Diabetic retinopathy is a predictor of progression of diabetic kidney disease: a systematic review and meta-analysis

Authors: Gupta M, Rao IR, Nagaraju SP, Bhandary SV, Gupta J, Babu GTC.

Geographical coverage: Japan, Taiwan, China, USA, Saudi Arabia, Singapore and Korea

Sector: Biomedical

Sub-sector: Diagnosis, prediction

Equity focus: Not reported

Study population: Patients with diabetic retinopathy

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: The proportion of people with diabetes mellitus (DM) has significantly increased over the past few decades and is consistently rising, leading to the prediction that the number will rise to 643 million by 2030. A significant proportion of patients with DM develop diabetic kidney disease (DKD), a main cause of end-stage kidney disease (ESKD) attributed to lack of screening and late diagnosis. Epidemiological studies suggest that the presence of diabetic retinopathy (DR), a complication of DM, is a strong indicator of DKD as a cause of kidney disease. However, the role of DR as a predictor of progression to ESKD is not studied well.

Objectives: To evaluate the effect of DR on the risk of progression of DKD in patients with DM.

Main findings: A total of 18,275 articles were identified through the searches, of which 10 were included in this review. Of the 10 included studies, seven were prospective, and three were retrospective. All studies were of high methodological quality. DR was significantly associated with DKD progression (pooled hazard ratio (HR): 2.42 [95% CI: 1.70-3.45], pooled odds ratio (OR): 2.62 [95% CI: 1.76-3.89]). There was also a significant association between the severity of DR and risk of progression of DKD with a pooled OR of 2.13 (95% CI: 1.82-2.50) for non-proliferative DR and 3.56 (95% CI: 2.93-4.33) for proliferative DR. Sensitivity analysis did not exhibit any significant change, however, the funnel plot indicated some publication bias.

The review concluded that DR is a strong predictor of determining progression of CKD in patients with DKD. Screening for retinal vascular changes could help in prognostication and risk-stratification of patients with DKD. In addition, the severity of DR can also predict the progression of DKD. The authors proposed conducting large prospective studies to confirm the findings of this review.

Methodology: The searches were conducted in PubMed, EMBASE and Google Scholar to identify relevant studies from inception to September 2021. Searches were limited to full-text articles published in the English language.

Studies were included if they were longitudinal studies, conducted on diabetic patients with DKD (presumed or biopsy-proven), and reported the presence of DR, and progression of DKD. Cross-sectional studies and studies with insufficient data were excluded.

Two reviewers conducted screening independently. The reviewers assessed the quality of included studies using the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort studies. The results were synthesised using inverse variance method meta-analysis. Heterogeneity was assessed using I² statistics. Publication bias was assessed using the funnel plot test. Sensitivity analysis was conducted (to ascertain the results of the analysis) by excluding retrospective studies, and the studies that did not have biopsy-proven DKD patients.

Applicability/external validity:

The authors did not discuss the applicability or external validity of the results.

Geographic focus:

The review focused on the association between diabetic retinopathy and diabetic kidney disease progression in patients with diabetes, regardless of their income level or geographic location. The review did not mention any specific challenges or implications for low and middle income countries in terms of screening, diagnosis or management of these complications. Therefore, the generalisability and relevance of the review findings to low and middle income countries are unclear.

Summary of quality assessment:Authors used appropriate methods to screen studies for inclusion and synthesise data of studies included in the review. However, literature searches were not extensive, and the authors did not avoid language bias. Additionally, the authors did not report whether a rigorous approach was employed when extracting data of included studies. For these reasons, a low confidence was attributed to the conclusions of this study.