SUN-508 Intravenous Bisphosphonates Induced Renal Injury with Nephrotic Range Proteinuria in a Patient with Severe Hypercalcemia Secondary to Parathyroid Carcinoma

Abstract

Background: Bisphosphonates is a known therapeutic option for PTH dependent hypercalcemia. We report a patient who developed nephrotic range proteinuria after treatment with Bisphosphonates for severe hypercalcemia in parathyroid carcinoma (PTHCa). Clinical Case: A 43 year old male with PTHCa presented with corrected serum calcium (Sr Ca) of 16.1 [8.5-10.5 mg/dl] and iPTH of 1116 [6.0-65.0 pg/mL]. He had undergone two surgeries for the parathyroid mass 7 years prior to presentation at another hospital and was lost to follow up for 5 years. At admission he was treated with IV fluids, calcitonin and IV Pamidronate [IVP] 90mg with improvement in calcium within 1-2 day. Imaging showed a 1.7cm mediastinal mass. Subsequently he had frequent hospitalizations due to recurrence of hypercalcemia. He was started on cinacalcet and was unable to tolerate it due to severe nausea. Hence, he received almost weekly bisphosphonate infusions, 6 doses of IVP and 2 doses of IV zoledronic acid (ZA) in 3 months. He then underwent surgery to removal the mediastinal mass which was lymphoid tissue only. He had persistent high iPTH (1206 pg/ml) and Sr Ca 17.4 mg/dl. He received 3 cycles of chemotherapy with transient improvement in Sr Ca, with subsequent recurrence of hypercalcemia. As there was no structural disease noted on imaging, he was treated medically. During the subsequent 6 month after surgery, patient received further 8 doses of IVP 90mg and 3 doses of IV ZA 4mg. Repeat imaging 4 months later, showed a new mediastinal mass, 2.6 cm invading trachea for which he had another surgery. Post-surgery, iPTH was low (84.6 pg/ml) and he developed hypocalcemia. However, hypercalcemia recurred and he was noted to have proteinuria with progressive worsening serum creatinine from baseline 1.3 [0.6-1.4 mg/dl] to 4.1 mg/dl. This was seen after 14 doses of IVP 90mg and 5 doses of ZA over a period of 9 months. 24-hour urine protein was 12gm/24hr. Workup for proteinuria including Hepatitis panel, HIV, RPR, ANA, C3/C4, SPEP were unremarkable. Renal US showed markedly echogenic kidneys suggesting medical renal disease. Patient declined renal biopsy. Bisphosphonate induced focal segmental glomerulosclerosis [FSGS] with nephrotic range proteinuria was diagnosed after exclusion of other etiologies. Conclusion: In experimental models, bisphosphonates especially Pamidronate has shown to cause kidney injury in a dose-dependent pattern. It is a rare complication with very few cases reported in the literature and most of them in breast cancer patients. We are reporting the same in a patient with PTHCa. Multiple mechanisms have been proposed to cause nephrotic range proteinuria including collapsing FSGS, mitochondrial apoptosis in podocytes and/or proximal tubular cells by IVP and ATN by ZA. In patients requiring large and frequent dose of bisphosphonates monitoring for proteinuria may help in early detection.