Association Between Elevated Blood Eosinophils and Chronic Kidney Disease Progression: Analyses of a Large United States Electronic Health Records Database

Abstract

Background

Blood eosinophils can increase in response to infection, inflammation, and hypersensitivity reactions, yet their involvement in the progression of chronic kidney disease (CKD) is poorly understood. This study explores the relationship between blood eosinophils and CKD progression among patients in a real-world setting.

Methods

This retrospective study analyzed data obtained from the Optum^® de-identified electronic health records dataset in the United States. Patients diagnosed with CKD stage 3 or 4 (International Classification of Diseases diagnosis code or estimated glomerular filtration rate [eGFR] <60 mL/min) between January 2011 and March 2018 were included and followed until progression to the next CKD stage, death, or dropout. The primary objective of this study was to assess the relationship between blood eosinophil counts (bEOS) and CKD progression, adjusting for clinical and demographic features as well as known risk factors for CKD stages 3–4. The primary outcomes were CKD progression and all-cause mortality.

Results

We found that high eosinophilic levels (bEOS ≥300 cells/µL) were associated with CKD progression from stage 3 to stages 4 or 5 (hazard ratio [HR] ranging from 1.30 to 1.50) and from stages 4 to 5 (HR ranging from 1.28 to 1.50). Among patients with CKD progression, those with blood eosinophils ≥300 cells/µL appeared to have a relatively lower eGFR, higher all-cause mortality, and reduced time to CKD progression and death than those with <300 cells/µL. Factors including sex, race, hypertension, anemia, and treatments for cardiovascular and hematopoietic drugs were associated with CKD progression.

Conclusion

Elevated eosinophils may increase the risk for CKD progression. Larger studies are needed to assess whether the risk of mortality is increased among patients with elevated eosinophils.

Keywords:

• eosinophilic inflammation
• renal insufficiency
• glomerular filtration rate

Abbreviations

CCI, Charlson Comorbidity Index; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; EHR, electronic health records; EID, eosinophilic immune dysfunction; ESRD, end-stage renal disease; HR, hazard ratio; ICD-9-CM, International Classification of Diseases, 9th Revision; ICD-10-CM, International Classification of Diseases, 10th Revision.

Data Sharing Statement

The data that support the findings of this study are available from Optum^®, but restrictions apply to the availability of these data, which were used under license for the current study. They may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure and with permission from Optum^®.

Ethics Approval and Consent to Participate

This study was conducted in accordance with the Declaration of Helsinki, ICH GCPs, and the Guidelines for Good Pharmacoepidemiology Practice (GPP) published by the International Society of Pharmacoepidemiology (ISPE) and the applicable legislation on non-interventional studies and observational studies. All data within the US administrative database, Optum™ PANTHER, is certified as de-identified by an independent statistical expert following HIPAA statistical de-identification rules and managed according to Optum^® customer data use agreements. Institutional Review Board approval was not required because the data is exempt under the United States Code of Federal Regulations (45 CFR 46.101(b) (4)).

Acknowledgments

The authors would like to acknowledge Superior Medical Experts for editorial assistance.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Danuta Kielar, Andrew M. Jones, Xia Wang, Heide Stirnadel-Farrant, and Rohit K. Katial are or were employed by AstraZeneca at the time of study conduct and may own stock/stock options. Manu Garg, Chandrakant Sharma, Abhinav Bansal, Shubhankar Thakar, and Qin Ye are consultants from ZS, which received funding from AstraZeneca to conduct this study.

Additional information

Funding

This work was funded by AstraZeneca. In collaboration with ZS Associates, AstraZeneca was involved in the study design, interpretation of data, review of the manuscript, and decision to submit for publication. All authors had full access to the data and shared responsibility for the decision to submit the article for publication.