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Diker Cohen T, Polansky A, Bergman I, Ayada G, Babich T, Akirov A, Steinmetz T, Dotan I. Safety of sodium-glucose cotransporter 2 inhibitors in kidney transplant recipients with diabetes mellitus. DIABETES & METABOLISM 2025; 51:101627. [PMID: 39956453 DOI: 10.1016/j.diabet.2025.101627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/11/2025] [Accepted: 02/12/2025] [Indexed: 02/18/2025]
Abstract
AIM Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important anti-hyperglycemic medications with reno-protective benefits for patients with diabetic kidney disease. Their utilization in kidney transplant recipients (KTRs) remains underexplored due to safety concerns, particularly regarding urinary tract infections. This study investigates the safety profile of SGLT2i therapy in KTRs. METHODS We conducted a retrospective analysis of KTRs with diabetes mellitus, comparing those treated with SGLT2i to those on standard diabetes therapy, monitored over three years at a tertiary center. The primary outcome was a renal composite of dialysis, re-transplantation, acute kidney failure, or acute rejection. Secondary outcomes included urinary tract infections, diabetic ulcers, fractures, amputations, diabetic ketoacidosis, all-cause mortality, and glycemic control. RESULTS Two hundred forty individuals using SGLT2i (median age 63, 20 % female) were matched with non-users. SGLT2i users had a lower incidence of the composite renal outcome (8.9 vs. 13.3 events per 100 patient-years), but after adjustment for independent predictors, the risk was similar (HR 0.99, 95 % CI 0.65-1.52, P = 0.970). Other outcomes showed comparable or lower risks in SGLT2i users. Glycemic control improved more significantly in SGLT2i users. CONCLUSION In KTRs with diabetes, SGLT2i therapy improved glycemic control without increased safety concerns compared to standard treatments. Both groups exhibited similar risks of significant kidney-related events and all-cause mortality. These findings provide crucial insights into the existing limited data concerning this vulnerable population, which faces elevated risks of renal complications and medication-related adverse effects. Ongoing randomized controlled trials will provide additional safety data for SGLT2i in KTRs.
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Affiliation(s)
- Talia Diker Cohen
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Polansky
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Idan Bergman
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal Medicine C, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Gida Ayada
- Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel of Technology, Bat Galim, Haifa, Israel
| | - Tanya Babich
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Research authority, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Amit Akirov
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tali Steinmetz
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Nephrology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Idit Dotan
- Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Salvadori M, Rosati A, Rosso G. Update on Sodium Glucose Cotransporter Type 2 Inhibitors Use in Kidney Transplant Patients. TRANSPLANTOLOGY 2024; 5:224-233. [DOI: 10.3390/transplantology5030022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Sodium glucose cotransporter type 2 inhibitors are a new class of drugs that act on the cardiovascular system, kidneys and metabolism in a multiple ways. Indeed, even though their principal action involves the transport of sodium and glucose in the convoluted distal tubule, they have multiple actions, such as antifibrotic and endothelial protective effects. Their principal mechanism consists of the loss of sodium and glucose. Therefore, they affect blood pressure and glucose metabolism. Their first use was in the diabetic general population; later, some studies documented their activity in the nondiabetic general population and in heart failure in chronic kidney disease patients. Only in recent years have several small studies documented the efficacy of these drugs in diabetic and nondiabetic kidney transplant patients; relatively large studies are rare, very recent, and open new routes for the development of these drugs.
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Affiliation(s)
- Maurizio Salvadori
- Department of Renal Transplantation, Careggi University Hospital, Viale Pieraccini 18, 50139 Florence, Italy
| | - Alberto Rosati
- Division of Nephrology, San Giovanni di Dio Hospital, 50143 Florence, Italy
| | - Giuseppina Rosso
- Division of Nephrology, San Giovanni di Dio Hospital, 50143 Florence, Italy
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Molaei E, Molaei A, Dashti-Khavidaki S, Nasiri-Toosi M, Abbasi MR, Jafarian A. Could the administration of SGLT2i agents serve as a viable prophylactic approach against CNI-induced toxicities? Med Hypotheses 2024; 189:111417. [DOI: 10.1016/j.mehy.2024.111417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Schork A, Eberbach ML, Artunc F, Bohnert BN, Eisinger F, Heister DJ, Vosseler D, Nadalin S, Birkenfeld AL, Heyne N, Guthoff M. SGLT2 Inhibitors Correct Fluid Overload in Adult Kidney Transplant Recipients-A Prospective Observational Study. Transpl Int 2024; 37:12879. [PMID: 38915756 PMCID: PMC11194332 DOI: 10.3389/ti.2024.12879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 05/29/2024] [Indexed: 06/26/2024]
Abstract
In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m2 (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.
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Affiliation(s)
- Anja Schork
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Marie-Luise Eberbach
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Ferruh Artunc
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
- Department of Cardiology and Nephrology, Sindelfingen Hospital, Sindelfingen, Germany
| | - Bernhard N. Bohnert
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Felix Eisinger
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - David J. Heister
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Dorothea Vosseler
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Silvio Nadalin
- Department of General and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Andreas L. Birkenfeld
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Nils Heyne
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
| | - Martina Guthoff
- Department of Internal Medicine IV, Division of Diabetology, Endocrinology, Nephrology, University Hospital Tübingen, Tübingen, Germany
- Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Tübingen, Germany
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Mreyoud H, Walter K, Wilpula E, Park JM. The efficacy and safety of sodium-glucose cotransporter-2 inhibitors in solid organ transplant recipients: A scoping review. Pharmacotherapy 2024; 44:444-466. [PMID: 38773917 DOI: 10.1002/phar.2928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 04/03/2024] [Accepted: 04/06/2024] [Indexed: 05/24/2024]
Abstract
Sodium glucose co-transporter 2 (SGLT2) inhibitors are used for the treatment of diabetes and for their cardiovascular and kidney benefits in patients with or without diabetes. Use in solid organ transplant recipients is controversial because transplant recipients were excluded from the major clinical trials assessing SGLT2 inhibitors. The goal of this review was to assess the available literature regarding the use of SGLT2 inhibitors in solid organ transplant recipients. A PubMed search was conducted for studies published in English through December 31, 2023. Studies were excluded if they were meta-analyses, review articles, commentaries, single case reports, or in vitro studies, or did not involve the use of SGLT2 inhibitors in solid organ transplant recipients with a diabetic, cardiovascular, or kidney outcome being assessed. In the final review, 20 studies were included: kidney (n = 15), heart (n = 4), and liver/lung/kidney (n = 1) transplant recipients. SGLT2 inhibitors had similar A1c reduction efficacy and were found to be weight neutral with possible weight reduction effects. Cardiovascular and kidney outcomes were not adequately assessed in the available studies. Adverse effects were reported to occur at a similar rate in transplant recipients compared to the general population. SGLT2 inhibitors were initiated ≥1-year post-transplant in most transplant recipients included in these studies. The overall safety and antihyperglycemic efficacy of SGLT2 inhibitors in kidney and heart transplant recipients is similar to the general population. Data assessing SGLT2 inhibitors use in solid organ transplant recipients for longer durations are needed.
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Affiliation(s)
| | | | | | - Jeong M Park
- Michigan Medicine, Ann Arbor, Michigan, USA
- College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA
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6
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Polychronopoulou E, Bourdon F, Teta D. SGLT2 inhibitors in diabetic and non-diabetic kidney transplant recipients: current knowledge and expectations. FRONTIERS IN NEPHROLOGY 2024; 4:1332397. [PMID: 38685973 PMCID: PMC11056593 DOI: 10.3389/fneph.2024.1332397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 04/03/2024] [Indexed: 05/02/2024]
Abstract
The beneficial effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown recently in numerous randomized controlled trials (RCT) and systematic reviews. According to KDIGO guidelines, SGLT2i currently represent a first choice for diabetic patients with chronic kidney disease (CKD). In addition, a recent meta-analysis of 13 large led by the 'SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium' (SMART-C) provided solid evidence of SGLT2i beneficial effects in CKD or in patients with heart failure, with and without diabetes. Collectively, the patients treated with SGLT2i had a decreased risk of CKD progression, acute kidney injury (AKI), end-stage kidney disease (ESKD) or death from heart failure. Whether these cardio-renal benefits should be extrapolated to kidney transplant recipients (KTR) needs to be assessed in further studies. In this article, we report recent data accumulated so far in the literature, looking at the efficacy and safety of SGLT2i in diabetic and non-diabetic KTR. We found encouraging data regarding the use of SGLT2i in KTR with diabetes. These agents appeared to be safe, and they reduced body weight and blood pressure in this group of patients. Potential effects on kidney graft function and survival are yet to be investigated.
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Affiliation(s)
- Erietta Polychronopoulou
- Service of Nephrology, Hôpital du Valais, Sion, Switzerland
- Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Fanny Bourdon
- Service of Nephrology, Hôpital du Valais, Sion, Switzerland
| | - Daniel Teta
- Service of Nephrology, Hôpital du Valais, Sion, Switzerland
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7
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Mottl AK, Nicholas SB. KDOQI Commentary on the KDIGO 2022 Update to the Clinical Practice Guideline for Diabetes Management in CKD. Am J Kidney Dis 2024; 83:277-287. [PMID: 38142396 DOI: 10.1053/j.ajkd.2023.09.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 09/20/2023] [Indexed: 12/25/2023]
Abstract
The Kidney Disease: Improving Global Outcomes (KDIGO) guideline for diabetes management in chronic kidney disease (CKD) was updated in 2022, just 2 years after the previous update. The need for this rapid update is reflective of the recent and unprecedented positive results of numerous clinical trials aimed at reducing kidney and cardiovascular morbidity and mortality in people with diabetes. The Kidney Disease Outcomes Quality Initiative (KDOQI) work group for diabetes in CKD, convened by the National Kidney Foundation, provides herein a commentary on these changes, particularly the implications for health care in the United States. Changes to the KDIGO guideline mirror the evolution of sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists from purely antihyperglycemic agents to cardiorenal-metabolic therapeutics, and the lower estimated glomerular filtration rate of≥20mL/min/1.73m2 for SGLT2 inhibitor initiation. New data have also brought the addition of the first-in-class, Federal Drug Administration-approved nonsteroidal mineralocorticoid receptor antagonist finerenone as an agent to reduce cardiorenal end points. While there has been significant progress in innovation, there remain serious challenges to implementation, particularly in the United States where inequities in insurance coverage and high costs limit their use, particularly in vulnerable populations, ultimately widening health care disparities.
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Affiliation(s)
- Amy K Mottl
- Division of Nephrology, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina, Chapel Hill, North Carolina.
| | - Susanne B Nicholas
- Divisions of Nephrology and Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
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Sharif A, Chakkera H, de Vries APJ, Eller K, Guthoff M, Haller MC, Hornum M, Nordheim E, Kautzky-Willer A, Krebs M, Kukla A, Kurnikowski A, Schwaiger E, Montero N, Pascual J, Jenssen TG, Porrini E, Hecking M. International consensus on post-transplantation diabetes mellitus. Nephrol Dial Transplant 2024; 39:531-549. [PMID: 38171510 PMCID: PMC11024828 DOI: 10.1093/ndt/gfad258] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Indexed: 01/05/2024] Open
Abstract
Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Harini Chakkera
- Division of Nephrology and Hypertension, Mayo Clinic, Scottsdale, AZ, United States of America
| | - Aiko P J de Vries
- Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Kathrin Eller
- Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz Austria
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany
| | - Maria C Haller
- Ordensklinikum Linz, Elisabethinen Hospital, Department of Medicine III, Nephrology, Hypertension, Transplantation, Rheumatology, Geriatrics, Linz, Austria
- Medical University of Vienna, CeMSIIS, Section for Clinical Biometrics, Vienna, Austria
| | - Mads Hornum
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Espen Nordheim
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Nydalen, Norway
- Department of Nephrology, Oslo University Hospital-Ullevål, Oslo, Nydalen, Norway
| | - Alexandra Kautzky-Willer
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
| | - Michael Krebs
- Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
| | - Aleksandra Kukla
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States of America
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States of America
| | - Amelie Kurnikowski
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Elisabeth Schwaiger
- Department of Internal Medicine, Brothers of Saint John of God Eisenstadt, Eisenstadt, Austria
| | - Nuria Montero
- Nephrology Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, University of Barcelona, Barcelona Spain
| | - Julio Pascual
- Institute Mar for Medical Research-IMIM, Barcelona,Spain
- Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Trond G Jenssen
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Nydalen, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Esteban Porrini
- Instituto de Tecnologías Biomédicas (ITB), University of La Laguna, Research Unit Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Manfred Hecking
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
- Center for Public Health, Department of Epidemiology, Medical University of Vienna, Vienna, Austria
- Kuratorium for Dialysis and Kidney Transplantation (KfH), Neu-Isenburg, Germany
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Pham NYT, Cruz D, Madera-Marin L, Ravender R, Garcia P. Diabetic Kidney Disease in Post-Kidney Transplant Patients. J Clin Med 2024; 13:793. [PMID: 38337487 PMCID: PMC10856396 DOI: 10.3390/jcm13030793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/09/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a common occurrence in post-kidney transplantation and is associated with greater mortality, allograft failure, and increased risk of infections. The primary goal in the management of PTDM is to achieve glycemic control to minimize the risk of complications while balancing the need for immunosuppression to maintain the health of the transplanted kidney. This review summarizes the effects of maintenance immunosuppression and therapeutic options among kidney transplant recipients. Patients with PTDM are at increased risk of diabetic kidney disease development; therefore, in this review, we focus on evidence supporting the use of novel antidiabetic agents and discuss their benefits and potential side effects in detail.
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Affiliation(s)
- Ngoc-Yen T. Pham
- Division of Nephrology, University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
| | - Diego Cruz
- Hospital General San Juan de Dios, Guatemala City 01001, Guatemala;
| | - Luis Madera-Marin
- Division of Nephrology, University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
| | - Raja Ravender
- Division of Nephrology, University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
| | - Pablo Garcia
- Division of Nephrology, University of New Mexico School of Medicine, Albuquerque, NM 87106, USA
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Lukic N, Macvanin MT, Gluvic Z, Rizzo M, Radak D, Suri JS, Isenovic ER. SGLT-2 Inhibitors: The Next-generation Treatment for Type 2 Diabetes Mellitus. Curr Med Chem 2024; 31:4781-4806. [PMID: 37855338 DOI: 10.2174/0109298673251493231011192520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/19/2023] [Accepted: 08/17/2023] [Indexed: 10/20/2023]
Abstract
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years, primarily in highly developed Western societies. T2DM causes systemic complications, such as atherosclerotic heart disease, ischemic stroke, peripheral artery disease, kidney failure, and diabetes-related maculopathy and retinopathy. The growing number of T2DM patients and the treatment of long-term T2DM-related complications pressurize and exhaust public healthcare systems. As a result, strategies for combating T2DM and developing novel drugs are critical global public health requirements. Aside from preventive measures, which are still the most effective way to prevent T2DM, novel and highly effective therapies are emerging. In the spotlight of next-generation T2DM treatment, sodium-glucose co-transporter 2 (SGLT-2) inhibitors are promoted as the most efficient perspective therapy. SGLT-2 inhibitors (SGLT2i) include phlorizin derivatives, such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2, along with SGLT-1, is a member of the SGLT family of proteins that play a role in glucose absorption via active transport mediated by Na+/K+ ATPase. SGLT-2 is only found in the kidney, specifically the proximal tubule, and is responsible for more than 90% glucose absorption. Inhibition of SGLT-2 reduces glucose absorption, and consequently increases urinary glucose excretion, decreasing blood glucose levels. Thus, the inhibition of SGLT-2 activity ultimately alleviates T2DM-related symptoms and prevents or delays systemic T2DM-associated chronic complications. This review aimed to provide a more detailed understanding of the effects of SGLT2i responsible for the acute improvement in blood glucose regulation, a prerequisite for T2DM-associated cardiovascular complications control.
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Affiliation(s)
- Nikola Lukic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Mirjana T Macvanin
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Clinic for Internal Medicine, Faculty of Medicine, Zemun Clinical Hospital, University of Belgrade, Belgrade, Serbia
| | - Manfredi Rizzo
- Department of Internal Medicine and Medical Specialties (DIMIS), Università degli Studi di Palermo (UNIPA), 90128 Palermo, Italy
| | - Djordje Radak
- Department of Vascular Surgery, Serbian Academy of Art and Sciences, Euromedic Clinic, 11000, Belgrade, Serbia
| | | | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
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11
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Mehtani R, Saigal S. Long Term Complications of Immunosuppression Post Liver Transplant. J Clin Exp Hepatol 2023; 13:1103-1115. [PMID: 37975039 PMCID: PMC10643541 DOI: 10.1016/j.jceh.2023.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 06/18/2023] [Indexed: 11/19/2023] Open
Abstract
Improvement in immunosuppression has led to a remarkable improvement in short-term and long-term outcomes post-liver transplant (LT). However, with improvements in long-term survival, complications related to immunosuppressive drugs, either directly or indirectly, have also increased. The adverse events could be drug-specific, class-specific, or generic. Calcineurin inhibitors (cyclosporine and tacrolimus) are the backbone of the immunosuppression after LT and the main culprit associated with most of the complications, including renal failure, post-transplant diabetes mellitus (PTDM), and metabolic syndrome. Steroids are also implicated in the development of diabetes, osteoporosis, and metabolic syndrome post-LT. The development of infections and de novo malignancies (DNMs) is a generic effect linked to the overall cumulative immunosuppression. The development of these complications significantly hampers the quality of life and leads to increased morbidity and mortality post-LT. Thus, it is important to minimize the cumulative immunosuppression dose while simultaneously preventing allograft rejection. This review provides up-to-date, comprehensive knowledge of the complications of long-term immunosuppression post-LT along with associated risk factors and strategies to minimize the risk of complications.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Amrita Institute of Medical Sciences and Research, Faridabad, Haryana – 121001, India
| | - Sanjiv Saigal
- Transplant Hepatology, Centre for Liver and Biliary Sciences, Max Superspecialty Hospital, Saket, New Delhi, India
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Demir ME, Özler TE, Merhametsiz Ö, Sözener U, Uyar M, Ercan Z, Bardak Demir S, Sezer S, Türkmen Sarıyıldız G. The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers. Int Urol Nephrol 2023; 55:2989-2999. [PMID: 37289399 PMCID: PMC10248967 DOI: 10.1007/s11255-023-03645-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Accepted: 05/20/2023] [Indexed: 06/09/2023]
Abstract
PURPOSE Sodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract infections (UTI) in kidney transplant recipients (KTR). In this study, we present the results of SGLT-2i use in KTR, including the early post-transplant period. METHODS Participants were divided into two groups: SGLT-2i-free diabetic KTR (Group 1, n = 21) and diabetic KTR using SGLT-2i (Group 2, n = 36). Group 2 was further divided into two subgroups according to the posttransplant prescription day of SGLT-2i; < 3 months (Group 2a) and ≥ 3 months (Group 2b). Groups were compared for development of genital and urinary tract infections, glycated hemoglobin a1c (HgbA1c), estimated glomerular filtration rate (eGFR), proteinuria, weight change, and acute rejection rate during 12-month follow-up. RESULTS Urinary tract infections prevalence was 21.1% and UTI-related hospitalization rate was 10.5% in our cohort. Prevalence of UTI and UTI-related hospitalization, eGFR, HgbA1c levels, and weight gain were similar between the SGLT-2i group and SGLT-2i-free group, at the 12-month follow-up. UTI prevalence was similar between groups 2a and 2b (p = 0.871). No case of genital infection was recorded. Significant proteinuria reduction was observed in Group 2 (p = 0.008). Acute rejection rate was higher in the SGLT-2i-free group (p = 0.040) and had an impact on 12-month follow-up eGFR (p = 0.003). CONCLUSION SGLT-2i in KTR is not associated with an increased risk of genital infection and UTI in diabetic KTR, even in the early posttransplant period. The use of SGLT-2i reduces proteinuria in KTR and has no adverse effects on allograft function at the 12-month follow-up.
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Affiliation(s)
- Mehmet Emin Demir
- Department of Nephrology and Organ Transplantation, Atılım University School of Medicine, Medicana International Ankara Hospital, Ankara, Turkey
| | - Tuba Elif Özler
- Department of Nephrology and Organ Transplantation, Yeni Yuzyil University Private Gaziosmanpaşa Hospital, Istanbul, Turkey
| | - Özgür Merhametsiz
- Department of Nephrology and Organ Transplantation, Beykent University Hospital, Istanbul, Turkey
| | - Ulaş Sözener
- Department of General Surgery and Organ Transplantation, Atılım University School of Medicine, Medicana International Ankara Hospital, Ankara, Turkey
| | - Murathan Uyar
- Department of Nephrology and Organ Transplantation, Aydın University Medical School, Istanbul, Turkey
| | - Zafer Ercan
- Department of Nephrology, Sakarya University School of Medicine, Sakarya, Turkey
| | - Simge Bardak Demir
- Department of Nephrology, Yenimahalle Education and Research Hospital, Ankara, Turkey.
| | - Siren Sezer
- Department of Nephrology and Organ Transplantation, Atılım University School of Medicine, Medicana International Ankara Hospital, Ankara, Turkey
| | - Gülçin Türkmen Sarıyıldız
- Department of General Surgery and Organ Transplantation, Atılım University School of Medicine, Medicana International Ankara Hospital, Ankara, Turkey
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Ramakrishnan P, Garg N, Pabich S, Mandelbrot DA, Swanson KJ. Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients. World J Transplant 2023; 13:239-249. [PMID: 37746038 PMCID: PMC10514750 DOI: 10.5500/wjt.v13.i5.239] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/19/2023] [Accepted: 06/14/2023] [Indexed: 09/15/2023] Open
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel oral hypoglycemic agents garnering much attention for their substantial benefits. These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease (CKD) and heart failure management. SGLT2i use post-kidney transplant is an emerging area of research. Highlights from this mini review include the following: Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients (KTRs), median time from transplant to initiation was 3 years (range: 0.88-9.6 years). Median baseline estimated glomerular filtration rate (eGFR) was 66.7 mL/min/1.73 m2 (range: 50.4-75.8). Median glycohemoglobin (HgbA1c) at initiation was 7.7% (range: 6.9-9.3). SGLT2i were demonstrated to be effective short-term impacting HgbA1c, eGFR, hemoglobin/hematocrit, serum uric acid, and serum magnesium levels. They are shown to be safe in KTRs with low rates of infections, hypoglycemia, euglycemic diabetic ketoacidosis, and stable tacrolimus levels. More data is needed to demonstrate long-term outcomes. SGLT2i appear to be safe, effective medications for select KTRs. Our present literature, though limited, is founded on precedent robust research in CKD patients with diabetes. Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient, graft and cardiovascular outcomes of these agents, but also to augment management in KTRs.
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Affiliation(s)
- Pavithra Ramakrishnan
- Department of Medicine, University of Minnesota, Minneapolis, MN 55455, United States
| | - Neetika Garg
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Samantha Pabich
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Didier A Mandelbrot
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
| | - Kurtis J Swanson
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, United States
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Sweiss H, Selznick L, Contreras J, Long C, Hall R, Bhayana S, Patel R, Klein K. Safety and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Solid Organ Transplant Recipients. Prog Transplant 2023; 33:261-265. [PMID: 37491859 DOI: 10.1177/15269248231189880] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may be effective in reducing body weight and hemoglobin A1c (HbA1c) post-kidney transplantation. Limited literature exists on use of these agents outside of kidney transplant. The purpose of this program evaluation was to evaluate the safety and efficacy of SGLT2i in kidney, liver, and lung transplant recipients. Methods: This was a retrospective program evaluation of adult kidney, liver, and lung transplant recipients between August 31, 2016 and July 31, 2021. Patients initiated on SGLT2i for diabetes for a minimum of 90 days with at least 1 follow-up appointment were screened for inclusion. Outcomes were compared between SGLT2i initiation to nadir values 3-12-months post-initiation. Outcomes included change in hemoglobin A1c, fasting blood glucose, actual body weight, and body mass index. Safety outcomes included adverse effects, cardiovascular events, death-censored graft loss, and all-cause mortality. Results: Forty-nine patients met inclusion criteria, (26 liver, 18 kidney, 4 lung, and 1 simultaneous liver-kidney recipient). The median time from transplant to SGLT2i initiation was 1216 days (IQR 524-2256). Glycemic and weight loss outcomes showed a statistically significant benefit from SGLT2i use. Total safety outcome incidence was minimal at 12 months. No patient experienced myocardial infarctions, graft loss, or mortality at 3-12 months. One incidence of urinary tract infection and stroke occurred each. The most common adverse effects included hypotension and hypoglycemia. Conclusion: This program evaluation demonstrated that SGLT2i can be used safely in solid organ transplant recipients. These agents can provide an additional non-insulin agent for post-transplant diabetes mellitus management in solid organ transplant.
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Affiliation(s)
- Helen Sweiss
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Leah Selznick
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Jillian Contreras
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Christina Long
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Feik School of Pharmacy, The University of Incarnate Word, San Antonio, TX, USA
| | - Reed Hall
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Suverta Bhayana
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Department of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Rupal Patel
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Department of Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Kelsey Klein
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, TX, USA
- University Health Transplant Institute, University Health System, San Antonio, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Pharmacotherapy Division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
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De La Flor JC, Villa D, Cruzado L, Apaza J, Valga F, Zamora R, Marschall A, Cieza M, Deira J, Rodeles M. Efficacy and Safety of the Use of SGLT2 Inhibitors in Patients on Incremental Hemodialysis: Maximizing Residual Renal Function, Is There a Role for SGLT2 Inhibitors? Biomedicines 2023; 11:1908. [PMID: 37509547 PMCID: PMC10377393 DOI: 10.3390/biomedicines11071908] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/11/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023] Open
Abstract
SGLT-2i are the new standard of care for diabetic kidney disease (DKD), but previous studies have not included patients on kidney replacement therapy (KRT). Due to their high risk of cardiovascular, renal complications, and mortality, these patients would benefit the most from this therapy. Residual kidney function (RKF) conveys a survival benefit and cardiovascular health among hemodialysis (HD) patients, especially those on incremental hemodialysis (iHD). We retrospectively describe the safety and efficacy of SGLT2i regarding RKF preservation in seven diabetic patients with different clinical backgrounds who underwent iHD (one or two sessions per week) during a 12-month follow-up. All patients preserved RKF, measured as residual kidney urea clearance (KrU) in 24 h after the introduction of SGLT2i. KrU levels improved significantly from 4.91 ± 1.14 mL/min to 7.28 ± 1.68 mL/min at 12 months (p = 0.028). Pre-hemodialysis blood pressure improved 9.95% in mean systolic blood pressure (SBP) (p = 0.015) and 10.95% in mean diastolic blood pressure (DBP) (p = 0.041); as a result, antihypertensive medication was modified. Improvements in blood uric acid, hemoglobin A1c, urine albumin/creatinine ratio (UACR), and 24 h proteinuria were also significant. Regarding side effects, two patients developed uncomplicated urinary tract infections that were resolved. No other complications were reported. The use of SGLT2i in our sample of DKD patients starting iHD on a 1-2 weekly regimen appears to be safe and effective in preserving RKF.
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Affiliation(s)
- José C De La Flor
- Department of Nephrology, Hospital Central Defense Gomez Ulla, 28047 Madrid, Spain
| | - Daniel Villa
- Department of Nephrology, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Leónidas Cruzado
- Department of Nephrology, Hospital General Elche, 03203 Elche, Spain
| | - Jacqueline Apaza
- Department of Nephrology, Hospital Fuensanta, 28942 Madrid, Spain
| | - Francisco Valga
- Department of Nephrology, Hospital Universitario Doctor Negrin de Gran Canarias, 35016 Las Palmas de Gran Canarias, Spain
| | - Rocío Zamora
- Department of Nephrology, Hospital Universitario General Villalba, 28400 Madrid, Spain
| | - Alexander Marschall
- Department of Cardiology, Central Defense Gomez Ulla Hospital, 28047 Madrid, Spain
| | - Michael Cieza
- Teaching Coordination Unit, Universidad Peruana Cayetano Heredia, Lima 15012, Peru
| | - Javier Deira
- Department of Nephrology, Hospital San Pedro de Alcántara, 10003 Cáceres, Spain
| | - Miguel Rodeles
- Department of Nephrology, Hospital Central Defense Gomez Ulla, 28047 Madrid, Spain
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Sánchez Fructuoso AI, Bedia Raba A, Banegas Deras E, Vigara Sánchez LA, Valero San Cecilio R, Franco Esteve A, Cruzado Vega L, Gavela Martínez E, González Garcia ME, Saurdy Coronado P, Morales NDV, Zarraga Larrondo S, Ridao Cano N, Mazuecos Blanca A, Hernández Marrero D, Beneyto Castello I, Paul Ramos J, Sierra Ochoa A, Facundo Molas C, González Roncero F, Torres Ramírez A, Cigarrán Guldris S, Pérez Flores I. Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study. Clin Kidney J 2023; 16:1022-1034. [PMID: 37260993 PMCID: PMC10229265 DOI: 10.1093/ckj/sfad007] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. METHODS This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. RESULTS Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. CONCLUSIONS SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.
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Affiliation(s)
- Ana I Sánchez Fructuoso
- Nephrology Department, Hospital Clínico San Carlos IdSSC, Complutense University, Madrid, Spain
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Isabel Pérez Flores
- Nephrology Department, Hospital Clínico San Carlos IdSSC, Complutense University, Madrid, Spain
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17
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Crannage EF, Nguyen KL, Ellebrecht MD, Challen LM, Crannage AJ. Use of Sodium-Glucose Cotransporter-2 Inhibitor for Diabetes Management in Patients Following Kidney Transplantation. J Pharm Technol 2023; 39:147-155. [PMID: 37323766 PMCID: PMC10268042 DOI: 10.1177/87551225231169620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023] Open
Abstract
Objective: To evaluate data sources pertaining to the safety and efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitor use for diabetes management in patients following kidney transplantation. Data Sources: A literature search was conducted through PubMed (1966-January 2023), EMBASE (1973-January 2023), and clinicaltrials.gov databases using the search terms kidney transplantation, diabetes mellitus, and SGLT2 inhibitor or empagliflozin, dapagliflozin, and canagliflozin. Study Selection and Data Extraction: Studies evaluating human kidney transplant recipients (KTR) receiving SGLT2 inhibitors treatment and published in the English language were included. Eight case series or retrospective analyses, 4 prospective observational studies, and 1 randomized controlled trial were identified. Data Synthesis: Available literature provides evidence that the addition of SGLT2 inhibitors may provide modest benefits on glycemic control, body weight, and serum uric acid levels in certain KTR. Various studies and case reports found that incidence of urinary tract infections was low, but still present. Overall, there are limited data on mortality and graft survival; however, one study reported a benefit of SGLT2 inhibitor use in KTR relative to these outcomes. Conclusions: The current literature evaluated demonstrates that there may be benefit to the addition of SGLT2 inhibitors for diabetes management in select KTR. However, the limited evidence within a large diverse population and extended duration of treatment makes it difficult to definitively identify the true efficacy and safety of SGLT2 inhibitor use in this population.
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Affiliation(s)
- Erica F. Crannage
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Katherine L. Nguyen
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Morgan D. Ellebrecht
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Laura M. Challen
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Andrew J. Crannage
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
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18
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Oliveras L, Montero N, Cruzado JM. Searching in the maze: sodium-glucose cotransporter-2 inhibitors in kidney transplant recipients to improve survival. Clin Kidney J 2023; 16:909-913. [PMID: 37260989 PMCID: PMC10229278 DOI: 10.1093/ckj/sfad045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Indexed: 11/29/2023] Open
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve cardiovascular and renal outcomes in chronic kidney disease patients with and without diabetes. Kidney transplant recipients have been excluded from landmark trials using SGLT2is and literature on safety and efficacy are scarce. Recent studies suggest that the SGLT2i use in kidney transplant recipients with diabetes is safe, paving the way to investigate whether SGLT2is could also reduce cardiovascular events and kidney function deterioration in kidney allograft recipients.
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Affiliation(s)
- Laia Oliveras
- Nephrology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain
| | - Núria Montero
- Nephrology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain
| | - Josep M Cruzado
- Nephrology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Catalonia, Spain
- Biomedical Research Institute (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Catalonia, Spain
- Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, L'Hospitalet de Llobregat, Catalonia, Spain
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19
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Valencia-Morales ND, Rodríguez-Cubillo B, Loayza-López RK, Moreno de la Higuera MÁ, Sánchez-Fructuoso AI. Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review. Life (Basel) 2023; 13:1265. [PMID: 37374048 DOI: 10.3390/life13061265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection. Studies with SGLT2i performed in KTRs are much less potent than in the general population and therefore no benefits in terms of patient or graft survival have been clearly demonstrated in this population to date. Additionally, the most frequently observed side effects could be potentially harmful to this population profile, including severe or recurrent urinary tract infections and impaired kidney function. However, benefits demonstrated in KTRs are in line with a known potential effects in cardiovascular and renal protection, which may be essential for the outcome of transplant recipients. Better studies are still needed to confirm the benefits of these new oral antidiabetics in the renal transplant population. Understanding the characteristics of these drugs may be critical for KTRs to be able to benefit from their effects without being damaged. This review discusses the results of the most important published studies on KTRs with GLP1-RA and SGLT2i as well as the potential beneficial effects of these drugs. Based on these results, approximate suggestions for the management of diabetes in KTRs were developed.
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20
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Lawrence SE, Chandran MM, Park JM, Sweiss H, Jensen T, Choksi P, Crowther B. Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation. Clin Transplant 2023; 37:e14922. [PMID: 36708369 DOI: 10.1111/ctr.14922] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/16/2023] [Accepted: 01/23/2023] [Indexed: 01/29/2023]
Abstract
Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.
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Affiliation(s)
- S Elise Lawrence
- Univeristy of Colorado School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.,Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
| | - Mary Moss Chandran
- Department of Pharmacy, University of North Carolina Medical Center, Chapel Hill, North Carolina, USA
| | - Jeong M Park
- University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA
| | - Helen Sweiss
- Department of Pharmacotherapy and Pharmacy Services, University Health System, San Antonio, Texas
| | - Thomas Jensen
- University of Colorado Department of Medicine - Endocrinology, Diabetes, and Metabolism, Aurora, Colorado, USA
| | - Palak Choksi
- University of Colorado Department of Medicine - Endocrinology, Diabetes, and Metabolism, Aurora, Colorado, USA
| | - Barrett Crowther
- Univeristy of Colorado School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.,Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
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Lim MA, Bloom RD. How to maximize graft survival. Curr Opin Organ Transplant 2023; 28:55-63. [PMID: 36579685 DOI: 10.1097/mot.0000000000001039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Kidney transplant failure results in significant patient morbidity and mortality, increased financial burden and exacerbates the organ shortage faced by kidney transplant candidates. The different strategies to maximize graft survival in kidney transplant recipients is presented in this review. RECENT FINDINGS Maximizing kidney graft survival requires optimizing immunosuppression, preventing and managing recurrent disease and using general chronic kidney disease strategies to slow allograft injury. Herein, we review: 1) strategies to tailor immunosuppression to the individual patient to avoid over and underimmunosuppression, and avoid immunosuppression-related drug toxicities, 2) latest findings in the following recurrent diseases: focal segmental glomerulosclerosis, membranous nephropathy, complement-mediated kidney disease and monoclonal gammopathy of renal significance, and, 3) approaches to slow allograft injury including BP control, and the use of antiproteinuric agents and SGLT-2 inhibitors. SUMMARY The last two decades has seen significant improvement in allograft outcomes resulting from advances in immunosuppression. With the federal government's renewed focus on kidney disease and transplantation, and recent advances in biomarkers, genetic testing, big data analytics and machine learning, we hope to see further outcome improvements in the next decade.
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Affiliation(s)
- Mary Ann Lim
- Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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22
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Lin Y, Mok M, Harrison J, Battistella M, Farrell A, Leung M, Cheung C. Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review. Transplant Rev (Orlando) 2023; 37:100729. [PMID: 36427372 DOI: 10.1016/j.trre.2022.100729] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 10/30/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. METHOD We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. RESULTS Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. CONCLUSIONS While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.
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Affiliation(s)
- Yolanda Lin
- Vancouver General Hospital, Vancouver, BC, Canada.
| | - Merisa Mok
- Richmond Health Services, Richmond, BC, Canada
| | - Jennifer Harrison
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada
| | - Marisa Battistella
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Nephrology, University Health Network, Toronto, ON, Canada.
| | - Ashley Farrell
- Library and Information Services, University Health Network, Toronto, ON, Canada.
| | - Marianna Leung
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; St. Paul's Hospital, Providence Healthcare, Vancouver, BC, Canada V6Z 1Y6
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23
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Pham PTT, Pham PCT. Optimal use of SGLT2 inhibitors in diabetic kidney transplant recipients. FRONTIERS IN NEPHROLOGY 2022; 2:1014241. [PMID: 37674999 PMCID: PMC10479656 DOI: 10.3389/fneph.2022.1014241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/17/2022] [Indexed: 09/08/2023]
Abstract
Sodium-glucose cotransporter 2 inhibitor (SGLT2i), a glucosuric agent initially approved for use as an antidiabetic agent, was unexpectedly found to confer cardio-and reno-protective effects in individuals with or without type 2 diabetes mellitus. Despite mounting evidence suggesting that SGLT2i provides cardio- and reno-protective benefits in both diabetic and non-diabetic and in chronic kidney disease (CKD) patients in the general population, reservations for its use in the transplant setting persist due to concerns for increased risk of genital mycotic and urinary tract infections. A comprehensive review of the literature on the efficacy and safety of SGLT2i use in diabetic kidney transplant recipients is herein presented followed by authors' opinion on its optimal use in this patient population.
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Affiliation(s)
- Phuong-Thu T. Pham
- Nephrology Division, Kidney Transplant Program David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, CA, United States
| | - Phuong-Chi T. Pham
- Division of Nephrology and Hypertension Olive-View University of California at Los Angeles (UCLA) Medical Center, Sylmar, CA, United States
- David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, CA, United States
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24
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Kansara A, Mubeen F, Shakil J. SGLT2 Inhibitors in Patients with Chronic Kidney Disease and Heart Disease: A Literature Review. Methodist Debakey Cardiovasc J 2022; 18:62-72. [PMID: 36132575 PMCID: PMC9461689 DOI: 10.14797/mdcvj.1120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/28/2022] [Indexed: 11/11/2022] Open
Abstract
Sodium-glucose transport protein 2 inhibitors, commonly referred to as SGLT2i, are a group of prescription pharmaceuticals that are approved by the United States Food and Drug Administration for use with diet and exercise to lower blood glucose in adults with type 2 diabetes. Diabetes is a well-recognized major contributor to cardiovascular and renal disease burden. In addition to blood glucose control, SGLT2i have been shown to provide significant cardiovascular and renoprotective benefits in patients with and without diabetes. In this review, we describe current evidence related to the renal and cardiovascular benefits of using SGLT2i.
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Affiliation(s)
- Abhishek Kansara
- Houston Methodist Hospital, Houston, Texas, US
- Weill Cornell College of Medicine, Ithaca, New York, US
- Texas A&M College of Medicine, Houston, Texas, US
| | | | - Jawairia Shakil
- Houston Methodist Hospital, Houston, Texas, US
- Weill Cornell College of Medicine, Ithaca, New York, US
- Texas A&M College of Medicine, Houston, Texas, US
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25
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The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients. Transplantation 2022; 106:e404-e412. [PMID: 35768908 DOI: 10.1097/tp.0000000000004228] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND The efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been investigated in kidney transplant recipients (KTRs) with diabetes. We evaluated the impact of SGLT2i in a multicenter cohort of diabetic KTRs. METHODS A total of 2083 KTRs with diabetes were enrolled from 6 transplant centers in Korea. Among them, 226 (10.8%) patients were prescribed SGLT2i for >90 d. The primary outcome was a composite outcome of all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2i use. RESULTS During the mean follow-up of 62.9 ± 42.2 mo, the SGLT2i group had a lower risk of primary composite outcome than the control group in the multivariate and propensity score-matched models (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78; P = 0.006 and adjusted hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = 0.013, respectively). Multivariate analyses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2i group. The overall eGFR remained stable without the initial dip after SGLT2i use. A minority (15.6%) of the SGLT2i users showed acute eGFR dip during the first month, but the eGFR recovered thereafter. The risk factors for the eGFR dip were time from transplantation to SGLT2i usage and mean tacrolimus trough level. CONCLUSIONS SGLT2i improved a composite of all-cause mortality, DCGF, or serum creatinine doubling in KTRs. SGLT2i can be used safely and have beneficial effects on preserving graft function in diabetic KTRs.
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Aziz F, Jorgenson M, Garg N, Parajuli S, Mohamed M, Raza F, Mandelbrot D, Djamali A, Dhingra R. New Approaches to Cardiovascular Disease and Its Management in Kidney Transplant Recipients. Transplantation 2022; 106:1143-1158. [PMID: 34856598 DOI: 10.1097/tp.0000000000003990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Cardiovascular events, including ischemic heart disease, heart failure, and arrhythmia, are common complications after kidney transplantation and continue to be leading causes of graft loss. Kidney transplant recipients have both traditional and transplant-specific risk factors for cardiovascular disease. In the general population, modification of cardiovascular risk factors is the best strategy to reduce cardiovascular events; however, studies evaluating the impact of risk modification strategies on cardiovascular outcomes among kidney transplant recipients are limited. Furthermore, there is only minimal guidance on appropriate cardiovascular screening and monitoring in this unique patient population. This review focuses on the limited scientific evidence that addresses cardiovascular events in kidney transplant recipients. Additionally, we focus on clinical management of specific cardiovascular entities that are more prevalent among kidney transplant recipients (ie, pulmonary hypertension, valvular diseases, diastolic dysfunction) and the use of newer evolving drug classes for treatment of heart failure within this cohort of patients. We note that there are no consensus documents describing optimal diagnostic, monitoring, or management strategies to reduce cardiovascular events after kidney transplantation; however, we outline quality initiatives and research recommendations for the assessment and management of cardiovascular-specific risk factors that could improve outcomes.
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Affiliation(s)
- Fahad Aziz
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Margaret Jorgenson
- Department of Pharmacology, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Neetika Garg
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Maha Mohamed
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Farhan Raza
- Cardiovascular Division, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Didier Mandelbrot
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Arjang Djamali
- Division of Nephrology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
| | - Ravi Dhingra
- Cardiovascular Division, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, WI
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27
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Lemke A, Brokmeier HM, Leung SB, Mara KC, Mour GK, Wadei HM, Hill JM, Stegall M, Kudva YC, Shah P, Kukla A. Sodium-glucose cotransporter 2 inhibitors for treatment of diabetes mellitus after kidney transplantation. Clin Transplant 2022; 36:e14718. [PMID: 35593882 DOI: 10.1111/ctr.14718] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/25/2022] [Accepted: 05/12/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Diabetes mellitus in kidney transplant recipients is a risk factor for cardiovascular events and premature death. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly used in nontransplant populations to improve diabetes control and cardiovascular and renal benefits. Limited literature exists regarding the safety and efficacy of these agents in renal transplant recipients. METHODS We retrospectively reviewed all kidney transplant recipients within our health system who were prescribed a SGLT2i after transplantation for diabetes. The safety, tolerability, and effectiveness of SGLT2i were analyzed. RESULTS Thirty-nine kidney transplant recipients were initiated on SGLT2i therapy, twenty-seven of which remained on therapy for at least 1 year. Ten (25%) patients experienced an adverse event while on a SGLT2i, with urinary tract infections (UTI) being the most common. Seventeen patients (43%) discontinued the SGLT2i at the time of chart review, most commonly due to cost and kidney function decline. The median [IQR] hemoglobin A1c (HbA1c) at SGLT2i initiation of 8.4% [7.8-9.2] decreased to 7.5% [6.8-8.0%] after 3 months and 7.5% [6.5-7.9] after 12 months. No meaningful change in kidney function or tacrolimus exposure was observed. CONCLUSION SGLT2i may be a safe and effective treatment for diabetes in kidney transplant recipients. Cost is a barrier to SGLT2i therapy, and UTIs were the most frequently encountered adverse events in this cohort. More studies are needed to understand the safety profile and determine the effect of SGLT2i on diabetes-related comorbidities among kidney transplant recipients.
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Affiliation(s)
- Adley Lemke
- Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Sarah B Leung
- Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA
| | - Kristin C Mara
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
| | - Girish K Mour
- Department of Internal Medicine Division of Nephrology, Mayo Clinic, Phoenix, Arizona, USA
| | - Hani M Wadei
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
| | - Jennifer M Hill
- Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Mark Stegall
- Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA.,Department of Surgery and Immunology, Mayo Clinic, Rochester, Minnesota, USA
| | - Yogish C Kudva
- Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA.,Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic Rochester, Minnesota, USA
| | - Pankaj Shah
- Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic Rochester, Minnesota, USA
| | - Aleksandra Kukla
- Von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA.,Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
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28
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Miyazaki R, Miyagi K. Empagliflozin in kidney transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome: Five Japanese cases. BMC Nephrol 2022; 23:168. [PMID: 35501824 PMCID: PMC9063183 DOI: 10.1186/s12882-022-02793-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 04/18/2022] [Indexed: 11/10/2022] Open
Abstract
Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert cardiorenal protective effects in diabetic patients and are widely used clinically. In addition, an increasing number of reports now suggest these drugs may even be beneficial in non-diabetic patients. However, SGLT2 inhibitors are rarely prescribed for kidney transplant recipients due to the risk of renal graft damage and urogenital infections. Case presentation We report the cases of 5 renal transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome who were administered the SGLT2 inhibitor empagliflozin, which yielded beneficial results in 4 cases. With the exception of one patient with an initial estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m2, administration of empagliflozin elicited beneficial metabolic effects. There were no significant reductions in eGFR before or after empagliflozin administration, and no dehydration or urogenital infections were observed during the treatment course. Conclusion Empagliflozin showed some positive effects in 4 cases with better renal function than CKD stage 4. Further studies will be required to clarify the efficacy and safety of SGLT2 inhibitors in a larger group of patients with similar medical conditions.
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Affiliation(s)
- Ryoichi Miyazaki
- Department of Internal Medicine, Fujita Memorial Hospital, 4-15-7, Fukui, Fukui, 910-00004, Japan.
| | - Kyoko Miyagi
- Department of Internal Medicine, Fujita Memorial Hospital, 4-15-7, Fukui, Fukui, 910-00004, Japan
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29
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Yau K, Dharia A, Alrowiyti I, Cherney DZ. Prescribing SGLT2 Inhibitors in Patients with Chronic Kidney Disease: Expanding Indications and Practical Considerations. Kidney Int Rep 2022; 7:1463-1476. [PMID: 35812300 PMCID: PMC9263228 DOI: 10.1016/j.ekir.2022.04.094] [Citation(s) in RCA: 87] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/08/2022] [Accepted: 04/25/2022] [Indexed: 12/20/2022] Open
Affiliation(s)
- Kevin Yau
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Atit Dharia
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ibrahim Alrowiyti
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - David Z.I. Cherney
- Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- Correspondence: David Z.I. Cherney, Division of Nephrology, Department of Medicine, Toronto General Hospital, 585 University Avenue, 8N-845, Toronto, Ontario, M5G 2N2, Canada.
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30
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Sridhar VS, Ambinathan JPN, Gillard P, Mathieu C, Cherney DZI, Lytvyn Y, Singh SK. Cardiometabolic and Kidney Protection in Kidney Transplant Recipients With Diabetes: Mechanisms, Clinical Applications, and Summary of Clinical Trials. Transplantation 2022; 106:734-748. [PMID: 34381005 DOI: 10.1097/tp.0000000000003919] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the therapy of choice for patients with end-stage renal disease. Preexisting diabetes is highly prevalent in kidney transplant recipients (KTR), and the development of posttransplant diabetes is common because of a number of transplant-specific risk factors such as the use of diabetogenic immunosuppressive medications and posttransplant weight gain. The presence of pretransplant and posttransplant diabetes in KTR significantly and variably affect the risk of graft failure, cardiovascular disease (CVD), and death. Among the many available therapies for diabetes, there are little data to determine the glucose-lowering agent(s) of choice in KTR. Furthermore, despite the high burden of graft loss and CVD among KTR with diabetes, evidence for strategies offering cardiovascular and kidney protection is lacking. Recent accumulating evidence convincingly shows glucose-independent cardiorenal protective effects in non-KTR with glucose-lowering agents, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Therefore, our aim was to review cardiorenal protective strategies, including the evidence, mechanisms, and rationale for the use of these glucose-lowering agents in KTR with diabetes.
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Affiliation(s)
- Vikas S Sridhar
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Jaya Prakash N Ambinathan
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Pieter Gillard
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - Chantal Mathieu
- Department of Endocrinology, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium
| | - David Z I Cherney
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Yuliya Lytvyn
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Sunita K Singh
- Division of Nephrology, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
- The Kidney Transplant Program and the Ajmera Tranplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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31
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van der Aart-van der Beek AB, de Boer RA, Heerspink HJL. Kidney and heart failure outcomes associated with SGLT2 inhibitor use. Nat Rev Nephrol 2022; 18:294-306. [PMID: 35145275 DOI: 10.1038/s41581-022-00535-6] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Chronic kidney disease (CKD) and heart failure affect many people worldwide. Despite the availability of pharmacological treatments, both diseases remain associated with considerable morbidity and mortality. After observations that sodium-glucose co-transporter 2 (SGLT2) inhibitors - originally developed as glucose-lowering agents - improved cardiovascular and renal outcomes in patients with type 2 diabetes, dedicated trials were initiated to evaluate the cardiovascular and kidney protective effects in patients with CKD or heart failure. The results of these clinical trials and subsequent detailed analyses have shown that the benefits of SGLT2 inhibitors are consistent across many patient subgroups, including those with and without type 2 diabetes, at different stages of CKD, and in patients with heart failure with preserved or reduced ejection fraction. In addition, post-hoc analyses revealed that SGLT2 inhibitors reduce the risk of anaemia and hyperkalaemia in patients with CKD. With respect to their safety, SGLT2 inhibitors are generally well tolerated. More specifically, no increased risk of hypoglycaemia has been observed in patients with CKD or heart failure without diabetes and they do not increase the risk of acute kidney injury. SGLT2 inhibitors therefore provide clinicians with an exciting new treatment option for patients with CKD and heart failure.
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Affiliation(s)
- Annemarie B van der Aart-van der Beek
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands.,Department of Clinical Pharmacy, Martini Hospital, Groningen, Netherlands
| | - Rudolf A de Boer
- Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands. .,The George Institute for Global Health, Sydney, NSW, Australia.
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Ujjawal A, Schreiber B, Verma A. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in kidney transplant recipients: what is the evidence? Ther Adv Endocrinol Metab 2022; 13:20420188221090001. [PMID: 35450095 PMCID: PMC9016587 DOI: 10.1177/20420188221090001] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 03/04/2022] [Indexed: 12/15/2022] Open
Abstract
Several recent randomized controlled trials (RCTs) have demonstrated the wide clinical application of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in improving kidney and cardiovascular outcomes in patients with native kidney disease. In April 2021, Dapagliflozin became the first SGLT2 inhibitor to be approved by the Food and Drug Administration (FDA) for the treatment of chronic kidney disease (CKD) regardless of diabetic status. However, while these agents have drawn much acclaim for their cardiovascular and nephroprotective effects among patients with native kidney disease, little is known about the safety and efficacy of SGLT2i in the kidney transplant setting. Many of the mechanisms by which SGLT2i exert their benefit stand to prove equally as efficacious or more so among kidney transplant recipients as they have in patients with CKD. However, safety concerns have excluded transplant recipients from all large RCTs, and clinicians and patients alike are left to wonder if the benefits of these amazing drugs outweigh the risks. In this review, we will discuss the known mechanisms SGLT2i exploit to provide their beneficial effects, the potential benefits, and risks of these agents in the context of kidney transplantation, and finally, we will discuss current findings of the published literature for SGLT2i use in kidney transplant recipients and propose potential directions for future research.
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New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice. Drugs 2021; 82:97-108. [PMID: 34932209 DOI: 10.1007/s40265-021-01655-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2021] [Indexed: 12/17/2022]
Abstract
Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.
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Ibrahim HN, Murad DN, Knoll GA. Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney Transplantation. Clin J Am Soc Nephrol 2021; 16:1890-1897. [PMID: 33757985 PMCID: PMC8729499 DOI: 10.2215/cjn.15070920] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.
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Affiliation(s)
- Hassan N. Ibrahim
- Division of Renal Diseases and Hypertension, Department of Medicine, Houston Methodist Hospital, Houston, Texas
| | - Dina N. Murad
- Division of Renal Diseases and Hypertension, Department of Medicine, Houston Methodist Hospital, Houston, Texas
| | - Greg A. Knoll
- Division of Nephrology, Department of Medicine, Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Abstract
Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.
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Affiliation(s)
- Kelly A. Birdwell
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Meyeon Park
- Division of Nephrology, Department of Medicine, University of California, San Francisco, California
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36
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Jenssen TG. Efficacy and safety of Sodium-Glucose-Transporter-2 inhibitors in kidney transplant patients. Curr Opin Nephrol Hypertens 2021; 30:577-583. [PMID: 34507336 DOI: 10.1097/mnh.0000000000000749] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW This review discusses current evidence and future perspectives for use of SLT2 inhibitors in kidney transplant recipients (KTRs). RECENT FINDINGS Sodium-Glucose-Transporter-2 inhibitors (SGLT2is) lower plasma glucose in patients with type 2 diabetes, and protect against heart failure and progression of chronic kidney disease by a glucose-independent mechanism. Most of the current studies with SGLT2is in kidney transplant patients are however short-term retrospective case studies. These, together with one small randomized clinical trial, show that SGLT2is lower glucose also in KTRs with type 2 diabetes or posttransplant diabetes mellitus. Larger reductions in HbA1c (-0.5 to 1.5% points) are seen only in patients with estimated GFR > 60 ml/min/1.73m2 and HbA1c > 8%. With lower gomerular filtration rate (GFR) or glycated hemoglobin (HbA1c) the glucose-lowering effect is trivial. However, a reduction in body weight, blood pressure and uric acid is also seen, whereas the frequency of side effects (mycotic or urinary tract infections) does not seem to exceed what is seen in nontransplanted patients. Long-term effects on GFR have not been studied in kidney transplanted patients, but SGLT2is induce an early dip in GFR also in these patients. This could signal a beneficial long-term effect on renal hemodynamics. SUMMARY SGLT2is lower glucose safely also in patients with single kidney grafts, but long-term kidney function and patient survival are yet to be explored.
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Affiliation(s)
- Trond G Jenssen
- University Hospital of Oslo, Rikshospitalet, Department of Organ Transplantation, University of Oslo, Institute of Clinical Medicine, Oslo, Norway
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37
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Martinez Cantarin MP. Diabetes in Kidney Transplantation. Adv Chronic Kidney Dis 2021; 28:596-605. [PMID: 35367028 DOI: 10.1053/j.ackd.2021.10.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 11/11/2022]
Abstract
Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be present before transplant but post-transplant DM (PTDM) refers to diabetes that is diagnosed after solid organ transplantation. Despite its high prevalence, optimal treatment to prevent complications of PTDM is unknown. Medical therapy of pre-existent DM or PTDM after transplant is challenging because of frequent interactions between antidiabetic and immunosuppressive agents. There is also frequent need for medication dose adjustments due to residual kidney disease and a higher risk of medication side effects in patients treated with immunosuppressive agents. Sodium-glucose cotransporter 2 inhibitors have demonstrated a favorable cardio-renal profile in patients with DM without a transplant and hence hold great promise in this patient population although there is concern about the higher risk of urinary tract infections. The significant gaps in our understanding of the pathophysiology, diagnosis, and management of DM after kidney transplantation need to be urgently addressed.
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Ravindran S, Munusamy S. Renoprotective mechanisms of sodium-glucose co-transporter 2 (SGLT2) inhibitors against the progression of diabetic kidney disease. J Cell Physiol 2021; 237:1182-1205. [PMID: 34713897 DOI: 10.1002/jcp.30621] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 10/02/2021] [Accepted: 10/08/2021] [Indexed: 12/19/2022]
Abstract
Sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) have emerged as a promising class of antidiabetic drugs with cardioprotective and renoprotective effects in patients with type 2 diabetes (T2D). The sodium-glucose co-transporters 1 and 2 (SGLT 1 and SGLT2) located in the renal proximal tubules are responsible for glucose reabsorption from the glomerular filtrate back into the systemic circulation. Inhibition of SGLT2, which accounts for about 90% of the glucose reabsorption, leads to a significant reduction in blood glucose levels and a concomitant increase in the urinary excretion of glucose (glycosuria). Multiple mechanisms contribute to the nephroprotective effects of SGLT2-Is in T2D patients. These include: (1) Restoration of the tubuloglomerular feedback by increasing sodium delivery at macula densa, leading to afferent arteriolar constriction and reduced glomerular hyperfiltration, (2) Decreased activation of the intra-renal renin-angiotensin-aldosterone system, which also contributes to reducing glomerular hyperfiltration, (3) Increased production of ketone bodies, which serves as an alternate fuel for adenosine triphosphate production in mitochondria, which helps in attenuating inflammation, and (4) Protection against hypoxia, oxidative stress, and fibrosis. This review elaborates on the key mechanisms that underlie the nephroprotective effects and the adverse effects of SGLT2-Is in T2D patients with progressive diabetic kidney disease.
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Affiliation(s)
| | - Shankar Munusamy
- Department of Pharmaceutical and Administrative Sciences, Drake University College of Pharmacy and Health Sciences, Des Moines, Iowa, USA
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39
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Safety and Efficacy of Sodium-glucose Cotransporter 2 Inhibitors in Kidney Transplant Recipients With Pretransplant Type 2 Diabetes Mellitus: A Retrospective, Single-center, Inverse Probability of Treatment Weighting Analysis of 85 Transplant Patients. Transplant Direct 2021; 7:e772. [PMID: 34646935 PMCID: PMC8500668 DOI: 10.1097/txd.0000000000001228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 07/20/2021] [Accepted: 08/06/2021] [Indexed: 01/01/2023] Open
Abstract
Supplemental Digital Content is available in the text. Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can be used effectively and safely in kidney transplant (KT) recipients with pretransplant type 2 diabetes as the primary cause of end-stage renal disease (ESRD) remains unclear. In this study, we retrospectively analyzed the efficacy and safety of SGLT2 inhibitors compared with other oral hypoglycemic agents (OHAs) in KT recipients with pretransplant type 2 diabetes as the primary cause of ESRD.
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Suárez Fernández ML, Ridao Cano N, Álvarez Santamarta L, Gago Fraile M, Blake O, Díaz Corte C. A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients. Diagnostics (Basel) 2021; 11:1456. [PMID: 34441390 PMCID: PMC8392421 DOI: 10.3390/diagnostics11081456] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/26/2021] [Accepted: 08/05/2021] [Indexed: 12/23/2022] Open
Abstract
Urinary tract infection (UTI) represents the most common infection after kidney transplantation and remains a major cause of morbidity and mortality in kidney transplant (KT) recipients, with a potential impact on graft survival. UTIs after KT are usually caused by Gram-negative microorganisms. Other pathogens which are uncommon in the general population should be considered in KT patients, especially BK virus since an early diagnosis is necessary to improve the prognosis. UTIs following kidney transplantation are classified into acute simple cystitis, acute pyelonephritis/complicated UTI, and recurrent UTI, due to their different clinical presentation, prognosis, and management. Asymptomatic bacteriuria (ASB) represents a frequent finding after kidney transplantation, but ASB is considered to be a separate entity apart from UTI since it is not necessarily a disease state. In fact, current guidelines do not recommend routine screening and treatment of ASB in KT patients, since a beneficial effect has not been shown. Harmful effects such as the development of multidrug-resistant (MDR) bacteria and a higher incidence of Clostridium difficile diarrhea have been associated with the antibiotic treatment of ASB.
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Affiliation(s)
- María Luisa Suárez Fernández
- Unidad de Gestión Clínica de Nefrología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain; (N.R.C.); (L.Á.S.); (M.G.F.); (C.D.C.)
| | - Natalia Ridao Cano
- Unidad de Gestión Clínica de Nefrología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain; (N.R.C.); (L.Á.S.); (M.G.F.); (C.D.C.)
| | - Lucia Álvarez Santamarta
- Unidad de Gestión Clínica de Nefrología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain; (N.R.C.); (L.Á.S.); (M.G.F.); (C.D.C.)
| | - María Gago Fraile
- Unidad de Gestión Clínica de Nefrología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain; (N.R.C.); (L.Á.S.); (M.G.F.); (C.D.C.)
| | | | - Carmen Díaz Corte
- Unidad de Gestión Clínica de Nefrología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain; (N.R.C.); (L.Á.S.); (M.G.F.); (C.D.C.)
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41
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Patel N, Hindi J, Farouk SS. Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For? KIDNEY360 2021; 2:1174-1178. [PMID: 35368347 PMCID: PMC8786095 DOI: 10.34067/kid.0000732021] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 04/22/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Niralee Patel
- Division of Nephrology, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
| | - Judy Hindi
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Samira S. Farouk
- Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
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42
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Schwarzenbach M, Bernhard FE, Czerlau C, Sidler D. Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation: A review of literatures. World J Transplant 2021; 11:254-262. [PMID: 34316450 PMCID: PMC8290999 DOI: 10.5500/wjt.v11.i7.254] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
Solid organ transplantation offers life-saving treatment for patients with end-organ dysfunction. Patient survival and quality of life have improved over the past few decades as a result of pharmacological development, expansion of the donor pool, technological advances and standardization of practices related to transplantation. Still, transplantation is associated with cardiovascular complications, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus, but also from specific post-transplant risk factors such as metabolic side effects of immunosuppressive drugs, post-transplant viral infections and hypomagnesemia. Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients. However, the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited. The favourable risk/benefit ratio, which is suggested by large-scale and long-term studies on new glucose-lowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, makes studies warranted to assess the potential role of these agents in the management of PTDM.
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Affiliation(s)
- Marlene Schwarzenbach
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Flavia Elena Bernhard
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Cecilia Czerlau
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, University Hospital Insel Bern, Bern 3010, Switzerland
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43
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Codina S, Manonelles A, Tormo M, Sola A, Cruzado JM. Chronic Kidney Allograft Disease: New Concepts and Opportunities. Front Med (Lausanne) 2021; 8:660334. [PMID: 34336878 PMCID: PMC8316649 DOI: 10.3389/fmed.2021.660334] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/10/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic kidney disease (CKD) is increasing in most countries and kidney transplantation is the best option for those patients requiring renal replacement therapy. Therefore, there is a significant number of patients living with a functioning kidney allograft. However, progressive kidney allograft functional deterioration remains unchanged despite of major advances in the field. After the first post-transplant year, it has been estimated that this chronic allograft damage may cause a 5% graft loss per year. Most studies focused on mechanisms of kidney graft damage, especially on ischemia-reperfusion injury, alloimmunity, nephrotoxicity, infection and disease recurrence. Thus, therapeutic interventions focus on those modifiable factors associated with chronic kidney allograft disease (CKaD). There are strategies to reduce ischemia-reperfusion injury, to improve the immunologic risk stratification and monitoring, to reduce calcineurin-inhibitor exposure and to identify recurrence of primary renal disease early. On the other hand, control of risk factors for chronic disease progression are particularly relevant as kidney transplantation is inherently associated with renal mass reduction. However, despite progress in pathophysiology and interventions, clinical advances in terms of long-term kidney allograft survival have been subtle. New approaches are needed and probably a holistic view can help. Chronic kidney allograft deterioration is probably the consequence of damage from various etiologies but can be attenuated by kidney repair mechanisms. Thus, besides immunological and other mechanisms of damage, the intrinsic repair kidney graft capacity should be considered to generate new hypothesis and potential therapeutic targets. In this review, the critical risk factors that define CKaD will be discussed but also how the renal mechanisms of regeneration could contribute to a change chronic kidney allograft disease paradigm.
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Affiliation(s)
- Sergi Codina
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Anna Manonelles
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
| | - Maria Tormo
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Anna Sola
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
| | - Josep M. Cruzado
- Department of Nephrology, Hospital Universitari Bellvitge, Barcelona, Spain
- Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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44
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Kanbay M, Demiray A, Afsar B, Karakus KE, Ortiz A, Hornum M, Covic A, Sarafidis P, Rossing P. Sodium-glucose cotransporter 2 inhibitors for diabetes mellitus control after kidney transplantation: Review of the current evidence. Nephrology (Carlton) 2021; 26:1007-1017. [PMID: 34263502 DOI: 10.1111/nep.13941] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 12/21/2022]
Abstract
Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are promising drugs to treat chronic kidney disease patients with or without diabetes mellitus (DM). Besides improving glycemic control, SGLT2i are cardioprotective and kidney protective and decrease bodyweight, serum uric acid, blood pressure, albuminuria and glomerular hyperfiltration. These effects may benefit graft function and survival in kidney transplant (KT) patients. In this review, we evaluate data on the efficacy and safety of SGLT2i for KT patients with DM. Eleven studies with 214 diabetic KT patients treated with SGLT2i have been reported. SGLT2i lowered haemoglobin A1c and bodyweight. While glomerular filtration rate may be reduced in the short-term, it remained similar to baseline after 3-12 months. In two studies, blood pressure decreased and remained unchanged in the others. There were no significant changes in urine protein to creatinine ratio. Regarding safety, 23 patients had urinary tract infections, 2 patients had a genital yeast infection, one had acute kidney injury, and one had mild hypoglycaemia. No cases of ketoacidosis or acute rejection were reported. In conclusion, the limited experience so far suggests that SGLT2i are safe in KT patients with DM, decrease bodyweight and improve glycemic control. However, some of the benefits observed in larger studies in the non-KT population have yet to be demonstrated in KT recipients, including preservation of kidney function, reduction in blood pressure and decreased proteinuria.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Atalay Demiray
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Division of Nephrology, Department of Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Kagan E Karakus
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Alberto Ortiz
- IIS-Fundacion Jimenez Diaz, Department of Medicine, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania.,Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. Parhon' University Hospital, Iasi, Romania
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Copenhagen Denmark and University of Copenhagen, Copenhagen, Denmark
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45
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Nissaisorakarn P, Pavlakis M, Aala A. Novel Glucose-Lowering Therapies in the Setting of Solid Organ Transplantation. Adv Chronic Kidney Dis 2021; 28:361-370. [PMID: 34922692 DOI: 10.1053/j.ackd.2021.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 11/11/2022]
Abstract
Post-transplant diabetes mellitus is a frequent consequence of or a pre-existing comorbidity in solid organ transplantation (SOT) that is associated with greater morbidity and mortality. Novel glucose-lowering agents that have been shown to have cardiovascular morbidity/mortality benefit and renal protective effects such as sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists are being incorporated into new standard of care for diabetes mellitus. There is a paucity of data regarding the use of these agents in SOT. In this article, we will aim to review available literature on newer glucose-lowering therapeutics in SOT, mainly sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, their mechanism of action, benefits, risks, and safety profiles.
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46
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Ertuglu LA, Porrini E, Hornum M, Demiray A, Afsar B, Ortiz A, Covic A, Rossing P, Kanbay M. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation. Transpl Int 2021; 34:1341-1359. [PMID: 33880815 DOI: 10.1111/tri.13883] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/22/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre-existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long-term management of PTDM or pre-existent T2DM. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP-1RA may counteract some of the driving forces for PTDM, as calcineurin-induced β cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP-1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized-controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP-1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre-existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.
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Affiliation(s)
- Lale A Ertuglu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Esteban Porrini
- Red de Investigación Renal (REDINREN), Instituto Carlos III-FEDER, Tenerife, Spain.,Department of Medicine, Hospital Universitario de Canarias, Tenerife, Spain.,Instituto de Tecnologías Biomédicas, University of La Laguna, Tenerife, Spain
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Atalay Demiray
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Baris Afsar
- Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Alberto Ortiz
- IIS-Fundacion Jimenez Diaz, Department of Medicine, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Adrian Covic
- Department of Nephrology, Grigore T. Popa' University of Medicine, Iasi, Romania
| | - Peter Rossing
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Steno Diabetes Center Copenhagen, Copenhagen, Denmark
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
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47
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Shuster S, Al-Hadhrami Z, Moore S, Awad S, Shamseddin MK. Use of Sodium-Glucose Cotransporter-2 Inhibitors in Renal Transplant Patients With Diabetes: A Brief Review of the Current Literature. Can J Diabetes 2021; 46:207-212. [PMID: 34362679 DOI: 10.1016/j.jcjd.2021.06.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 06/13/2021] [Accepted: 06/14/2021] [Indexed: 11/28/2022]
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of oral hypoglycemic agents commonly prescribed in type 2 diabetes (T2D). They have been shown to slow the progression of diabetic nephropathy and improve cardiovascular outcomes in high-risk individuals, although major cardiovascular and renal outcome clinical trials have excluded renal transplant patients. The aim of this review was to determine the outcomes and safety with use of SGLT2 inhibitors in renal transplant patients with diabetes. We conducted a review of randomized controlled trials, cohort studies, case series and case reports that assessed use of SGLT2 inhibitors in patients post-renal transplant with either pre-existing T2D or new-onset diabetes after transplant. The outcomes assessed included blood pressure, renal allograft function (estimated glomerular filtration rate), proteinuria (urinary albumin-to-creatinine ratio), glycemic control, body weight and adverse effects. A total of 9 studies, which included 144 patients, were reviewed. SGLT2 inhibitor use in renal transplant patients demonstrates either a small or nonsignificant reduction in blood pressure and results in overall stable renal allograft function. It also results in modest improvement in glycemic control as well as weight reduction. The incidence of adverse effects is low and reversible, as reported in previous nontransplant clinical trials. Overall, our findings suggest beneficial outcomes with no significant adverse effects or complications with the use of SGLT2 inhibitors in renal transplant patients with diabetes; however, these findings are based on small trials, and thus well-designed trials in this population are warranted.
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Affiliation(s)
- Shirley Shuster
- Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada
| | - Zeyana Al-Hadhrami
- Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada; Division of Nephrology, Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada
| | - Sarah Moore
- Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada; Division of Endocrinology, Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada
| | - Sara Awad
- Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada; Division of Endocrinology, Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada
| | - M Khaled Shamseddin
- Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada; Division of Nephrology, Department of Medicine, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada.
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Hypertension in kidney transplantation: a consensus statement of the 'hypertension and the kidney' working group of the European Society of Hypertension. J Hypertens 2021; 39:1513-1521. [PMID: 34054055 DOI: 10.1097/hjh.0000000000002879] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.
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Montada-Atin T, Prasad GVR. Recent advances in new-onset diabetes mellitus after kidney transplantation. World J Diabetes 2021; 12:541-555. [PMID: 33995843 PMCID: PMC8107982 DOI: 10.4239/wjd.v12.i5.541] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/05/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
A common challenge in managing kidney transplant recipients (KTR) is post-transplant diabetes mellitus (PTDM) or diabetes mellitus (DM) newly diagnosed after transplantation, in addition to known pre-existing DM. PTDM is an important risk factor for post-transplant cardiovascular (CV) disease, which adversely affects patient survival and quality of life. CV disease in KTR may manifest as ischemic heart disease, heart failure, and/or left ventricular hypertrophy. Available therapies for PTDM include most agents currently used to treat type 2 diabetes. More recently, the use of sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase 4 inhibitors (DPP4i) has cautiously extended to KTR with PTDM, even though KTR are typically excluded from large general population clinical trials. Initial evidence from observational studies seems to indicate that SGLT2i, GLP-1 RA, and DPP4i may be safe and effective for glycemic control in KTR, but their benefit in reducing CV events in this otherwise high-risk population remains unproven. These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status, pre-existing burden of peripheral vascular disease, urinary tract infections due to immunosuppression and a surgically altered urinary tract, erythrocytosis from calcineurin inhibitors, and reduced kidney function from acute or chronic rejection.
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Affiliation(s)
- Tess Montada-Atin
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
| | - G V Ramesh Prasad
- Kidney Transplant Program, St. Michael's Hospital, Toronto M5C 2T2, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto M5C 2T2, Canada
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Miyazaki R, Miyagi K, Yoshida M. Two Japanese patients with stage G3b chronic kidney disease and impaired glucose metabolism after renal transplantation successfully treated with empagliflozin. RENAL REPLACEMENT THERAPY 2020. [DOI: 10.1186/s41100-020-00303-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Abstract
Background
Renal transplant recipients with chronic kidney disease (CKD) often develop abnormal glucose metabolism. Although recent studies have reported the protective effects of sodium-glucose transport protein 2 (SGLT2) inhibitors on the heart and kidneys, few have assessed their effect in renal transplant patients. Moreover, to our knowledge, there have been no studies on the effects of SGLT2 inhibitors in renal transplant recipients in Japan.
Case presentation
Case 1 was a 67-year-old male renal transplant recipient with post-transplant diabetes mellitus. He was administered empagliflozin 10 mg once a day for 9 months. Over time, his HbA1c levels decreased from 6.8 to 6.0%. Case 2 was a 56-year-old male renal transplant recipient with fatty liver disease. He was administered empagliflozin 10 mg once a day for 9 months. His ALT, γ-GTP, and LDL-cholesterol levels all decreased. In both patients, body weight and the urine albumin to creatinine ratio (UACR) decreased after empagliflozin administration, but there were no changes in the estimated glomerular filtration rate. No adverse events occurred in either case.
Conclusions
Administration of empagliflozin had favorable outcomes in two patients with stage G3b CKD and abnormal glucose metabolism after renal transplantation. Further studies will be required to clarify the efficacy and safety of SGLT2 inhibitors in a larger population of patients with similar medical conditions.
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