Abstract
BackgroundAcute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. Recently the first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/septic shock, in Finland.MethodsThis is a prospective, observational multicenter study. Of 2567 patients without chronic kidney disease and with genetic samples included in the Finnish Acute Kidney Injury (FINNAKI) study, 837 patients had sepsis and 627 patients had septic shock. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, considering stages 2 and 3 affected (severe AKI), stage 0 unaffected, and stage 1 indecisive. Genotyping was done using iPLEXTM Assay (Agena Bioscience). The genotyped SNPs were rs8094315 and rs12457893 in the intron of the BCL2 gene, rs2093266 in the SERPINA4 gene, rs1955656 in the SERPINA5 gene and rs625145 in the SIK3 gene. Association analyses were performed using logistic regression with PLINK software.ResultsWe found no significant associations between the SNPs and severe AKI in patients with sepsis/septic shock, even after adjustment for confounders. Among patients with septic shock (252 with severe AKI and 226 without AKI (149 with KDIGO stage 1 excluded)), the SNPs rs2093266 and rs1955656 were significantly (odds ratio 0.63, p = 0.04276) associated with stage 2–3 AKI after adjusting for clinical and demographic variables.ConclusionsThe SNPs rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with the development of severe AKI (KDIGO stage 2–3) in critically ill patients with septic shock. For the other SNPs, we did not confirm the previously reported associations.
Highlights
Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited
In logistic regression analysis in patients with sepsis, higher body mass index (BMI), not having chronic obstructive pulmonary disease (COPD), use of non-steroidal anti-inflammatory drugs (NSAID) as daily medication, administration of contrast medium prior to Intensive care unit (ICU) admission, simplified acute physiology score Simplified acute physiology score II (II) (SAPS II) without renal or age components, and source of infection were significantly associated with Kidney Disease: Improving Global Outcomes (KDIGO) stage 2–3 AKI (Additional file 5)
We found that single nucleotide polymorphisms (SNP) rs2093266 in the SERPINA4 and rs1955656 in the SERPINA5 were associated with KDIGO stage 2–3 AKI in critically ill patients in septic shock
Summary
Acute kidney injury (AKI) is a multifactorial syndrome, but knowledge about its pathophysiology and possible genetic background is limited. The first hypothesis-free genetic association studies have been published to explore individual susceptibility to AKI. We aimed to replicate the previously identified associations between five candidate single nucleotide polymorphisms (SNP) in apoptosis-related genes BCL2, SERPINA4, SERPINA5, and SIK3 and the development of AKI, using a prospective cohort of critically ill patients with sepsis/septic shock, in Finland. The incidence of acute kidney injury (AKI) is high - 39% in the recent prospective, observational, multicenter study, the Finnish Acute Kidney Injury (FINNAKI) study, which was conducted in Finnish intensive care units (ICUs) [1]. Genetic predisposition to AKI has been previously studied in candidate genes, by testing associations between single nucleotide polymorphisms (SNP) from candidate genes and a phenotype. In this study we aimed to replicate the aforementioned findings [9] in a prospective cohort of critically ill patients with sepsis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
