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Glomerulonephritis: vitamin B2 derivatives alleviate disease course
Most of these kidney inflammations show a chronic progressive course and can result in terminal renal insufficiency. But scientists improved renal chronic inflammatory processes.
Glomerulonephritis: a rare disease with many facets
The term glomerulonephritis covers various forms of chronic kidney inflammation that can result in a loss of kidney function. They are characterised by immune-mediated damage to the capillary endothelium, the mesangium or the basement membrane. In most cases, autoimmune inflammatory processes are the underlying cause. In some cases, treatment with immunosuppressants cannot stop the loss of kidney function. The progressive reduction in the glomerular filtration rate leads to the retention of uraemic toxins. Patients affected by this are left with only dialysis or a kidney transplant to detoxify their bodies.1-5
Figure 1: Immunofluorescence staining of MAIT cells (green; cell nuclei blue) next to mononuclear CD11b+ phagocytes (red; cell nuclei blue) in murine kidney tissue (B6-MAITCAST) with experimental glomerulonephritis.1
Primary and secondary forms of glomerulonephritis
The primary forms of glomerulonephritis include post-infectious glomerulonephritis (PIGN), mesangioproliferative glomerulonephritis (MesPGN), minimal change glomerulonephritis (MCGN), membranous glomerulonephritis (MGN), rapidly progressive glomerulonephritis (RPGN) and focal segmental glomerulosclerosis (FSGS). Secondary glomerulonephritis can occur in amyloidosis, lupus erythematosus or diabetes mellitus. Goodpasture's syndrome, microscopic polyangitis, granulomatosis with polyangitis and Schönlein-Henoch purpura can also lead to secondary glomerulonephritis.1-5
A major burden for affected patients and the healthcare system
Pathogenic immune reactions of the kidney often begin in the glomerulus and lead to glomerulonephritis. This can then spread to the tubulointerstitium and result in progressive impairment of kidney function. If the various forms of glomerulonephritis are taken together, they are not so rare: They cause up to 20% of chronic kidney diseases in industrialised nations and therefore represent a considerable financial burden for healthcare systems.1-5
Rapidly progressive glomerulonephritis in the mouse model
The most aggressive form of glomerulonephritis is rapidly progressive glomerulonephritis. Despite intensive immunosuppression, the progression of this rare disease cannot be halted. In addition, the often non-specific therapeutic regimens are frequently associated with severe systemic side effects. This makes it all the more important to develop specific therapeutic agents and to support the correct function of the immune system, e.g. by administering vitamin B2 derivatives. In the mentioned study, the effect of vitamin B2 derivatives on mucosa-associated invariant T cells (MAIT cells) was investigated in a mouse model of rapidly progressive glomerulonephritis. MAIT cell-deficient MR1 mice showed severe forms of rapidly progressive glomerulonephritis. In contrast, a higher number of MAIT cells, as found in B6-MAITCAST mice, offers a certain degree of protection against rapidly progressive glomerulonephritis. The research results suggest that MAIT cells play a protective role in the kidney. Treatment of experimental animals suffering from glomerulonephritis with artificial vitamin B2 metabolites alleviated the course of the disease.1
Vitamin B2 metabolites in glomerulonephritis: what now?
The protective effect of the administration of artificial vitamin B2 metabolites and the associated increase in MAIT cells was not strong enough to completely prevent experimental glomerulonephritis in animal models. However, vitamin B2 metabolites may have future therapeutic potential as an adjunct to immunosuppressive therapeutics. However, further research and clinical trials are required before the administration of artificial vitamin B2 metabolites is a viable therapeutic option.1