Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study

Bergmann, Lars; Nowak, Hartmuth; Siffert, Winfried; Adamzik, Michael; Koos, Björn; Rahmel, Tim

doi:10.3390/cells9040904

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…Specifically, AC carriers were found to be less likely to develop major adverse kidney events within the first 30 days. Furthermore, they presented with significantly lower risk of death within 90 days compared to patients carrying the AA genotype [ 84 ].…”

Section: The Role Of Aquaporin Single-nucleotide Polymorphisms In Cli...mentioning

confidence: 99%

Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

Lotsios,

Keskinidou,

Dimopoulou

et al. 2023

IJMS

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Sepsis is an inflammatory disorder caused by the host’s dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years, it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with a role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at transcriptional, post-transcriptional, translational, and post-translational levels in sepsis by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single-nucleotide polymorphisms in the setting of sepsis.

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Section: The Role Of Aquaporin Single-nucleotide Polymorphisms In Cli...mentioning

confidence: 99%

Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

Lotsios,

Keskinidou,

Dimopoulou

et al. 2023

IJMS

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“…We described a functional single nucleotide (-1364A/C, rs3759129) polymorphism in the AQP5 gene promoter previously [ 7 ]. The C-allele (CC and AC) of this polymorphism occurs in around 28% of all individuals (Hardy-Weinberg-equilibrium) [ 9 ]. The substitution of C for A at position-1364 was associated with decreased AQP5 mRNA and AQP5 protein expression and decreased neutrophil migration [ 10 ] which we ascribe to different water-influx followed by aberrant formation of lamellipodia.…”

Section: Introductionmentioning

confidence: 99%

AQP5-1364A/C Polymorphism Affects AQP5 Promoter Methylation

Rump

Spellenberg

Busch

et al. 2022

IJMS

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The quantity of aquaporin 5 protein in neutrophil granulocytes is associated with human sepsis-survival. The C-allele of the aquaporin (AQP5)-1364A/C polymorphism was shown to be associated with decreased AQP5 expression, which was shown to be relevant in this context leading towards improved outcomes in sepsis. To date, the underlying mechanism of the C-allele—leading to lower AQP5 expression—has been unknown. Knowing the detailed mechanism depicts a crucial step with a target to further interventions. Genotype-dependent regulation of AQP5 expression might be mediated by the epigenetic mechanism of promoter methylation and treatment with epigenetic-drugs could maybe provide benefit. Hence, we tested the hypothesis that AQP5 promoter methylation differs between genotypes in specific types of immune cells.: AQP5 promoter methylation was quantified in cells of septic patients and controls by methylation-specific polymerase chain reaction and quantified by a standard curve. In cell-line models, AQP5 expression was analyzed after demethylation to determine the impact of promoter methylation on AQP5 expression. C-allele of AQP5-1364 A/C promoter polymorphism is associated with a five-fold increased promoter methylation in neutrophils (p = 0.0055) and a four-fold increase in monocytes (p = 0.0005) and lymphocytes (p = 0.0184) in septic patients and healthy controls as well. In addition, a decreased AQP5 promoter methylation was accompanied by an increased AQP5 expression in HL-60 (p = 0.0102) and REH cells (p = 0.0102). The C-allele which is associated with lower gene expression in sepsis is accompanied by a higher methylation level of the AQP5 promoter. Hence, AQP5 promoter methylation could depict a key mechanism in genotype-dependent expression.

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Heterogeneity in the definition of major adverse kidney events: a scoping review

Maeda,

Inokuchi,

Bellomo

et al. 2024

Intensive Care Med

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Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions.

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Major Adverse Kidney Events Are Associated with the Aquaporin 5 -1364A/C Promoter Polymorphism in Sepsis: A Prospective Validation Study

Cited by 7 publications

References 35 publications

Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

Aquaporin Expression and Regulation in Clinical and Experimental Sepsis

AQP5-1364A/C Polymorphism Affects AQP5 Promoter Methylation

Heterogeneity in the definition of major adverse kidney events: a scoping review

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