Background: Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD). Methods: A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events. Results: Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QT_c). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration. Conclusions: A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

ABSTRACT:Management of mental health issues in the post-transplant setting can be difficult given the potential for medication related neurotoxicity. The lack of established guidelines in this area further compounds this difficulty. The current report details the course of patient with stable bipolar affective disorder prior to renal transplantation, who developed de novo psychosis post-transplantation as an adverse effect of her tacrolimus therapy. The patient was unable to take her usual oral immunosuppressants due to the severity of her psychosis and she eventually required alemtuzumab parenterally as rescue therapy from rejection. This case highlights the diagnostic and therapeutic challenges when dealing with transplant recipients with significant psychosis.

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