RESUMO
Acute kidney injury (AKI) is a common and devastating complication of hospitalization. Here, we identified genetic loci associated with AKI in patients hospitalized between 2002-2019 in the Million Veteran Program and data from Vanderbilt University Medical Center's BioVU. AKI was defined as meeting a modified KDIGO Stage1 or more for two or more consecutive days or kidney replacement therapy. Control individuals were required to have one or more qualifying hospitalizations without AKI and no evidence of AKI during any other observed hospitalizations. Genome-wide association studies (GWAS), stratified by race, adjusting for sex, age, baseline estimated glomerular filtration rate (eGFR), and the top ten principal components of ancestry were conducted. Results were meta-analyzed using fixed effects models. In total, there were 54,488 patients with AKI and 138,051 non-AKI individuals included in the study. Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09)) and rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96)). These loci colocalized with previous studies of kidney function, and genetic correlation indicated significant shared genetic architecture between AKI and eGFR. Notably, the association at the FTO locus was attenuated after adjustment for BMI and diabetes, suggesting that this association may be partially driven by obesity. Both FTO and the SHROOM3 loci showed nominal evidence of replication from diagnostic-code-based summary statistics from UK Biobank, FinnGen, and Biobank Japan. Thus, our large GWA meta-analysis found two loci significantly associated with AKI suggesting genetics may explain some risk for AKI.
RESUMO
To further elucidate the question whether the criteria for assessing alcohol-induced unfitness to drive should be stricter for night-time than for day-time driving (cf. Schewe et al., 1977) 64 test persons performed automobile driving tests in daylight and in darkness while being sober and while under the influence of alcohol. The first set of tests was done in daylight. A test course of approx. 600 m involving six everyday driving maneuvers had to be covered, first in the sober state and then at blood alcohol concentrations (BAC) of 1.1 g % and 1.4 g %. The driving tests in the dark were performed on the same test course, first in the sober state and then at a BAC of 1.1 g%. In both test series the errors were counted and the driving times measured. Statistical evaluation of the test results was done parametrically (t-test for dependent random samples) and distribution-free (Wilcoxon's test for paired comparison). In the sober state 2.1 errors were made on average during the day and 3.2 errors, i.e. one error more, at night. At 1.1 g %, 4.3 errors occurred during the day but 8.0 errors at night (i.e. 3.7 errors more than during the day). The differences were statistically significant. With 8 errors during night-time driving at 1.1 g % the number of errors was still higher than the average number of 6.8 errors made during day-time driving at 1.4 g %. The average driving times required in the sober state were 241 s during the day and 256 s at night. At 1.1 g %, 243 s were needed during the day and 272 s at night, i.e. on average 17 s more than for day-time driving at 1.4 g % for which 255 s were needed. For an orienting comparison of driving performance it can be assumed that "performance" in the sense meant here is reciprocally proportional to the number of errors and reciprocally proportional to the time required, i.e. on the whole reciprocally proportional to the product from number of errors and time. The deterioration of performance can be illustrated best by assuming performance in the sober state during the day to be 100% and relating the other "performances" thereto.(ABSTRACT TRUNCATED AT 250 WORDS)
