Current Understanding of Complement Proteins as Therapeutic Targets for the Treatment of Immunoglobulin A Nephropathy.
Drugs
; 83(16): 1475-1499, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37747686
ABSTRACT
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a frequent cause of kidney failure. Currently, the diagnosis necessitates a kidney biopsy, with routine immunofluorescence microscopy revealing IgA as the dominant or co-dominant immunoglobulin in the glomerular immuno-deposits, often with IgG and sometimes IgM or both. Complement protein C3 is observed in most cases. IgAN leads to kidney failure in 20-40% of patients within 20 years of diagnosis and reduces average life expectancy by about 10 years. There is increasing clinical, biochemical, and genetic evidence that the complement system plays a paramount role in the pathogenesis of IgAN. The presence of C3 in the kidney immuno-deposits differentiates the diagnosis of IgAN from subclinical glomerular mesangial IgA deposition. Markers of complement activation via the lectin and alternative pathways in kidney-biopsy specimens are associated with disease activity and are predictive of poor outcome. Levels of select complement proteins in the circulation have also been assessed in patients with IgAN and found to be of prognostic value. Ongoing genetic studies have identified at least 30 loci associated with IgAN. Genes within some of these loci encode complement-system regulating proteins that can interact with immune complexes. The growing appreciation for the central role of complement components in IgAN pathogenesis highlighted these pathways as potential treatment targets and sparked great interest in pharmacological agents targeting the complement cascade for the treatment of IgAN, as evidenced by the plethora of ongoing clinical trials.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Renal
/
Glomerulonefrite por IGA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Drugs
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos