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Abstract: SA-PO537

Association Between Renal Fibrosis and Early Renal Decline in Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Ihara, Katsuhito, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Skupien, Jan, Jagiellonian University Medical College, Krakow, Poland
  • O'Neil, Kristina V., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Wilson, Jonathan Matthew, Eli Lilly and Company, Indianapolis, Indiana, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background

The association between fibrosis and early progressive renal decline in diabetes is unclear. Recently, MMP-7 (Matrilysin) and WFDC2 (WAP four-disulfide core domain protein 2) were postulated to be markers of renal fibrosis. We hypothesized that renal fibrosis may be involved in early renal decline in type 2 diabetes (T2D).

Methods

Patients for this nested case-controls study were selected from among those participating in the 2nd Joslin Kidney Study with T2D, CKD stage 1 and 2, and normo-/microalbuminuria at enrollment. Patients were followed for 6-12 years. The primary outcome was eGFR decline defined as eGFR slope ≤-5 mL/min/1.73m2/year. We developed the fibrosis index by integrating serum and urinary MMP-7 and plasma WFDC2 into a predictive probability model of renal decline using logistic regression, after verifying that these markers were not highly correlated between each other. To estimate the effect of fibrosis index on eGFR decline, multivariable logistic regression was applied adjusting for eGFR, ACR, plasma TNF-R1, plasma KIM-1, and urinary EGF/MCP-1 ratio at baseline. The markers included in our model were based on our previous prediction model (Nowak et al. Kidney Int 2018).

Results

One hundred sixty patients were enrolled. Median age was 57.5, 43.1% were women, 75.6% were Caucasian, median HbA1c was 7.7%, and median duration of diabetes was 10.0 years. eGFR and ACR at baseline were 97.0 mL/min/1.73m2 and 24.1 mg/g, respectively. One hundred patients experienced eGFR decline, and 60 were non-decliners. In comparison with non-decliners the group of eGFR decline at baseline had elevated plasma TNF-R1, KIM-1, WFDC2, serum and urinary MMP-7, whereas urinary EGF/MCP-1 ratio was decreased. Quartile change of the fibrosis index was significantly associated with eGFR decline [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.38-3.03] and was consistent in patients with normoalbuminuria (OR 5.18; 95% CI 2.00-13.41) and microalbuminuria (OR 2.33; 95% CI 1.38-3.96). The effects of the fibrosis index on eGFR decline were robust across sex, HbA1c, duration of diabetes, and use of renin-angiotensin system inhibitors in subgroup analyses.

Conclusion

Renal fibrosis is associated with early progressive renal decline in type 2 diabetes, even in patients without albuminuria.

Funding

  • NIDDK Support