Combination Therapy of Denosumab and Calcitriol for a Renal Transplant Recipient with Severe Bone Loss due to Therapy-Resistant Hyperparathyroidism.

Denosumab (DMAb), a complete human type monoclonal antibody directed against the receptor activator of nuclear factor-κB ligand, has gained attention as a novel treatment for osteoporosis. However, its efficacy in patients with chronic kidney disease (CKD) remains unclear. We describe a 64-year-old man with severe bone loss and persistent secondary hyperparathyroidism (SHPT) after renal transplantation, whose condition failed to respond to conventional pharmacologic or surgical interventions. He underwent parathyroidectomy with left forearm autograft of crushed tiny parathyroid gland (PTG) particles. However, the autografted PTGs became swollen and caused persistent SHPT in spite of two additional parathyroidectomies of the left forearm. A single subcutaneous administration of DMAb induced hypocalcemia, which was corrected by calcium supplementation and high-dose calcitriol. Eventually, combination therapy with DMAb and calcitriol led to a decline in the patient's elevated serum parathyroid hormone levels, normalization of laboratory markers of bone metabolism, and improvement in bone mineral density in a short period of time. To the best of our knowledge, this is the first case report of severe bone loss with persistent SHPT in a renal transplant recipient effectively treated with the combination therapy of DMAb and vitamin D (VD). Although DMAb itself exerts no direct effects on PTGs, the DMAb treatment improved the patient's bone loss. In addition, administration of DMAb allowed for high-dose VD therapy which ultimately controlled SHPT and prevented DMAb-induced hypocalcemia. Therefore, this combination therapy might be a reasonable therapeutic strategy to reverse severe bone loss due to therapy-resistant SHPT in patients with CKD.

Light-Chain Deposition Disease Successfully Treated with Bortezomib in an Elderly Patient: A Case Report and Review of the Literature.

We herein report the case of an elderly patient with light-chain deposition disease (LCDD) successfully treated with bortezomib. An 83-year-old woman was admitted because of nephrotic syndrome. She was diagnosed to have monoclonal gammopathy of undetermined significance (IgG-κ type) and LCDD, on the basis of serum and urinary immunoelectrophoresis and renal biopsy. She responded to a modified regimen of bortezomib-based chemotherapy with disappearance of proteinuria without any adverse effects. According to a literature review of 16 cases, including the present case, bortezomib-based chemotherapy appears to be a convincing strategy for the treatment of LCDD even in elderly patients.

Intravenous phosphate loading increases fibroblast growth factor 23 in uremic rats.

Oral phosphate loading and calcitriol stimulate Fibroblast growth factor 23 (FGF23) secretion, but the mechanisms underlying the stimulation of FGF23 remain to be studied. We compared the effect of intravenous phosphate loading with that of oral loading on FGF23 levels in normal and 5/6 nephrectomized uremic rats. Uremic rats (Nx) and sham-operated rats were fed a normal phosphate diet for 2 weeks and then divided into 3 groups: 1) with the same phosphate diet (NP), 2) with a high phosphate diet (HP), and 3) NP rats with intravenous phosphate infusion using a microinfusion pump (IV). Blood and urine were obtained 1 day (early phase) and 7 days (late phase) after the interventions. In the early and late phases, serum phosphate levels and fractional excretion of phosphate (FEP) were comparable in the HP and IV groups in both Sham and Nx rats. Serum phosphate levels in the HP and IV groups were equally and significantly higher than those in the NP group only in the late phase in Nx rats. In the early phase, FGF23 levels were comparable in the NP, HP, and IV groups, but were significantly higher in the HP and IV groups compared to the NP group in the late phase in Nx rats. 1α-hydroxylase and sodium dependent phosphate co-transporter 2a expression levels in the kidney in Nx rats were equally and significantly decreased in the HP and IV groups compared with the NP group, while 24-hydroxylase expression was equally and significantly increased. These results show that chronic intravenous phosphate loading increases bioactive FGF23, indicating that an alternative pathway for FGF23 regulation, in addition to the dietary route, may be present. This pathway is clearer under conditions produced by a kidney injury in which phosphate is easily overloaded.