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      Treatment of Calciphylaxis in CKD: A Systematic Review and Meta-analysis

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          Abstract

          Background

          Calciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD.

          Methods

          Electronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses.

          Results

          A total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71–1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75–1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71–1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44–1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69–1.13).

          Conclusion

          This systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies.

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          Most cited references177

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          Calciphylaxis: risk factors, diagnosis, and treatment.

          Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in patients with chronic kidney failure treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal kidney function. In this review, we discuss the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and nonuremic calciphylaxis. High-quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence and poorly understood pathogenesis and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by a multidisciplinary team for patients with calciphylaxis.
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            Vascular calcification in chronic kidney disease: an update.

            Cardiovascular calcification is both a risk factor and contributor to morbidity and mortality. Patients with chronic kidney disease (and/or diabetes) exhibit accelerated calcification of the intima, media, heart valves and likely the myocardium as well as the rare condition of calcific uraemic arteriolopathy (calciphylaxis). Pathomechanistically, an imbalance of promoters (e.g. calcium and phosphate) and inhibitors (e.g. fetuin-A and matrix Gla protein) is central in the development of calcification. Next to biochemical and proteinacous alterations, cellular processes are also involved in the pathogenesis. Vascular smooth muscle cells undergo osteochondrogenesis, excrete vesicles and show signs of senescence. Therapeutically, measures to prevent the initiation of calcification by correcting the imbalance of promoters and inhibitors appear to be essential. In contrast to prevention, therapeutic regression of cardiovascular calcification in humans has been rarely reported. Measures to enhance secondary prevention in patients with established cardiovascular calcifications are currently being tested in clinical trials.
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              Distinguishing case series from cohort studies.

              Case series are a commonly reported study design, but the label "case series" is used inconsistently and sometimes incorrectly. Mislabeling impairs the appropriate indexing and sorting of evidence. This article tries to clarify the concept of case series and proposes a way to distinguish them from cohort studies. In a cohort study, patients are sampled on the basis of exposure and are followed over time, and the occurrence of outcomes is assessed. A cohort study may include a comparison group, although this is not a necessary feature. A case series may be a study that samples patients with both a specific outcome and a specific exposure, or one that samples patients with a specific outcome and includes patients regardless of whether they have specific exposures. Whereas a cohort study, in principle, enables the calculation of an absolute risk or a rate for the outcome, such a calculation is not possible in a case series.
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                Author and article information

                Contributors
                Journal
                Kidney Int Rep
                Kidney Int Rep
                Kidney International Reports
                Elsevier
                2468-0249
                09 October 2018
                February 2019
                09 October 2018
                : 4
                : 2
                : 231-244
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
                [2 ]Department of Medicine, St. Elizabeth’s Medical Center, Boston, Massachusetts, USA
                [3 ]Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA
                Author notes
                [] Correspondence: Paweena Susantitaphong, Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 10330. pesancerinus@ 123456hotmail.com
                Article
                S2468-0249(18)30223-7
                10.1016/j.ekir.2018.10.002
                6365410
                30775620
                305f6712-056b-476c-9a56-c33a7c4f536b
                © 2018 International Society of Nephrology. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 5 August 2018
                : 20 September 2018
                : 1 October 2018
                Categories
                Clinical Research

                calciphylaxis,chronic kidney disease,meta-analysis,systematic review

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