AA-amyloidosis in captive northern tree shrews (Tupaia belangeri)

A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews ( Tupaia belangeri) in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis. The kidneys were predominantly affected (80%), where amyloid deposits ranged from mild to severe and was predominantly located in the renal medulla. In addition, many kidneys contained numerous cysts with atrophy of the renal parenchyma. There was no significant association between concurrent neoplastic or inflammatory processes and amyloidosis. The lack of distinctive predisposing factors suggests a general susceptibility of captive T. belangeri to develop amyloidosis. Clinical and laboratory findings of a female individual with pronounced kidney alterations were indicative of renal failure. The observed tissue tropism with pronounced kidney alterations, corresponding renal dysfunction, and an overall high prevalence suggests amyloidosis as an important disease in captive tree shrews.

Dismal Prognosis of Acute Allergic Tubulointerstitial Nephritis in Patients with AA Amyloidosis

<b><i>Introduction:</i></b> Patients with AA amyloidosis may present with acute kidney injury that progresses to end-stage kidney disease in a short period of time. Acute allergic tubulointerstitial nephritis (aTIN) is a frequent cause of acute kidney injury in patients with AA amyloidosis. Although aTIN has a favorable prognosis in the general population, the course of aTIN in patients with AA amyloidosis was not previously reported. In this retrospective study, we determined the prognosis of aTIN superimposed on AA amyloidosis. <b><i>Methods:</i></b> Thirty-two patients with combined pathological diagnosis of AA amyloidosis + aTIN and 32 patients with isolated aTIN were compared in terms of 1-year renal functions after the biopsies were performed with an indication of acute kidney injury. Baseline renal functions and number of patients requiring hemodialysis at the time of biopsy was similar in both groups. <b><i>Results:</i></b> At the end of the 12-month follow-up period, 29 of 32 patients in the amyloidosis + aTIN group and 1 of 32 patients in the isolated aTIN group required dialysis. Most of these patients with AA amyloidosis had completely normal renal function before the episode of acute kidney injury and had clear exposures to drugs associated with aTIN. <b><i>Conclusion:</i></b> In contrary to the patients without AA amyloidosis, patients with AA amyloidosis have extremely high risk of permanent renal failure in case of development of aTIN. Great caution should be exercised in prescribing drugs that are associated with aTIN, in patients with AA amyloidosis.

Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis

Background and purpose We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). Methods We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990–1999 (n = 48); period 2, 2000–2009(n = 57); period 3, 2010–2019 (n = 51). Results Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010–2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1–3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time. Conclusion Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.

AA-amyloidosis in autoinflammatory diseases

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.

Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

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.

Diagnosis of Cardiac Involvement in Amyloid A Amyloidosis by Cardiovascular Magnetic Resonance Imaging

Background: Diagnosis of cardiac involvement in amyloid A (AA) amyloidosis is challenging since AA amyloidosis is a rare disease and cardiac involvement even less frequent. The diagnostic yield of currently available non-invasive imaging methods is not well-studied and rather limited, and invasive endomyocardial biopsy (EMB) is rarely performed due to the potential risk of this procedure. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization by late-gadolinium-enhancement (LGE) imaging and novel-mapping approaches may increase the diagnostic yield in AA amyloidosis.Methods: Two patients with AA amyloidosis in whom cardiac involvement was suspected based on CMR findings and subsequently proven by biopsy work-up are presented. CMR studies were performed on a 1.5-T system and comprised a cine steady-state free precession pulse sequence for ventricular function and a late-gadolinium-enhancement (LGE) sequence for detection of myocardial pathology. Moreover, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was applied in basal, mid and apical short-axes prior to contrast agent administration and ~20 min thereafter to determine native T1 and ECV values.Results: Both patients showed slightly dilated left ventricles (LV) with mild to moderate LV hypertrophy and preserved systolic function. Only a very subtle pattern of LGE was observed in both patients with AA amyloidosis. However, markedly elevated native T1 (max. 1,108 and 1,112 ms, respectively) and extracellular volume fraction (ECV) values (max. 39 and 48%, respectively) were measured in the myocardium suggesting the presence of cardiac involvement - with subsequent EMB-based proof of AA amyloidosis.Conclusion: We recommend a multi-parametric CMR approach in patients with AA amyloidosis comprising both LGE-based contrast-imaging and T1-mapping-based ECV measurement of the myocardium for non-invasive work-up of suspected cardiac involvement. The respective CMR findings may be used as gatekeeper for additional invasive procedures (such as EMB) and as a non-invasive monitoring tool regarding assessment and modification of ongoing treatments.