A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury

Zhao, Bixiao; Lu, Qiongshi; Cheng, Yu‐Wei; Belcher, Justin M.; Siew, Edward D.; Leaf, David E.; Body, Simon C.; Fox, Amanda A.; Waikar, Sushrut S.; Collard, Charles D.; Thiessen-Philbrook, Heather; İkizler, T. Alp; Ware, Lorraine B.; Edelstein, Charles L.; Garg, Amit X.; Choi, Murim; Schaub, Jennifer A.; Zhao, Hongyu; Lifton, Richard P.; Parikh, Chirag R.

doi:10.1164/rccm.201603-0518oc

Cited by 32 publications

(28 citation statements)

References 45 publications

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“…We used the genotyping v1.9.4 module clustering algorithm from Illumina GenomeStudio software for SNP calling (San Diego, California, USA). Patients with sample genotype call rate under 97% and patients with a discrepancy between X chromosome zygosity and reported sex were excluded (86). We extracted SNPs within a 2-Mb region surrounding the HP gene (Hg19 chr16:71,036,975-73,063,764), then phased the target region and imputed HP genotype using the Beagle version 3.3.2 algorithm (87) with a phased reference panel provided by Boettger et al (36).…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis

et al. 2019

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Conflict of interest: LBW reports consulting fees from CSL Behring, Bayer, and Quark Pharmaceuticals as well as a research contract with CSL Behring (current) and past research contracts with Boehringer Ingelheim and Global Blood Therapeutics, all unrelated to the current manuscript. CRP is a named inventor on provisional patent number 62/716,465 titled "System and methods for diagnosing acute interstitial nephritis," which is unrelated to the current manuscript.

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Section: Methodsmentioning

confidence: 99%

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis

et al. 2019

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“…No consensus method exists to establish pre-AKI baseline serum creatinine in the absence of previous values (recent or distant) 4647. Furthermore, changes in serum creatinine are often delayed owing to renal reserve and the kinetics of AKI.…”

Section: Early Detection Of Sa-akimentioning

confidence: 99%

Sepsis associated acute kidney injury

Poston

Koyner

2019

BMJ

487

381

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Sepsis is defined as organ dysfunction resulting from the host’s deleterious response to infection. One of the most common organs affected is the kidneys, resulting in sepsis associated acute kidney injury (SA-AKI) that contributes to the morbidity and mortality of sepsis. A growing body of knowledge has illuminated the clinical risk factors, pathobiology, response to treatment, and elements of renal recovery that have advanced our ability to prevent, detect, and treat SA-AKI. Despite these advances, SA-AKI remains an important concern and clinical burden, and further study is needed to reduce the acute and chronic consequences. This review summarizes the relevant evidence, with a focus on the risk factors, early recognition and diagnosis, treatment, and long term consequences of SA-AKI. In addition to literature pertaining to SA-AKI specifically, pertinent sepsis and acute kidney injury literature relevant to SA-AKI was included.

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“…More recently a genome-wide association study of patients with AKI (including septic AKI) found that polymorphism of the likely controller of a transcription factor (on chromosome 4) involved in innate immunity pathways was associated with greater risk of AKI. Similarly, another gene involved in the likely control of transforming growth factor beta (on chromosome 22) was also associated with greater risk [23]. The outcomes of critically ill patients with sepsis [24] and AKI requiring RRT [25], however, have improved in recent years.…”

Section: Table 1 Criteria and Staging For Acute Kidney Injurymentioning

confidence: 99%

Acute kidney injury in sepsis

et al. 2017

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Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.

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A Genome-Wide Association Study to Identify Single-Nucleotide Polymorphisms for Acute Kidney Injury

Abstract: Our findings reveal two genetic loci that are associated with acute kidney injury. Additional studies should be conducted to functionally evaluate these loci and to identify other common genetic variants contributing to acute kidney injury.

Cited by 32 publications

References 45 publications

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis

Sepsis associated acute kidney injury

Acute kidney injury in sepsis

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