Kidney Week

Abstract: TH-PO568

Plasma Testican-2 and MGT5A Are Potential Markers of Membranous Nephropathy

Session Information

• Glomerular Diseases: Omics, Biomarkers, and Tools
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Kim, Taesoo, Massachusetts General Hospital, Boston, Massachusetts, United States

Taesoo Kim, MD

• Surapaneni, Aditya L., NYU Langone Health, New York, New York, United States

Aditya L. Surapaneni, PhD

• Schmidt, Insa Marie, Boston Medical Center, Boston, Massachusetts, United States

Insa Marie Schmidt, MD, MPH

• Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States

Sahir Kalim, MD, MS, MSc, FASN

• Srivastava, Anand, University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

Anand Srivastava, MD, MPH

• Palsson, Ragnar, Massachusetts General Hospital, Boston, Massachusetts, United States

Ragnar Palsson, MD, FASN

• Stillman, Isaac Ely, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Isaac Ely Stillman, MD

• Grams, Morgan, NYU Langone Health, New York, New York, United States

Morgan Grams, MD, PhD

• Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States

Sushrut S. Waikar, MD, MPH

• Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States

Eugene P. Rhee, MD

Background

Membranous nephropathy (MN) is a rare cause of chronic kidney disease, most of which require biopsy to diagnose. In select cases, serologic assays such as PLA2R antibodies may help diagnose MN where kidney biopsy is contraindicated, but additional specific markers are needed.

Methods

Among 434 individuals who underwent native kidney biopsy adjudicated by 2 expert pathologists, 39 were diagnosed with MN. We examined the associations between the diagnosis of MN and the 6592 plasma protein levels measured by aptamers using linear regression models adjusted for eGFR, proteinuria and demographic factors. Combined cases of normal kidney and thin basement membrane disease served as a control group (n=26). In sensitivity analysis, we evaluated the associations between each plasma protein level and the diagnosis of MN versus all other diagnoses if the reason for biopsy was proteinuria (n=231). For the proteins identified, we examined the kidney expression of the corresponding genes using publicly available single cell RNA sequencing data from the Kidney Precision Medicine Project (KPMP).

Results

Twelve proteins were associated with the diagnoses of MN. Testican-2 (P=4.0 x 10^-11) and MGT5A (P=5.8 x 10^-10) were the top 2 proteins with significant associations with MN, higher levels of which were associated with a diagnosis of MN. Both Testican-2 (P=1.2 x 10^-8) and MGT5A (P=3.6 x 10^-10) remained associated with MN in the sensitivity analysis. In KPMP, SPOCK2 (encodes Testican-2) and MGAT5 (encodes MGT5A) showed significant enrichment in podocytes (89% and 71% respectively).

Conclusion

These findings identify Testican-2 and MGT5A as candidate plasma markers of MN, both with literature outlining potential biologic relevance. Additional studies should be directed towards external replication.

Volcano plot of proteins (Log2-transformed) associated MN in linear models adjusted for age, sex, ethnicity, eGFR and proteinuria. Each dot represents an aptamer measuring protein. Some proteins were measured by multiple aptamers. Proteins meeting statistical significance (P < 0.05/6592) are labeled

Funding

• NIDDK Support