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Acute kidney injury in Japanese type 2 diabetes patients receiving sodium-glucose cotransporter 2 inhibitors: A nationwide cohort study.

ABSTRACT: The present retrospective study aimed to identify factors associated with an increased risk of acute kidney injury in Japanese patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors. We identified 171,622 patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors; among them, 476 (0.3%) patients developed acute kidney injury. The hazard ratio for acute kidney injury occurrence risk was analyzed using a Cox proportional hazards model adjusted for patient characteristics at baseline and use of concomitant agents. In the adjusted model, patients who developed acute kidney injury were mostly men, aged ≥65 years, had lower body mass index, had a history of heart failure and used diuretics more frequently than those who did not. These findings suggest that associated clinical risk factors should be thoroughly evaluated before administering sodium-glucose cotransporter 2 inhibitors to minimize acute kidney injury onset.

SUBMITTER: Horii T

PROVIDER: S-EPMC8756339 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Acute kidney injury in Japanese type 2 diabetes patients receiving sodium-glucose cotransporter 2 inhibitors: A nationwide cohort study.

Horii Takeshi T Oikawa Yoichi Y Kunisada Narumi N Shimada Akira A Atsuda Koichiro K

Journal of diabetes investigation 20210802 1

The present retrospective study aimed to identify factors associated with an increased risk of acute kidney injury in Japanese patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors. We identified 171,622 patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors; among them, 476 (0.3%) patients developed acute kidney injury. The hazard ratio for acute kidney injury occurrence risk was analyzed using a Cox proportional hazards model adjuste ...[more]

PMID: 34255919

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Project description:Background and objectivesSodium-glucose cotransporter-2 (SGLT2) inhibitors have been associated with a higher risk of skeletal fractures in some randomized, placebo-controlled trials. Secondary hyperparathyroidism and increased bone turnover (also common in CKD) may contribute to the observed fracture risk. We aimed to determine if SGLT2 inhibitor use associates with a higher risk of fractures compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, which have no known association with fracture risk. We hypothesized that this risk, if present, would be greatest in patients with lower eGFR.Design, setting, participants, & measurementsWe conducted a population-based cohort study in Ontario, Canada between 2015 and 2019 using linked provincial administrative data to compare the incidence of fracture between new users of SGLT2 inhibitors and DPP-4 inhibitors. We used inverse probability of treatment weighting on the basis of propensity scores to balance the two groups of older adults (≥66 years of age) on indicators of baseline health. We compared the 180- and 365-day cumulative incidence rates of fracture between groups. Prespecified subgroup analyses were conducted by eGFR category (≥90, 60 to <90, 45 to <60, and 30 to <45 ml/min per 1.73 m2). Weighted hazard ratios were obtained using Cox proportional hazard regression.ResultsAfter weighting, we identified a total of 38,994 new users of a SGLT2 inhibitor and 37,449 new users of a DPP-4 inhibitor and observed a total of 342 fractures at 180 days and 689 fractures at 365 days. The weighted 180- and 365-day risks of a fragility fracture did not significantly differ between new users of a SGLT2 inhibitor versus a DPP-4 inhibitor: weighted hazard ratio, 0.95 (95% confidence interval, 0.79 to 1.13) and weighted hazard ratio, 0.88 (95% confidence interval, 0.88 to 1.00), respectively. There was no observed interaction between fracture risk and eGFR category (P=0.53).ConclusionsIn this cohort study of older adults, starting a SGLT2 inhibitor versus DPP-4 inhibitor was not associated with a higher risk of skeletal fracture, regardless of eGFR.

Project description:Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

Project description:BackgroundWe conducted a systematic review and meta-analysis to summarize the available literature and comprehensively appraise the renal profiles of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Japanese patients with type 2 diabetes mellitus (T2DM).MethodsThe electronic databases MEDLINE, Ichushi-web, and ClinicalTrials.gov were searched for studies without language restrictions from their inception until 20 July 2023 and CENTRAL until 21 September 2021. Studies were included if they were double-masked randomized controlled trials (RCTs) (1) including Japanese patients with T2DM aged > 18 years who received SGLT2i or a placebo, (2) reporting at least one renal outcome of serum creatinine or the estimated glomerular filtration rate (eGFR), and (3) with a follow-up of > 12 weeks. Cross-over and open label trials were excluded. The risk of bias based on the Cochrane risk-of-bias tool for randomized trials (RoB 2) was appraised. We computed the weighed mean difference with 95%CI for each renal outcome and used a random-effects model (inverse variance method).ResultsWe ultimately retrieved 13 RCTs including 2687 individuals in our review. The durations of RCTs ranged between 12 and 104 weeks. Only one trial had a longer duration of more than one year. Ten out of 13 RCTs reported serum creatinine, while nine included eGFR. Serum creatinine and eGFR were slightly worse with SGLT2i than with a placebo [mean difference 0.01 (95%CI 0.00 to 0.02) mg/dL, p = 0.002, mean difference - 1.30 (95%CI -2.23 to -0.37) mL/min/1.73 m2, p = 0.006, respectively]. Merged results revealed insignificant heterogeneity (I2 < 30%).ConclusionThese results suggest that SGLT2i slightly worsens serum creatinine and eGFR in Japanese patients with T2DM. However, since the durations of most RCTs were short, the effects of eGFR in particular may be transient. Further evidence is needed from rigorous studies that focus on renal outcomes with a longer duration to confirm the present results.

Dataset Information

Acute kidney injury in Japanese type 2 diabetes patients receiving sodium-glucose cotransporter 2 inhibitors: A nationwide cohort study.

Publications

Acute kidney injury in Japanese type 2 diabetes patients receiving sodium-glucose cotransporter 2 inhibitors: A nationwide cohort study.

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