Kidney Week

Abstract: FR-OR111

Aptamer-Based Plasma Proteomic Profiling Reveals Candidate Proteins Associated with Slow or No Renal Decline in CKD Stage 3 Diabetic Patients

Session Information

• Translating Discovery to Patients with Diabetic Kidney Disease
  November 08, 2019 | Location: 207, Walter E. Washington Convention Center
  Abstract Time: 04:30 PM - 04:42 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States

Zaipul I Md Dom, PhD

• Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States

Eiichiro Satake,

• Skupien, Jan, Jagiellonian University Medical College, Krakow, Poland

Jan Skupien,

• Ihara, Katsuhito, Joslin Diabetes Center, Boston, Massachusetts, United States

Katsuhito Ihara,

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

Andrzej S. Krolewski,

Background

Patients with diabetes and chronic kidney disease (CKD) stage 3 are at high risk of developing end-stage renal disease (ESRD). However, the rate of renal decline leading to onset of ESRD varies tremendously among these patients. This study aimed to identify biomarkers associated with slow or no renal decline (slow decliners) in two independent cohorts of diabetic patients with CKD stage 3.

Methods

The study comprised an exploratory cohort of 214 individuals with Type 1 diabetes (T1D) with 129 slow decliners, and a replication cohort of 144 individuals with Type 2 diabetes (T2D) with 96 slow decliners. Both cohorts were followed for 7-10 years. Serial measurements of serum creatinine were used to estimate the rate of eGFR decline. Slow renal decline was defined as eGFR slope of ≥ –5 ml/min/year. Baseline plasma specimens were assayed by the SOMAscan proteomics platform. Relationships of plasma proteins with eGFR slopes were evaluated based on Spearman’s rank correlation coefficients. Multivariable logistic regression models investigated the odds ratio (OR) between plasma proteins and being a slow decliner.

Results

In slow decliners, the median (25^th, 75^th percentiles) eGFR slope was -2.4 (-3.5, -1.3) and -1.8 (-3.1, -0.1) ml/min/year in T1D and T2D cohorts, respectively. In the exploratory cohort, 76 plasma proteins were significantly and positively associated with eGFR slope (FDR P<0.005). Eighteen of these proteins were replicated in the T2D cohort (P<0.05). Multivariable logistic analyses in the combined cohorts with T1D and T2D demonstrated that all proteins were significantly associated with slow renal decline in models adjusted for type of diabetes, eGFR and HbA1c. In models further adjusted for TNF-R1, the ORs remained statistically significant for 11 of the 19 proteins. TNFSF12 (OR (95% CI): 1.46 (1.2, 1.9), P=0.0017) was the most significant independent predictor of slow or no renal decline with higher TNFSF12 plasma levels protecting against progressive renal decline.

Conclusion

Our findings suggest that several circulating plasma proteins are associated with slow or no renal decline in both types of diabetes, and these proteins may represent new targets that can be used therapeutically for slowing the progression of renal function decline.

Funding

• NIDDK Support