FP760SOLUBLE ADHESION MOLECULES ICAM AND VCAM IN CHILDREN WITH REMISSION OF ATYPICAL HEMOLITIC UREMIC SYNDROME (AHUS)

Abstract

Introduction and Aims: HUS is a thrombotic microangiopathy (TMA) affecting mainly the kidneys. It develops due to endothelial injury, caused by bacterial shiga toxin in typical, shiga toxin associated HUS (tHUS), or by inappropriate complement activation in atypical, complement mediated HUS (AHUS). THUS is an acute disease with no recurrence, while aHUS often has a relapsing, progressive course leading to chronic kidney disease (CKD) or death. Therapy with eculizumab (monoclonal antibodies to C5 complement factor) inhibits membrane attack complex on the endothelial surface and induce hematological remission of aHUS and renal function recovery. Spontaneous or plasma induced remission can be observed, too. However, without eculizumab therapy subclinical complement activation and endothelial injury may persist during remission, causing the consumption of C3 complement factor and changes in level ofsICAM and sVCAM.The aim ofthe study was tocompare markers ofendo-thelial injury during remission aHUS in patients on eculizumab therapy and without it. Method(s): Serum levels ofC3, sICAM, sVCAM were investigatedin42 patients (pts) (21 boys). In 25 pts aHUS was previously diagnosed, of them 14 were on eculisumab therapy (group 1), 11-without eculisumab therapy (group 2). 17 children with history of tHUS were included in comparison group3. Children of the3dgroup were younger (NS). Time after acute episode of HUS didn't differ between groups. There were more pts with CKD stage 3in the 1st group (36%vs 9% in the 2nd group and 0%in the 3d), thereafter serum creatinine were higher and eGRF lower in the 1st group. Pts had no signs of overt TMA or inflammation (table 1; * h <0,05 vs groups 2 and 3;[ h<0,05 vs group 2) Results: Serum levels of C3, sICAM, sVCAM were close to the normal ranges in all groups, with slightly but significantly decreased C3 and increased sICAM in pts on eculisu-mab therapy (table 2). This difference can be explained by more severe defect of the complement alternative pathway regulation and less preserved renal function in those patients. Conclusion(s): Based onthe levelsofsICAM and sVCAM,wehaven't revealed reliable signs of endothelial injury during remission aHUS in patients without eculisumab therapy comparing with patient on eculisumab therapy and children with a history of tHUS.