Nivethika Jeyakumar

BACKGROUND: Regulatory agencies warn about the risk of acute kidney injury (AKI) after the initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors. Our objective was to quantify the 90-day risk of AKI in older adults after initiation of SGLT2 inhibitors in routine clinical practice. METHODS: We conducted a population-based retrospective cohort study in Ontario, Canada, involving adults with diabetes who were aged 66 years or older and who were newly dispensed either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor in an outpatient setting between 2015 and 2017. We used inverse probability of treatment weighting based on a propensity score to balance the 2 groups on measured baseline characteristics. The primary outcome was 90-day risk of a hospital encounter (i.e., visit to the emergency department or admission to hospital) with AKI, which we defined by a 50% or greater increase in the concentration of serum creatinine from the baseline value or an absolute increase of at least 27 μmol/L after an SGLT2 or DDP4 inhibitor was dispensed. We obtained weighted risk ratios using modified Poisson regression and weighted risk differences using binomial regression. RESULTS: We included 39 094 patients with a median age of 70 (interquartile range 68-74) years in the study. Relative to new use of a DPP4 inhibitor, initiation of a SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19 611 patients (1.10%) versus 388 events in 19 483 patients (1.99%); weighted risk ratio 0.79 (95% confidence interval 0.64-0.98). INTERPRETATION: In routine care of older adults, new use of SGLT2 inhibitors compared with use of DPP4 inhibitors was associated with a lower risk of AKI. Together with previous evidence, our findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors are unwarranted.

Significance Statement AKI is common among hospitalized neonates and children and associated with adverse short- and long-term kidney outcomes. However, data for long-term outcomes of children with episodes of dialysis-treated AKI are limited. Using Ontario provincial health administrative databases, the authors identified 1688 pediatric survivors hospitalized and treated with dialysis for AKI episodes in 1996–2017, and followed them for a median of 9.6 years. Compared with matched hospitalized comparators, AKI survivors were at significantly increased risk of long-term kidney failure or death. The authors also observed significantly higher long-term rates of CKD and hypertension among the dialysis-treated AKI survivors. These findings support enhanced surveillance of kidney function and blood pressure after episodes of severe childhood AKI, with the aim of improving long-term kidney and patient survival. Background AKI is common during pediatric hospitalizations and associated with adverse short-term outcomes. However, long-term outcomes among survivors of pediatric AKI who received dialysis remain uncertain. Methods To determine the long-term risk of kidney failure (defined as receipt of chronic dialysis or kidney transplant) or death over a 22-year period for pediatric survivors of dialysis-treated AKI, we used province-wide health administrative databases to perform a retrospective cohort study of all neonates and children (aged 0–18 years) hospitalized in Ontario, Canada, from April 1, 1996, to March 31, 2017, who survived a dialysis-treated AKI episode. Each AKI survivor was matched to four hospitalized pediatric comparators without dialysis-treated AKI, on the basis of age, sex, and admission year. We reported the incidence of each outcome and performed Cox proportional hazards regression analyses, adjusting for relevant covariates. Results We identified 1688 pediatric dialysis–treated AKI survivors (median age 5 years) and 6752 matched comparators. Among AKI survivors, 53.7% underwent mechanical ventilation and 33.6% had cardiac surgery. During a median 9.6-year follow-up, AKI survivors were at significantly increased risk of a composite outcome of kidney failure or death versus comparators. Death occurred in 113 (6.7%) AKI survivors, 44 (2.6%) developed kidney failure, 174 (12.1%) developed hypertension, 213 (13.1%) developed CKD, and 237 (14.0%) had subsequent AKI. AKI survivors had significantly higher risks of developing CKD and hypertension versus comparators. Risks were greatest in the first year after discharge and gradually decreased over time. Conclusions Survivors of pediatric dialysis–treated AKI are at higher long-term risks of kidney failure, death, CKD, and hypertension, compared with a matched hospitalized cohort.

Importance: Physicians self-report high levels of symptoms of anxiety and depression, and surveys suggest these symptoms have been exacerbated by the COVID-19 pandemic. However, it is not known whether pandemic-related stressors have led to increases in health care visits related to mental health or substance use among physicians. Objective: To evaluate the association between the COVID-19 pandemic and changes in outpatient health care visits by physicians related to mental health and substance use and explore differences across physician subgroups of interest. Design, Setting, and Participants: A population-based cohort study was conducted using health administrative data collected from the universal health system (Ontario Health Insurance Plan) of Ontario, Canada, from March 1, 2017, to March 10, 2021. Participants included 34 055 physicians, residents, and fellows who registered with the College of Physicians and Surgeons of Ontario between 1990 and 2018 and were eligible for the Ontario Health Insurance Plan during the study period. Autoregressive integrated moving average models and generalized estimating equations were used in analyses. Exposures: The period during the COVID-19 pandemic (March 11, 2020, to March 10, 2021) compared with the period before the pandemic. Main Outcomes and Measures: The primary outcome was in-person, telemedicine, and virtual care outpatient visits to a psychiatrist or family medicine and general practice clinicians related to mental health and substance use. Results: In the 34 055 practicing physicians (mean [SD] age, 41.7 [10.0] years, 17 918 [52.6%] male), the annual crude number of visits per 1000 physicians increased by 27%, from 816.8 before the COVID-19 pandemic to 1037.5 during the pandemic (adjusted incident rate ratio per physician, 1.13; 95% CI, 1.07-1.19). The absolute proportion of physicians with 1 or more mental health and substance use visits within a year increased from 12.3% before to 13.4% during the pandemic (adjusted odds ratio, 1.08; 95% CI, 1.03-1.14). The relative increase was significantly greater in physicians without a prior mental health and substance use history (adjusted incident rate ratio, 1.72; 95% CI, 1.60-1.85) than in physicians with a prior mental health and substance use history. Conclusions and Relevance: In this study, the COVID-19 pandemic was associated with a substantial increase in mental health and substance use visits among physicians. Physician mental health may have worsened during the pandemic, highlighting a potential greater requirement for access to mental health services and system level change.