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Abstract: FR-PO169

Circulating ADAM17 Activity as a Marker of CKD Progression

Session Information

Category: CKD (Non-Dialysis)

  • 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Palau, Vanesa, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
  • Soler, Maria Jose, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
  • Benito, David, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
  • Valdivielso, Jose M., IRB LLEIDA, LLEIDA, Spain
  • Betriu, Angels, IRB LLEIDA, LLEIDA, Spain
  • Fernandez, Elvira, IRB LLEIDA, LLEIDA, Spain
  • Pascual, Julio, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
  • Riera, Marta, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Background

Several substrates for ADAM17 have been identified, including TNF-α, EGFR ligands, L-selectin, VCAM-1 and angiotensin converting enzyme(ACE)2.We have studied circulating ADAM17 in chronic kidney disease(CKD) patients from the NEFRONA cohort study.

Methods

2032 patients without history of CV disease from an observational and multicenter study (NEFRONA project) divided into two groups: non-dialysis CKD stage 3-5 patients and control patients were studied.

Baseline circulating ADAM17 activity was analyzed using a fluorimetric assay in plasma samples. Increased serum creatinine and dialysis requirement after 24months of follow-up depending on basal circulating ADAM17 activity were studied. Logistic regression analyses were used to identify predictors of increasing serum creatinine and risk of dialysis requirement.

Results

Circulating ADAM17 activity was significantly increased in CKD3-5 patients as compared to CONT(p<0.05). Baseline circulating ADAM17 activity was higher in patients with a 30% increase in serum creatinine levels after 2 years(p<0.05). Circulating ADAM17 activity was also higher in patients that needed dialysis in comparison with patients that maintained kidney function(p<0.05). After multivariate logistic regression analysis we found an interaction between sex and sADAM17 activity for increasing 30% serum creatinine, dialysis requirement and composite renal outcome(p<0.05). Therefore, we decided to perform the analysis stratifying by sex. Increased ADAM17 activity was independently associated with CKD progression regarding 30% increase in serum creatinine, dialysis requirement and composite renal end point but only in males. In females, ADAM17 activity was not associated with CKD progression.

Conclusion

Circulating ADAM17 activity was increased in CKD patients. Circulating ADAM17 activity was increased in patients that doubled serum creatinine and/or patients that need dialysis therapy being an independent predictor of worsening renal function in males.

Funding

  • Government Support - Non-U.S.