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Siglec-7 as a Novel Biomarker to Predict Mortality in Decompensated Cirrhosis and Acute Kidney Injury

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Abstract

Background

Patients with decompensated cirrhosis have high morbidity and are commonly hospitalized with acute kidney injury.

Aims

We examined serum levels of Siglec-7, a transmembrane receptor that regulates immune activity, as a biomarker for mortality in patients with cirrhosis and acute kidney injury.

Methods

Serum Siglec-7 was measured in hospitalized patients with cirrhosis and acute kidney injury, as well as in reference groups with acute liver injury/acute kidney injury, cirrhosis without acute kidney injury, and sepsis without liver disease. Clinical characteristics and subsequent outcomes were examined using univariate and multivariable analyses according to initial Siglec-7 levels. Primary outcome was death by 90 days.

Results

One hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute kidney injury and were used in the primary analysis. Average Model for End-Stage Liver Disease (MELD) score was 24 [95 % CI 23, 26], and serum creatinine was 2.5 [2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of 1.96 [1.04, 3.69; p = 0.04]. There was no difference in Siglec-7 levels by etiology of AKI (p = 0.24). Addition of serum Siglec-7 to MELD score improved discrimination for 90-day mortality [category-free net reclassification index = 0.38 (p = 0.04); integrated discrimination increment = 0.043 (p = 0.04)].

Conclusion

Serum Siglec-7 was associated with increased mortality among hospitalized patients with cirrhosis and acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination to predict 90-day mortality.

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Abbreviations

MELD:

Model for End-Stage Liver Disease

AKI:

Acute kidney injury

HRS:

Hepatorenal syndrome

AKIN:

Acute Kidney Injury Network

ROC:

Receiver operating characteristic

ANOVA:

Analysis of variance

NRI:

Net reclassification index

IDI:

Integrated discrimination index

APRI:

AST to platelet ratio index

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Acknowledgments

ASA is supported by NIH Grant 5T32DK007540-30. RTC is supported by NIH Grant K24DK078772. RIT is supported by NIH Grants R01DK094486 and K24DK094872. SAK was supported by funds from the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, GRB 1008, Boston, MA, 02114, USA

    Andrew S. Allegretti, Sahir Kalim, Joshua Wibecan, Dihua Xu & Ravi I. Thadhani

  2. Department of Medicine, St. Elizabeth’s Hospital, Boston, MA, USA

    Guillermo Ortiz

  3. Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Dongsheng Zhang & S. Ananth Karumanchi

  4. Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA

    Hui Yi Shan

  5. Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Raymond T. Chung

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  1. Andrew S. Allegretti
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  7. Dihua Xu
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Correspondence to Andrew S. Allegretti.

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Allegretti, A.S., Ortiz, G., Kalim, S. et al. Siglec-7 as a Novel Biomarker to Predict Mortality in Decompensated Cirrhosis and Acute Kidney Injury. Dig Dis Sci 61, 3609–3620 (2016). https://doi.org/10.1007/s10620-016-4316-x

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