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Real-World Evidence of Adverse Kidney Outcomes for Intravitreal Use of Vascular Endothelial Growth Factor (VEGF) Inhibitors Among Patients with Diabetic Retinopathy

Chen, Nai-Chia (2022) Real-World Evidence of Adverse Kidney Outcomes for Intravitreal Use of Vascular Endothelial Growth Factor (VEGF) Inhibitors Among Patients with Diabetic Retinopathy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Objective: Studies of kidney injury following the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections among patients with diabetic retinopathy have mixed results and are limited by sample size and study design. Our objective was to determine whether intravitreal use of anti-VEGF agents was associated with adverse kidney outcomes compared to treatment with traditional laser photocoagulation. Methods: Adult patients with diabetic retinopathy and use of intravitreal anti-VEGF injections or laser photocoagulation were identified from January 2011, through December 2020 in a large nationally representative database of administrative and electronic health record information for commercially insured and Medicare/Medicaid Advantage patients. Outcomes assessed included diagnosis of new chronic kidney disease (CKD) or worsening CKD as primary endpoints, a composite endpoint of overall hospitalization or death, and thromboembolic events as secondary endpoints, and a 40% eGFR reduction within one and two years as exploratory endpoints. We applied inverse probability treatment weighting using propensity scores and adjusted for demographics, comorbidities, and CKD stages at baseline. We performed Cox proportional regression models and accelerated time failure models to assess the study endpoints. Results: A total of 2,427 patients met the inclusion criteria, with 1,327 patients receiving intravitreal anti-VEGF injections and 1,100 patients receiving laser photocoagulation. Patients in the anti-VEGF group did not have a statistically significant higher hazard for either newly developed CKD (HR=1.16; 95% CI: 0.99, 1.36) or worsening of pre-existing CKD (HR=0.88; 95% CI: 0.71, 1.08) compared to patients in the laser group after adjustment. However, patients treated with intravitreal anti-VEGF injections had significantly higher hazards of overall hospitalizations or mortality compared to those treated with laser photocoagulation (HR=1.18; 95% CI: 1.05, 1.33) but there was no difference in the risk of thromboembolic events (HR=1.11; 95% CI: 0.97, 1.27). Our exploratory endpoints showed no significant difference in patients experiencing a 40% eGFR reduction within one year (HR= 1.15; 95% CI: 0.94, 1.40) and within two years (HR=1.24; 95% CI: 0.99, 1.54). Conclusions: While the use of anti-VEGF intravitreal injections was not associated with new or worsening CKD, thromboembolic events, and a significant eGFR reduction compared to laser photocoagulation, patients had a higher risk of hospitalization or death. These results continue to question the effects anti-VEGF injections have on adverse systemic or kidney outcomes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Chen, Nai-ChiaNAC139@pitt.edunac1390000-0002-2923-3735
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSuh, Kanghokas551@pitt.edukas5510000-0002-7906-9398
Committee CoChairKane-Gill, SandraKane-Gill@pitt.eduslk540000-0001-7523-4846
Committee MemberKirisci, Leventlevent@pitt.edulevent
Date: 8 April 2022
Date Type: Publication
Defense Date: 25 March 2022
Approval Date: 8 April 2022
Submission Date: 7 April 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 106
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: intravitreal anti-vascular endothelial growth factor, diabetic retinopathy, adverse kidney event, systemic severe adverse event, renal function
Date Deposited: 08 Apr 2022 15:57
Last Modified: 08 Apr 2022 15:57


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