Overview of pathophysiology and treatment of human lupus nephritis

Curr Opin Rheumatol. 2016 Sep;28(5):460-7. doi: 10.1097/BOR.0000000000000319.

Abstract

Purpose of review: Despite recent developments and treatment successes, the outcome, and prognosis of patients with lupus nephritis (LuN) have not greatly changed since the 1980s. This review covers the application of new concepts to the understanding of renal inflammation and the study of new pharmacologic agents to improve patient outcomes.

Recent findings: Studies have shown that the presence of anti-vimentin antibodies and T follicular helper cells in patient biopsies is associated with more severe interstitial inflammation, which has been tied to faster disease progression and onset of end-stage renal disease. Additionally, data regarding the role of serum IgE antidouble-stranded DNA antibodies in LuN by means of mediating IFN1 production by plasmacytoid dendritic cells are highlighted. Finally, a thorough review of completed and currently open clinical trials of therapeutic agents is provided.

Summary: Current management of LuN is guided almost exclusively by glomerular involvement. Based on the data provided in this review, we argue that renal tubulointerstitial inflammation is no less important and represents an overlooked feature in the current clinical approach to patients. Tubulointerstitial inflammation is driven by both adaptive and innate immune mechanisms that are still poorly understood. Studying these pathogenic processes promises to reveal new therapeutic opportunities for those LuN patients with the worst prognosis.

Video abstract: Alternate video abstract introduction (see Video, Supplemental Digital Content 1, with introduction by two of the authors - VL and KT). Abstract Video: http://links.lww.com/COR/A35.

Publication types

  • Review

MeSH terms

  • Abatacept / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Autoantibodies / immunology*
  • Biopsy
  • Cyclophosphamide / therapeutic use
  • Dendritic Cells / immunology*
  • Disease Progression
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Inflammation
  • Interferon Type I / immunology*
  • Kidney Failure, Chronic / etiology
  • Lupus Nephritis / complications
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Maintenance Chemotherapy
  • Mycophenolic Acid / therapeutic use
  • Prognosis
  • Quinolones / therapeutic use
  • Recombinant Fusion Proteins / therapeutic use
  • Remission Induction
  • Ribonucleosides / therapeutic use
  • Severity of Illness Index
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Treatment Outcome
  • Vimentin / immunology

Substances

  • AMG623 peptibody
  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • Glucocorticoids
  • Immunosuppressive Agents
  • Interferon Type I
  • Quinolones
  • Recombinant Fusion Proteins
  • Ribonucleosides
  • Vimentin
  • mizoribine
  • belimumab
  • Abatacept
  • Cyclophosphamide
  • laquinimod
  • Mycophenolic Acid