Novel glucose-lowering drugs and the risk of acute kidney injury in routine care; the Stockholm CREAtinine Measurements (SCREAM) project

Springer Science and Business Media LLC
Jim Alkas1, Alessandro Bosi1, Arvid Sjölander1, Peter Bárány2, Carl‐Gustaf Elinder2, Edouard L Fu3, Juan Jesús Carrero4
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
3Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA
4Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden

Tóm tắt

Abstract Introduction

Little is known about the comparative effects of sodium glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), or dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of acute kidney injury (AKI) in routine care, which may differ from the controlled setting of trials.

 Methods

Observational study comparing risks of AKI among new users of SGLT2i, GLP1-RA or DPP-4i in the region of Stockholm, Sweden, during 2008–2018. AKI was defined by ICD-10 codes and creatinine-based KDIGO criteria. We used inverse probability of treatment weighting (IPTW) to adjust for 60 potential confounders, weighted Kaplan–Meier curves and Cox regression to estimate hazard ratios and absolute risks.

 Results

We included 17,407 participants who newly initiated DPP-4i (N = 10,605), GLP1-RA (N = 4448) or SGLT2i (N = 2354). Mean age was 63 years (39% women) and median (IQR) eGFR was 89 (73–100) ml/min/1.73 m2. During a median follow-up of 2.5 years, 1411 participants experienced AKI. SGLT2i users had the lowest incidence rate of AKI, 18.3 [CI 95% 14.1–23.4] per 1000 person years, followed by GLP1-RA (22.5; 19.9–25.3) and DPP-4i (26.6; 25–28.2). The weighted 3-year absolute risk for AKI was 5.79% [3.63–8.52] in the SGLT2i group, compared with 7.03% [5.69–8.69] and 7.00% [6.43–7.58] in the GLP1-RA and DPP-4i groups, respectively. The adjusted hazard ratio was 0.73 [CI 95% 0.45–1.16] for SGLT2i vs. DPP-4i, and 0.98 [CI 95% 0.82–1.18] for GLP1-RA vs. DPP-4i.

 Conclusion

This study of routine care patients initiating novel glucose-lowering drugs showed similar occurrence of AKI between therapies, and suggests lower risk for SGLT2i.

Từ khóa


Tài liệu tham khảo

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

Gallo LA, Wright EM, Vallon V (2015) Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diabetes Vasc Dis Res 12(2):78–89

Heerspink HJL et al (2020) Dapagliflozin in patients with chronic kidney disease. N Engl J Med 383(15):1436–1446

Perkovic V et al (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24):2295–2306

Neal B et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377(7):644–657

Wanner C et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334

Zinman B et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117–2128

Buse JB et al (2020) 2019 Update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 63(2):221–228

Cosentino F et al (2020) 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 41(2):255–323

Hahn K et al (2016) Acute kidney injury from SGLT2 inhibitors: potential mechanisms. Nat Rev Nephrol 12(12):711–712

FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). 2016. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin. Accessed Jan 2022

Zhao M et al (2020) Network meta-analysis of novel glucose-lowering drugs on risk of acute kidney injury. Clin J Am Soc Nephrol 16(1):70–78

Rampersad C 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 e1-479 e1

Iskander C 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

Nadkarni GN et al (2017) Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care 40(11):1479–1485

Ueda P et al (2018) Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 363:k4365

Zhuo M et al (2021) 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

Pasternak B et al (2020) Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study. BMJ 369:m1186

Carrero JJ, Elinder CG (2022) The Stockholm CREAtinine Measurements (SCREAM) project: fostering improvements in chronic kidney disease care. J Intern Med 291(3):254–268

Levey AS et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 2012. https://kdigo.org/guidelines/ckd-evaluation-and-management/. Accessed Jan 2022

(2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138.

McCaffrey DF et al (2013) A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat Med 32(19):3388–3414

Austin PC, Small DS (2014) The use of bootstrapping when using propensity-score matching without replacement: a simulation study. Stat Med 33(24):4306–4319

Fu EL et al (2019) Merits and caveats of propensity scores to adjust for confounding. Nephrol Dial Transplant 34(10):1629–1635

Nespoux J, Vallon V (2018) SGLT2 inhibition and kidney protection. Clin Sci (Lond) 132(12):1329–1339

Vallon V 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 Ren Physiol 304(2):F156–F167

Cherney DZ et al (2014) Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129(5):587–597

O’Neill J et al (2015) Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats. Am J Physiol Ren Physiol 309(3):F227–F234

Dekkers CCJ et al (2018) Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes Obes Metab 20(8):1988–1993

Grams ME et al (2014) Performance and limitations of administrative data in the identification of AKI. Clin J Am Soc Nephrol 9(4):682–689

Kidney Disease Improving Global Outcomes Diabetes Work, G., KDIGO (2020) 2020 Clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 98(4S):S1–S115

McDonagh TA et al (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726

Forxiga (Dapagliflozin). Summary of European public assessment report (EPAR).

Invokana (Canagliflozin). Summary of European public assessment report (EPAR).

Jardiance (Empagliflozin). Summary of European public assessment report (EPAR).

Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Thông tin tác giả