SAT-415 SEVERE GLOMERULAR ENDOTHELIAL INJURY AND MILD TO MODERATE PROTEINURIA DUE TO TAFRO SYNDROME WITH RENAL DYSFUNCTION

Abstract

TAFRO syndrome has been recognized as a severe subtype of idiopathic multicentric Castleman’ s disease(iMCD), and renal dysfunction is a life threatening complication of this disease. We previously reported two case-reports about renal biopsies of TAFRO syndrome, showing endocapillary proliferative glomerulonephritis, but precise mechanism and clinical course have not been elucidated yet. To further evaluate the characteristics of renal dysfunction due to TAFRO syndrome, we conducted a cross-sectional study. The object of patients were either diagnosed as iMCD or TAFRO syndrome who were extracted from 4,248 renal biopsies performed between 2001 and 2018. The renal biopsies were evaluated by light microscopy, immunofluorescence staining, and electron microscopy. Clinical and laboratory data were collected from electrical medical chart. Statistical analysis was conducted by using R version 3.6.1. This observational study was approved by IRB and informed consent was obtained from all living patients. Fifteen cases were eligible for the study, and seven were diagnosed as TAFRO syndrome while eight were as iMCD without TAFRO syndrome (iMCD-NOS). Patients with TAFRO were lower platelet count (36 [28-115]*103/μL in TAFRO syndrome vs 308 [130-424*103/μL] in iMCD-NOS, p-value <0.01), higher serum ALP (641 [534-1438] IU/L vs199 [85-352]IU/L, p<0.01), total protein(5.2 [5.0-6.8] g/dL vs 10.5 [7.7-14.8]g/dL, p<0.01), and lower IgG level(835 [684-1449]mg/dL vs 5249 [2800-8198]mg/dL). Proteinuria in TAFRO syndrome was mild to moderate level and lower than iMCD-NOS, but this was not statistically significant (0.45[0.28-3.71]g/gCre vs 1.07[0.04-5.34]g/gCre, p=0.43). There was no statistical difference in serum creatinine level, serum albumin level and hematuria. In renal biopsy, severe endothelial injury such as endothelial swelling and narrowing of glomerular tuft was commonly observed in TAFRO syndrome (figure), while varieties of histological diagnosis were found in iMCD-NOS; AA amyloidosis (2 cases), membranous nephritis(2 cases), minor glomerular abnormality (2 cases), nephrosclerosis(1 case), IgA deposition(1case), renal sclerosis (1 case). In addition, any deposition was not detected by electron dense deposit or immunofluorescence staining in TAFRO syndrome. Hemodialysis was required for 4 out of 7 patients with TAFRO syndrome and all of them recovered after the initiation of anti IL-6 receptor antibody or anti CD20 monoclonal antibody. On the other hand, 3 out of 8 patients with iMCD-NOS required maintenance hemodialysis despite of anti IL-6 receptor antibody based immunosuppressive therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Mild to moderate proteinuria, severe endothelial injury without any deposit were common characteristic of TAFRO syndrome compared with iMCD-NOS. Cytokine targeted immunosuppressive therapy was effective in severe renal dysfunction due to TAFRO syndrome even if hemodialysis was required. The difference in treatment response between TAFRO syndrome and iMCD-NOS might be related to the pathogenesis of glomerular changes of both diseases.