AA amyloidosis is an emerging cause of nephropathy in obese patients

Stojanovic, Katia Stankovic; Georgin‐Lavialle, Sophie; Poitou, Christine; Buob, David; Amselem, Serge; Grateau, Gilles; Salle, Valery; Mathian, Alexis; Khayat, Rateb; Duflot, L.; Urbanski, G.; Grosbois, B.; Easy, Firas; Klein, Alexandre; Christides, C.; Guichard, Jean-François; Abboud, Imad; Audard, Vincent

doi:10.1016/j.ejim.2017.02.004

Cited by 13 publications

(5 citation statements)

References 8 publications

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“…Conversely, increased plasma triglycerides are expected to augment AA amyloidosis. This idea is consistent with clinical studies reporting a direct correlation between idiopathic AA amyloidosis and obesity, a condition wherein plasma triglycerides are elevated [ 93 , 97 ].…”

Section: Therapeutic Targeting Of Aa Amyloidosissupporting

confidence: 89%

Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve

Gursky

2020

Curr Atheroscler Rep

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Purpose of Review This review addresses normal and pathologic functions of serum amyloid A (SAA), an enigmatic biomarker of inflammation and protein precursor of AA amyloidosis, a life-threatening complication of chronic inflammation. SAA is a small, highly evolutionarily conserved acute-phase protein whose plasma levels increase up to one thousand-fold in inflammation, infection, or after trauma. The advantage of this dramatic but transient increase is unclear, and the complex role of SAA in immune response is intensely investigated. This review summarizes recent advances in our understanding of the structure-function relationship of this intrinsically disordered protein, outlines its newly emerging beneficial roles in lipid transport and inflammation control, and discusses factors that critically influence its misfolding in AA amyloidosis. Recent Findings High-resolution structures of lipid-free SAA in crystals and fibrils have been determined by x-ray crystallography and electron cryo-microscopy. Low-resolution structural studies of SAA-lipid complexes, together with biochemical, cell-based, animal model, genetic, and clinical studies, have provided surprising new insights into a wide range of SAA functions. An emerging vital role of SAA is lipid encapsulation to remove cell membrane debris from sites of injury. The structural basis for this role has been proposed. The lysosomal origin of AA amyloidosis has solidified, and its molecular and cellular mechanisms have emerged. Summary Recent studies have revealed molecular underpinnings for understanding complex functions of this Cambrian protein in lipid transport, immune response, and amyloid formation. These findings help guide the search for much-needed targeted therapies to block the protein deposition in AA amyloidosis.

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Section: Therapeutic Targeting Of Aa Amyloidosissupporting

confidence: 89%

Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve

Gursky

2020

Curr Atheroscler Rep

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“…Patients with idiopathic AA amyloidosis have higher body mass index, are older and are more likely to be female compared to those with AA amyloidosis secondary to inflammatory conditions [91]. Obesity has been suggested as a possible cause for the increase in the incidence of AA amyloidosis of unknown aetiology [91,92].…”

Section: Attr Amyloidosismentioning

confidence: 99%

Systemic amyloidosis from A (AA) to T (ATTR): a review

et al. 2020

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Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry-based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.

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“…Obesity-induced chronic inflammation and its association with AA amyloidosis in humans was first described two decades ago in one of two sisters with extreme obesity due to a genetic leptin receptor deficiency [ 10 ]. In a retrospective analysis of the French national center for AA amyloidosis database, 13 patients, representing 12% of all AA amyloidosis cases, had obesity (including moderate, severe, and morbid obesity) as the cause of chronic inflammation [ 11 ]. Further, Blank et al [ 12 ] substantiated these observations by their finding on obesity as a susceptibility factor in patients with idiopathic AA amyloidosis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Kidney biopsy typically reveals a glomerular pattern in 90% and vascular pattern in 10% of patients [ 13 ]. However, the percentage of vascular AA amyloidosis might be higher if kidney biopsies were performed in cases of mild kidney dysfunction with low or no proteinuria [ 11 ]. Polymorphisms in SAA1 were shown to be associated with a higher risk of AA amyloidosis in obesity.…”

Section: Discussionmentioning

confidence: 99%

Kidney dysfunction due to AA amyloidosis in a morbidly obese female

Izzedine¹,

Nimkar²,

Bharati³

et al. 2023

CNCS

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Kidneys are commonly involved in systemic amyloidosis. Systemic AA amyloidosis is known to be associated with states of chronic inflammation such as autoimmune conditions, chronic infections, and malignancies. Obesity is increasingly recognized to be a risk factor for low-grade, chronic inflammation. We report a 48-year-old female with morbid obesity who presented with unexplained persistent mild kidney dysfunction and low-grade proteinuria. Attempt at evaluating the cause of kidney dysfunction included performing kidney biopsy despite technical challenges. Kidney biopsy showed AA amyloidosis with predominant vascular deposition, explaining the absence of nephrotic-range proteinuria. Evaluation for secondary causes of systemic AA amyloidosis was negative. While our patient was treated with sleeve gastrectomy for morbid obesity with reasonable response, it is likely that ongoing chronic inflammation, reflected by her laboratory markers, resulted in AA amyloidosis. Treatment with anakinra, an interleukin-1 antagonist, led to improvement in the laboratory markers in the next 6 months, and her kidney function remained stable. This report highlights an important cause of kidney dysfunction in morbid obesity, an atypical presentation of AA amyloidosis, and emphasizes the value of kidney biopsy in such patients.

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AA amyloidosis is an emerging cause of nephropathy in obese patients

Cited by 13 publications

References 8 publications

Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve

Structural Basis for Vital Function and Malfunction of Serum Amyloid A: an Acute-Phase Protein that Wears Hydrophobicity on Its Sleeve

Systemic amyloidosis from A (AA) to T (ATTR): a review

Kidney dysfunction due to AA amyloidosis in a morbidly obese female

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