Abstract: TH-PO512

Multiple Determinants of Early Renal Decline in Type 2 Diabetes

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Nowak, Natalia Z., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Skupien, Jan, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Smiles, Adam, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Yamanouchi, Masayuki, Okinaka Memorial Institute for Medical Research, Tokyo, Japan
  • Niewczas, Monika A., Joslin Diabetes Center, Boston, Massachusetts, United States
  • Duffin, Kevin L., Eli Lilly and Company, Indianapolis, Indiana, United States
  • Breyer, Matthew D., Lilly Research Laboratories, Indianapolis, Indiana, United States
  • Pullen, Nick, Phizer Inc., Boston, Massachusetts, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

There has been a significant effort to identify the mechanisms for progressive renal decline in diabetic patients with chronic kidney disease (late progressive renal decline). Much less is known about the mechanisms, determinants and markers of early progressive renal decline. We aimed to evaluate several markers as determinants of early renal decline in 1032 patients with Type 2 diabetes (T2D), enrolled into the 2nd Joslin Kidney Study. With these data, we aimed to develop a multi-marker index to improve the identification of patients with incipient renal decline.

Methods

At enrollment, all patients had preserved GFR (median of 98 mL/min (1st and 3rd quartile; 85 -110), 58% had normoalbuminuria (urinary ACR median of 4 µg/mg) and 42% had albuminuria (ACR median of 44 µg/mg). Early renal decline (defined as GFR loss from baseline of 30% per < 5 years) occurred in 38 (6%) normoalbuminurics and in 76 (18%) albuminurics. As predictors of the decline we examined: (1) baseline clinical characteristics, (2) several blood markers proposed by previous targeted studies, (2) new urinary biomarkers.

Results

When analyzed jointly with other markers/predictors, baseline systolic BP, plasma TNFR1, KIM-1 as well as urinary ACR predicted early renal decline; a strongest, negative association with the risk of early renal decline was found for the urinary EGF normalized to MCP1, expressed as EGF/MCP1 ratio (Nowak et al, submitted). Integration of the independent biomarkers into multi-marker index resulted in significant improvement of the accuracy of prediction, compared with a model with ACR and systolic BP alone (c-statistics=0.81 vs c-statistics=0.73; p<0.001).

Conclusion

Our study underscores the power of examining multiple pathways in plasma and urine for understanding the mechanisms of early renal decline in T2D. Two novel markers of tubular injury, KIM-1 and EGF/MCP ratio in urine, had independent effects on risk of early renal decline in T2D.

Funding

  • NIDDK Support