Renal involvement in monogenic autoinflammatory diseases: A narrative review

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)-alpha, and proteins belonging to type I-interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low-molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro-inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non-amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.

Automated summary

Autoinflammatory diseases (AIDs) are primarily caused by dysfunctions in single genes encoding for proteins involved in innate immunity regulation. Renal health is frequently affected by unprovoked inflammation due to the deposition of amyloid A (AA) fibrils in the glomeruli. AA amyloidosis, caused by elevated levels of serum amyloid A (SAA) and a genetic predisposition, is the most common form of amyloidosis in children. This review focuses on describing the renal implications in pediatric patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs, aiming to improve their clinical course and quality of life.