MO057REGIONAL IMPORTANCE OF FIBRINOGEN A Α-CHAIN MUTATION ON RENAL AMYLOIDOSIS
Authors: Homem Melo Marques Sofia , Lopes-de-Almeida Maria , Carvalho Renata , Ribeiro Bárbara , Vaz Raquel , Medeiros Joana , Costa Rui , Rmalheiro António 
Published: May 2021

Abstract

Background and Aims
Renal amyloidosis include amyloid A (AA) and light chain (AL) as well as amyloidogenic leukocyte chemotactic factor 2 (ALECT2) and numerous hereditary forms. After identifying amyloidosis by its suggestive pale pink amorphous appearance in optic microscopy (OM) and Congo red positivity, a correct diagnosis of the amyloidogenic precursor protein is determinant to establish prognosis and treatment. Immunohistochemistry (IHC) and immunofluorescence (IF) studies use a limited number of antibodies to detect specific epitopes and may be difficult to interpret. The gold standard has become proteomics but laser microdissection and mass spectroscopy are not routinely available. Other options include electron microscopy with immunogold staining and complementary exams such as scintigraphy with 99mTc-DPD to detect transthyretin-related amyloidosis. Since the cause of amyloidosis vary among regions, analyzing local patterns can help establish a diagnostic procedure. We aimed at describing cases of kidney amyloidosis identified by biopsy during a 4-year interval and discuss possible implication for future diagnosis.

Method
We analyzed our kidney biopsy database and selected all cases of renal amyloidosis collecting clinical, laboratory and imaging data.

Results
From January 2016 until December 2019, 194 kidney biopsies were performed at the Hospital of Braga in the Portuguese province of Minho. Among these, 8 (4.1%) revealed amyloidosis. Mean age was 63.8±9.2 years of age, 5 were female, 6 were referred for nephrotic syndrome and 2 for what seemed like acute kidney injury. Mean creatinine at presentation was 3.2±2.3mg/dL. Among them, 2 had AL amyloidosis with light chain restriction by IF, 1 had AA amyloidosis with intense IHC stain and 5 patients had non-AL and non-AA forms of amyloidosis. Of these, 3 had probable fibrinogen A alpha-chain (AFib) amyloidosis, after a heterozygous mutation FGA p.Glu545Val was detected, 1, who did not have IHC performed, was assumed as having AA amyloidosis due to a history of serious recurrent infections and 1 is still under study. Four performed scintigraphy with 99mTc-DPD which was negative. The 2 patients with AL amyloidosis had, by OM, in one case glomerular and tubulointerstitial and on the other, glomerular and vascular involvement and, by IF, both had k light chain restriction. Both had additional cardiac and neurovegetative involvement, were treated with cyclophosphamide-bortezomib-dexamethasone and oral doxycycline with complete hematologic response and stabilization of kidney function. In 1 case, proteinuria only showed a slow decline 2 years after treatment. The 2 patients with AA amyloidosis had glomerular, vascular and tubular deposits. One had bronchiectasis and allergic bronchopulmonary aspergillosis and the other had common variable immunodeficiency with recurrent gastrointestinal and urinary infections with frequent bacteremia. None of them had confirmed extra-renal involvement, although the latter had hepatic fibrosis awaiting biopsy. Both progressed to dialysis soon after diagnosis. The 3 patients with AFib amyloidosis all had glomerular amyloidosis with additional amyloid deposition at tubular, vascular and both respectively. Two had had an increased creatinine and subnephrotic proteinuria for some years whereas 1 had kidney function decline and nephrotic syndrome in the course of few months. All were hypertensive and none had evident extra-renal deposits.

Conclusion
Identifying the amyloidogenic precursor may be difficult. Algorithms for diagnosis may vary according to local prevalence of specific types and available resources. AFib amyloidosis was very significant in our series. It was also described in 4.5% of hemodialysis patients in the district of Braga making it one of the first causes of amyloidosis in our region. This high prevalence may justify early genetic testing for the specific mutation in non-AL and non-AA forms.