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      SGLT-2 inhibitors may increase ultrafiltration in incident peritoneal dialysis patients: a case report

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          Abstract

          Background

          Adequate fluid removal to achieve euvolemic status can be difficult in patients with incident peritoneal dialysis (PD). Limited treatments such as increased high dextrose PD solutions and icodextrin are currently available. We reported four incident PD patients whose’ ultrafiltration volume was increased after sodium-glucose cotransporter-2 inhibitors.

          Case presentation.

          The four reported cases were diabetic kidney disease stage 5 (cases 1–3) and IgA nephritis (case 4) patients whostartedt PD because of acute pulmonary edema (case 1 and 3), nausea vomiting (case 2), and hyperkalemia (case 4). They had an ultrafiltration volume of 700-1000 ml per day but hpersistentted peripheral pitting edema or pulmonary edema. Their ultrafiltration volincreased after dapagliflozin 5 mg daily, and the fluid overload symptoms ere improved. No hypotension, or hypoglycemia was found, and the urine was not increased during dapagliflozin treatment.

          Conclusions

          SGLT-2 inhibitors may increase ultrafiltration in incident PD patients. More studies are needed to support the safety of SGLT-2 inhibitors in PD patients.

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          Most cited references6

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          Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects.

          Dapagliflozin selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter-2 (SGLT2). It was developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug were evaluated in single-ascending-dose (SAD; 2.5-500 mg) and multiple-ascending-dose (MAD; 2.5-100 mg daily for 14 days) studies in healthy subjects. Dapagliflozin exhibited dose-proportional plasma concentrations with a half-life of approximately 17 h. The amount of glucosuria was also dose-dependent. Cumulative amounts of glucose excreted on day 1, relating to doses from 2.5-100 mg (MAD), ranged from 18 to 62 g; day 14 values were comparable to day 1 values, with no apparent changes in glycemic parameters. Doses of approximately 20-50 mg provided close-to-maximal SGLT2 inhibition for at least 24 h. Dapagliflozin demonstrates pharmacokinetic (PK) characteristics and dose-dependent glucosuria that are sustained over 24 h, which indicates that it is suitable for administration in once-daily doses and suggests that further investigation of its efficacy in T2DM patients is warranted.
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            The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

            Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of these new therapy classes and if they have renoprotective effects in patients with CKD.
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              SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate

              Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. PM structural changes, ultrafiltration capacity, and peritoneal equilibration testing (PET) status for glucose, urea, and creatinine were analyzed. Expression of SGLT and facilitative glucose transporters (GLUT) was analyzed by real-time PCR, immunofluorescence, and immunohistochemistry. Peritoneal effluents were analyzed for cellular and cytokine composition. We found that peritoneal SGLT2 was expressed in mesothelial cells and in skeletal muscle. Dapagliflozin significantly reduced effluent transforming growth factor (TGF-β) concentrations, peritoneal thickening, and fibrosis, as well as microvessel density, resulting in improved ultrafiltration, despite the fact that it did not affect development of high-glucose transporter status. In vitro, dapagliflozin reduced monocyte chemoattractant protein-1 release under high-glucose conditions in human and murine peritoneal mesothelial cells. Proinflammatory cytokine release in macrophages was reduced only when cultured in high-glucose conditions with an additional inflammatory stimulus. In summary, dapagliflozin improved structural and functional peritoneal health in the context of high-glucose PD.
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                Author and article information

                Contributors
                cychou.chou@gmail.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                22 April 2023
                22 April 2023
                2023
                : 24
                : 106
                Affiliations
                [1 ]GRID grid.252470.6, ISNI 0000 0000 9263 9645, Division of Nephrology, , Asia University Hospital, ; Wufeng, Taichung, Taiwan
                [2 ]GRID grid.411508.9, ISNI 0000 0004 0572 9415, Division of Nephrology, , China Medical University Hospital, ; Taichung, Taiwan
                [3 ]GRID grid.252470.6, ISNI 0000 0000 9263 9645, Department of Post-Baccalaureate Veterinary Medicine, , Asia University, ; NO 222, Fuxin Rd, Wufeng Dist, Taichung 413, Taiwan
                Author information
                http://orcid.org/0000-0003-4029-9097
                Article
                3164
                10.1186/s12882-023-03164-8
                10122385
                37087421
                1f94ad29-e120-44d3-80d7-965c4ea98a21
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 January 2021
                : 11 April 2023
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2023

                Nephrology
                peritoneal dialysis,ultrafiltration,sglt-2 inhibitors,case report
                Nephrology
                peritoneal dialysis, ultrafiltration, sglt-2 inhibitors, case report

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