Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study
Since the functionally important <i>AQP5</i> -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this <i>AQP5&l...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/904 |
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| author | Lars Bergmann Hartmuth Nowak Winfried Siffert Jürgen Peters Michael Adamzik Björn Koos Tim Rahmel |
| author_facet | Lars Bergmann Hartmuth Nowak Winfried Siffert Jürgen Peters Michael Adamzik Björn Koos Tim Rahmel |
| author_sort | Lars Bergmann |
| collection | DOAJ |
| description | Since the functionally important <i>AQP5</i> -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this <i>AQP5</i> polymorphism is associated with major adverse kidney events and also validated its impact on 90-day survival. In this prospective observational monocentric genetic association study 282 septic patients were included and genotyped for the <i>AQP5</i> –1364A/C polymorphism (rs3759129). The primary endpoint was the development of major adverse kidney events within 30 days. In AC/CC genotypes, major adverse kidney events were less frequent (41.7%) than in AA genotypes (74.3%; OR:0.34; 95%-CI: 0.18–0.62; <i>p</i> < 0.001). Ninety-day survival was also associated with the <i>AQP5</i> polymorphism (<i>p</i> = 0.004), with 94/167 deaths (56.3%) in AA genotypes, but only 46/115 deaths (40.0%) in C-allele carriers. Multiple proportional hazard analysis revealed AC/CC genotypes to be at significantly lower risk for death within 90 days (HR: 0.60; 95%-CI: 0.42-0.86; <i>p</i> = 0.006). These findings confirm the important role of the <i>AQP5</i> -1364A/C polymorphism as an independent prognostic factor in sepsis. Furthermore, we demonstrate a strong association between this <i>AQP5</i> polymorphism and susceptibility for major adverse kidney events suggesting a promising characteristic in terms of precision medicine. |
| first_indexed | 2024-03-10T20:37:06Z |
| format | Article |
| id | doaj.art-bec4b5d23bec40d7a86b5982a9b343e8 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:37:06Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bec4b5d23bec40d7a86b5982a9b343e82023-11-19T20:56:17ZengMDPI AGCells2073-44092020-04-019490410.3390/cells9040904Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation StudyLars Bergmann0Hartmuth Nowak1Winfried Siffert2Jürgen Peters3Michael Adamzik4Björn Koos5Tim Rahmel6Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, GermanyInstitut für Pharmakogenetik, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, GermanyKlinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, D-44892 Bochum, GermanySince the functionally important <i>AQP5</i> -1364A/C single nucleotide promoter polymorphism alters key mechanisms of inflammation and survival in sepsis, it may affect the risk of an acute kidney injury. Accordingly, we tested the hypothesis in septic patients that this <i>AQP5</i> polymorphism is associated with major adverse kidney events and also validated its impact on 90-day survival. In this prospective observational monocentric genetic association study 282 septic patients were included and genotyped for the <i>AQP5</i> –1364A/C polymorphism (rs3759129). The primary endpoint was the development of major adverse kidney events within 30 days. In AC/CC genotypes, major adverse kidney events were less frequent (41.7%) than in AA genotypes (74.3%; OR:0.34; 95%-CI: 0.18–0.62; <i>p</i> < 0.001). Ninety-day survival was also associated with the <i>AQP5</i> polymorphism (<i>p</i> = 0.004), with 94/167 deaths (56.3%) in AA genotypes, but only 46/115 deaths (40.0%) in C-allele carriers. Multiple proportional hazard analysis revealed AC/CC genotypes to be at significantly lower risk for death within 90 days (HR: 0.60; 95%-CI: 0.42-0.86; <i>p</i> = 0.006). These findings confirm the important role of the <i>AQP5</i> -1364A/C polymorphism as an independent prognostic factor in sepsis. Furthermore, we demonstrate a strong association between this <i>AQP5</i> polymorphism and susceptibility for major adverse kidney events suggesting a promising characteristic in terms of precision medicine.https://www.mdpi.com/2073-4409/9/4/904major adverse kidney eventsacute kidney injurysepsissurvivalaquaporin 5<i>AQP5</i> |
| spellingShingle | Lars Bergmann Hartmuth Nowak Winfried Siffert Jürgen Peters Michael Adamzik Björn Koos Tim Rahmel Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study Cells major adverse kidney events acute kidney injury sepsis survival aquaporin 5 <i>AQP5</i> |
| title | Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study |
| title_full | Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study |
| title_fullStr | Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study |
| title_full_unstemmed | Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study |
| title_short | Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study |
| title_sort | major adverse kidney events are associated with the aquaporin 5 1364a c promoter polymorphism in sepsis a prospective validation study |
| topic | major adverse kidney events acute kidney injury sepsis survival aquaporin 5 <i>AQP5</i> |
| url | https://www.mdpi.com/2073-4409/9/4/904 |
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