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The importance of determining cystatin C for assessment of glomerular filtration disturbance

dc.contributor.advisorStojimirović, Biljana
dc.contributor.otherBogdanović, Radovan
dc.contributor.otherĐurić, Dragan
dc.contributor.otherMajkić-Singh, Nada
dc.creatorObrenović, Radmila Ž.
dc.date.accessioned2016-01-05T12:05:34Z
dc.date.available2016-01-05T12:05:34Z
dc.date.available2020-07-03T08:52:59Z
dc.date.issued2012-07-12
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/2349
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=212
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:5467/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=42634767
dc.description.abstractZbog značaja koji bubreg ima u organizmu važno je rano prepoznati poremećaj njegove funkcije. Do oštećenja bubrega i do poremećaja funkcije mogu da dovedu različiti uzroci. Za procenu stanja bubrega najčešće se u kliničkoj praksi koristi kreatinin koji zavisi od pola, starosne dobi i rase, pa je zato nepouzdana za preciznu procenu JGF i to naročito kod početnih oštećenja bubrežne funkcije, a neki od ovih nedostataka mogu da budu prevaziđeni upotrebom renalnog klirensa kreatinina. Pored klirensa kreatinina primenjuje se i klirens supstanci obeleženih radioakivnim elementima, kao 99mTc-DTPA. Izotopske metode su reproducibilne i u visokoj korelaciji sa klirensom inulina kao zlatnim standardom za određivanje JGF. Postoji široko naučno interesovanje za utvrđivanje primenljivosti cistatina C za određivanje jačine glomerulske filtracije, kojom se u prvom redu procenjuju filtracioni procesi u glomerulu, ali se ipak nameće kao mera za praćenje najvećeg broja promena u funkciji bubrega i progresije njihovog oštećenja. Zbog male molekulske mase cistatin C se lako filtrira kroz bazalnu membranu glomerula i na taj način skoro se potpuno eliminiše iz cirkulacije posle čega se u tubulima u potpunosti kataboliše i ne vraća se u cirkulaciju, što znači da njegova koncentarcija u serumu prvenstveno zavisi od jačine glomerulske filtracije. Ispitano je u studiji preseka koja je trajala 4 godine i obuhvatila 337 ispitanika, 62 bubrežna bolesnika, 109 zdravih trudnica, 33 trudnica sa hipertenzijom izazvanom trudnoćom, 57 bolesnika sa endemskom nefropatijom, 30 bolesnika sa nefrotskim sindromom i 15 zdravih ispitanika kao i 31 bolesnik sa šećernom bolešću. Ispitivanje je sprovedeno u Kliničkom centru Srbije uz saglasnost bolesnika u skladu sa Helsinškom deklaracijom o medicinskim istraživanjima i uz odobrenje Etičkog komiteta Medicinskog fakulteta u Beogradu. Laboratorijska ispitivanja su urađena u laboratorijama Centra za medicinsku biohemiju Kliničkog centra Srbije iz preostalih alikvota krvi korišćene za rutinske laboratorijske analize. Za sva ispitivanja uzorci krvi i mokraće uzimani su ujutru. Uzorak 24h urina sakupljan je od 6h ujutro prvog dana do 6h ujutro narednog dana. Uzorci venske krvi su sakupljani u vakutajnerima (BD) bez aditiva, centrifugirani na 3500 rpm, (≈2000 g) i posle separacije serum je čuvan na minus 80 oC do određivanja. Cistatin C u serumu je određivan PENIA metodom (Particle-Enhancesd Nephelometric Immuno-Assay) testovima firme Dade Behring (Marburg, Germany) na laserskom nefelometru (BN II Dade Behring). Cilj rada je bio da se utvrdi da li je cistatin C pouzdan pokazatelj: 1) jačine glomerulske filtracije (JGF), tj. u kakvoj je vezi sa klirensom 99mTc-DTPA; 2) da se utvrdi u kakvoj je on vezi sa kreatininom u serumu i klirensom kreatinina; 3) da se utvrdi kako životna dob utiče na nivo cistatina C; 4) početnog oštećenja JGF i da li je pouzdaniji od kreatinina; 5) JGF kod obolelih od nefrotskog sindroma i kako proteinurija i životna dob bolesnika utiče na nivo cistatina C u serumu; 6) JGF kod osoba sa endemskom nefropatijom; 7) JGF kod obolelih od dijabetesa tipa 2; 8) kako gestacioni periodi trudnica sa normalnim bubrežnom funkcijom utiču na nivo cistatina C; 9) kako životna dob trudnica utiče na nivo cistatina C; 10) odnos nivoa cistatina C, serumskog kreatinina i klirensa kreatinina u različitim gestacionim periodima u normalnoj i u trudnoći komplikovanoj trudnoćom izazavanom hipertenzijom, da li cistatin C u ovoj grupi može da se koristi kao marker JGF. Da bi se ustanovilo da li cistatin C može da se primeni za procenu JGF određivan je klirens 99mTc-DTPA, zlatni standard za procenu JGF, serumski kreatinin i cistatin C kod bolesnika sa različitim bolestima bubrega. Za razliku od kreatinina, cistatin C i klirens 99mTc-DTPA ne zavise od pola bolesnika a cistatin C ne zavisi ni od starosne dobi bolesnika. Ustanovljeno je visoko slaganje vrednosti klirensa 99mTc-DTPA i cistatina C, što potvrđuje da je cistatin C pouzdan pokazatelj jačine glomerulske filtracije...sr
dc.description.abstractmainstay for detecting impaired kidney function is serum creatinine. Unfortunately, serum creatinine is an insensitive marker of kidney injury, since it depends on sex, age and race. Furthermore, it does not reflect mildly diminshed renal function. Some of these shortcomings can be overcome by the creatinine clearance. However, creatinine clearance may be inaccurate because of tubular creatinine secretion and errors in specimen collection. Measurements of the renal clearance of infused tracers such as 99mTc-DTPA provide accurate measurements of GFR and correlates well with inulin clearance, which is the gold standard for determining GFR. There has been an ongoing search for improved markers for impaired renal function or injury. Cystatin C seems to be a promising candidate to assess GFR, but also other functional chnages in the kidney and their progression. It is produced by all nucleated cells and is small enough to be freely filtered at the glomerulus and completely removed from blood. It is then fully catabolized in the tubules, meaning that its serum concentration depends mainly on GFR. In this cross-sectional study we aimed to: 1) determine is cystatin C reliable marker of GFR, by determinig its correlation with 99mTc-DTPA clearance; 2) determine the relationship between serum cystatin C concentration, serum creatinine and creatinine clearance; 3) determine the correlation between serum cystatin C and age; 4) determine is cystatin C a reliable marker of mildly diminshed renal function; 5) determine is serum cystatin C a reliable marker of GFR in nephrotic syndrome and how proteinuria and age influence its serum concentration; 6) determine if serum cystatin C is a reliable marker of renal function in nedemic nephropathy; 7) determine is serum cystatin C a reliable marker of renla function in nephropathy caused by type 2 diabetes; 8) determine correlation between serum cystatin C and gestational period in healthy pregnant women; 9) determine correlation between age and serum cystatin C in healthy pregnant women and 10) assess relationship between cystatin C, creatinine and creatinine clearance in different gestational period in normal and hypertensive pregnancies. Over the period of 4 years we investigated 337 persons: 62 renal failure patients, 109 healthy pregnant women, 33 preagnant women with pregnancy induced hypertension (PIH), 57 patients with Balkan endemic nephropathy (BEN), 30 patients with nephrotic syndrome, 31 patients with type 2 diabetes and 15 healthy subjects. All individuals gave their informed consent for participation the study, accordnig to the Declaration of Helsinki. The study was approved by the Ethical Commitee of University School of Medicine in Belgrade and conducted in the Clinical Center of Serbia. Laboratory investigations were performed in the Center for Medical Biochemistry at the Clinical Center of Serbia from the remaining aliquotes of blood used for routine analyses. All blood and urine samples were taken in the morning. The 24-hour udine was collected between 6 A.M. one day and 6 A.M. the next day. Venous blood samples were collected in vacutainers (BD) without aditives, centrifuged at 3500 rpm (≈2000 g) and preserved at 80°C after separation. Cystatin C serum concentration was determined by the PENIA method (Particle-Enhancesd Nephelometric Immuno-Assay), using the Dade Behring (Marburg, Germany) tests, on a laser nephelometer (BN II Dade Behring). In order to determine if cystatin C can be used as a marker of GFR, its correlation with 99mTc- DTPA clearance and serum creatinine was determined in patients with different renal diseases. Unlike creatinine, cystatin C and 99mTc-DTPA clearance do not depend on sex, and cystatin C also does not depend on patients age. Serum creatinine is significantly inversely correlated with 9mTc-DTPA clearance (p<0,001) and significantly correlated with serum cystatin C concentration (p<,0001)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectJGFsr
dc.subjectGFRen
dc.subjectcistatin Csr
dc.subjectkreatininsr
dc.subjectklirens kreatininasr
dc.subjectklirens 99mTc-DTPAsr
dc.subjecttrudnoćasr
dc.subjectPIHsr
dc.subjectnefrotski sindromsr
dc.subjectdijabetessr
dc.subjectBENsr
dc.subjectcystatin Cen
dc.subjectcreatinineen
dc.subjectcreatinine clearanceen
dc.subject99mTc-DTPA clearanceen
dc.subjectpregnancyen
dc.subjectPIHen
dc.subjectnephrotic syndromeen
dc.subjectdiabetesen
dc.subjectBENen
dc.titleZnačaj određivanja cistatina C za procenu poremećaja glomerulske filtracijesr
dc.titleThe importance of determining cystatin C for assessment of glomerular filtration disturbanceen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractСтојимировић, Биљана; Мајкић-Сингх, Нада; Богдановић, Радован; Ђурић, Драган; Обреновић, Радмила Ж.; Значај одређивања цистатина Ц за процену поремећаја гломерулске филтрације; Значај одређивања цистатина Ц за процену поремећаја гломерулске филтрације;
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/10778/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/10778/Disertacija.pdf
dc.identifier.doi10.2298/bg20120712obrenovic
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_2349


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