Frequency of TGF-βand IFN-γGenotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients

Genetic variations in TGF-βand IFN-γmay interfere with proinflammatory cytokine production and, consequently, may be involved with inflammatory diseases, as acute kidney injury (AKI). We considered that genetic polymorphisms of these cytokines may have a crucial role in the outcome of critically ill patients. To investigate whether the genetic polymorphisms of rs1800470 (codon 10 T/C), rs1800471 (codon 25 C/G) from the TGF-β, and rs2430561 (+874 T/A) from IFN-γmay be a risk factor for ICU patients to the development of AKI and/or death. In a prospective nested case-control study, were included 139 ICU patients who developed AKI, 164 ICU patients without AKI, and 244 healthy individuals. We observed a higher frequency to T/A genotype for IFN-γ(intermediate producer phenotype) and higher frequency of TT GG and TC GG genotype (high producer) for TGF-βpolymorphism in overall population. However, these polymorphisms have not been shown as a predictor of risk for AKI and death. We found an increased prevalence of high and intermediate producer phenotypes from TGF-βand IFN-γ, respectively, in patients in ICU setting. However, the studied genetic polymorphism of the TGF-βand IFN-γwas not associated as a risk factor for AKI or death in our population.

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Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case–control study

BMJ Open ◽

10.1136/bmjopen-2020-041543 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041543

Author(s):

Keiko Ikuta ◽

Shunsaku Nakagawa ◽

Kenji Momo ◽

Atsushi Yonezawa ◽

Kotaro Itohara ◽

...

Keyword(s):

Acute Kidney Injury ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Case Control Study ◽

Kidney Injury ◽

Case Control ◽

Renal Diseases ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

ObjectivesThis study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI).DesignA nested case–control study.SettingA health insurance claims database constructed by the Japan Medical Data Center.ParticipantsPatients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women.InterventionsCurrent use of PPIs, NSAIDs, or antibiotics.Primary outcome measuresAcute kidney injury.ResultsDuring a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case–control study.ConclusionsConcomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

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