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Abstract: PO1944

Serum and Urinary Metabolites Discriminate Disease Activity in ANCA-Associated Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Kant, Sam, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Le, Anne, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Attarwala, Nabeel, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Geetha, Duvuru, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Background

Relapse of disease and treatment related morbidity due to lack of a reliable biomarker for disease activity continue to be a significant issue in patients with ANCA associated vasculitis (AAV). Renal biopsy is currently gold standard for reliable detection of active disease. Metabolomics have been used to successfully discern disease activity in a number of autoimmune diseases. We sought to investigate the use of serum and urinary metabolomics to discriminate disease activity in ANCA associated GN

Methods

Ten patients with AAV renal disease had paired serum and urine supernatant sample collections during active and remission phases of disease. Active renal disease was defined by presence of hematuria >5 RBC/hpf, urinary RBC casts or an increase in serum creatinine > 30% or < in eGFR by 25% or biopsy proven GN. The samples were then subjected to targeted metabolomics data acquisition using a Thermo scientific Q Exactive plus Orbitrap Mass Spectrometer Plus with a Vanquish UPLC at our metabolomics facility.

Results

The mean age in this cohort was 61 years, with 6 patients each being male and Caucasian. Nine patients had biopsy proven renal disease, with clinical diagnosis in one. Mean BVAS and mean GFR was 17 and 28 respectively. Intensities of urinary citrate and iso-citrate are significantly higher in the remission group compared to the active group (Fig 1A). Similar trend of higher citrate and iso-citrate intensities present in serum of patients in remission versus active disease (Fig 1B). There was a disproportionately high intensity difference in citrate and iso-citrate levels in serum and urine samples compared to other metabolites of the TCA cycle implying involvement of additional metabolic pathways.

Conclusion

This study indicates that serum and urinary citrate and iso-citrate may be utilized to monitor disease activity in AAV and emerge as an alternative to kidney biopsy.