Toksične nefropatije

master's thesis

• Title (english): Toxic nephropathies
• Author: Mario Halinčić
• Mentor: Živka Dika (mentor)
• Committee member: Bojan Jelaković (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Živka Dika (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Toksične nefropatije su ozljede bubrega uzrokovane izlaganjem organizma nefrotoksinima. Bubreg je zbog svojih posebnih anatomskih, fizioloških i biokemijskih karakteristika organ izuzetno podložan oštećenju toksinima. Čimbenici rizika za razvoj toksične nefropatije uključuju stariju životnu dob, ženski spol, hipoalbuminemiju, sniženu brzinu glomerularne filtracije bilo koje etiologije te brojne druge metaboličke i genetske čimbenike. Toksične nefropatije uzrokovane lijekovima zahvaćaju različite segmente nefrona ovisno o mehanizmu djelovanja pojedinog lijeka. Nesteroidni protuupalni lijekovi uzrokuju smanjenu proizvodnju prostaglandina što vodi smanjenju GFR-a te izlučivanja vode i elektrolita. Aminoglikozidi oštećuju proksimalni tubul i distalne tubule ometanjem funkcije fosfolipida, mitohondrija i oksidativnim stresom. Cisplatina uzrokuje o dozi ovisnu akutnu tubularnu nekrozu stanica proksimalnog tubula. Metotreksat se u kiselom urinu kristalizira i taloži u tubulima. Inhibitori kalcineurina smanjuju protok krvi kroz bubreg i uzrokuju intersticijsku fibrozu. Litij uzrokuje nefrogeni diabetes insipidus, acidozu i intersticijsku fibrozu. Radiološki jodni kontrasti oštećuju bubreg ishemijom i direktnim toksičnim djelovanjem na tubule. Teški metali su zbog onečišćenja tla i pitke vode važan uzrok toksične nefropatije. Oštećuju stanice proksimalnog tubula raznim mehanizmima, uglavnom oksidativnim stresom i ometanjem unutarstaničnih signalnih puteva. Aristolohična kiselina uzrokuje balkansku endemsku nefropatiju karakteriziranu tubulointersticijskim oštećenjem i razvojem karcinoma prijelaznog epitela. Etanol uzrokuje poremećaje elektrolita i acidobaznog statusa zbog generalizirane disfunkcije tubula. Etilen-glikol uzrokuje stvaranje kristala kalcijevog oksalata u tubulima. Halogenirani ugljikovodici preko svojih toksičnih metabolita i oksidativnog stresa oštećuju proksimalni tubul. Melamin se veže za cijanuričnu ili mokraćnu kiselinu i dovodi do nefrolitijaze. Nefrotoksini su brojni i raznoliki, a važno je pomišljati na njih u kliničkoj praksi radi pravovremne prevencije i liječenja toksičnih nefropatija.

Abstract (english)

Toxic nephropathies are kidney injuries caused by exposure of organism to nephrotoxins. Kidney is an organ especially susceptible to nephrotoxin damage because of its special anatomical, physiological and biochemical characteristics. Risk factors for development of toxic nephropathy include older age, female sex, hypoalbuminemia, decreased glomerular filtration rate of any aetiology and numerous other metabolic and genetic factors. Drug-induced toxic nephropathies affect different nephron segments depending on the mechanism of action of a particular drug. Nonsteroidal anti-inflammatory drugs cause a decrease of prostaglandin production which leads to a decrease in GFR and excretion of water and electrolytes. Aminoglycosides damage the proximal tubule and distal tubules by a disruption of phospholipid and mitochondrial function and by oxidative stress. Cisplatin causes dose-dependent acute tubular necrosis of proximal tubule cells. Methotrexate crystallizes in acidic urine and precipitates in tubules. Calcineurine inhibitors lower renal blood flow and cause interstitial fibrosis. Lithium causes nephrogenic diabetes insipidus, acidosis and interstitial fibrosis. Radiological iodine contrasts damage the kidney by ischaemia and direct tubular toxicity. Heavy metals are an important cause of toxic nephropathy because of environmental and drinking water pollution. They damage the proximal tubule cells by a variety of mechanisms, mainly by oxidative stress and by disruption of intracellular signal pathways. Aristolochic acid causes Balkan endemic nephropathy characterised by tubulointerstitial damage and urothelial cancer. Ethanol causes electrolyte and acid-base balance disturbances because of generalized tubule dysfunction. Ethylene-glycol causes formation of calcium oxalate crystals in tubules. Halogenated hydrocarbons damage the proximal tubule via their toxic metabolites and oxidative stress. Melamine bonds to cynauric or uric acid and leads to nephrolithiasis. Nephrotoxins are numerous and diverse, and its important to think about them in clinical practice for the timely prevention and treatment of toxic nephropathy.

• Keywords: toksična nefropatija; nefrotoksičnost; lijekovi; teški metali
• Keywords (english): toxic nephropathy; nephrotoxicity; drugs; heavy metals
• Language: croatian
• URN:NBN: urn:nbn:hr:105:302778
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-01-07 13:36:15