Bisphosphonates May Treat Calciphylaxis in Kidney Transplant Recipients

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.

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