1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Severe Hypocalcemia and Dramatic Increase in Parathyroid Hormone after Denosumab in a Dialysis Patient: A Case Report and Review of the Literature

      case-report
      1 , 2 , , 2 , 2 , 3
      Case Reports in Nephrology
      Hindawi

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequently present in advanced stages of chronic kidney disease (CKD) patients with high risk of fracture and elevated socioeconomic burden. Denosumab, an injectable human monoclonal antibody with affinity for nuclear factor-kappa ligand (RANKL), is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, the pharmacokinetics and pharmacodynamics of denosumab are not influenced by the renal function and are being increasingly used for patients having CKD-MBD with low bone mineral density (BMD) to reduce the risk of fragility fractures. Hypocalcemia is a known side effect of this drug along with compensatory increase in parathyroid hormone (PTH). However, limited information is available in the literature regarding this potentially life-threatening side effect with denosumab in end-stage renal disease (ESRD) patients on dialysis. We present a patient with ESRD on peritoneal dialysis who developed severe symptomatic hypocalcemia and dramatic increase in PTH following denosumab therapy. She was conservatively managed with calcium supplementation and appropriate adjustment in calcium dialysate. We have also reviewed the literature on the use of denosumab in dialysis patients and looked at additional factors that may precipitate severe hypocalcemia in these patients. We believe that denosumab should be used with caution in dialysis patients since it may lead to profound hypocalcemia. Clinicians should ensure special attention in recognizing patients at risk of developing this serious adverse effect, so that prompt treatment and preventive strategies can be implemented.

          Related collections

          Most cited references14

          • Record: found
          • Abstract: found
          • Article: not found

          Elimination mechanisms of therapeutic monoclonal antibodies.

          Targeted therapies using monoclonal antibodies have achieved important therapeutic applications in the treatment of various human diseases. Understanding the factors that impact the pharmacokinetics of monoclonal antibodies is of high importance for effective therapy. Many factors related to the target antigen, antibody and patients can affect antibody elimination. Evaluation of these factors will facilitate the understanding of the processes involved in antibody elimination.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Relationship between age, renal function and bone mineral density in the US population.

            Bisphosphonate drugs for treating osteoporosis are excreted by the kidney. However, many of the major trials on efficacy and safety of the bisphophonates for treating osteoporosis excluded patients with significant renal compromise. Since both osteoporosis and renal insufficiency become more prevalent with age, it seems prudent for physicians to be aware of the prevalence of renal dysfunction in patients with osteoporosis who are candidates for treatment with bisphosphonates. Data on 13,831 men and women aged 20+ from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) were used to study the occurrence of compromise in renal clearance function in men and women with osteopenia and osteoporosis. To estimate creatinine clearance (CCr), a measure of renal function, serum creatinine (sCr), weight and age were inserted into the Cockcoft-Gault (C-G) formula. The World Health Organization gender specific bone mineral density (BMD) cut-offs were used to define the populations with osteopenia and osteoporosis. For women ages 20-80+ with osteoporosis, the percent prevalence (95% CI) for mild to moderate compromise of CCr
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              Hypocalcemia Post Denosumab in Patients with Chronic Kidney Disease Stage 4-5

              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.
                Bookmark

                Author and article information

                Contributors
                Journal
                Case Rep Nephrol
                Case Rep Nephrol
                CRIN
                Case Reports in Nephrology
                Hindawi
                2090-6641
                2090-665X
                2019
                21 March 2019
                : 2019
                : 3027419
                Affiliations
                1Division of Pulmonary and Critical Care, St. Mary's of Michigan Medical Center, Saginaw, MI, USA
                2Department of Internal Medicine, Wayne State University, Detroit, MI, USA
                3Division of Nephrology, Department of Internal Medicine, Wayne State University, Detroit, MI, USA
                Author notes

                Academic Editor: Rumeyza Kazancioglu

                Author information
                http://orcid.org/0000-0001-8736-6811
                http://orcid.org/0000-0002-7733-8398
                http://orcid.org/0000-0003-1960-1730
                Article
                10.1155/2019/3027419
                6448326
                aa842da6-d7db-47b7-8b14-ea38049d7b04
                Copyright © 2019 Ravinder D. Bhanot et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 January 2019
                : 5 March 2019
                Categories
                Case Report

                Comments

                Comment on this article