Cytoplasmic WT1 in IgA nephropathy, an indicator of poor prognosis associated with mesangial/peri-mesangial C4d


TAŞAR KAPAKLI G. E., ÜZERK KİBAR M., Dag O., Erdem Y., BAYDAR D., Saglam A.

INTERNATIONAL UROLOGY AND NEPHROLOGY, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1007/s11255-022-03357-4
  • Journal Name: INTERNATIONAL UROLOGY AND NEPHROLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Gender Studies Database, MEDLINE
  • Keywords: ADAM10, C4d, IgA nephropathy, WT1, DEPOSITION, GLOMERULOSCLEROSIS, ALBUMINURIA, ACTIVATION, EXPRESSION, PODOCYTES, PATHWAY
  • Hacettepe University Affiliated: Yes

Abstract

Background We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis. Materials and methods Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up. Results We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters. Conclusion This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.