Medizinische Universität Graz - Research portal
Selected Publication:
Haefner, J.
Investigation of the role of tubulointerstitial changes on the long-term clinical outcome and therapeutic response in patients with ANCA-associated vasculitis
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 94
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- Authors Med Uni Graz:
- Advisor:
- Eller Kathrin
- Odler Balazs
- Altmetrics:
- Abstract:
- Background: Several approaches using different serological and clinical markers have shown inconsistencies and varying reliabilities in predicting treatment outcome in ANCA-associated vasculitis (AAV). This study tries to demonstrate the impact of tubulointerstitial alterations and the role of CD3+-, CD20+- and CD138+-cells in AAV-patients on the clinical course and their potential in predicting disease outcome. Methods: Forty AAV-patients, treated between 1.1.2014 and 1.11.2018 at the Division of Nephrology of the Medical University of Graz were included and followed for 36 months. Kidney biopsies using the Banff classification were analyzed to describe the tubulointerstitial changes and divide the patients into groups with no/low or medium/severe tubulointerstitial immune cell (i0/i1 and i2/i3). Moreover, immunohistochemistry analysis was performed to subclassify the patients, based on their CD3-, CD20- and CD138 positive cell expression. Outcome between patients older and younger than 60 years old was compared. Primary endpoint was relapse rate (RR), while secondary endpoints were initiation of renal replacement therapy (RRT), such as dialysis or kidney transplantation. Additionally, the course of kidney function using albumin/creatinine ration (ACR) and estimated glomerular filtration rate (eGFR) during the follow-up time were compared between the different groups. Results: For the primary endpoint there was no significant difference observable between the mentioned groups. The course of mean ACR and mean eGFR between the i0/i1 and i2/i3 group showed descriptively worse outcome in the i2/i3 group and there was a significant difference in mean ACR levels between groups i0/i1 and i2/i3 observable during month 36 of follow up (p=0.016), favouring group i0/i1. No correlation between CD3+-, CD20+- and CD138+-cells and renal outcome, measured by endpoints and course of eGFR and ACR, ACR was observed, but N=21 (72.4%) patients had a high renal infiltration of interstitial CD138+ plasma cells. Patients younger than 60 years had a significantly higher rate of kidney transplantations (p=0.024) and significantly worse mean ACR rates during month 24 until month 36 in comparison to over 60 year olds (p=0.025, p=0.042, p=0.035, respectively). Conclusions: Our findings go along with already existing data on the correlation between tubulointerstitial alterations and worse kidney outcome. Patients with extended tubulointerstitial changes might be at higher risk for worse renal outcome. Our data show a significant proportion of CD138+-plasma cells in human kidney specimens of patients with AAV, providing additional insights on the renal B-cell clusters in patients with AAV.