The macula is the part of the retina with the highest concentration of cone photoreceptor cells, which are fundamental to central vision (1). Age-related macular degeneration (AMD), or simply macular degeneration, affects one in eight individuals aged 60 years or older (2) and is recognized as one of the leading causes of irreversible blindness globally (3). Early AMD is manifested by a slow and progressive degeneration of the retinal pigment epithelium and photoreceptors, with drusen and pigmentary changes. Late AMD, on the other hand, is manifested by geographical atrophy (dry AMD) or neovascularization (wet AMD) (4, 5).

By the year 2021, more than 850 million people were estimated suffer from some form of kidney disease, as indicated by a joint statement from the American Society of Nephrology, European Renal Association, and International Society of Nephrology (6). According to the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline, chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for a minimum of 3 months, with implications for health (6). Both as end-organ targets of systemic diseases, the comorbidity of the kidney and eye has been linked to factors such as diabetes, hypertension, and uremia (7, 8). As a result, the relationship between AMD and CKD has become a focus of research in many studies. CKD features the accumulation of uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) that drive endothelial dysfunction, vascular calcification, and pro-inflammatory signaling in the vasculature (9, 10). In AMD, oxidative stress-driven retinal pigment epithelium (RPE) dysfunction with impaired phagocytosis/autophagy and disturbed angiogenic responses are key pathological processes (11). Mendelian randomization evidence further links systemic inflammatory regulators with AMD risk (12). Together, these systemic and retinal alterations provide a plausible mechanistic bridge between impaired renal clearance and retinal degeneration (13). Two previous reviews (3, 14) have provided insight into the correlation between the two diseases. However, there exists a need for a meta-analytic update since both reviews included studies that the other did not, and there are relevant studies never included in previous reviews (15, 16).

Hence, the objective of this systematic review and meta-analysis is to review the latest clinical evidence on the relationship between AMD and CKD (measured in eGFR) and to provide a comprehensive conclusion for relevant clinical care providers.

The current systematic and meta-analytic review indicates a positive relationship between the diseases of CKD and AMD. Our results revealed that, regardless of the AMD stages, the positive status of CKD was associated with a higher prevalence of AMD.

Clinically, this association underscores the importance of cross-disciplinary disease surveillance between nephrology and ophthalmology. CKD patients frequently exhibit systemic inflammation, oxidative stress, and endothelial injury, all of which are also key contributors to retinal degeneration. Accordingly, regular ophthalmologic evaluations should be incorporated into the routine management of CKD, especially among elderly individuals or those with diabetes and hypertension. Early detection of subclinical AMD in this population may enable timely preventive interventions, such as lifestyle modification, antioxidant supplementation, and anti-inflammatory therapy, to delay disease progression.

From a mechanistic standpoint, CKD-related uremic toxins such as indoxyl sulfate and p-cresyl sulfate can penetrate the blood–retinal barrier, promote oxidative injury, and compromise retinal pigment epithelium integrity. Dysregulation of the complement pathway, particularly involving complement factor D, is implicated in both CKD-associated chronic inflammation and AMD pathogenesis. Furthermore, endothelial dysfunction and microvascular calcification, which are frequently observed in CKD, may reduce choroidal perfusion and induce retinal hypoxia, ultimately contributing to photoreceptor loss.

Collectively, these findings suggest that a multidisciplinary approach involving nephrologists and ophthalmologists is warranted. For patients with declining renal function, routine retinal imaging and visual function assessment may allow an earlier diagnosis of AMD. Conversely, ophthalmologists managing AMD should be aware of the underlying renal impairment, as systemic inflammation and metabolic imbalance could influence treatment response and disease progression.

In addition to the diagnostic and preventive perspectives, potential therapeutic implications can also be derived from the shared pathophysiology of CKD and AMD. Antioxidant and anti-inflammatory therapies have shown promise in attenuating oxidative injury in both renal and retinal tissues. Agents, such as N-acetylcysteine, vitamin E, and resveratrol analogs, may mitigate the accumulation of reactive oxygen species and improve endothelial function. Similarly, lifestyle modifications such as smoking cessation, dietary control, and optimization of blood pressure and glycemic status can synergistically protect both renal and ocular microvasculature.

Targeting the complement pathway is another emerging approach. Complement factor D inhibitors (e.g., lampalizumab and other anti-CFD biologics) have been demonstrated to reduce geographic atrophy progression in AMD, and comparable anti-complement strategies are under investigation in CKD to curb chronic inflammation. This overlap supports the notion that systemic complement regulation could simultaneously benefit both organs.

Moreover, endothelial-protective and renoprotective agents—such as SGLT2 inhibitors, renin–angiotensin system blockers, and nitric oxide–enhancing compounds—have been shown to improve vascular integrity in CKD populations, and such vascular benefits may extend to retinal microcirculation (30). Their potential to stabilize choroidal and retinal circulation may represent a promising therapeutic avenue for patients with dual CKD–AMD pathology.

Collectively, these findings emphasize that the management of CKD should not only be limited to renal endpoints alone but should also aim to preserve retinal health through systemic anti-oxidative and anti-inflammatory strategies.

Common risk factors have been proposed to explain the co-existence of CKD and AMD, one of which is the action of complements on the inflammatory process. The complement factor D (CFD) is an activator of the alternative complement pathway. As CFD elevation is considered to be linked to chronic inflammation in CKD (31), CFD being identified as a possible target in the treatment of AMD (32) should explain the correlation between CKD and AMD. Recent mechanistic and clinical evidence further supports complement dysregulation and systemic inflammation as shared drivers of CKD–AMD pathology. A bidirectional Mendelian randomization study demonstrated that elevated systemic inflammatory regulators are causally associated with a higher risk of AMD, reinforcing the role of chronic inflammation beyond local retinal processes (12). Dysregulated activation of the complement cascade—particularly complement factor D—links renal and retinal microvascular inflammation, providing a unifying explanation for their coexistence.

In addition, phase 3 clinical data have confirmed the translational relevance of this pathway: the OAKS and DERBY trials showed that complement C3 inhibition with pegcetacoplan significantly slowed the progression of geographic atrophy secondary to AMD over 24 months (33). These findings highlight that complement-targeted therapy can effectively attenuate retinal degeneration and suggest that modulating complement activity may also benefit patients with concurrent CKD by mitigating inflammation-driven microvascular injury.

Indoxyl sulfate (IS) and p-cresol sulfate (PCS) are two protein-bound uremic toxins in CKD. They are reported to generate oxidative stress (9), endothelial dysfunction (10) and vascular calcification (34). From a structural perspective, the blood–retinal barrier (BRB) is made up of retinal pigmented epithelium (RPE) cells and the retinal vessel endothelium. RPE cell functionality impairment, which is the hallmark of AMD, was indicated to arise from oxidative stress (11). Consistently, a bidirectional Mendelian randomization study linked systemic inflammatory regulators to AMD risk, reinforcing the plausibility that CKD-related systemic inflammation contributes to retinal degeneration (12). Where endothelial dysfunction is concerned, circulating endothelial cells, a potential biomarker for such a disorder (35), were suggested to possibly promote AMD (36). With regards to calcification, a pro-calcific environment hampers ischemia-driven angiogenesis (37). Thus, IS and PCS are expected to decrease angiogenesis, which, along with the subsequently decreased RPE cell survival, may lead to dry AMD (13). With the above considered, we speculate that the actions of IS and PCS are built on their ability to trespass the BRB, as a rat model reported that IS breaches the BRB and accumulates in the intraocular fluid (38), while another previous study showed that PCS damages the blood–brain barrier function, whose inner layer shares similarity with the BRB (39).

Another risk factor is the acceleration of atherosclerosis, which has been indicated in CKD due to multiple speculated mechanisms. These mechanisms include elevated serum homocysteine (40) and lipoprotein (41). With studies also supporting the connection between atherosclerosis and AMD (42, 43), it would be feasible to attribute the prevalence of AMD in CKD patients to the influence of atherosclerosis.

In the current review, no significant difference was observed in the prevalence of AMD between patients of moderate and advanced CKD stages (Figure 5), which is opposite to what we originally hypothesized. However, only three studies (16, 19, 20) were considered eligible for meta-analysis on this subtopic, and the current result appears to be lopsided by the large number of patients in one of the studies (16). Therefore, further analyses are required when more relevant studies that grade kidney functions become available.

To the best of our knowledge, there was only one previous meta-analysis that addressed the connection between CKD and AMD (14). Incorporating 12 observational studies (with 3 cohorts, 2 case controls, and 7 cross-sectionals), this study suggested a significant association between the 2 diseases.

There are several limitations to the current study. First, the majority of the included patients in our study are Asian, which restricted the generalizability of our article. Second, since we included only cross-sectional studies, the inherent weakness of our results is the causal inference. In addition, the review process was limited by the potential omission of gray literature and non-English-language publications, which may contribute to selection bias. Data extraction was performed by two reviewers, but no automation tools were used, which could introduce human error. Other causes that might result from the prevalence of AMD in the CKD population were not fully considered. Reviews that investigate the incidence of AMD in CKD are required to strengthen our findings. Finally, the influence of sex difference has not been investigated in the current study. The above limitations are expected to be addressed by future studies to provide a more comprehensive view of the current topic.

Furthermore, most of the included studies were conducted among Asian populations, which may limit the generalizability of our findings to other ethnic or geographic groups. Differences in genetic background, dietary habits, and environmental exposures could alter both the prevalence and the strength of the CKD–AMD association. For example, risk variants in the CFH and ARMS2 genes show different allele frequencies between Asian and Western populations, potentially affecting susceptibility to AMD and the inflammatory response related to CKD. Therefore, caution should be exercised when extrapolating our results to non-Asian populations. Future large-scale studies incorporating multi-ethnic and regionally diverse cohorts are warranted to validate these findings and enhance external validity.

Based on our findings from the current study, we concluded that CKD is a risk factor for AMD. Our findings highlight the need for closer ophthalmic surveillance in patients with chronic kidney disease, especially among those with declining eGFR or metabolic comorbidities. Early fundus screening may facilitate timely detection and intervention for AMD in this population. Clinicians should also be aware that systemic inflammation and vascular dysfunction observed in CKD could modify the response to AMD therapy. Future research should validate these associations through longitudinal and multi-ethnic cohorts, integrating biochemical markers (e.g., complement factors and uremic toxins) and imaging biomarkers to clarify causal pathways and optimize individualized management strategies.