A Richard Kitching

A Richard Kitching
Monash University (Australia) · Monash Centre for Inflammatory Diseases

MB ChB (with distinction) PhD, FRACP, FASN, FAMHS

About

282
Publications
22,876
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8,071
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Introduction
Richard Kitching is an academic nephrologist-scientist whose research is focussed on autoimmune kidney disease, aiming towards using more targeted therapies for these diseases. In 2018 he and colleagues founded ANZVASC, a patient facing multidisciplinary society to improve vasculitis education, research and care in ANZ. His publications include papers in Nature, Nature Medicine, Nature Rev Dis Primers, PNAS, JCI, Nature Comms, Blood, J Am Soc Nephrol, Kidney Int and Nature Rev Nephrol.
Additional affiliations
December 2018 - present
Australia and New Zealand Vasculitis Society (ANZVASC)
Position
  • Chair
Description
  • In late 2018 he and colleagues in Australia and New Zealand from the disciplines of Clinical Immunology, Nephrology and Rheumatology founded the ANZ Vasculitis Society (ANZVASC), a patient facing multidisciplinary professional society to improve vasculitis education, research and care in Australia and New Zealand. He is Chair of the Board and Chairs the ANZVASC Registry Establishment Committee
January 2010 - present
Monash University (Australia)
Position
  • Professor (Full)
January 2005 - December 2009
Monash University (Australia)
Position
  • Professor (Associate)
Education
July 1995 - March 1999
Monash University (Australia)
Field of study
  • Immunology, Renal Disease
March 1992 - July 1995
The Royal Australasian College of Physicians
Field of study
  • Nephrology, Fellow of the RACP (FRACP)
February 1983 - December 1987
University of Otago
Field of study
  • Medicine

Publications

Publications (282)
Article
Full-text available
In contrast with many capillary beds, the glomerulus readily supports leukocyte recruitment. However, little is known regarding the actions of leukocytes following their recruitment to glomeruli. We used multiphoton confocal microscopy to examine leukocyte behavior in the glomerular microvasculature. In normal glomeruli, neutrophils and monocytes w...
Article
Susceptibility and protection against human autoimmune diseases, including type I diabetes, multiple sclerosis, and Goodpasture disease, is associated with particular human leukocyte antigen (HLA) alleles. However, the mechanisms underpinning such HLA-mediated effects on self-tolerance remain unclear. Here we investigate the molecular mechanism of...
Article
Since the first association between HLA and diseases of native kidneys was described almost 50 years ago, technological and conceptual advances in HLA biology and typing, together with better case ascertainment, have led to an improved understanding of HLA associations with a variety of renal diseases. A substantial body of evidence now supports th...
Article
Full-text available
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomato...
Preprint
In recent trials for the treatment of systemic lupus erythematosus (SLE), belimumab (a recombinant human IgG1-monoclonal antibody that inhibits B lymphocyte stimulator), in addition to standard immunosuppression, has been shown to improve renal and non‐renal outcomes. We report our experience using belimumab in two cases of refractory lupus nephrit...
Article
Background and objectives Outcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology–Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outc...
Article
Full-text available
B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline nov...
Article
Full-text available
We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.¹ • Ch...
Article
Purpose of review: Vasculitis describes a wide spectrum of rare, inflammatory, multisystem disorders. These heterogenous diseases all have inflammation of blood vessels as a central feature. However, they differ in terms of their genetic and environmental risk factors, disease pathogenesis, clinical presentations and treatment strategies. Many ani...
Article
Full-text available
Introduction Patients with glomerular disease experience symptoms that impair their physical and mental health while managing their treatments, diet, appointments and monitoring general and specific indicators of health and their illness. We sought to describe the perspectives of patients and their care partners on self-management in glomerular dis...
Article
The leukocyte-restricted tetraspanin CD53 has been shown to promote lymphocyte homing to lymph nodes and myeloid cell recruitment to acutely inflamed peripheral organs, and accelerate the onset of immune-mediated disease. However, its contribution in the setting of chronic systemic autoimmunity has not been investigated. We made use of the Lyn-/- a...
Article
Objectives Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease characterised by small blood vessel inflammation, commonly affecting the kidneys and respiratory tract. It is unclear why the incidence of this condition increases with age. Previous studies in a passive antibody transfer system in aged mice have i...
Article
The actions of immune cells within the kidney are of fundamental importance in kidney homeostasis and disease. In disease settings such as acute kidney injury, anti-neutrophil cytoplasmic antibody-associated vasculitis, lupus nephritis and renal transplant rejection, immune cells resident within the kidney and those recruited from the circulation p...
Article
Objective: To compare the frequency of rare variants in genes of the pathophysiologically relevant endosomal Toll-like receptor (eTLR) pathway and any quantifiable differences in variant rarity, predicted deleteriousness, or molecular proximity in patients with systemic lupus erythematosus (SLE) and healthy controls. Patients and methods: 65 gen...
Article
Aim: Although antineutrophil cytoplasmic antibody-associated vasculitis (AAV) most commonly affects older individuals, many patients develop the disease during their most productive working years. The aim of this study was to examine the effects of AAV on employment and work disability in a cohort of Australian patients of working age. Methods:...
Article
Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glo...
Article
Background Myeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease. Methods MPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN. Results Anti-CD20 mAb treatment increased the numbers and...
Article
Membranous nephropathy, like many forms of glomerulonephritis, is an HLA-associated autoimmune disease that can recur in the transplanted kidney. In this issue of Kidney International, Berchtold and colleagues publish an intriguing and important paper on risk factors for recurrent post-transplant membranous nephropathy due to autoimmunity to PLA2R1...
Article
Full-text available
Diseases of the glomerular basement membrane (GBM), such as Goodpasture’s disease (GP) and Alport syndrome (AS), are a major cause of chronic kidney failure and an unmet medical need. Collagen IVα345 is an important architectural element of the GBM that was discovered in previous research on GP and AS. How this collagen enables GBM to function as a...
Article
Tertiary lymphoid tissues are peripheral foci of immune activity that develop in kidneys and other peripheral organs in the context of chronic inflammation. In this issue of Kidney International, Sato and colleagues present a detailed characterization of tertiary lymphoid tissues in mouse and human kidneys in the context of acute kidney injury, chr...
Article
Background: Antiglomerular basement membrane (anti-GBM) disease is associated with HLA-DRB1*1501 (the major predisposing genetic factor in the disease), with α3127-148 as a nephritogenic T and B cell epitope. Although the cause of disease remains unclear, the association of infections with anti-GBM disease has been long suspected. Methods: To in...
Article
Full-text available
Background and objectives: Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements: We pur...
Article
Full-text available
Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare and severe autoimmune multisystemic disease. Its pathogenesis involves multiple arms of the immune system, as well as complex interactions between immune cells and target organs. Experimental animal models of disease can provide the crucial link from human disease to...
Article
Full-text available
Background: Goodpasture's disease (GP) is mediated by autoantibodies that bind the glomerular and alveolar basement membrane, causing rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. The autoantibodies bind neoepitopes formed upon disruption of the quaternary structure of α345NC1 hexamer, a critical structural domain of...
Article
Full-text available
Autoimmune diseases resulting from MHC class II-restricted autoantigen-specific T cell immunity include the systemic inflammatory autoimmune conditions, rheumatoid arthritis and vasculitis. While currently treated with broad-acting immunosuppressive drugs, a preferable strategy is to regulate antigen-specific effector T cells (Teff) to restore tole...
Article
Background Because of their capacity to induce antigen-specific immunosuppression, tolerogenic dendritic cells are a promising tool for treatment of autoimmune conditions, such as GN caused by autoimmunity against myeloperoxidase (MPO). Methods: We sought to generate tolerogenic dendritic cells to suppress anti-MPO GN by culturing bone marrow cel...
Article
Full-text available
Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD391-410) is part...
Article
Background: Myeloperoxidase (MPO)-ANCA-associated GN is a significant cause of renal failure. Manipulating autoimmunity by inducing regulatory T cells is potentially a more specific and safer therapeutic option than conventional immunosuppression. Methods: To generate MPO-specific regulatory T cells, we used a modified protein-conjugating compou...
Article
Full-text available
Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE...
Article
Goodpasture's disease manifests as rapidly progressive glomerulonephritis. Current immunosuppressive treatments do not specifically target the pathological immune response and have significant side effects. Like most autoimmune diseases, the strongest genetic association is with the HLA alleles. Inheritance of HLA-DR15 confers susceptibility, and s...
Article
Anti-myeloperoxidase nephritogenic autoimmunity induces severe glomerulonephritis. To assess the therapeutic potential of monoclonal antibodies targeting T helper (Th) subset differentiation determining cytokines, we studied a murine model of anti-myeloperoxidase glomerulonephritis. The temporal participation of T helper subsets was determined by q...
Article
Renal lymphatics are implicated in renal disease, but their function in inflammatory kidney diseases is relatively poorly defined. In the current issue, Kasinath et al. examine the role of the kidney draining lymph node in experimental glomerulonephritis, as well the role of fibroblastic reticular cells within lymph nodes. Removing the kidney-drain...
Article
Full-text available
The Kidney Disease: Improving Global Outcomes (KDIGO) initiative organized a Controversies Conference on glomerular diseases in November 2017. The conference focused on the 2012 KDIGO guideline with the aim of identifying new insights into nomenclature, pathogenesis, diagnostic work-up, and, in particular, therapy of glomerular diseases since the g...
Article
Platelet-leukocyte interactions promote acute glomerulonephritis. However, neither the nature of the interactions between platelets and immune cells nor the capacity of platelets to promote leukocyte activation has been characterized in this condition. We used confocal intravital microscopy to define the interactions of platelets with neutrophils,...
Article
Introduction: We examined the clinical relevance of urinary concentrations of B-cell-activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). Methods: We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndro...
Article
Full-text available
Objective To characterise the clinical relevance of urinary macrophage migration inhibitory factor (uMIF) concentrations in patients with systemic lupus erythematosus (SLE). Methods MIF, adjusted for urine creatinine, was quantified by ELISA in urine samples from 64 prospectively recruited patients with SLE. Serum MIF and urinary monocyte chemoatt...
Chapter
Inflammasomes influence a diverse range of kidney disease, including acute and chronic kidney diseases, and those mediated by innate and adaptive immunity. Both IL-18 and in particular IL-1β are validated therapeutic targets in several kidney diseases. In addition to leukocyte-derived inflammasomes, renal tissue cells express functional inflammasom...
Article
Crescentic glomerulonephritis, a complication of severe immune glomerular injury, is the pathological correlate of rapidly progressive glomerulonephritis, mediated by both humoral and cellular effectors. In the current issue of the JCI, Chen et al. have implicated Bowman's capsule in functionally isolating potentially immune effectors, specifically...
Article
Background: The functional relevance of OX40 ligand (OX40L) in the effector phase of crescentic glomerulonephritis (GN) is unknown. These studies defined the role of endogenous OX40L during the effector stage of murine crescentic GN. Methods: GN was induced by immunization with sheep globulin/adjuvant on Day 0 and injection of sheep anti-mouse g...
Article
In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4 and TLR9 expression and renal injury in AAV, testing the h...
Article
The effects of formyl peptide receptors (FPRs) on effector T cells and inflammation-causing tissue-resident cells are not well known. Here, we explored the effect of FPR activation on efferent T cell responses in models of rheumatoid arthritis (RA) and on the expansion of fibroblast-like synoviocytes (FLS). Compound 43 (Cpd43; FPR1/2 agonist) was a...
Article
Full-text available
Goodpasture's (GP) disease is an autoimmune disorder characterized by the deposition of pathogenic autoantibodies in basement membranes of kidney and lung eliciting rapidly progressive glomerulonephritis and pulmonary hemorrhage. The principal autoantigen is the α345 network of collagen IV, which expression is restricted to target tissues. Recent d...
Article
Full-text available
Although effector CD4+T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4+T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII i...
Article
Full-text available
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to t...
Article
Full-text available
The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are autoimmune diseases associated with significant morbidity and mortality. They often affect the kidney causing rapidly progressive glomerulonephritis. While signalling by complement anaphylatoxin C5a though the C5a receptor is important in this disease, the role of the anaph...
Data
Mouse genotyping. Primers C1 and A201+ yield a fragment of 726 bp, denoting WT allele. Primers C1 and NeoA yield a fragment of 537 bp denoting the C3ar-/- allele. (TIFF)
Data
Anti-MPO IgG titres. Anti-MPO IgG titres were measured by ELISA in WT and C3ar-/- mice (n = 5-7/group). Anti-MPO IgG titres were higher in C3ar-/- mice compared to WT. Data shown as mean ± SEM. (EPS)
Article
p>In 2017, progress was made in several aspects of immune-mediated kidney disease. Mechanistic studies provided new insights into the underlying signals that confer risk to, or protection from, immune pathways, whereas new approaches to the treatment of immunological kidney disease will hopefully translate into a move away from the use of toxic cor...
Article
The prospects for complement-targeted therapy in ANCA-associated vasculitis have been enhanced by a recent clinical trial in which C5a receptor 1 (C5aR1) inhibition safely replaced glucocorticoids in induction treatment. C5aR1 primes neutrophils for activation by anti-neutrophil cytoplasmic antibody (ANCA) and is therefore required in models of glo...
Article
Myeloperoxidase (MPO) anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis results from autoimmunity to MPO. IL-17A plays a critical role in generating this form of autoimmune injury but its cell of origin is uncertain. We addressed the hypothesis that IL-17A-producing γδ T cells are a nonredundant requisite in the development of MPO autoimm...
Article
Our understanding of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has developed greatly since the discovery of ANCA, directed against neutrophil components, in 1982. Observations in human disease, and increasingly sophisticated studies in vitro and in rodent models in vivo, have allowed a nuanced understanding of many aspects of...
Article
Full-text available
Epstein-Barr virus (EBV) is typically associated with post transplant lymphoproliferative disease (PTLD) after solid organ and stem cell transplantation. However, it is rarely associated with neurological complications. We report a case of severe encephalitis complicating primary EBV infection six months post renal transplantation, and review the l...
Conference Paper
The kidney, particularly the glomerulus, is vulnerable to immune and inflammatory injury via a variety of humoral and cellular mechanisms. In lupus nephritis, both arms of the adaptive effector response, together with innate effectors, can be prominent participants. Furthermore, in systemic lupus erythematosus (SLE) there is reactivity to multiple...
Article
Neutrophil extracellular traps (NETs) have been documented in glomeruli of patients with glomerulonephritis. However, the dynamics of NET formation in the glomerulus and their functional contribution to acute glomerular injury are poorly understood. Herein, we used in vivo multiphoton microscopy to investigate NET formation in the acutely inflamed...
Article
Background/aims: Interleukin (IL)-17A and IL-17F are proinflammatory cytokines, which signal through a receptor complex consisting of IL-17RA and IL-17RC subunits. We sought to define the role of IL-17RA expression by leukocytes and stromal cells in nephritogenic immunity and injury in experimental glomerulonephritis. Methods: Glomerulonephritis...
Article
The kidney can be negatively affected by a range of innate and adaptive immune responses, resulting in alterations in the functions of the kidney and, in some cases, progression to renal failure. In many of these responses, infiltration of blood-borne leukocytes into the kidney is central to the response. In addition, a large population of mononucl...