Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan.

Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.