Kidney Week

Abstract: SA-PO311

Complement Pathway Correlates with Rapid Progression of Type 2 Diabetic Kidney Disease in Korean and American Cohorts

Session Information

• Diabetic Kidney Disease: Clinical Pathology, Diagnostic and Treatment Advances
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Yun, Donghwan, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Donghwan Yun, MD

• Kim, Dong Ki, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Dong Ki Kim, MD, PhD

• Kim, Yon Su, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Yon Su Kim, MD, PhD

• Afkarian, Maryam, University of California Davis, Davis, California, United States

Maryam Afkarian, MD, PhD

• Han, Seung Seok, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)

Seung Seok Han, MD, PhD

Background

Rapid progression of certain patients with diabetic kidney disease (DKD) remains a threatening issue despite existing treatments. However, their pathophysiological characteristics have not been well defined. This study addresses this gap by examining both Korean and American type 2 DKD cohorts through untargeted and targeted urinary proteomics, respectively.

Methods

We conducted untargeted proteomics on urine samples collected at the time of kidney biopsy from Korean patients diagnosed with biopsy-confirmed DKD (SNUH-DN cohort) in the context of type 2 diabetes (n=64) and validated the findings using targeted proteomics on those collected at the time of enrollment in the Chronic Renal Insufficiency Cohort study (n=282, CRIC-T2D cohort). Kidney progression as an outcome was defined as either doubling of serum creatinine, ≥50% decrease in eGFR, or the development of ESKD. For untargeted proteomics, analyses for pathways were employed to identify urinary biomarkers associated with kidney progression.

Results

A total of 1,877 proteins were quantified from the patients in SNUH-DN cohort with eGFR of 55 ml/min/1.73m² (IQR 44–75) and a random uPCR of 3.1g/g (1.7–7.0). The urinary proteins were clustered into two groups, and kidney progression was primarily observed in one group. This group, exhibiting a tendency for rapid kidney progression, had an elevated complement pathway as a proteomic set. When certain complement proteins were measured as a target in the patients from CRIC-T2D cohort with a baseline estimated glomerular rate of 42ml/min/1.73m² (37–49) and 24-hr urine protein of 0.48g (0.10–1.87), those with a high abundance of complements experienced rapid kidney progression compared to those with low abundance.

Conclusion

Urinary proteomic profiling confirms the involvement of the complement pathway in the rapid progression of type 2 DKD. The results will serve as the basis for studies aimed at manipulating relevant complements for the treatment of patients with type 2 DKD.

(A) UMAP of untargeted proteomics. (B) Adjusted survival curves for kidney progression according to clustering in SNUH-DN cohort.

Funding

• Clinical Revenue Support