Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD

BACKGROUND AND OBJECTIVES: There have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m2 and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m2 were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m2 or eGFR decline ≥30% with reference to baseline. RESULTS: After a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m2 and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m2 (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41). CONCLUSIONS: Nonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m2 and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3

Greater variability in lipid measurements associated with kidney diseases in patients with type 2 diabetes mellitus in a 10-year diabetes cohort study.

This study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45-84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008-2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m2) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15-1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30-1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74-2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10-1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26-1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46-2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability

Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series

BACKGROUND: Because evidence on the safety of COVID-19 vaccines in older adults is scarce, we aimed to evaluate the incidence and risk of adverse events after CoronaVac (Sinovac Biotech) vaccination in adults aged 60 years or older. METHODS: In this modified self-controlled case series, we enrolled adults aged 60 years or older who had received at least one dose of CoronaVac in Hong Kong between Feb 23, 2021, and Jan 31, 2022. We extracted population-based, electronic health record data from the clinical management system of the Hospital Authority on adverse events of special interest (from Jan 1, 2005, to Feb 23, 2022) and patients' demographic information (from Jan 1, 2018, to Jan 31, 2022), previous diagnoses (from Jan 1, 2018, to Jan 31, 2022), medication history (from Jan 1, 2018, to Jan 31, 2022), and laboratory tests, including those for SARS-CoV-2 infection (from Jan 1, 2018, to Jan 31, 2022). Details of vaccination status were provided by the Department of Health of the Hong Kong Government and were linked to data from the Hospital Authority with identity card numbers or passport numbers. Our outcomes were the overall incidence of any adverse event of special interest and the incidence rates of 30 adverse events of special interest, as suggested by the WHO Global Advisory Committee on Vaccine Safety, in the inpatient setting within 21 days (2 days for anaphylaxis) of either the first, second, or third CoronaVac dose compared with a baseline period. Individuals who had a history of a particular event between Jan 1, 2005, and Feb 23, 2021, were excluded from the corresponding analysis. We evaluated the risk of an adverse event of special interest using conditional Poisson regression, adjusting for seasonal effects. FINDINGS: Of 1 253 497 individuals who received at least one dose of CoronaVac during the study period, 622 317 (49·6%) were aged at least 60 years and were included in the analysis. Our analysis sample received 1 229 423 doses of CoronaVac and had a mean age of 70·40 years (SD 8·10). 293 086 (47·1%) of 622 317 participants were men and 329 231 (52·9%) were women. The incidence of individual adverse events of interest ranged from 0·00 per 100 000 people to 57·49 per 100 000 people (thromboembolism). The first and third doses of CoronaVac were not associated with a significant excess risk of an adverse event of special interest within 21 days (or 2 days for anaphylaxis) of vaccination. After the second dose, the only significantly increased risk was for anaphylaxis (adjusted incidence rate ratio 2·61, 95% CI 1·08–6·31; risk difference per 100 000 people 0·61, 95% CI 0·03–1·81). INTERPRETATION: Because older age is associated with poor outcomes after SARS-CoV-2 infection, the benefits of CoronaVac vaccination in older adults outweigh the risks in regions where COVID-19 is prevalent. Ongoing monitoring of vaccine safety is warranted. FUNDING: The Food and Health Bureau of the Government, Hong Kong Special Administrative Region, China and AIR@InnoHK, administered by the Innovation and Technology Commission. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section