). To facilitate wound healing, they substituted tacrolimus (2.5mg daily) for sirolimus. Despite 4 months of intravenous sodium thiosulphate (STS; 25g thrice weekly), the patient did not improve. The clinicians then attempted intravenous pamidronic acid (30mg every 2 weeks for 5 doses). The man experienced complete remission of calciphylaxis in 4 months with no side effects. Hyperparathyroidism persisted (iPTH 20.1pmol/L), but the ALP decreased slightly (226 IU/L).

In the second case, a 60-year old man developed a painful nodule over the left thigh over 3 weeks that became ulcerated and discharged pus. Despite antibiotic therapy and surgical debridement, the ulcer failed to heal.

His history included a deceased donor kidney transplant following focal segmental glomerulosclerosis. The man subsequently experienced new-onset diabetes mellitus and numerous complications, including surgical wound dehiscence, Pneumocystis jiroveci pneumonia, and acute T cell-mediated rejection followed by polyoma BK virus-associated nephropathy.

At presentation, his eGFR was stable at 45mL/min/1.73m2, but he had persistent hyperparathyroidism with mild hypercalcemia.

The clinicians administered intravenous STS (25g thrice weekly) but stopped after 3 doses due to nausea and vomiting. They prescribed oral alendronic acid (70mg weekly for 2 doses). The ulcer healed more than halfway within a month with no side effects.

SHPT persisted (iPTH 24.4 pmol/L), but ALP fell from 318 to 127 IU/L. So the man underwent total parathyroidectomy. Complete remission of calciphylaxis occurred within 3 months.

 “Bisphosphonates appear to be an effective therapy for [kidney transplant recipients] with calciphylaxis who cannot tolerate or respond poorly to STS, particularly if they have persistent hyperparathyroidism post-transplantation,” Dr Sin’s team concluded.

Reference

Sin HK, Wong PN, Lo KY, et al. Successful treatment of calciphylaxis with bisphosphonates in kidney transplant recipients suffering from secondary hyperparathyroidism: A report of two cases. Transplant Rep. doi:10.1016/j.tpr.2020.100068

This article originally appeared on Renal and Urology News