A Clinical Study on the Association of Sodium-Glucose Cotransporter 2 Inhibitors and Acute Kidney Injury Among Diabetic Chinese Population

Abstract

Purpose To investigate the association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and acute kidney injury in comparison to other classes of drugs. Patients and Methods A total of 4966 diabetes mellitus patients were investigated for developing Acute Kidney Injury (AKI) who were under prescription with the following class of drugs viz. SGLT2 Inhibitors, Dipeptidyl peptidase-4 (DDP4) inhibitors, Nonsteroidal anti-inflammatory drugs (NSAIDs), first-line drugs and anti-biotics. The primary outcome was based on the hospital encounter and Kidney Disease Improving Global Outcome (KDIGO) threshold values were used to assess the serum creatinine concentration. The secondary outcome was assessed based on the concentration level of serum creatinine after 90 days of hospital admission and evaluation of the KDIGO threshold values. Results The study observed that the risk of causing AKI for SGLT2 inhibitors was 5.59% which was comparatively low compared to other class of the investigated drugs (DPP4 inhibitors = 6.47%, antibiotics = 6.30%, first-line drugs = 6.82% and NSAIDs = 10.65%). The multivariate analysis observed that ibuprofen, celecoxib, indomethacin, insulin, cephalexin, and alogliptin were mostly associated with an increased rate of AKI. SGLT2 inhibitors have the lowest risk for developing AKI compared to other drugs and control. Conclusion AKI incidence is relatively low after initiation of SLGT2 inhibitors and concludes that regulatory warnings from certain health agencies about its risk for AKI on prescription are unwarranted.

The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management

“…In clinical studies, SGLT2 inhibitors had the lowest risk of AKI (5.59%) compared with other drugs and controls [ 150 ]. Several recent meta-analyses indicated that SGLT2 inhibitors can reduce the risk of AKI [ 151 , 152 ].…”

Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice

“…In coronary artery bypass surgery, taking aspirin within 24 h before surgery reduced the incidence of AKI after surgery by 36% and was independently associated ( Aboul-Hassan et al, 2020 ). In contrast, ibuprofen, celecoxib, indomethacin, insulin, cefotaxin, and alogliptin were primarily associated with an increased incidence of AKI ( Shen et al, 2021 ). These drugs or molecular compounds were mentioned in our study and could be potential drugs for the treatment of IRI-AKI in the future.…”

Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts

“…In particular, decreased baseline eGFR should be considered a risk for AKI when 2‐DM patients are prescribed SGLT2i 186 . Several clinical population‐based cohort studies from the US, Canada, and China provided stronger evidence that SGLT2i has no or reduced risk of AKI compared with initiation of a DPP‐4i, for adults and the elderly 187–190 . Apart from sporadic reports, SGLT2i is not a frequent cause of AKI.…”

“…Prevented oxidative stress and ROS production to protect tubular cell death and renal repair in AKI 177,178 Reduced 30-day mortality in patients with AKI and DM. Accumulation in AKI kidney induces lactic acidosis 179,180 DPP-4 inhibitor Accelerated tubule regeneration and functional recovery from toxic AKI through an anti-inflammatory effect 181 DPP4i associated with a lower risk of incident AKI and risk of dialysis-requiring AKI 182,183 SGLT2 inhibitor Increased hypoxia-inducible factor 1, AMP-activated protein kinase, extracellular-regulated kinase, and human proximal tubular cell survival 80,184 Reduced the risk of AKI [185][186][187][188][189][190] GLP-1R agonist Ameliorated cisplatin-and ischemia-induced AKI and reduced kidney damage in diabetic rats after AKI 191,192 Lowered the risk of kidney and cardiovascular outcomes 193 Finerenone Mitigated ischemic AKI, preventing AKI to CKD transition [194][195][196] Failed to reduce the incidence of AKI in patients undergoing cardiovascular surgery 197 energy to generate ATP. 177 Meanwhile, it can reduce oxidative stress and ROS production to protect tubular cells.…”