Ab1161 Decreased Adamts13 Activity in Scleroderma Renal Crisis

Background: Thrombotic microangiopathy (TMA) is associated with the progression of scleroderma renal crisis (SRC). TMA may be involved in normotensive renal crisis, which has a poor prognosis. A disintegrin-like and metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 is useful for the diagnosis of TMA, but its association in SRC has not been elucidated. Objectives: The aim of this study is to investigate the association of ADAMTS13 activities and inhibitors with SRC. Methods: SRC events were extracted from the Kyoto University Systemic Sclerosis Registry (n = 330). ADAMTS13 activity and its inhibitors in sera at the onset of SRC were measured. The associations between ADAMTS13 and clinical information including hemolytic anemia, renal function, and 1-year survival were analyzed. ADAMTS13 activity was compared in the two groups classified by 1-year survival or induction of hemodialysis by using Mann-Whitney U test and Fisher's exact test. Hypertension was defined as systolic blood pressure ≥130 mmHg, and malignant hypertension as diastolic blood pressure ≥110 mmHg. Results: SRC events were observed in 24 of the 330 patients with systemic sclerosis (SSc). Hemolytic anemia (n = 21, 88%), thrombocytopenia (n = 18, 75%), fever (n = 19, 76%) and psychiatric symptoms (n = 2, 8%) were observed. All patients with SRC were treated with ACE inhibitors, resulting in high frequencies of induction of hemodialysis (n = 15, 63%) and inadequate 1-year survival (n = 13, 54%). The 1-year survival rates were observed for patients with hypertension (n = 12/20, 60%) and normotension (n = 1/4, 25%) (p = 0.30). Furthermore, the 1-year survival rates were for patients with malignant hypertension (n = 9/13, 69%) and non-malignant hypertension (n = 4/11, 36%) (p = 0.22). ADAMTS13 at the onset was measured in 15 patients. None were positive for ADAMTS13 inhibitors. ADAMTS13 activity was 44.0 ± 17.8(%) (normal range, 50-150%) (Figure 1). ADAMTS13 activity was mildly decreased in all patients, and was under normal levels in 8 patients. There were no subjects under 10% in ADAMTS13 activity, the baseline level referred to thrombotic thrombocytopenic purpura (TTP). ADAMTS13 activity was not significantly correlated with levels of hemoglobin and platelet. When ADAMTS13 activity was compared in the two groups classified by 1-year survival or induction of hemodialysis, there were no significant differences between the two groups: survived patients, 36.9 ± 14.0% vs. deceased patients, 50.3 ± 17.3% (p = 0.15); patients without hemodialysis, 46.1 ± 16.3% vs. patients with hemodialysis, 43.5 ± 17.4% (p = 0.83). Conclusion: Normotensive renal crisis tended to have a poor prognosis. ADAMTS13 activity was slightly decreased at the onset of SRC. ADAMTS13 inhibitors were not detected. There was no significant association between ADAMTS13 activity with outcomes of SRC. REFERENCES: 1 Autoantibody profiles associated with morbidity and mortality in scleroderma renal crisis. 2 Tsuji H, Kuramoto N, Sasai T, Shirakashi M, Onizawa H, Kitagori K, Akizuki S, Nakashima R, Watanabe R, Onishi A, Murakami K, Yoshifuji H, Tanaka M, Hashimoto M, Ohmura K, Morinobu A. Rheumatology (Oxford). 2022 Oct 6;61(10):4130-4135. doi: 10.1093/rheumatology/keac047. Acknowledgements: NIL. Disclosure of Interests: None declared.