Abstract: FR-PO843
Novel Urine Metabolite in Human as a New Differential Diagnosis Biomarker for Lupus Nephritis
Session Information
- Glomerular Diseases: Immunology, Inflammation - I
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Akiyama, Shin'ichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Hirayama, Akiyoshi, Keio University, Tsuruoka, Japan
- Hachiya, Asaka, Nagoya University, Nagoya, Japan
- Soga, Tomoyoshi, Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
- Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background
Lupus nephritis (LN) is one of the major causes of mortality and disability in patients with systemic lupus erythematosus (SLE). LN shows many phenotypes so diagnosis is not easy and takes time and labor. Non-invasive biomarkers are required to accelerate diagnosis. The present study aimed to identify urine metabolites as new biomarkers for screening for LN from another nephritis.
Methods
Using capillary electrophoresis and mass spectrometry (MS), we analyzed low molecular weight metabolites in a total of 394 urine samples obtained from Japanese patients with biopsy-proven LN (n=27, n=13), membranous nephropathy (n=78, n=43), diabetic nephropathy (n=29, n=14), MCNS (n=74, n=22), FSGS (n=29, n=10), IgA-nephropathy (n=18, n=10), and rheumatoid arthritis (n=19, n=8), in discovery (n=274) and validation (n=120) cohorts, respectively. All urine samples were collected at the time of diagnosis. Multivariate analyses were used for the identification of marker candidates and development of discriminative models. Identification of chemical structure was made on the basis of NMR and liquid chromatography and MS/MS.
Results
We found that an initially unknown metabolite (peak ID: CU040) was present in the urine of LN patients and that measurement of its concentration could distinguish LN from another nephritis. Logistic regression models facilitated the discrimination between LN and other nephritis and yielded high areas under receiver-operating characteristic curves. The area under the curve values, sensitivity, and specificity were 0.8218, 0.7037 and 0.9717 in the discovery cohort, and 0.8698, 0.8462 and 0.9346 in the validation cohort, respectively. Based on the result of chemical structure analysis, the CU040 was identified as 3',4'-didehydro-3'-deoxycytidine (C9H11N3O4, MW 225.07).
To the authors’ knowledge, this metabolite has not been detected in humans, but it has been reported in 2013 as a novel biomarker for infection of Plasmodium berghei in the urine of malaria model mice（PMID: 24067624）.
Conclusion
The 3',4'-didehydro-3'-deoxycytidine in urine was a novel and excellent differential diagnosis biomarker for LN. Our results may suggest the existence of a common molecular mechanism between malaria and SLE, and it is also very interesting from the viewpoint of understanding the pharmacological effect of Hydroxychloroquine.
Funding
- Government Support - Non-U.S.