Clinico-pathological Associations with Serum Thrombomodulin Level in Patients with Lupus Nephritis

Abstract

BACKGROUND: Conventional serological markers do not always correlate with clinical activity or histolopathology in lupus nephritis (LN). There is evidence of endothelial activation and injury in LN pathogenesis. Thrombomodulin (TM), a component of endothelial glycocalyx, is shed into the circulation in endothelial cell injury. We investigated clinico-pathological associations of circulating TM level. METHODS: TM level was measured by ELISA in sera collected serially every 3-4 months over >2 years (n=482) from 31 patients with biopsy-proven Class III/IV LN. Patients with non-renal SLE or non-lupus kidney diseases (CKD) and healthy subjects were included as Controls. RESULTS: Patients with active LN had the highest serum TM level, compared with LN patients in remission, patients with active non-renal SLE, CKD patients, or healthy subjects (P<0.01, for all). Serum TM level correlated with anti-dsDNA antibody titre, proteinuria, serum creatinine, SLEDAI-2K and renal SLEDAI-2K score; and inversely correlated with eGFR and C3 (P<0.05, for all). 8 patients had blood samples collected before disease flare, and 6 showed increased TM level (3.65±2.16 months before clinical flare). All episodes of LN flare were accompanied by elevated TM level, which decreased after treatment. A temporal relationship was noted between TM level and anti-dsDNA titre and C3 levels, proteinuria, SLEDAI-2K and renal SLEDAI-2K scores. TM level also correlated with renal interstitial inflammation score (r=0.54, P=0.0081). ROC analysis showed that serum TM level distinguished active LN from healthy subjects (sensitivity 100.00%, specificity 100.00%), from LN in remission (sensitivity 89.66%, specificity 68.97%), from active non-renal SLE (sensitivity 90.91%, specificity 100.00%), and from CKD (sensitivity 89.66%, specificity 56.52%) (P<0.001, for all). CONCLUSION: Determination of serum TM level may facilitate early diagnosis of active LN, and may be useful in monitoring the response to treatment.