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FRI0439 Urinary Collagen Fragments Are Reduced in Lupus Nephritis Subjects with Renal Dysfunction
  1. N. Wisniacki1,
  2. R. Wei2,
  3. B. Gao2,
  4. C. Stebbins2,
  5. A. Dearth2,
  6. A. Ranger3,
  7. H. Mischak4,
  8. J. Siwy5,
  9. M. Petri6,
  10. L. Burkly7
  1. 1Immunology Clinical Development, Biogen Idec, London, United Kingdom
  2. 2Translational Medicine, Biogen Idec, Cambridge, United States
  3. 3Translational Medicine, Biogen Idec, Cambridge
  4. 4Proteomic and System Medicine Unit, Univeristy of Glasgow
  5. 5Mosaic Diagnositcs, Glasgow, United Kingdom
  6. 6Rheumatology, Johns Hopkins School of Medicine, Baltimore
  7. 7Immunology Research, Biogen Idec, Cambridge, United States

Abstract

Background Interstitial fibrosis is a key component of chronic kidney injury in lupus nephritis (LN) and a critical determinant of the disease progression as it leads to the reduction of functioning renal mass and the development of renal failure. A non-invasive method of quantifying renal fibrosis may allow a better monitoring of disease progression as this usually relies on changes in renal function as assessed by eGFR or serum creatinine. Prior studies in subjects with chronic kidney disease (CKD) demonstrated a reduction in certain collagen fragments in urine suggesting changes in collagen turnover and extracellular matrix with increased accumulation in kidney.

Objectives The aim of our study was to explore whether urinary collagen fragments were also reduced in LN patients as potential markers of kidney fibrosis.

Methods The study was conducted in patients from the SPARE study: a prospective, longitudinal, observational study conducted at the Johns Hopkins Lupus Center. 18 female subjects with LN and renal dysfunction (elevated serum creatinine) as well as 17 female subjects with active SLE (SLEDAI >4) and no current or historical renal involvement were included. A group of 39 female healthy volunteers were included as a control group. Subjects and controls were matched for gender, age and race.

Urine samples were processed by filtering out high molecular weight polypeptides/proteins. Urinary peptides were then analyzed by capillary electrophoresis–mass spectrometry. Detected and identified peptides with frequency of occurrence >70% in at least one of the groups (HV, SLE or LN) were included in the analysis. Kruskal-Wallis test followed by Mann-Whitney U test were used to compare peptide levels between groups.

Results Patients' demographics and clinical characteristics are shown in the table.

Proteomic analysis identified a total of 1536 urinary peptides, including 761 collagen fragments. Differences in 288 peptides in at least one pair-wise comparison were detected. 21 collagen peptides differed in LV vs. HV and LN vs. SLE, but not SLE vs. HV. 18 of the collagen peptides mapped to 3 collagen proteins (I, II, III) and 3 mapped to collagen proteins XVIII, and XXIII. Most of the urine collagen I, II and III peptides in the LN group were down-regulated in the range of 1.5-117 folds, while collagen XVIII and XXIII peptides are up-regulated 22-388 folds

Conclusions A number of urinary collagen fragments were reduced in patients with LN with renal dysfunction consistent with previous studies in subjects with CKD of other origins. The correlation of urinary collagen fragments with renal histology and its use to monitor renal disease progression warrants further investigation.

Disclosure of Interest N. Wisniacki Shareholder of: Biogen Idec, Employee of: Biogen Idec, R. Wei Shareholder of: Biogen Idec, Employee of: Biogen Idec, B. Gao Shareholder of: Biogen Idec, Employee of: Biogen Idec, C. Stebbins Shareholder of: Biogen Idec, Employee of: Biogen Idec, A. Dearth Shareholder of: Biogen Idec, Employee of: Biogen Idec, A. Ranger Shareholder of: Biogen Idec, Employee of: Biogen Idec, H. Mischak: None declared, J. Siwy: None declared, M. Petri: None declared, L. Burkly Shareholder of: Biogen Idec, Employee of: Biogen Idec

DOI 10.1136/annrheumdis-2014-eular.2850

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