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Acute kidney injury events in patients with diabetes using sodium glucose transporter 2 inhibitors: a meta-analysis of cohort studies

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Abstract

Aims

To conduct a meta-analysis of cohort studies to explore the association between acute kidney injury (AKI) and the effect of sodium glucose transporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM).

Materials and methods

PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were comprehensively searched for eligible studies until April 4, 2023 on the association between AKI and use of SGLT2 inhibitors in T2DM patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel method.

Results

A total of 10 cohort studies (20 cohorts) and 526,863 participants were included in the meta-analysis. Compared with other glucose-lowering drugs (oGLDs), SGLT2 inhibitors were associated with a decreased risk of AKI (OR = 0.50, 95% CI 0.38–0.66, I2 = 96%). Meanwhile, SGLT2 inhibitors demonstrated a significant reduction in the incidence of AKI hospitalization compared with oGLDs (OR = 0.54, 95% CI 0.43–0.68, I2 = 92.0%). The result was consistent across different subgroups, and was robust to sensitivity analysis.

Conclusions

Compared with oGLDs, SGLT2 inhibitors reduced the risk of suffering AKI and AKI hospitalization in the real-world setting. Vigilance to the occurrence of AKI should not be an obstacle to discourage clinicians from prescribing SGLT2 inhibitors.

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References

  1. Zheng Y, Ley SH, Hu FB (2018) Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 14(2):88–98. https://doi.org/10.1038/nrendo.2017.151

    Article  PubMed  Google Scholar 

  2. Perkovic V, Jardine MJ, Neal B et al (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24):2295–2306. https://doi.org/10.1056/NEJMoa1811744

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Wiviott SD, Raz I, Bonaca MP et al (2019) Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 380(4):347–357. https://doi.org/10.1056/NEJMoa1812389

    Article  CAS  PubMed  Google Scholar 

  5. Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117–2128. https://doi.org/10.1056/NEJMoa1504720

    Article  CAS  PubMed  Google Scholar 

  6. Heidenreich PA, Bozkurt B, Aguilar D et al (2022) AHA/ACC/HFSA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation 145(18):e876–e894. https://doi.org/10.1161/CIR.0000000000001062

    Article  Google Scholar 

  7. Authors/Task Force M, McDonagh TA, Metra M et al (2022) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 24(1):4–131. https://doi.org/10.1002/ejhf.2333

    Article  Google Scholar 

  8. Communication FDS (2023) FDA strengthens kidney warnings for diabetes medicines canaglifozin (Invokana, Invokamet) and dapaglifozin (Farxiga, Xigduo XR). Accessed 14 June 2016. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin

  9. Wanner C, Inzucchi SE, Lachin JM et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334. https://doi.org/10.1056/NEJMoa1515920

    Article  CAS  PubMed  Google Scholar 

  10. Menne J, Dumann E, Haller H et al (2019) Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: a systematic review and meta-analysis. PLoS Med 16(12):e1002983. https://doi.org/10.1371/journal.pmed.1002983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhang X, Zhong Z, Li Y et al (2020) Long-term renal outcomes associated with sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev 36(5):e3303. https://doi.org/10.1002/dmrr.3303

    Article  CAS  PubMed  Google Scholar 

  12. Alkas J, Bosi A, Sjolander A et al (2023) Novel glucose-lowering drugs and the risk of acute kidney injury in routine care; the Stockholm CREAtinine Measurements (SCREAM) project. J Nephrol 36(3):705–711. https://doi.org/10.1007/s40620-022-01505-8

    Article  CAS  PubMed  Google Scholar 

  13. Zhuo M, Paik JM, Wexler DJ et al (2022) SGLT2 inhibitors and the risk of acute kidney injury in older adults with type 2 diabetes. Am J Kidney Dis 79(6):858–867. https://doi.org/10.1053/j.ajkd.2021.09.015

    Article  CAS  PubMed  Google Scholar 

  14. Rampersad C, Kraut E, Whitlock RH et al (2020) Acute kidney injury events in patients with type 2 diabetes using SGLT2 inhibitors versus other glucose-lowering drugs: a retrospective cohort study. Am J Kidney Dis 76(4):471–479. https://doi.org/10.1053/j.ajkd.2020.03.019

    Article  CAS  PubMed  Google Scholar 

  15. Nadkarni GN, Ferrandino R, Chang A et al (2017) Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care 40(11):1479–1485. https://doi.org/10.2337/dc17-1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Alkabbani W, Zongo A, Minhas-Sandhu JK et al (2021) Renal effectiveness and safety of the sodium-glucose cotransporter-2 inhibitors: a population-based cohort study. BMJ Open Diabetes Res Care. https://doi.org/10.1136/bmjdrc-2021-002496

    Article  PubMed  PubMed Central  Google Scholar 

  17. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wells GA, Shea B, O’Connell D, et al. (2023) The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

  19. Julian PT, Thompson SG (2022) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Google Scholar 

  20. Ge V, Subramaniam A, Banakh I et al (2021) Management of sodium-glucose cotransporter 2 inhibitors during the perioperative period: a retrospective comparative study. J Perioper Pract 31(10):391–398. https://doi.org/10.1177/1750458920948693

    Article  PubMed  Google Scholar 

  21. Iskander C, Cherney DZ, Clemens KK et al (2020) Use of sodium-glucose cotransporter-2 inhibitors and risk of acute kidney injury in older adults with diabetes: a population-based cohort study. CMAJ 192(14):E351–E360. https://doi.org/10.1503/cmaj.191283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cahn A, Melzer-Cohen C, Pollack R et al (2019) Acute renal outcomes with sodium-glucose co-transporter-2 inhibitors: real-world data analysis. Diabetes Obes Metab 21(2):340–348. https://doi.org/10.1111/dom.13532

    Article  CAS  PubMed  Google Scholar 

  23. Norhammar A, Bodegard J, Nystrom T et al (2017) Dapagliflozin is associated with lower risk of hospitalization for heart failure, major adverse cardiovascular events and all-cause death compared to DPP-4i in T2D patients: CVD-REAL nordic. Can J Diabetes. https://doi.org/10.1016/j.jcjd.2017.08.134

    Article  Google Scholar 

  24. Ueda P, Svanstrom H, Melbye M et al (2018) Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 363:k4365. https://doi.org/10.1136/bmj.k4365

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lin DS, Lee JK, Chen WJ (2021) Clinical adverse events associated with sodium-glucose cotransporter 2 inhibitors: a meta-analysis involving 10 randomized clinical trials and 71 553 individuals. J Clin Endocrinol Metab 106(7):2133–2145. https://doi.org/10.1210/clinem/dgab274

    Article  PubMed  Google Scholar 

  26. Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists Consortium (2022) Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 400(10365):1788–1801. https://doi.org/10.1016/S0140-6736(22)02074-8

    Article  Google Scholar 

  27. Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369(14):1317–1326. https://doi.org/10.1056/NEJMoa1307684

    Article  CAS  PubMed  Google Scholar 

  28. Rosenstock J, Perkovic V, Johansen OE et al (2019) Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA 321(1):69–79. https://doi.org/10.1001/jama.2018.18269

    Article  CAS  PubMed  Google Scholar 

  29. White WB, Cannon CP, Heller SR et al (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369(14):1327–1335. https://doi.org/10.1056/NEJMoa1305889

    Article  CAS  PubMed  Google Scholar 

  30. Advani A (2020) Acute kidney injury: a bona fide complication of diabetes. Diabetes 69(11):2229–2237. https://doi.org/10.2337/db20-0604

    Article  CAS  PubMed  Google Scholar 

  31. Hapca S, Siddiqui MK, Kwan RSY et al (2021) The Relationship between AKI and CKD in patients with type 2 diabetes: an observational cohort study. J Am Soc Nephrol 32(1):138–150. https://doi.org/10.1681/ASN.2020030323

    Article  CAS  PubMed  Google Scholar 

  32. Vallon V, Rose M, Gerasimova M et al (2013) Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 304(2):F156-167. https://doi.org/10.1152/ajprenal.00409.2012

    Article  CAS  PubMed  Google Scholar 

  33. Li J, Neal B, Perkovic V et al (2020) Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes. Kidney Int 98(3):769–777. https://doi.org/10.1016/j.kint.2020.04.051

    Article  CAS  PubMed  Google Scholar 

  34. Hahn K, Ejaz AA, Kanbay M et al (2016) Acute kidney injury from SGLT2 inhibitors: potential mechanisms. Nat Rev Nephrol 12(12):711–712. https://doi.org/10.1038/nrneph.2016.159

    Article  CAS  PubMed  Google Scholar 

  35. Peng J, Li X, Zhang D et al (2015) Hyperglycemia, p53, and mitochondrial pathway of apoptosis are involved in the susceptibility of diabetic models to ischemic acute kidney injury. Kidney Int 87(1):137–150. https://doi.org/10.1038/ki.2014.226

    Article  CAS  PubMed  Google Scholar 

  36. Yin WJ, Liu F, Li XM et al (2012) Noninvasive evaluation of renal oxygenation in diabetic nephropathy by BOLD-MRI. Eur J Radiol 81(7):1426–1431. https://doi.org/10.1016/j.ejrad.2011.03.045

    Article  PubMed  Google Scholar 

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Author information

Author notes

  1. Yanjing Shi and Shujie Dong: Shared first-authorship.

Authors and Affiliations

  1. Department of Pharmacy, Peking University Third Hospital, No.49 Huayuan North Road, Haidian District, Beijing, 100191, China

    Yanjing Shi, Shujie Dong, Li Yang & Rongsheng Zhao

  2. Department of Pharmacy, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, China

    Yanjing Shi

  3. Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China

    Yang Xu & Dongze Ji

  4. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

    Yang Xu & Dongze Ji

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Correspondence to Rongsheng Zhao.

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Shi, Y., Dong, S., Xu, Y. et al. Acute kidney injury events in patients with diabetes using sodium glucose transporter 2 inhibitors: a meta-analysis of cohort studies. Acta Diabetol (2024). https://doi.org/10.1007/s00592-024-02252-x

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