Abstract: SA-PO098

Urinary Metabolomic Study in Patients with Membranous Nephropathy

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Jo, Hyung Ah, Seoul National University Hospital, Jong ro Gu, SEOUL, Korea (the Republic of)
  • Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jong ro Gu, SEOUL, Korea (the Republic of)
Background

Membranous nephropathy (MN) is a leading cause of adult-onset nephrotic syndrome. Primary MN is an autoimmune disease caused by autoantibodies such as phospholipase A2 receptor antibody (PLA2RAb) and thrombospondin type 1 domain-containing 7A antibody against the podocyte antigen. Many previous studies showed that the prognosis of patients with MN can be predicted by measuring the levels of these autoantibodies. However, the treatment response varies among individuals, and adverse reaction to immunosuppressive agent (ISA) is significant. The treatment response should be optimized and the adverse reaction to ISA should be minimized. Thus, we performed a urine metabolomic study to identify the predictive biomarker of the prognosis and treatment response in patients with MN.

Methods

We used urine samples from patients with biopsy-proven primary MN that were stored at the time of kidney biopsy in Seoul National University Hospital Biobank to find differences in urine metabolites between the MN (n = 79), minimal-change-disease (n = 74), and control groups (n=82). The 800-MHz nuclear magnetic resonance-based metabolomic method was used. We investigated the urine metabolites specific to MN after excluding outliers and matching factors such as age, sex, and presence of diabetes mellitus. Serum PLA2RAb level was examined using an enzyme-linked immunosorbent assay. Hard outcome was defined as initiation of dialysis, a 50% decrease in the estimated glomerular filtration rates, and doubling of serum creatinine levels. We reviewed the association of urine metabolites with each patient’s ISA response and the presence of hard outcome.

Results

After excluding outliers and matching for age, sex, and presence of diabetes mellitus, the levels of urine metabolites such as tyrosine, alanine, fumarate were higher than those measured in the control urine samples. The urinary fumarate level was significantly higher in the patients with steroid-resistant MN than that measured in the urine sample from the steroid-responsive patients. In this study, the patients with a hard outcome during the follow-up period showed urine fumarate levels 2.53-fold higher than those of the patients with a non-hard outcome.

Conclusion

Fumarate is a reliable biomarker for predicting the prognosis and treatment response of patients with MN. We have a plan to validate this metabolomic study.