Genetic risk scores may help identify diabetes patients at high risk of developing DKD

"The research reveals that there is moderate evidence to support the utility of genetic risk scores to identify diabetic patients who are at high risk of developing DKD." the researchers wrote. "In practice, a robust GRS could be used at the first clinical encounter with a person with diabetes to stratify their risk of complications."

A third of people with diabetes can develop diabetic kidney disease, which is the leading cause of end-stage renal disease. Measures to treat and prevent require better identification of patients most at risk.

Genome-wide association studies (GWAS) have found genetic variants associated with DKD risk, but it is difficult to translate findings into clinical benefit because individual variants explain a relatively small proportion of overall risk. However, a genetic risk score aggregates the individual effects of variants to increase their predictive power.

In the systematic review, Aleena Shujaat Ali, The University of Melbourne, Melbourne, Australia, and colleagues summarized the existing evidence of genetic risk scores and their utility for predicting DKD in patients with type 1 or type 2 diabetes.

For this purpose, the researchers searched the online databases in June 2022 to identify all relevant and existing literature. The main data items that were sought included sample size, study design, single nucleotide polymorphisms of interest, population, DKD-related outcomes, and relevant summary measures of result. The methodological quality of studies was evaluated using the Critical Appraisal Skills Programme checklist.

The researchers identified 400 citations, of which fifteen were included in the review. Overall, seven studies had positive results, 5 had mixed results, and negative results were seen in 3. Most studies with the strongest methodological quality (n = 9) reported favourable and statistically significant findings of a GRS’s association with at least one measure of DKD.

According to the authors, the systematic review is the first to support the GRS's utility to identify diabetes patients at high risk of DKD development. They added, "In practice, a robust GRS could be used at the finest clinical encounter for a diabetic person."

A report could be generated from a routine blood test, allowing the clinicians a targeted approach to the frequency of surveillance and diabetes medication selection. This would be particularly useful and allow high-risk people to be prioritized for review earlier in the course of the disease if done at the time of diagnosis.

"Renoprotective agents could then be used with close specialist surveillance to reduce DKD progression. This could ultimately delay or prevent the development of DKD," the researchers concluded.

Reference:

Ali, A. S., Pham, C., Morahan, G., & Ekinci, E. I. Genetic Risk Scores Identify People at High Risk of Developing Diabetic Kidney Disease: A Systematic Review. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgad704