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Abstract: FR-PO447

A Biomarker of Type VI Collagen Formation Is Associated with Diabetic Kidney Disease and Is a Risk Factor for Mortality in Elderly Women

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Genovese, Federica, Nordic Bioscience, Herlev, Denmark
  • Sparding, Nadja, Nordic Bioscience, Herlev, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark
  • Bager, Cecilie liv, Nordic Bioscience, Herlev, Denmark
Background

Diabetic kidney disease (DKD) is the leading cause of chronic dialysis and accounts for at large proportion of all cases of chronic kidney disease (CKD). Renal fibrosis is the hallmark of CKD and is caused by changes in the balance of extracellular matrix (ECM) remodeling. Type VI collagen is a crucial ECM molecule for the control of tissue organization. In this study, we investigated the association of PRO-C6 (collagen type VI formation) with DKD and with mortality in patients with DKD.

Methods

The study population included 5855 postmenopausal women from the Prospective Epidemiological Risk Factor Study (PERF) cohort. The women were examined at baseline (BL year, 2000) and serum PRO-C6 were measured. The dialysis, diagnosis and mortality information were extracted from Danish Health Registries at end of study (2015). DKD was defined as eGFR <60 ml/min/1.73m2, dialysis, or a renal diagnose (ICD10). Healthy women were defined as women with no history of chronic diseases (ICD10 chapter II, IX, X, XI, XIII, XIV). Women with DKD were stratified into quintiles based on BL PRO-C6 levels and compared with an ANOVA test. Cox regression was used to explore the association with all-cause mortality with 15 years of follow-up.

Results

A total of 75 and 308 women were diagnosed with DKD and diabetes at BL, and 450 were healthy. Serum PRO-C6 levels were higher in women with DKD (mean=10.7 ng/ml (SD=3.7), p<0.0001) and diabetic (mean=8.7 ng/ml (SD=2.7), p=0.004) compared to the healthy group (mean= 8.0 ng/mL (SD=3.0)). Levels of PRO-C6 were higher in women with DKD compared to the diabetic group (p<0.0001). The women with DKD were older (age, 74.6) than the diabetic women (age, 71.3) (p<0.0001), but the effect of age did not affect the independent association of PRO-C6 with DKD. Finally, DKD women in the 5th quintile of PRO-C6 had an increased risk of all-cause mortality compared to women in the 3th quintile (HR=2.6 (95% CI=0.9-7.3), p=0.08). The borderline-significance was probably due to lack of power.

Conclusion

In this study, we demonstrated that PRO-C6, a biomarker of collagen type VI formation, was increased in serum of post-menopausal women with DKD compared to women with diabetes without kidney involvement and healthy women. In addition, PRO-C6 was associated with mortality in women with DKD.