Inibitori del cotrasportatore sodio-glucosio di tipo 2 in pazienti sottoposti a trapianto renale

Aris Tsalouchos

doi:10.33393/gcnd.2023.2620

Authors

Aris Tsalouchos Ospedale SS. Cosma e Damiano, Pescia - Italy https://orcid.org/0000-0002-8565-4059

DOI:

https://doi.org/10.33393/gcnd.2023.2620

Keywords:

SGLT2 inhibitors, Kidney transplantation, Kidney outcomes

Abstract

Several recent randomized controlled trials (RCTs) have demonstrated the broad clinical application of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in improving kidney and cardiovascular outcomes in patients with native kidney disease. In January 2023, Dapagliflozin became the first SGLT2 inhibitor approved by the Italian Medicines Agency Administration (AIFA) for the treatment of chronic kidney disease (CKD) regardless of diabetic status. However, although these agents have received considerable praise for their cardiovascular and nephroprotective effects among patients with native kidney disease, the safety and efficacy of SGLT2i in the kidney transplant setting are not well-known as safety concerns have led to the exclusion of transplant recipients from all large RCTs. This review will discuss the known mechanisms SGLT2i employ to provide their beneficial effects, the potential benefits and risks of these agents in the context of kidney transplantation, and finally, it will examine the current findings of published literature on SGLT2i use in kidney transplant recipients and propose potential directions for future research.

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References

Wyld M, Morton RL, Hayen A, Howard K, Webster AC. A systematic review and meta-analysis of utility-based quality of life in chronic kidney disease treatments. PLoS Med. 2012;9(9):e1001307. https://doi.org/10.1371/journal.pmed.1001307 PMID:22984353 DOI: https://doi.org/10.1371/journal.pmed.1001307

Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341(23):1725-1730. https://doi.org/10.1056/NEJM199912023412303 PMID:10580071 DOI: https://doi.org/10.1056/NEJM199912023412303

Meier-Kriesche HU, Ojo AO, Port FK, Arndorfer JA, Cibrik DM, Kaplan B. Survival improvement among patients with end-stage renal disease: trends over time for transplant recipients and wait-listed patients. J Am Soc Nephrol. 2001;12(6):1293-1296. https://doi.org/10.1681/ASN.V1261293 PMID:11373354 DOI: https://doi.org/10.1681/ASN.V1261293

Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000;342(9):605-612. https://doi.org/10.1056/NEJM200003023420901 PMID:10699159 DOI: https://doi.org/10.1056/NEJM200003023420901

Foster BJ, Dahhou M, Zhang X, Platt RW, Hanley JA. Change in mortality risk over time in young kidney transplant recipients. Am J Transplant. 2011;11(11):2432-2442. https://doi.org/10.1111/j.1600-6143.2011.03691.x PMID:21831152 DOI: https://doi.org/10.1111/j.1600-6143.2011.03691.x

Lentine KL, Smith JM, Hart A, et al. OPTN/SRTR 2020 Annual Data Report: kidney. Am J Transplant. 2022;22(suppl 2):21-136. https://doi.org/10.1111/ajt.16982 PMID:35266618 DOI: https://doi.org/10.1111/ajt.16982

Birdwell KA, Park M. Post-Transplant Cardiovascular Disease. Clin J Am Soc Nephrol. 2021;16(12):1878-1889. https://doi.org/10.2215/CJN.00520121 PMID:34556500 DOI: https://doi.org/10.2215/CJN.00520121

Jenssen T, Hartmann A. Post-transplant diabetes mellitus in patients with solid organ transplants. Nat Rev Endocrinol. 2019;15(3):172-188. https://doi.org/10.1038/s41574-018-0137-7 PMID:30622369 DOI: https://doi.org/10.1038/s41574-018-0137-7

Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3(2):178-185. https://doi.org/10.1034/j.1600-6143.2003.00010.x PMID:12603213 DOI: https://doi.org/10.1034/j.1600-6143.2003.00010.x

Cosio FG, Hickson LJ, Griffin MD, Stegall MD, Kudva Y. Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am J Transplant. 2008;8(3):593-599. https://doi.org/10.1111/j.1600-6143.2007.02101.x PMID:1829415511. Sharif A, Hecking M, de Vries AP et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant. 2014 Sep;14(9):1992-2000. https://doi.org/10.1111/ajt.12850 PMID: 25307034 DOI: https://doi.org/10.1111/j.1600-6143.2007.02101.x

Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377(7):644-657. https://doi.org/10.1056/NEJMoa1611925 PMID:28605608 DOI: https://doi.org/10.1056/NEJMoa1611925

Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357. https://doi.org/10.1056/NEJMoa1812389 PMID:30415602 DOI: https://doi.org/10.1056/NEJMoa1812389

Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. https://doi.org/10.1056/NEJMoa1504720 PMID:26378978 DOI: https://doi.org/10.1056/NEJMoa1504720

Cannon CP, Pratley R, Dagogo-Jack S, et al; VERTIS CV Investigators. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020;383(15):1425-1435. https://doi.org/10.1056/NEJMoa2004967 PMID:32966714 DOI: https://doi.org/10.1056/NEJMoa2004967

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. https://doi.org/10.1056/NEJMoa2024816 PMID:32970396 DOI: https://doi.org/10.1056/NEJMoa2024816

Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. https://doi.org/10.1056/NEJMoa1811744 PMID:30990260 DOI: https://doi.org/10.1056/NEJMoa1811744

McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. https://doi.org/10.1056/NEJMoa1911303 PMID:31535829 DOI: https://doi.org/10.1056/NEJMoa1911303

Packer M, Anker SD, Butler J, et al; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424. https://doi.org/10.1056/NEJMoa2022190 PMID:32865377 DOI: https://doi.org/10.1056/NEJMoa2022190

Cherney DZI, Cosentino F, Dagogo-Jack S, et al; VERTIS CV Investigators. Ertugliflozin and Slope of Chronic eGFR: Prespecified Analyses from the Randomized VERTIS CV Trial. Clin J Am Soc Nephrol. 2021;16(9):1345-1354. https://doi.org/10.2215/CJN.01130121 PMID:34497110 DOI: https://doi.org/10.2215/CJN.01130121

Wanner C, Inzucchi SE, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334. https://doi.org/10.1056/NEJMoa1515920 PMID:27299675 DOI: https://doi.org/10.1056/NEJMoa1515920

Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018;6(9):691-704. https://doi.org/10.1016/S2213-8587(18)30141-4 PMID:29937267 DOI: https://doi.org/10.1016/S2213-8587(18)30141-4

AlKindi F, Al-Omary HL, Hussain Q, Al Hakim M, Chaaban A, Boobes Y. Outcomes of SGLT2 Inhibitors Use in Diabetic Renal Transplant Patients. Transplant Proc. 2020;52(1):175-178. https://doi.org/10.1016/j.transproceed.2019.11.007 PMID:31924404 DOI: https://doi.org/10.1016/j.transproceed.2019.11.007

Attallah N, Yassine L. Use of Empagliflozin in Recipients of Kidney Transplant: A Report of 8 Cases. Transplant Proc. 2019;51(10):3275-3280. https://doi.org/10.1016/j.transproceed.2019.05.023 PMID:31732204 DOI: https://doi.org/10.1016/j.transproceed.2019.05.023

Halden TAS, Kvitne KE, Midtvedt K, et al. Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. 2019;42(6):1067-1074. https://doi.org/10.2337/dc19-0093 PMID:30862658 DOI: https://doi.org/10.2337/dc19-0093

Mahling M, Schork A, Nadalin S, Fritsche A, Heyne N, Guthoff M. Sodium-Glucose Cotransporter 2 (SGLT2) Inhibition in Kidney Transplant Recipients with Diabetes Mellitus. Kidney Blood Press Res. 2019;44(5):984-992. https://doi.org/10.1159/000501854 PMID:31437852 DOI: https://doi.org/10.1159/000501854

Rajasekeran H, Kim SJ, Cardella CJ, et al. Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2 Diabetes: A Case Series. Diabetes Care. 2017;40(7):e75-e76. https://doi.org/10.2337/dc17-0237 PMID:28416475 DOI: https://doi.org/10.2337/dc17-0237

Schwaiger E, Burghart L, Signorini L, et al. Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am J Transplant. 2019;19(3):907-919. https://doi.org/10.1111/ajt.15223 PMID:30585690 DOI: https://doi.org/10.1111/ajt.15223

Shah M, Virani Z, Rajput P, Shah B. Efficacy and Safety of Canagliflozin in Kidney Transplant Patients. Indian J Nephrol. 2019;29(4):278-281. https://doi.org/10.4103/ijn.IJN_2_18 PMID:31423063 DOI: https://doi.org/10.4103/ijn.IJN_2_18

Song CC, Brown A, Winstead R, et al. Early initiation of sodium-glucose linked transporter inhibitors (SGLT-2i) and associated metabolic and electrolyte outcomes in diabetic kidney transplant recipients. Endocrinol Diabetes Metab. 2020;4(2):e00185. https://doi.org/10.1002/edm2.185 PMID:33855198 DOI: https://doi.org/10.1002/edm2.185

kong J, Joon J, Chul Y, et al. SP770 sodium/glucose cotransporter 2 inhibitors for the treatment of diabetes in kidney transplant patients. Nephrol Dial Transplant 2019; 34(Suppl.1). https://doi.org/10.1093/ndt/gfz103.SP770 DOI: https://doi.org/10.1093/ndt/gfz103.SP770

Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020;17(12):761-772. https://doi.org/10.1038/s41569-020-0406-8 PMID:32665641 DOI: https://doi.org/10.1038/s41569-020-0406-8

Vallon V, Verma S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu Rev Physiol. 2021;83(1):503-528. https://doi.org/10.1146/annurev-physiol-031620-095920 PMID:33197224 DOI: https://doi.org/10.1146/annurev-physiol-031620-095920

Heerspink HJL, Cherney DZI. Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation. Clin J Am Soc Nephrol. 2021;16(8):1278-1280. https://doi.org/10.2215/CJN.02480221 PMID:33879500 DOI: https://doi.org/10.2215/CJN.02480221

Halimi JM. Low-grade proteinuria and microalbuminuria in renal transplantation. Transplantation. 2013;96(2):121-130. https://doi.org/10.1097/TP.0b013e31828719fb PMID:23435457 DOI: https://doi.org/10.1097/TP.0b013e31828719fb

Halimi JM, Buchler M, Al-Najjar A, et al. Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients. Am J Transplant. 2007;7(3):618-625. https://doi.org/10.1111/j.1600-6143.2007.01665.x PMID:17217438 DOI: https://doi.org/10.1111/j.1600-6143.2007.01665.x

Formica RN Jr, Friedman AL, Lorber MI, Smith JD, Eisen T, Bia MJ. A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period. Nephrol Dial Transplant. 2006;21(5):1389-1394. https://doi.org/10.1093/ndt/gfk058 PMID:16431893 DOI: https://doi.org/10.1093/ndt/gfk058

Barnett AH, Mithal A, Manassie J, et al; EMPA-REG RENAL trial investigators. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369-384. https://doi.org/10.1016/S2213-8587(13)70208-0 PMID:24795251 DOI: https://doi.org/10.1016/S2213-8587(13)70208-0

Kohan DE, Fioretto P, Tang W, List JF. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85(4):962-971. https://doi.org/10.1038/ki.2013.356 PMID:24067431 DOI: https://doi.org/10.1038/ki.2013.356

Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508. https://doi.org/10.1172/JCI72227 PMID:24463454 DOI: https://doi.org/10.1172/JCI72227

Hoogeveen EK, Aalten J, Rothman KJ, et al. Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up. Transplantation. 2011;91(8):869-874. https://doi.org/10.1097/TP.0b013e3182100f3a PMID:21326138 DOI: https://doi.org/10.1097/TP.0b013e3182100f3a

Majewski C, Bakris GL. Blood pressure reduction: an added benefit of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes. Diabetes Care. 2015;38(3):429-430. https://doi.org/10.2337/dc14-1596 PMID:25715414 DOI: https://doi.org/10.2337/dc14-1596

Tang J, Ye L, Yan Q, Zhang X, Wang L. Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Water and Sodium Metabolism. Front Pharmacol. 2022;13:800490. https://doi.org/10.3389/fphar.2022.800490 PMID:35281930 DOI: https://doi.org/10.3389/fphar.2022.800490

Ferrannini E, Baldi S, Frascerra S, et al. Renal Handling of Ketones in Response to Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care. 2017;40(6):771-776. https://doi.org/10.2337/dc16-2724 PMID:28325783 DOI: https://doi.org/10.2337/dc16-2724

Griffin M, Rao VS, Ivey-Miranda J, et al. Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects. Circulation. 2020;142(11):1028-1039. https://doi.org/10.1161/CIRCULATIONAHA.120.045691 PMID:32410463 DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.045691

Hallow KM, Helmlinger G, Greasley PJ, McMurray JJV, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018;20(3):479-487. https://doi.org/10.1111/dom.13126 PMID:29024278 DOI: https://doi.org/10.1111/dom.13126

Verma A, Patel AB, Waikar SS. SGLT2 Inhibitor: Not a Traditional Diuretic for Heart Failure. Cell Metab. 2020;32(1):13-14. https://doi.org/10.1016/j.cmet.2020.06.014 PMID:32640243 DOI: https://doi.org/10.1016/j.cmet.2020.06.014

Oliva RV, Bakris GL. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. J Am Soc Hypertens. 2014;8(5):330-339. https://doi.org/10.1016/j.jash.2014.02.003 PMID:24631482 DOI: https://doi.org/10.1016/j.jash.2014.02.003

Wei R, Wang W, Pan Q, Guo L. Effects of SGLT-2 Inhibitors on Vascular Endothelial Function and Arterial Stiffness in Subjects With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2022;13:826604. https://doi.org/10.3389/fendo.2022.826604 PMID:35250882 DOI: https://doi.org/10.3389/fendo.2022.826604

Opelz G, Wujciak T, Ritz E. Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study. Kidney Int. 1998;53(1):217-222. https://doi.org/10.1046/j.1523-1755.1998.00744.x PMID:9453022 DOI: https://doi.org/10.1046/j.1523-1755.1998.00744.x

Weir MR, Slee A, Sun T, et al. Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Clin Kidney J. 2020;14(5):1396-1402. https://doi.org/10.1093/ckj/sfaa133 PMID:34221371 DOI: https://doi.org/10.1093/ckj/sfaa133

Zhao Y, Xu L, Tian D, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2018;20(2):458-462. https://doi.org/10.1111/dom.13101 PMID:28846182 DOI: https://doi.org/10.1111/dom.13101

Tang H, Zhang X, Zhang J, et al. Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials. Diabetologia. 2016;59(12):2546-2551. https://doi.org/10.1007/s00125-016-4101-6 PMID:27628105 DOI: https://doi.org/10.1007/s00125-016-4101-6

Miles CD, Westphal SG. Electrolyte Disorders in Kidney Transplantation. Clin J Am Soc Nephrol. 2020;15(3):412-414. https://doi.org/10.2215/CJN.09470819 PMID:32066594 DOI: https://doi.org/10.2215/CJN.09470819

Clive DM. Renal transplant-associated hyperuricemia and gout. J Am Soc Nephrol. 2000;11(5):974-979. https://doi.org/10.1681/ASN.V115974 PMID:10770978 DOI: https://doi.org/10.1681/ASN.V115974

Inzucchi SE, Zinman B, Fitchett D, et al. How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2018;41(2):356-363. https://doi.org/10.2337/dc17-1096 PMID:29203583 DOI: https://doi.org/10.2337/dc17-1096

Mazer CD, Hare GMT, Connelly PW, et al. Effect of Empagliflozin on Erythropoietin Levels, Iron Stores, and Red Blood Cell Morphology in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation. 2020;141(8):704-707. https://doi.org/10.1161/CIRCULATIONAHA.119.044235 PMID:31707794 DOI: https://doi.org/10.1161/CIRCULATIONAHA.119.044235

Ghanim H, Abuaysheh S, Hejna J, et al. Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis. J Clin Endocrinol Metab. 2020;105(4):dgaa057. https://doi.org/10.1210/clinem/dgaa057 PMID:32044999 DOI: https://doi.org/10.1210/clinem/dgaa057

Yabu JM, Winkelmayer WC. Posttransplantation anemia: mechanisms and management. Clin J Am Soc Nephrol. 2011;6(7):1794-1801. https://doi.org/10.2215/CJN.01190211 PMID:21734096 DOI: https://doi.org/10.2215/CJN.01190211

Schechter A, Gafter-Gvili A, Shepshelovich D, et al. Post renal transplant anemia: severity, causes and their association with graft and patient survival. BMC Nephrol. 2019;20(1):51. https://doi.org/10.1186/s12882-019-1244-y PMID:30760235 DOI: https://doi.org/10.1186/s12882-019-1244-y

Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357(25):2601-2614. https://doi.org/10.1056/NEJMra064928 PMID:18094380 DOI: https://doi.org/10.1056/NEJMra064928

Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: kidney. Am J Transplant. 2020;20(suppl s1):20-130. https://doi.org/10.1111/ajt.15672 PMID:31898417 DOI: https://doi.org/10.1111/ajt.15672

Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13507. https://doi.org/10.1111/ctr.13507 PMID:30793386 DOI: https://doi.org/10.1111/ctr.13507

Ariza-Heredia EJ, Beam EN, Lesnick TG, Kremers WK, Cosio FG, Razonable RR. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Ann Transplant. 2013;18:195-204. https://doi.org/10.12659/AOT.883901 PMID:23792521 DOI: https://doi.org/10.12659/AOT.883901

Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783-794. https://doi.org/10.1111/dom.12670 PMID:27059700 DOI: https://doi.org/10.1111/dom.12670

Palmer BF, Clegg DJ. Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor Therapy. Clin J Am Soc Nephrol. 2021;16(8):1284-1291. https://doi.org/10.2215/CJN.17621120 PMID:33563658 DOI: https://doi.org/10.2215/CJN.17621120

Liu J, Li L, Li S, et al. Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22(9):1619-1627. https://doi.org/10.1111/dom.14075 PMID:32364674 DOI: https://doi.org/10.1111/dom.14075

Watts NB, Bilezikian JP, Usiskin K, et al. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016;101(1):157-166. https://doi.org/10.1210/jc.2015-3167 PMID:26580237 DOI: https://doi.org/10.1210/jc.2015-3167

Nadkarni GN, Ferrandino R, Chang A, et al. Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis. Diabetes Care. 2017;40(11):1479-1485. https://doi.org/10.2337/dc17-1011 PMID:28827404 DOI: https://doi.org/10.2337/dc17-1011

Chang HY, Singh S, Mansour O, Baksh S, Alexander GC. Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity Amputation Among Patients With Type 2 Diabetes. JAMA Intern Med. 2018;178(9):1190-1198. https://doi.org/10.1001/jamainternmed.2018.3034 PMID:30105373 DOI: https://doi.org/10.1001/jamainternmed.2018.3034

Abbott KC, Bernet VJ, Agodoa LY, Yuan CM. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States. BMC Endocr Disord. 2003;3(1):1. https://doi.org/10.1186/1472-6823-3-1 PMID:12659645 DOI: https://doi.org/10.1186/1472-6823-3-1

Dhatariya KK, Glaser NS, Codner E, Umpierrez GE. Diabetic ketoacidosis. Nat Rev Dis Primers. 2020;6(1):40. https://doi.org/10.1038/s41572-020-0165-1 PMID:32409703 DOI: https://doi.org/10.1038/s41572-020-0165-1

Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med. 2007;357(8):797-805. https://doi.org/10.1056/NEJMra064398 PMID:17715412 DOI: https://doi.org/10.1056/NEJMra064398

Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002983. https://doi.org/10.1371/journal.pmed.1002983 PMID:31815931 DOI: https://doi.org/10.1371/journal.pmed.1002983

Katsurada K, Nandi SS, Sharma NM, Patel KP. Enhanced Expression and Function of Renal SGLT2 (Sodium-Glucose Cotransporter 2) in Heart Failure: Role of Renal Nerves. Circ Heart Fail. 2021;14(12):e008365. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008365 PMID:34789005 DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.121.008365

Katsurada K, Nandi SS, Sharma NM, Patel KP. Role of the renal nerves in regulating SGLT2 inhibitor-induced diuresis and natriuresis in rats with heart failure. FASEB J. 2020;34(S1):1-1. https://doi.org/10.1096/fasebj.2020.34.s1.05832 DOI: https://doi.org/10.1096/fasebj.2020.34.s1.05832

Devineni D, Polidori D, Curtin C, Stieltjes H, Tian H, Wajs E. Single-dose Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Selective Inhibitor of Sodium Glucose Cotransporter 2, in Healthy Indian Participants. Clin Ther. 2016;38(1):89-98.e1. https://doi.org/10.1016/j.clinthera.2015.11.008 PMID:26687552 DOI: https://doi.org/10.1016/j.clinthera.2015.11.008

Kaushal S, Singh H, Thangaraju P, Singh J. Canagliflozin: A Novel SGLT2 Inhibitor for Type 2 Diabetes Mellitus. N Am J Med Sci. 2014;6(3):107-113. https://doi.org/10.4103/1947-2714.128471 PMID:24741548 DOI: https://doi.org/10.4103/1947-2714.128471

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. 2022;46(2):207-212. https://doi.org/10.1016/j.jcjd.2021.06.003 PMID:34362679 DOI: https://doi.org/10.1016/j.jcjd.2021.06.003

Chewcharat A, Prasitlumkum N, Thongprayoon C, et al. Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis. Med Sci (Basel). 2020;8(4):47. https://doi.org/10.3390/medsci8040047 PMID:33213078 DOI: https://doi.org/10.3390/medsci8040047

KwonH, Son SH, Kim K et al. Sodium/glucose cotransporter 2 inhibitors reduce microalbuminuria in diabetic renal transplant patients.. Transplantation 104(S3):p S430. https://doi.org/10.1097/01.tp.0000700792.22109.b0 DOI: https://doi.org/10.1097/01.tp.0000700792.22109.b0

Patel N, Hindi J, Farouk SS. Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For? Kidney360. 2021;2(7):1174-1178. https://doi.org/10.34067/KID.0000732021 PMID:35368347 DOI: https://doi.org/10.34067/KID.0000732021