Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Distribution in a Mexican Population.

OBJECTIVES: To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population. METHODS: The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations. RESULTS: Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study. CONCLUSIONS: This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands.

Renal amyloidosis: a new time for a complete diagnosis

Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.

Amiloidose renal secundária ao mieloma múltiplo: relato de caso / Renal amyloidosis caused by multiple myeloma: case report

JUSTIFICATIVA E OBJETIVOS: O mieloma múltiplo (MM) é uma neoplasia maligna grave da medula óssea que ocorre principalmente em pessoas idosas, ocasionalmente complicado por amiloidose. O objetivo deste estudo foi relatar um caso de mieloma múltiplo com amiloidose renal. RELATO DO CASO: Paciente do sexo feminino, 58 anos, apresentou edema, proteinúria (1,5 g/dia), dor lombar e disfunção renal (creatinina sérica de 3,5 mg/dL, depuração de creatinina de 23,4 mL/min/1,73m2), hipercalcemia (cálcio = 10,7 mg/dL), anemia (hemoglobina = 6,7 g/dL), pesquisa de proteínas urinárias de Bence Jones positiva. Radiografias revelaram lesões líticas ósseas. A biópsia renal evidenciou depósitos hialinos (amiloide)no interstício renal e nos glomérulos. Análise de aspirado de medula óssea mostrou proliferação clonal de plasmócitos. Tratada com nifedipina (40 mg/dia), furosemida (40 mg/dia), eritropoetina (8.000 U/semana), ácido fólico (5 mg/dia), carbonato de cálcio (1,5 g/dia), quimioterapia (prednisolona, melfalan, dexametasona,talidomida, vincristina, doxorrubicina) e radioterapia localizada. A evolução mostrou regressão do edema, a função renal ficou estável e ocorreu remissão dos sintomas clínicos durante oito anos. CONCLUSÃO: Relatou-se um caso de mieloma múltiplo complicado com amiloidose. Aspectos sobre o diagnóstico e o tratamentoforam revisados.

BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a serious malignant neoplasm of bone marrow, and mostly occurs in the elderly persons. It is occasionally complicated by amyloidosis. The objective of this study was report a case of multiple myeloma with amyloidosis.CASE REPORT: Female patient, 58 year-old, had edema, proteinuria (1.5 g/day), lumbar pain and renal dysfunction (at admission her renal function was noticed to be abnormal, serum creatinine of 3.5 mg/dL; creatinine clearance of 23.4 mL/min/1.73m2), hypercalcemia (calcium = 10.7 mg/dL), anemia(hemoglobin level 6.7 g/dL), urinary Bence Jones protein positive.Skeletal radiographs revealed lytic lesions. Renal biopsy revealed hyaline deposits (amyloid) in the renal interstitium and the glomeruli. Bone marrow aspirate analysis revealed clonal plasma cells. Treated by nifedipine (40 mg/day), furosemide (40 mg/day), erythropoietin (8,000 U/week), folic acid (5 mg/day),calcium carbonate (1.5 g/day), chemotherapy (prednisolone,melphalan, dexametasona, vincristine, thalidomide, doxorubicin)and located radiotherapy. Follow-up showed regression of edema, stable renal function and remission of clinical symptoms during eight years.CONCLUSION: We report a case of multiple myeloma complicated by amyloidosis. Features about the diagnosis and treatment were revised.

Terapia com anti-TNF na amiloidose renal em artrite reumatoide refratária: uma nova perspectiva terapêutica / Anti-TNF therapy in renal amyloidosis in refractory rheumatoid arthritis: a new therapeutic perspective

As amiloidoses são um grupo heterogêneo de doenças caracterizadas pelo depósito extracelular de uma substância amiloide composta por agregados de proteínas mal acopladas que se depositam longe do sítio de síntese, causando disfunção do órgão-alvo e doença clínica. A forma sistêmica mais comum é a amiloidose A (AA) secundária às infecções e às inflamações crônicas, sendo a artrite reumatoide (AR) a causa mais frequente. O tratamento da amiloidose AA consiste no controle ou na resolução da doença de base. O objetivo do presente estudo é relatar um caso de amiloidose renal secundária em paciente com AR refratária de longa duração que apresentou melhora clínica sustentada após o uso de anti-TNFα (etanercepte).

Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposits of a material composed of aggregates of amyloid - a poorly coupled protein - far from the site of synthesis, causing target organ dysfunction and clinical disease. Systemic amyloidosis A (AA), secondary to infections and chronic inflammation, especially rheumatoid arthritis (RA), is the most common form of amyloid deposition. Treatment of AA consists in the control or resolution of the baseline condition. The objective of the present study was to report a case of secondary renal amyloidosis in a patient with long-term refractory RA who presented sustained clinical improvement after the use of anti-TNFα (etanercept).