Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study

A study investigating the link between Type 2 diabetes (T2D) and chronic kidney disease (CKD) has identified specific proteins that may play a role in mediating this relationship. Chronic kidney disease affects 20-50% of people with T2D and is the primary cause of kidney failure globally. The researchers used proteomics data from large-scale studies to pinpoint circulating proteins whose levels are altered by genetic predisposition to T2D.

They identified five proteins - INHBC, GNPTG, LPO, AGRN, and CTSD - that were linked to three kidney traits: blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and CKD risk. Higher levels of the INHBC protein, in particular, were found to be associated with lower eGFR and higher BUN, according to mendelian randomization analyses.

The findings were replicated in additional cohorts, providing further evidence of the consistency in the results. Observational data also showed that increased INHBC levels were associated with a higher risk of kidney disease diagnosis in a large UK Biobank cohort. The researchers estimate that INHBC levels explain 1.3% of the association between T2D and kidney disease.

However, the study does have some limitations. The researchers noted untestable violations to the assumptions of the mendelian randomization technique and cautioned that their findings were based on independent population-based studies assessing diabetes and kidney function separately. Further functional analyses in disease-specific cohorts are needed to confirm these results.

Overall, the study suggests that T2D may influence the risk of CKD, at least in part, through elevated circulating INHBC levels.