Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Abstract

Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome.A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted.It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.

A case of cryopyrin-associated periodic syndrome with kidney transplant failure

“…Its efficacy in patients with CAPS is characterized by rapid resolution of disease symptoms [15]. To date, eight reports on the efficacy of anti-IL-1 agents for treatment of amyloidosis in patients with CAPS have been published [7][8][9][10][11][12][13][14]. In 17 patients reported in the eight references, a lack of efficacy was reported in two patients treated with anakinra [9,13].…”

“…As IL-1b plays a pivotal role in the pathogenesis of CAPS, anti-IL-1 treatment has been reported to be effective in patients with the syndrome. Thus, successful anti-IL-1 treatment of renal amyloidosis in patients with CAPS has been reported [7][8][9][10][11][12][13][14]. In this paper, we describe a patient with CAPS who received a renal transplant due to progressive renal insufficiency caused by amyloidosis.…”

How to Diagnose and Manage Systemic Autoinflammatory Diseases in Childhood

“…Placebocontrolled studies with anakinra, rilonacept and canakinumab in children and adults of all CAPS phenotypes demonstrated complete clinical and laboratory response in the majority of patients and led to EMA and FDA approval for this indication [44][45][46]. Anti-IL-1 blockade also showed to improve long-term complications such as progressive hearing loss and amyloidosis in MWS and NOMID patients [47][48][49].…”

The Clinical Spectrum of Amyloidosis

“…Renal involvement damages the glomerular membrane, resulting in nephrotic syndrome and proteinuria. Proteinuria is one of the earliest signs of AA amyloidosis, and seen in approximately 95% of patients with AA amyloidosis [2,11]. Persistent, untreated renal damage results in end stage renal disease (ESRD), requiring some form of renal substitute therapy-either dialysis or renal transplantation.…”