Letter to the Editor
LECT2-associated renal amyloidosis (ALECT2): A case report
Amiloidosis derivada del factor quimiotáctico de leucocitos 2 (ALECT2): a propósito de un caso
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Rosario Serrano Pardo, Amalia Lamana Dominguez, Begoña Santos Sánchez, Marta Sanz Sainz, Yamila Saharaui Catala, José Antonio Sánchez Tomero" "autores" => array:8 [ 0 => array:4 [ "nombre" => "Esther Ortega" "apellidos" => "Junco" "email" => array:1 [ 0 => "esther_3000_@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen Sánchez" "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Rosario Serrano" "apellidos" => "Pardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Amalia Lamana" "apellidos" => "Dominguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Begoña Santos" "apellidos" => "Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Marta Sanz" "apellidos" => "Sainz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Yamila Saharaui" "apellidos" => "Catala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "José Antonio Sánchez" "apellidos" => "Tomero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Inmunología, Hospital Universitario de La Princesa, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Amiloidosis derivada del factor quimiotáctico de leucocitos 2 (ALECT2): a propósito de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1786 "Ancho" => 3000 "Tamanyo" => 832812 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) View of two renal casts with amorphous hyaline deposits occupying the interstitium (haematoxylin-eosin, ×20); (b) The amorphous hyaline deposits in the glomeruli are markedly fewer than in the interstitium (haematoxylin-eosin, ×200); and (c) Amyloid deposits that turn apple-green under polarised light (Congo red, ×40).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We present the case of a 69-year-old woman, originally from Nicaragua, who attended our centre in December 2015 with a diagnosis of stage 4 chronic kidney disease (CKD) of unknown aetiology. She had a history of well controlled hypertension (HTN) and high cholesterol. She had no history of nephrotoxic drug use or lithiasis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">No known kidney disease in the parents; 5 siblings with hypertension and 3 children without cardiovascular risk factors.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On physical examination, her blood pressure was 135/78, with no oedema. No associated clinical symptoms.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood test results: haemoglobin 11.2<span class="elsevierStyleHsp" style=""></span>g/dl; creatinine 2.7<span class="elsevierStyleHsp" style=""></span>mg/dl; CKD-EPI glomerular filtration rate (GFR) 18<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. Total cholesterol 170<span class="elsevierStyleHsp" style=""></span>mg/dl and albumin 4.6<span class="elsevierStyleHsp" style=""></span>g/dl.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Weak positive ANA (40.66), positive atypical p-ANCA, negative anti-PR3 and anti-MPO.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Immunofixation in serum with a polyclonal pattern of Igs. Complement fixation normal. Serology for hepatitis B and C, HIV and syphilis negative. Alpha fetoprotein tumour markers, carcinoembryonic antigen, CA-125 and CA 19-9 were negative.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Urine sediment without microhaematuria, and a proteinuria of 0.28<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h. Renal ultrasound showed symmetrical kidneys of normal size and morphology, good corticomedullary differentiation and no signs of obstructive uropathy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">There was a subsequent deterioration of kidney function (GFR of 15.32<span class="elsevierStyleHsp" style=""></span>ml/m) with no new findings. Given the absence of a clear aetiology of CKD, the decision was to perform a renal biopsy.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Examination under an optical microscope revealed 29 glomeruli with only 7 preserved (glomerular sclerosis of 75%), with deposits in the mesangium and occasionally in the membrane, visible with H&E staining, with negative Masson's and methenamine silver stains. Major involvement of the cortical interstitium, with foci of chronic inflammation and eosinophils, notably amorphous eosinophilic material, which stained with Congo red and showed apple-green birefringence under polarised light, indicating the presence of amyloid. This occupies the entirety of the interstitium, leading to marked tubular atrophy; it was also observed in the walls of some interstitial vessels and very focally in the glomeruli (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Direct immunofluorescence I for gG, IgA, IgM, C3, C4, C1q and fibrinogen was negative in the glomeruli, tubules or vessels.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The immunohistochemical study with amyloid A, kappa and lambda light-chain antibodies was negative.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The absence of expression of these antibodies and uncharacteristic distribution of the amyloid deposits, with marked interstitial but little glomerular involvement, together with the absence of nephrotic syndrome, and in view of the patient's Central American origin, led us to conclude that the most likely diagnosis was ALECT2 renal amyloidosis (RA).</p><p id="par0065" class="elsevierStylePara elsevierViewall">Not having more renal tissue available, it was not possible to immunohistochemically confirm LECT2 or to send a sample for liquid chromatography–mass spectrometry analysis.</p><p id="par0070" class="elsevierStylePara elsevierViewall">With this suspected diagnosis, and since it has been suggested that this disease may be a hereditary amyloidosis with a genetic predisposition, a genetic analysis of the patient, two of her children and her nephew was performed using DNA sequencing.</p><p id="par0075" class="elsevierStylePara elsevierViewall">To find out the genotype of the single-nucleotide polymorphism rs31517 present in the LECT2 gene, a pair of oligonucleotides was designed to sequence a 646<span class="elsevierStyleMonospace">-</span>bp DNA fragment, using the following strands: 5′-ATATGGTTATTAGCACCTGCGG-3′ (sense) and 5′-CCCGATAGATATTTTTTTCTGATCC-3′ (antisense).</p><p id="par0080" class="elsevierStylePara elsevierViewall">We thus concluded that the four subjects were homozygotic for the G nucleotide in SNP rs31517, which is characteristic of this disease and confirmed our suspicion.</p><p id="par0085" class="elsevierStylePara elsevierViewall">We present a case of a little-known variety of amyloidosis that has not previously been recorded in Spain; so-called ALECT2 or leucocyte chemotactic factor 2 amyloidosis. First described in 2008 by Benson and James,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> its importance was not realised until 2013, when Said et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> described it as the third leading cause of RA in the USA and the most common in the south-eastern region, with clear over-representation in the Hispanic population (88%).</p><p id="par0090" class="elsevierStylePara elsevierViewall">In 2016, Larsen et al. recorded it as the second leading cause of RA in the Egyptian population, indicating that it is probably a common, if little-known, disease in populations around the world.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Its aetiology is currently unknown. The strong ethnic association and evidence of a hereditary element suggest a genetic aetiology. No mutations in the LECT2 gene have been detected but all patients studied were found to be homozygotic for the G nucleotide in a non-synonymous SNP in position 172. This polymorphism is more common in Mexican lineages and has therefore been associated with Hispanic origins and not with the pathogenesis of the disease, being considered a necessary but insufficient condition to cause the disease.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">ALECT2 is characterised by an atypical presentation compared to other amyloidoses, with late-onset (mean age of 70 years) progressive CKD, with full nephrotic syndrome being rare. Urine sediment is often unremarkable, with proteinuria absent in up to a third of patients and a mean of 0.9<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h; so frequently the disease is not diagnosed, as renal biopsy, the only method of diagnosis, is not indicated.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Histologically, it predominantly affects the cortical interstitium, in contrast with other forms of amyloidosis.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">There is no specific treatment and a 30% of patients progress to end-stage renal disease. Survival is higher than in other types of amyloidosis due to the absence of cardiac involvement.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Kidney transplant is a good option, but cases of recurrence of the disease have been reported.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">We consider important to recognise this disease and be included in the differential diagnosis for CKD in routine practice, given the frequency with which it has been reported in recent years.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Junco EO, González CS, Pardo RS, Dominguez AL, Sánchez BS, Sainz MS, et al. Amiloidosis derivada del factor quimiotáctico de leucocitos 2 (ALECT2): a propósito de un caso. Nefrologia. 2018;38:558–560.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1786 "Ancho" => 3000 "Tamanyo" => 832812 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) View of two renal casts with amorphous hyaline deposits occupying the interstitium (haematoxylin-eosin, ×20); (b) The amorphous hyaline deposits in the glomeruli are markedly fewer than in the interstitium (haematoxylin-eosin, ×200); and (c) Amyloid deposits that turn apple-green under polarised light (Congo red, ×40).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leukocyte chemotactic factor 2: a novel renal amyloid protein" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.D. Benson" 1 => "S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 71 | 43 | 114 |
| 2024 September | 97 | 37 | 134 |
| 2024 August | 93 | 69 | 162 |
| 2024 July | 95 | 38 | 133 |
| 2024 June | 88 | 32 | 120 |
| 2024 May | 81 | 39 | 120 |
| 2024 April | 81 | 33 | 114 |
| 2024 March | 63 | 27 | 90 |
| 2024 February | 82 | 43 | 125 |
| 2024 January | 48 | 30 | 78 |
| 2023 December | 54 | 22 | 76 |
| 2023 November | 68 | 35 | 103 |
| 2023 October | 96 | 31 | 127 |
| 2023 September | 65 | 29 | 94 |
| 2023 August | 45 | 25 | 70 |
| 2023 July | 72 | 33 | 105 |
| 2023 June | 49 | 21 | 70 |
| 2023 May | 70 | 50 | 120 |
| 2023 April | 63 | 38 | 101 |
| 2023 March | 90 | 59 | 149 |
| 2023 February | 96 | 24 | 120 |
| 2023 January | 50 | 31 | 81 |
| 2022 December | 75 | 35 | 110 |
| 2022 November | 76 | 37 | 113 |
| 2022 October | 85 | 58 | 143 |
| 2022 September | 56 | 34 | 90 |
| 2022 August | 50 | 52 | 102 |
| 2022 July | 48 | 46 | 94 |
| 2022 June | 71 | 41 | 112 |
| 2022 May | 98 | 35 | 133 |
| 2022 April | 111 | 57 | 168 |
| 2022 March | 82 | 50 | 132 |
| 2022 February | 103 | 45 | 148 |
| 2022 January | 109 | 36 | 145 |
| 2021 December | 101 | 51 | 152 |
| 2021 November | 50 | 31 | 81 |
| 2021 October | 80 | 47 | 127 |
| 2021 September | 85 | 42 | 127 |
| 2021 August | 73 | 42 | 115 |
| 2021 July | 74 | 44 | 118 |
| 2021 June | 77 | 29 | 106 |
| 2021 May | 76 | 60 | 136 |
| 2021 April | 121 | 83 | 204 |
| 2021 March | 106 | 29 | 135 |
| 2021 February | 71 | 39 | 110 |
| 2021 January | 72 | 27 | 99 |
| 2020 December | 56 | 22 | 78 |
| 2020 November | 65 | 25 | 90 |
| 2020 October | 37 | 20 | 57 |
| 2020 September | 36 | 13 | 49 |
| 2020 August | 50 | 12 | 62 |
| 2020 July | 39 | 13 | 52 |
| 2020 June | 64 | 30 | 94 |
| 2020 May | 71 | 21 | 92 |
| 2020 April | 57 | 27 | 84 |
| 2020 March | 52 | 13 | 65 |
| 2020 February | 55 | 17 | 72 |
| 2020 January | 61 | 31 | 92 |
| 2019 December | 62 | 31 | 93 |
| 2019 November | 65 | 26 | 91 |
| 2019 October | 56 | 19 | 75 |
| 2019 September | 44 | 25 | 69 |
| 2019 August | 44 | 33 | 77 |
| 2019 July | 31 | 26 | 57 |
| 2019 June | 46 | 34 | 80 |
| 2019 May | 57 | 39 | 96 |
| 2019 April | 108 | 50 | 158 |
| 2019 March | 46 | 26 | 72 |
| 2019 February | 54 | 24 | 78 |
| 2019 January | 48 | 33 | 81 |
| 2018 December | 114 | 46 | 160 |
| 2018 November | 234 | 25 | 259 |
| 2018 October | 114 | 7 | 121 |
| 2018 September | 47 | 14 | 61 |
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