Title Membranska glomerulopatija i udruženost s tumorima Title (english) Membranous glomerulopathy associated with tumors Author Luka Miličević Mentor Ivana Vuković Brinar (mentor)Committee member Bojan Jelaković (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Ivana Vuković Brinar (član povjerenstva)Granter University of Zagreb Defense date and country 2020-07-17, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Membranska glomerulopatija čest je uzrok nefrotskoga sindroma u odraslih. Postoji primarni/idiopatski i sekundarni oblik bolesti. Najčešće se klinički očituje pojavom edema, a dodatnom dijagnostikom ustanovi se nefrotska proteinurija uz različite stupnjeve bubrežne insuficijencije te hiperlipidemija. Dijagnoza se postavlja perkutanom biopsijom bubrega na kojoj su svjetlosnom i elektronskom mikroskopijom vidljivi subepitelni depoziti i zadebljanje glomerularne bazalne membrane, a imunofluorescentnim metodama imuni kompleksi. Dva su vida liječenja: simptomatska terapija za kontrolu simptoma i znakova bolesti (hipertenzija, hiperlipidemija, edemi) i specifična terapija imunosupresivima (alkilirajući agensi, inhibitori kalcineurina, glukokortikoidi). Od šezdesetih godina dvadesetoga stoljeća intenzivno se istražuje udruženost membranske glomerulopatije s tumorima. Procjenjuje se da je prevalencija zloćudnih bolesti u ovih bolesnika oko 10%. Predloženo je nekoliko patofizioloških mehanizama ove povezanosti, a posljednje studije upućuju na ulogu protutijela koja se stvaraju protiv antigena THSD7A prisutnoga na podocitima i malignim stanicama nekih tumora. S druge strane, prisutnost anti-PLA2R protutijela govori u prilog idiopatske membranske glomerulopatije. Osim što membranska glomerulopatija može biti posljedica paraneoplastičnoga sindroma, epidemiološki potvrđena udruženost s tumorima mogla bi se objasniti i kancerogenim utjecajem imunosupresivnih lijekova korištenih u idiopatskoj membranskoj glomerulopatiji. U patohistološkom nalazu bioptata bolesnika s glomerulopatijom udruženom s tumorom mikroskopski se češće uočava infiltracija upalnim stanicama, subendotelni i mezangijski depoziti, uz uobičajene subepitelne depozite. Kod svih bolesnika kojima je dijagnosticirana membranska glomerulopatija, trebalo bi učiniti iscrpan klinički pregled i daljnju dijagnostičku obradu zbog mogućega supkliničkog maligniteta. Posebno, za starije od 60 godina preporučuje se opsežnija obrada u smislu aktivnoga traženja maligne bolesti najčešćih sijela: pluća, prostate, hematološkoga sustava, gastrointestinalnoga trakta, mokraćnoga mjehura, bubrega i uterusa.
Abstract (english) Membranous glomerulopathy is a frequent cause of nephrotic syndrome in adults. It can be primary/idiopathic or secondary. It is usually manifested by edema, proteinuria, renal insufficiency and hyperlipidemia. Diagnosis is made on the basis of percutaneous kidney biopsy. Subepithelial deposits and thickening of the glomerular basement membrane can be seen under the microsope, as well as immune complexes using immunofluorescence. There are two aspects of treatment: conservative therapy to control symptoms and signs of the disease (hypertension, hyperlipidemia, edema) and specific therapy – immunosuppressive drugs (alkylating agents, calcineurin inhibitors, glucocorticoids). Since 1960s, association of membranous glomerulopathy with tumors has been intensively investigated. Estimated prevalence of malignancy in these patients is 10%. Several pathophysiologic mechanisms have been proposed. Recent studies suggest the role of antibodies against THSD7A antigen found on podocytes and malignant cells of certain tumors. On the other hand, presence of anti-PLA2R antibodies, found in idiopathic membranous glomerulopathy, reduces the probability of the underlying malignancy. Besides by taking membranous glomerulopathy as a paraneoplastic phenomenon, epidemiologically confirmed association with tumors can be explained by carcinogenicity of immunossuppresive drugs used in idiopathic membranous glomerulopathy. In the kidney bioptates of patients with glomerulopathy associated with tumors, cellular infiltration and subendothelial deposits are more frequently seen under the microscope, along with subepithelial deposits. All patients diagnosed with membranous glomerulopathy should undergo a thorough physical examination and a basic screening because of possible malignancy. More extensive assessment is recommended for patients over age of 60 in order to exlude or cofirm the most common malignancies: of lungs, prostate, hematological system, gastrointestinal tract, urinary bladder, kidney and uterus.
Keywords
membranska glomerulopatija
maligna bolest
THSD7A
PLA2R
kancerogenost
Keywords (english)
membranous glomerulopathy
malignancy
THSD7A
PLA2R
carcinogenicity
Language croatian URN:NBN urn:nbn:hr:105:779859 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2021-07-30 07:50:03
