Novel aspects in the pathophysiology and diagnosis of glomerular diseases

Abstract

Immune deposits/complexes are detected in a multitude of tissues in autoimmune disorders, but no organ has attracted as much attention as the kidney. Several kidney diseases are characterised by the presence of specific configurations of such deposits, and many of them are under a ‘shared care’ between rheumatologists and nephrologists. This review focuses on five different diseases commonly encountered in rheumatological and nephrological practice, namely IgA vasculitis, lupus nephritis, cryoglobulinaemia, anti-glomerular basement membrane disease and anti-neutrophil cytoplasm-antibody glomerulonephritis. They differ in disease aetiopathogenesis, but also the potential speed of kidney function decline, the responsiveness to immunosuppression/immunomodulation and the deposition of immune deposits/complexes. To date, it remains unclear if deposits are causing a specific disease or aim to abrogate inflammatory cascades responsible for tissue damage, such as neutrophil extracellular traps or the complement system. In principle, immunosuppressive therapies have not been developed to tackle immune deposits/complexes, and repeated kidney biopsy studies found persistence of deposits despite reduction of active inflammation, again highlighting the uncertainty about their involvement in tissue damage. In these studies, a progression of active lesions to chronic changes such as glomerulosclerosis was frequently reported. Novel therapeutic approaches aim to mitigate these changes more efficiently and rapidly. Several new agents, such as avacopan, an oral C5aR1 inhibitor, or imlifidase, that dissolves IgG within minutes, are more specifically reducing inflammatory cascades in the kidney and repeat tissue sampling might help to understand their impact on immune cell deposition and finally kidney function recovery and potential impact of immune complexes/deposits.

Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study

“…The clinical hallmarks of kidney involvement used to diagnose GN are proteinuria, hematuria, and reduced GFR. The presence and/or severity of each of these signs depends on the underlying disease or risk factors [34].…”

Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis

“…The hyperproliferation of mesangial cells (MCs) and stromal dilation result in a decrease in the filtration rate [ 14 ]. In addition, disturbance of the vascular endothelium promotes fibrosis of the arterial lining and monocyte and lymphocyte infiltration in tubular areas, contributing to interstitial tubulointerstitial pathologies [ 15 , 16 ].…”

C/EBPβ isoform‐specific regulation of podocyte pyroptosis in lupus nephritis‐induced renal injury

“…Interferon-α and other inflammatory mediators are released as a result of abnormal adaptive and innate immune responses, amplifying glomerular lesions. These glomerular mechanisms may be responsible for the diverse clinical, biochemical, and histological manifestations of renal disease [3]. Podocytes, which are differentiated cells with a high degree of specialization, make up the glomerular filtration barrier's top layer [4].…”