# Systematic review of ocular and circulatory cytokines linking diabetic retinopathy to kidney disease

## TL;DR

This study reviews how eye and blood cytokines in diabetic retinopathy are linked to kidney disease, suggesting shared inflammatory pathways.

## Contribution

It systematically reviews clinical evidence supporting a shared inflammatory and angiogenic basis for diabetic retinopathy and kidney disease.

## Key findings

- VEGF and pro-inflammatory cytokines like TNF-α and IL-17A are elevated in proliferative DR and correlate with kidney dysfunction markers.
- Biomarkers such as s(P)RR and FABP4 show consistent trends with microvascular damage in both eye and kidney.
- The findings suggest retinal cytokines could serve as non-invasive biomarkers for kidney disease risk in diabetes.

## Abstract

Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are major microvascular complications of diabetes that contribute substantially to visual disability and renal failure worldwide. Increasing evidence supports the concept of an “eye–kidney axis,” whereby inflammatory and angiogenic dysregulation may drive parallel microvascular injury in the retina and kidney. The present systematic review aimed to synthesize current clinical evidence on the association between vitreous and serum cytokines and renal impairment in patients with DR.

Following PRISMA guidelines, PubMed, Embase, and Web of Science were systematically searched (2005–2025). We included observational human studies investigating vitreous or serum cytokines in adult patients with clinically staged DR and their associations with renal function parameters, including estimated glomerular filtration rate (eGFR) and albuminuria. Data on study characteristics, cytokine profiles, renal metrics, and major findings were extracted. Study quality was assessed using the modified Newcastle–Ottawa Scale. Due to heterogeneity in study design and outcomes, results were synthesized narratively.

Seventeen eligible studies involving patients with type 1 and type 2 diabetes were included. Key cytokines assessed included angiogenic factors (VEGF, PlGF, ANGPTL2/4) and inflammatory mediators (TNF-α, IL-6, IL-17A, MCP-1, sRAGE), measured predominantly using ELISA. Across studies, both vitreous and serum VEGF levels were consistently elevated in proliferative DR and showed significant associations with albuminuria and reduced eGFR. Pro-inflammatory cytokines including TNF-α, IL-17A, and progranulin correlated with DR severity and markers of DKD progression. Biomarkers such as s(P)RR, FABP4, and Ephrin-A1 also exhibited concordant trends with microvascular dysfunction in both organs. Overall, the compiled evidence indicates that inflammatory activation and aberrant angiogenesis are common molecular signatures linking retinal and renal microangiopathy.

This systematic review supports the hypothesis that DR and DKD share overlapping inflammatory and angiogenic pathways, reflected by synchronized changes in vitreous and systemic cytokine levels. These findings highlight the potential of retinal-derived biomarkers for non-invasive risk stratification of DKD, and suggest therapeutic value in combined anti-inflammatory and anti-angiogenic strategies to protect eye–kidney microvascular integrity. High-quality longitudinal and mechanistic studies are warranted to further establish causality within the eye–kidney axis and translate biomarker-based surveillance into clinical practice.