Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Abstract

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

The Clinical Chameleon of Autoinflammatory Diseases in Children

“…The most severe consequence of amyloidosis is nephrotic syndrome leading to end-stage kidney disease, though it may also involve the cardiovascular, gastrointestinal and central nervous systems. Microalbuminuria may be the first sign of early kidney impairment in FMF, and serum amyloid-A protein is a reliable indicator of overt or subclinical inflammation and indirectly of colchicine treatment compliance [ 18 ]. Many organs can be involved during FMF flares and a host of non-classical manifestations have been reported, such as different forms of vasculitis and neurological diseases [ 19 ].…”

The spectrum of urological disease in familial Mediterranean fever: amyloidosis and beyond

“…21 Long term urological complications: Secondary renal amyloidosis complicating FMF is the result of amyloid A renal deposition and is responsible for up to 8.6% of rapid progression to end-stage renal disease, ESRD. 22 Proteinuria and eventual uremia are the main presenting symptoms of secondary amyloidosis. 23 Patients may initially present with amyloidosis (2%) rather than typical febrile attacks of FMF.…”

“…43,44 It is considered a reliable indicator of subclinical inflammation and treatment adherence. 22 3) Mean platelet volume (MPV) is a potential predictor of FMF-related proteinuria and amyloidosis. MPV is higher in children with proteinuria compared to their FMF peers without proteinuria.…”

Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study

“…Elevated acute phase reactants are seen during the active episodes but return to reference values in attack-free periods. However, partial responders or non-responders may have ongoing sub-clinical inflammation during the asymptomatic period, and those patients may develop secondary amyloidosis due to increased serum amyloid A (SAA) protein [2]. AA amyloidosis causes chronic kidney disease, and it is the most serious morbidity in untreated or non-responder FMF patients.…”