Background and objectivesHigh BP variability may cause AKI because of inappropriate kidney perfusion. This study aimed to investigate the association between intraoperative BP variability and postoperative AKI in patients who underwent noncardiac surgery.Design, setting, participants, & measurementsWe performed a cohort study of adults undergoing noncardiac surgery in hospitals in South Korea. We studied three cohorts using the following recording windows for intraoperative BP: discovery cohort, 1-minute intervals; first validation cohort, 5-minute intervals; and second validation cohort, 2-second intervals. We calculated four variability parameters (SD, coefficient of variation, variation independent of mean, and average real variability) based on the measured mean arterial pressure values. The primary outcomes were postoperative AKI (defined by the Kidney Disease Improving Global Outcomes serum creatinine cutoffs) and critical AKI (consisting of stage 2 or higher AKI and post-AKI death or dialysis within 90 days).ResultsIn the three cohorts, 45,520, 29,704, and 7435 patients were analyzed, each with 2230 (443 critical), 1552 (444 critical), and 300 (91 critical) postoperative AKI events, respectively. In the discovery cohort, all variability parameters were significantly associated with risk of AKI, even after adjusting for intraoperative hypotension. For example, average real variability was associated with higher risks of postoperative AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.07 to 1.19) and critical AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.02 to 1.26). Associations were evident predominantly among patients who also experienced intraoperative hypotension. In the validation analysis with 5-minute-interval BP records, all four variability parameters were associated with the risk of postoperative AKI or critical AKI. In the validation cohort with 2-second-interval BP records, average real variability was the only significant variability parameter.ConclusionsHigher intraoperative BP variability is associated with higher risks of postoperative AKI after noncardiac surgery, independent of hypotension and other clinical characteristics.

Background: Metabolic syndrome (MetS) is linked to various chronic comorbidities, including chronic kidney disease (CKD). However, few large studies have addressed whether recovery from MetS is associated with reduction in the risks of such comorbidities. Methods: This nationwide population-based study in Korea screened 10,664,268 people who received national health screening ≥ 3 times between 2012 and 2016. Those with a history of major cardiovascular events or preexisting CKD were excluded. We classified study groups into four, according to the course of MetS state, as defined by the harmonizing criteria. The main study outcome was incidental CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m 2 which was persistent until the last health exams). The study outcomes were investigated using multivariable logistic regression analysis, which was adjusted for clinical variables and the previous severity of MetS. Results: Four study groups included 6,315,301 subjects: 4,537,869 people without MetS, 1,034,605 with chronic MetS, 438,287 who developed MetS, and 304,540 who recovered from preexisting MetS. Those who developed MetS demonstrated higher risk of CKD (adjusted odds ratio [OR],) than did those who did not develop MetS. In contrast, MetSrecovery was associated with decreased risk of CKD (adjusted OR,) than that in people with chronic MetS. Among the MetS components, change in hypertension was associated with the largest difference in CKD risk. Conclusion: Reducing or preventing MetS may reduce the burden of CKD on a population-scale. Clinicians should consider the clinical importance of altering MetS status for risk of CKD.

Background: An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. Methods: The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. Results: Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02-1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. Conclusion:The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation. Here we show two-sample summary-level Mendelian randomization (MR) analysis that examined the causality between serum IL levels and kidney function. Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for estimated glomerular filtration rate (eGFR) were obtained from CKDGen database. As a main MR analysis, multiplicative random-effects inverse-variance weighted method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighted median methods, were also implemented. We tested the causal estimates from nine ILs on eGFR traits. Among the results, higher genetically predicted serum IL-1 receptor antagonist level was significantly associated with higher eGFR values in the meta-analysis of CKDGen and the UK Biobank data. In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome. These findings support the clinical importance of IL-1 receptor antagonist-associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1 receptor antagonist.