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Kidney Week

Abstract: SA-OR040

The Pro-Fibrotic Serum Marker MMP7 Predicts Accelerated GFR Loss in the General Population

Session Information

  • Biomarkers in CKD
    November 09, 2019 | Location: 152, Walter E. Washington Convention Center
    Abstract Time: 04:54 PM - 05:06 PM

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Enoksen, Inger Therese Tonsberg, The Arctic University of Norway, UiT, Tromsø, Norway
  • Svistounov, Dmitri, The Arctic University of Norway, UiT, Tromsø, Norway
  • Norvik, Jon V., University Hospital of North Norway, Tromsø, Norway
  • Solbu, Marit D., The Arctic University of Norway, UiT, Tromsø, Norway
  • Eriksen, Bjorn Odvar, The Arctic University of Norway, UiT, Tromsø, Norway
  • Melsom, Toralf, The Arctic University of Norway, UiT, Tromsø, Norway

Group or Team Name

  • Metabolic and Renal Research Group, UiT The Arctic University of Norway
Background

Age related loss of glomerular filtration rate (GFR) is a major contributor to the global chronic kidney disease (CKD) epidemic. CKD is associated with increased morbidity and mortality and there is a need for novel biomarkers that identify at risk persons at an early stage to delay or prevent CKD onset. Matrix Metalloproteinase (MMP) 2 and 7 are key players in interstitial remodeling and mediate renal fibrosis development in animal models. We investigated whether serum MMP2, MMP7 and their inhibitor TIMP1, were associated with accelerated age-related GFR decline and incident CKD in middle-aged individuals from the general population.

Methods

In the Renal Iohexol Clearance Survey (RENIS) we performed GFR measurements (using iohexol clearance) in 1627 subjects, aged 50-62 years, from the general population without self-reported diabetes, kidney or cardiovascular disease. 1324 (81%) had follow-up measurements after a median of 5.6 years. The biomarkers were analyzed in baseline serum samples with a Bioplex 200 machine. Using multiple logistic regression analysis, we evaluated the risk of accelerated GFR decline (defined as subjects with the 10% steepest GFR slope) and incident CKD (defined as GFR <60ml/min/1.73m2).

Results

After adjustment for age, sex, baseline GFR and urinary albumin-creatinine ratio (ACR), higher levels of MMP7 were associated with an increased risk of accelerated GFR decline (Odds ratio (95% confidence interval)) per one SD increase in MMP7: 1.68 (1.39-2.04) and incident CKD: 1.71 (1.25-2.34). The results were attenuated, but remained significant in the fully adjusted model (1.48 (1.20-1.81) and 1.53 (1.08-2.18)). Prediction of accelerated GFR decline improved after addition of MMP7 to a model with age, sex, baseline GFR and ACR (aera under the ROC curve increased from 0.72 to 0.75 (p=0.054), continuous net reclassification improvement: 0.34 CI: 0.16-0.52). Similar results were obtained using alternative definitions of accelerated GFR decline such as ≤-3.0 ml/min/1.73m2/year or a GFR decline rate twice the cohort mean (≤-1.68 ml/min/1.73m2/year). MMP2 and TIMP1 showed no association with GFR decline.

Conclusion

The pro-fibrotic biomarker MMP7 was independently associated with increased risk of accelerated GFR decline and incident CKD in middle-aged persons from the general population.

Funding

  • Government Support - Non-U.S.