Kidney Week

Abstract: SA-OR111

Complement System and Rapid Renal Function Decline in Type 1 (T1D) and Type 2 Diabetes (T2D) – Application of Novel SOMAscan-Based Proteomic Technology

Session Information

• What's New in Diabetic Kidney Disease - II
  November 04, 2017 | Location: Room 290, Morial Convention Center
  Abstract Time: 04:30 PM - 04:42 PM

Category: Diabetes

• 502 Diabetes Mellitus and Obesity: Clinical

Authors

• Tsay, John J., Joslin Diabetes Center, Boston, Massachusetts, United States

John J. Tsay, MD

• Smiles, Adam, Joslin Diabetes Center, Boston, Massachusetts, United States

Adam Smiles,

• Croall, Stephanie E., Joslin Diabetes Center, Boston, Massachusetts, United States

Stephanie E. Croall,

• Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States

Joseph V. Bonventre,

• Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States

Andrzej S. Krolewski,

• Niewczas, Monika A., Joslin Diabetes Center, Boston, Massachusetts, United States

Monika A. Niewczas,

Background

We aimed to investigate inflammatory protein signatures in the urine associated with rapid renal function loss in subjects with diabetes.

Methods

In a case-control study of 60 subjects nested within the Joslin Kidney Study cohort of subjects with T1D, proteinuria and CKD 3 (discovery panel), we performed urinary baseline measurements of 194 inflammatory proteins using the SOMAscan platform. Subjects with a Rapid Renal Function Decline (eGFR loss >40% within 5 years) were defined as cases (n=29). Eighteen out of 29 subjects developed ESRD within this time period. Further, we performed urinary proteomic measurements in the validation panel of T2D patients. The 2^nd nested case-control study group consisted of 26 T2D subjects with eGFR loss >40% within 5 years (cases); 11 of these progressed to ESRD, and 26 controls remained alive with preserved renal function during the follow-up.

Results

Six major inflammatory classes of proteins were measured within the array. We identified 26 proteins that were concordantly associated with rapid eGFR loss in the discovery panel (Bonferroni corrected nominal p value) and in the validation panel (nominal p value < 10^-2 ). Candidate inflammatory proteins were particularly enriched for proteins from the complement system (χ² = 21.5; p<0.0001). Complements C3a, C5a and factor H were among the top proteins associated with an increased renal risk.

Conclusion

In our study we identified a robust inflammatory signature enriched for proteins of the complement system that are associated with rapid renal function decline in both types of diabetes. Our findings suggest that local kidney disturbances of the complement pathway are etiologically linked to the development of kidney complications in diabetes.

Funding

• NIDDK Support