Integrative analysis identifies novel proteins associated with chronic kidney disease in participants with abnormal glucose metabolism
Authors' conclusion
In conclusion, we identified 11 novel proteins associated with CKD in individuals with abnormal glucose metabolism, with ENPP6 emerging as a particularly compelling candidate due to its consistent protective association across multiple analytical approaches. These findings offer promising insights into CKD pathophysiology and highlight ENPP6 as a potential biomarker or therapeutic target. Further research is warranted to elucidate the mechanistic roles of these novel proteins in CKD development and progression.
Study context
- Population
- Participants with abnormal glucose metabolism, UK Biobank
- Outcome
- Proteins associated with CKD
Methodological detailsOrthogonal partial least squares discriminant analysis (OPLS-DA), Cox proportional hazards models, one-sample Mendelian randomization (MR) (two-stage least squares), two-sample MR (Wald ratio or inverse variance weighted (IVW)), sensitivity analyses
- OPLS-DA
- Cox proportional hazards models
- One-sample MR (two-stage least squares)
- Two-sample MR (Wald ratio or IVW)
- Sensitivity analyses
Main finding
As reported in the abstract
- Proteins significantly associated with chronic kidney disease (CKD) (integrated observational and MR analyses)
- 45
- Novel proteins: CD300C, CD300LG, CDNF, CDSN, CHRDL1, ENPP6, LEFTY2, MOG, RSPO3, TNFRSF13B, MYLPF
- 11
- ENPP6, observational analyses: HR
- 0.75 (95% CI 0.63-0.89)
- ENPP6, one-sample MR: OR
- 0.32 (95% CI 0.14-0.73)
- ENPP6, two-sample MR: OR
- 0.60 (95% CI 0.37-0.98)
Further findings
ENPP6 tissue specificity
- ENPP6 displayed kidney-specific expression, particularly within peritubular and proximal tubular cells
- Findings robustly validated through comprehensive sensitivity analyses
Original publication
Integrative analysis identifies novel proteins associated with chronic kidney disease in participants with abnormal glucose metabolism. Diabetes Res Clin Pract. Published 9 September 2025. doi:10.
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