IgA nephropathy: the lectin pathway and implications for targeted therapy

Kidney International, vol. 104, pp. 254–264

Abstract

Many patients with immunoglobulin A nephropathy (IgAN) progress to kidney failure even with optimal supportive care. An improved understanding of the pathophysiology of IgAN in recent years has led to the investigation of targeted therapies with acceptable tolerability that may address the underlying causes of IgAN or the pathogenesis of kidney injury. The complement system-particularly the lectin and alternative pathways of complement-has emerged as a key mediator of kidney injury in IgAN and a possible target for investigational therapy. This review will focus on the lectin pathway. The examination of kidney biopsies has consistently shown glomerular deposition of mannan-binding lectin (1 of 6 pattern-recognition molecules that activate the lectin pathway) together with IgA1 in up to 50% of patients with IgAN. Glomerular deposition of pattern-recognition molecules for the lectin pathway is associated with more severe glomerular damage and more severe proteinuria and hematuria. Emerging research suggests that the lectin pathway may also contribute to tubulointerstitial fibrosis in IgAN and that collectin-11 is a key mediator of this association. This review summarizes the growing scientific and clinical evidence supporting the role of the lectin pathway in IgAN and examines the possible therapeutic role of lectin pathway inhibition for these patients.

Authors 8

1. Jonathan Barratt

   University of Leicester

   Affiliation as printed

   Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

2. Richard A. Lafayette

   Stanford Health Care · Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Medicine, Division of Nephrology, Stanford Health Care, Stanford, California, USA

3. Hong Zhang

   Peking University

   Affiliation as printed

   Renal Division, Department of Internal Medicine, Peking University Institute of Nephrology, Beijing, China

4. Vladimı́r Tesař

   Charles University · General University Hospital in Prague

   Affiliation as printed

   Department of Nephrology, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

5. Brad H. Rovin

   The Ohio State University Wexner Medical Center · The Ohio State University

   Affiliation as printed

   Department of Internal Medicine, Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA

6. James Alan Tumlin

   Emory University

   Affiliation as printed

   Department of Medicine, Division of Renal Medicine, Emory University, Atlanta, Georgia, USA

7. Heather N. Reich

   University Health Network · University of Toronto

   Affiliation as printed

   Department of Medicine, Division of Nephrology, University of Toronto and University Health Network, Toronto, Ontario, Canada

8. Jürgen Floege corresponding Aachen Department of Nephrology and Rheumatology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Nephrology and Rheumatology, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: jfloege@ukaachen.de

   Department of Nephrology and Rheumatology, RWTH Aachen University Hospital, Aachen, Germany