Solitary Renal Impairment in a 68-Year-Old Patient Caused by an α- Fibrinogen Amyloidosis

Monika Beliančinová; Patrícia Kleinová; Matej Vnučák; Karol Graňák; Jana Kršiaková; Patrik Flódr; Marián Mokáň; Ivana Dedinská

Solitary Renal Impairment in a 68-Year-Old Patient Caused by an α- Fibrinogen Amyloidosis

Monika Beliančinová^1,2, Patrícia Kleinová^1,2*, Matej Vnučák^1,2, Karol Graňák^1,2, Jana Kršiaková³, Patrik Flódr⁴, Marián Mokáň², Ivana Dedinská^1,2

¹Transplant Centre, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia

²Department of Internal Medicine, University Hospital Martin, Jessenius Medical Faculty, Comenius University, 036 01 Martin, Slovakia

³Department of Genetics, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia

⁴Department of Clinical and Molecular Pathology, Faculty of Medicine, Palacký University Olomouc, 779 00 Olomouc, Czech Republic

^*Corresponding Author: Patrícia Kleinová, Transplant Centre, University Hospital Martin, Department of Internal Medicine, Jessenius Medical Faculty, Comenius University, Kollárova 2, 036 01 Martin, Slovakia.

Received Date: 20 April 2023

Accepted Date: 24 April 2023

Published Date: 26 April 2023

Citation: Beliančinová M, Kleinová P, Vnučák M, Graňák K, Kršiaková J, et al. (2023) Solitary Renal Impairment in a 68-YearOld Patient Caused by an α- Fibrinogen Amyloidosis. Ann Case Report 8: 1279. https://doi.org/10.29011/2574-7754.101279

Abstract

Amyloidosis represents a spectrum of serious diseases characterized by the deposition of excessive deposits of incorrectly confirmed proteins (amyloid structures) in extracellular spaces. Deposits tend to be only in one organ or the entire organ system. This disease can lead from minor organ damage to life-threatening conditions and death within a relatively short period. Currently, the most widely used diagnostic method for the diagnosis of amyloidosis is mass spectrophotometry and proteomic analysis, with the help of which it is possible to identify the type of amyloid and determine an adequate therapeutic procedure. We present a patient with fully developed nephrotic syndrome and a decline in kidney function. In addition, α-fibrinogen amyloidosis was confirmed based on proteomic analysis of a kidney biopsy sample.

Keywords: Amyloidosis; Alpha Fibrinogen; Kidneys

Abbreviations: AA Amyloidosis: A Amyloidosis; AANF:

Atrial Natriuretic Factor Amyloidosis; Aapoi: Apolipoprotein AI Amyloidóza; Aapoii: Apolipoprotein AII Amyloidosis; Aapoiv: Apolipoprotein AIV Amyloidosis; Acys: Amyloid Angiopathy; Icelandic Type; Afib: Alpha Fibrinogen Amyloidosis; Agel: Gelsolin Amyloidosis; AH Amyloidosisi: Mmunoglobulin Heavy Chain; Alac: Lactoferrin Amyloidosis; AL Amyloidosis: Light Chain Amyloidosis; ALECT2: Acquired Renal Amyloidosis Caused By Leucocytes Chemotactic Factor 2; Alyz: Lyzosyme Amyloidosis; Amed: Aortic Median Amyloidosis; APOA4: Apolipoprotein A4; APCS: Serum Amyloid P Component; APOE: Apolipoprotein E; Ascr: Spongiform Encephalopathy Amyloidosis Caused By A Prion; Aβ: Amyloid Β Precursor Protein Amyloidosis; Bripp: Familiar British Dementia; DNA: Deoxyribonucleic Acid; D-Score: Evaluate The Abundance Difference Between The First- And Second-Most Abundant Proteins; FGA: A Gene Of Fibrinogen Amyloidosis; FGB: B Gene Of Fibrinogen Amyloidosis; FBG: G Gene Of Fibrinogen Amyloidosis; HRCT: High-Resolution Computed Tomography; Iga: Immunoglobulin A; Igd:Immunoglobulin D; Ige: Immunoglobulin E; Igg: Immunoglobulin G; Kda: Kilodalton; Ktx: Kidney Transplantation; LMD-LC/ MS: Liquid Chromatography-Tandem Mass Spectrometry; MRI: Magnetic Resonance Imaging; P-Score: Refers To The Relative Protein Abundance Of Amyloid-Associated Components In Each Sample; RRT: Renal Replacement Therapy; SAA: Serum Amyloid A; TTR: Transthyretin

Introduction

Amyloidosis is a common name for several serious diseases, the common characteristic of which is the deposition of incorrectly confirmed otherwise soluble proteins (amyloid) in extracellular spaces. The type of amyloidosis varies according to the type of amyloid and where it is deposited. When the diagnosis is clarified, the affected organ is usually severely damaged. In the case of affecting several organs, the damage can be so severe that it leads to life-threatening conditions and death within a short period. Unfortunately, this disease has a low incidence. Therefore, it is often overlooked because of incorrectly chosen diagnostic procedures, leading to false negative results and delays in adequate treatment.

The character and progression of the disease depend on the kinetics of amyloid formation and the method of its degradation.

The diagnosis is based on unequivocal evidence in the form of tissue histology of the affected organ. However, evidence of the presence of amyloid by staining with Congo red is limited, which leads to an apple-green dichroic effect in polarized light microscopy. Other diagnostic methods, such as mass spectrophotometry and proteomic analysis, help identify a specific type of amyloid. We can identify several types of hereditary and acquired amyloidosis using proteomic analysis. The most common hereditary amyloidosis include, for example, AL amyloidosis (light chain amyloidosis), AA amyloidosis (A amyloidosis), TTR (transthyretin) amyloidosis or β2-microglobulin amyloidosis, which it can also be classified as acquired amyloidosis, but a hereditary form has also been proven. An α-fibrinogen amyloidosis is a rare type with approximately 30 other subtypes. Individual subtypes of amyloidosis and specific mutations can only be identified by genetic analysis (Table 1).

AL amyloidosis	Immunoglobulin light chain	Acquired	Kidney, heart, liver, gastrointestinal tract, spleen, nervous system, soft tissue, thyroid, adrenal gland
AH amyloidosis	Immunoglobulin heavy chain	Acquired, myeloma	Rare; kidney involvement, a small number of reported cases
Senile systemic amyloidosis	Transthyretin (wild type)	Accumulation of TTR	Heart, soft tissue
Familiar amyloid polyneuropathy	Transthyretin, gelsolin, Apo AI	Inherited	Neuropathy, heart, eye, soft tissue
AA amyloidosis (secondary)	SAA protein	Acquired, chronic disease	Kidney, liver, gastrointestinal tract, spleen, autonomic nervous system, thyroid
Aβ₂M amyloidosis	β₂-microglobulin	Chronic dialysis	Osteoarticular tissue; less common sites are the gastrointestinal tract, blood vessels, heart
Lyzosyme amyloidosis (ALyz)	lysozyme	Inherited	Kidney, liver, gastrointestinal tract, spleen, lymph nodes, lungs, thyroid, salivary glands
Apo AI amyloidóza (AApoI)	apolipoprotein AI	Inherited	Kidney (with predominant medullary deposition), liver, heart, skin, larynx
Apo AII amyloidosis (AApoII)	apolipoprotein AII	Inherited	Kidney
Apo AIV amyloidosis (AApoIV)	apolipoprotein AIV	Inherited	Kidney
Fibrinogen amyloidosis (AFib)	Aα chain fibrinogen	Inherited	Kidney, liver, and spleen; hypertension is familiar; kidney involvement is predominantly glomerular
Gelsolin amyloidosis (AGel)	gelsolin	Inherited	Cranial nerves, lattice corneal dystrophy
Amyloid angiopathy, Icelandic type (ACys)	Cystatin C	Inherited	Cerebral vessels
Familiar British dementia (BriPP a.)	Product of BRI2 gene	Inherited, stop codon	Vessels, brain parenchyma
Acquired renal amyloidosis (ALECT2)	Leucocytes chemotactic factor 2	acquired	Kidney
Aortic median amyloidosis (AMed)	cadherin	Form of AA amyloidosis	Arteries
Atrial amyloidosis (AANF)	Atrial natriuretic factor	Patients with atrial fibrillation	Heart
Amyloidosis associated with medullary carcinoma	calcitonin	Malignant disorders	Thyroid gland
Spongiform encefalopathy (AScr)	prion	Acquired	Brain
Islet polypeptide amyloidosis	Islet amyloid polypeptide	Langerhans isles, DM 2, insulinoma	Pancreatic tissue
Lactoferrin amyloidosis (ALac)	lactoferrin	Familiarity corneal amyloidosis	Corneal deposits, pancreas
Alzheimer´s disease	amyloid β precursor protein	Acquired	Brain tissue
Hereditary cerebral amyloidosis (Aβ)	amyloid β precursor protein	Inherited	Small vessels of the brain

Table 1: Types of some of the hereditary and acquired amyloidoses (21- 28)

The first sign of amyloidosis is often kidney function impairment due to amyloid deposition in glomerules, but some signs and symptoms occur before organ damage. These symptoms are often non-specific, like problems with breathing, malaise, fatigue, nausea, poor appetite, weight loss, headache, vertigo, diarrhea, acral dysesthesia, problems with speaking, enlarged tongue with rippled edges, swelling of lower limbs, palpitations, syncope, etc. [1].

In Slovakia, there hasn´t been documented case of alpha fibrinogen amyloidosis yet, possibly according to a small number of inhabitants (approximately 5,447 million). Still, there are several reported cases of AA amyloidosis or AL amyloidosis. In the United Kingdom, data suggest the incidence of systemic amyloidosis to 0,8/ 100 000 of the inhabitants [2]. Alpha Fibrinogen Amyloidosis (Afib) is a sporadic condition in general but the most prevalent type of hereditary amyloidosis in the United Kingdom (approximately 71 cases) [3]. In Asia, there are only five documented cases (Korea, China, Japan) [4].

Case Report

A 68-year-old man without a severe illness was hospitalized at the Department of Internal Medicine of Martin University Hospital for a fully developed nephrotic syndrome with retention of nitrogenous substances in 2019. After a complex diagnostic process, he was diagnosed with chronic kidney disease based on hypertensive nephropathy and possibly uric acid nephropathy. However, because of the progression of proteinuria and retention of the nitrogenous substances, the patient was referred to the Transplantation Centre of Martin University Hospital. Medical history includes arterial hypertension and the presence of methyltetrahydrofolate reductase polymorphism with fibrinogen gene mutation.

The patient complained about lower limb swelling and weight gain progression when admitted to our center. He also noticed increased tiredness, and the urine was often foamy. Although the patient also complained of arterial hypertension in the 150-160/85-90 mmHg range, he denied any other problems. At the time of admission to our center, we performed routine laboratory examinations, with the finding of retention of nitrogenous substances and proteinuria of 3.8 grams/24 hours. The objective result was only the swelling of the lower limbs up to the knees. During the hospitalization in the center, we started complex therapy for the nephrotic syndrome using loop diuretics and intravenous infusions of human albumin. After regressing the swelling and restoring the values of serum albuminemia, we performed a kidney biopsy. We did not detect any circulating autoantibodies.

After staining the histological sample of the kidney with Congo red, we proved the presence of amyloid in the form of massive glomerular deposits. (Figures 1-3)

Figure 1: Glomerules completely destructed by deposits of amyloid structures. (Hematoxylin-eosin, original magnification: 40x).

Figure 2: Detail of the completely destructed glomerule with the amyloid deposition (Hematoxylin-eosin, original magnification: 125x).