balcan endemic nephropathy in bosnia and herzegovina 50...

Balkanska endemska nefropatija u Bosni i Hercegovini50 godina istraživanja

Senaid Trnačević i saradnici

Klinički centar Univeziteta u Tuzli

Klinika za interne bolesti

Odjelenje za nefrologiju dijalizu i transplantaciju

IV kongres nefrologa u Bosni i Hercegovini sa

medjunarodnim učešćem

Sarajevo 2204 2015 do 26042015 godine

Balcan Endemic Nephropathy in Bosnia and Herzegovina50 years of research

Koatori rada

Enisa Mešić Evlijana Hasanović

Goran Imamović Amra Šakušić

Mirna Alečković Halilović Dinka Begić

Jasminka Mustedanagić Jugoslav Stahov

Ljiljana Lukić Emir Hodžić

Zlatko Maksimović Denijal Tulumović

Nenad Petković

Besim Prnjavorac

Emir Trnačević



Balkanska endemska nefropatija (BEN) je jedina bubrežna bolest koja se javlja

endemski

porodično

hronično



Balcan endemic nephropathy (BEN) is the only kidney disease that occurs

Endemic

Family

Chronically

Osnovne karakteristike BEN i distribucija



Basic characteristics of Balcan endemic nephropathy and its distribution

Prvi opisi BENa potiču Vojislava Danilovića i saradnika

The first descriptions of Balkan endemic nephropathy originate from Vojislav Danilović and associates

Danilovic V Djurisic M Mokranjac MStojimirović B Živojinović J Stojaković P Porodično obolenja bubrega u selu Šopić izazvano hroničnom intoksikacijom olovom Srpski arhiv 851115 1957

Danilovic V Djurisic M Mokranjac MStojimirović B Živojinović J Stojaković P Nephroitis chronqaee provoqaes par intoxication au plumb par voie digestive farine) La Presse Medicalae 65 2039ndash20401957





Vojislav Danilović Jakob Gaon

Sredinom 1957 godine ekipa stručnjaka Centralnog higijenskog zavoda i Interne klinike u Sarajevu nakon prvih orijentacionih ispitivanja na području opština sjevereoistočne Bosne potrvdjuje masovnu učestalost pojave bubrežnih bolesnika i sve češćoj smrti od uremije

Bilten Centralnog higijenskog zavoda Zaključci grupe stručnjaka o mjerema potrebnim za dalje ispitivanje i suzbijanje

epidemije nefritaSavezni zavod za zdravstvenu zaštituBeogradIzvještajiBilten Centralnog higijenskog zavoda BiH1957825

AranickiMi saradnici Epidemična pojava nefrita na području sreza Brčko Bilten Centralnog higijenskog zavoda BiH 1958 121

AranickiMisar dosadašnja ispitivanja epidemiologije endemske nefropatijeu BiHMed Arhiv19611599

In mid-1957 a team of experts from Central Public Health Institute and the Internal Medicine Clinic in Sarajevo after finishing the first research in the municipalities of northeastern Bosnia confirms the mass incidence of kidney patients and more frequent death from uremia



Početkom 1958 godine osnovaju se Dispanzeri za bubrežne bolesti-prvi u Bijeljini sa zadatkom da radi na detekcijiregistracijiliječenjusavjetovanju i sprovodjenju nekih preventivnih mjera na području 6 opština sjeveroistočne BiHldquo

In early 1958 the departments for kidney disease have been established ndashfirst one in Bijeljina with the aim of working on detection registration treatment consultation and implementation of some preventive measures in the endemic erea (six municipalities of northeastern Bosnia and Herzegov )

Alibegović ADispanzerski rad u proučavaju raširenosti dijagnostici i terapijii prevenciji Semberske nefropatije Zbornik radova Simpozijuma o endemskoj nefropatiji Niš 1971Prosveta 60-67



Uradjeno je sveobuhvatno epidemiološko-kliničko ispitivanje endemske nefropatije obavljena su perlustracijom stanovništva u 6 opština sjeveroistočne Bosne u vremenu od 1975 do 1978 godine

Pregledano je 244016 stanovnika od 6 do 60 godina a registrovano je 10541 protein pozitivan ispitanik a 1730 oboljelih od endemske nefropatije (BEN)

During four years (1975-1978) 244016 patients were examined ( 6 -60 years old) In 10541 patients positive proteinuria was registered 1730 patients were diagnosed with Balkan endemic nephropathy



Opštine u kojima postoji endemska nefropatija sa brojem pregledanih ispitanika i registrovanih bolesnika

Municipalities in the endemic area with the number of examined people and registrated patients

Fajeglj A i saradnici Trogodišnji (1975-1977) Republički program na otkrivanju i suzbijanju endemske nefropatije u SR Bosni i

Hercegovini Zbrornik radova I kongresa nefrologa Jugoslavije Beograd 1981 42-47

Opštine SR Bosne i Hercegovine u kojima je utvrdjena endemska nefropatija

Za završenom 1977godinom ukupno je registrovano 1730 bolesnika od BENa

1730 patients were diagnosed with Balkan endemic nephropathy

ldquoUtrvdjene stope obolevanja od endemske nefropatije iznose od 0347 do 0901 prosječno 0701 značajno su manje od onih koje su ranije nadjene u pojedinim grupama stanovnika i pojedinim naseljima Nadjene stope nisu alarmanente na ukupan broj pregledanih stanovnika No nadjene stope s druge strane sigurno govore i za to da je endemska nefropatija i dalje veoma ozbiljan problem kome u zaštiti zadravlja treba posvetiti najveću moguću pažnju i zbog toga treba nefrološku službu na tim regionima još više razvijati i jačatirdquo Fajgelj i saradnici 1981 (BEN)Ovaj je jedinstven projekat u svijetu postao prototip epidemioloških istraživanja i bio podpomognut WHO

bdquoThe disease rate of BEN amounts from 0347 to 0901 on average 0701 It is is signifcantly decreased but still the argument that presents BEN as the serious health problem which demands great attention This is the reason why nephrology healthcare should be developed constantly especially in the endemic areardquo Fajgelj et al 1981 (BEN) This project has become a worldwide prototype and was supported by WHO

Fajgelj A i sar Trogodišnji program ( 1975-1977) Republički program na otkrivanju i suzbijanju endemske nefropatije u SR

Bosni i Hercegovini Zbornik radova I kongresa nefrologa Jugoslavije 42-48 Institut za endemsku nefropatiju Lazarevac1981



Biomarkeri i endemska nefropatija

Urin ispitanika je pregledan sa stiksom i SSA uzimana je anamneza i pregledani su a protein pozitivni su upućivani na obradu u dispanzere i kliničke ustanove Traženi su specifičniji testovi (biomarkeri) za terensko istraživanje

Dosta istraživača je tražilo biomarkera za terensko istraživanje beta 2 mikroglobulin u serumu i urinuelektroforeze proteina u urinu Alfa 1 mikroglobunia

Biomarkeri su uporno traženi kao i danas a začetnici te ideje su Hall i saradnici koji je jedno vrijeme smatrao da je beta 2 mikroglobulin osim kao markera i uzročnik BEN

Biomarkers and Balcan Endemic Nephropathy

The subjects were surveyed examined family history was taken Urine was tested with Styx and SSA Patients with proteinuria were sent to to clinics on further examination Biomarkers were taken beta 2 microglobulin in serum and urine protein electrophoresis in the urine alpha 1-microglobulin

Biomarkers are still used for diagnosis Hall was the first who used them Once he even thought that beta 2 microglobulin was the cause of Balcan endemic nephropathy

HallPW and VasiljevicM Beta 2 microglobulin excretion as and index of renal tubular disorders with special reference to endemic Balkan nephropathyJLabclinMed 81897-9041973





Jedni su smatrali da imunopatogenski mehanizmi mogu učestvovati u nastanku BEN

Some researchers believed that the immune pathogenic mechanisms may participate

in the etiology of BEN

MacanovićMRezaković DzBašagić E Brkić NImunopatogenetski mehanizmi u endemskoj nefropatiji

Acta medica saliniana Tuzla decembar 1976Regionalni medicinski centar Dr Mustafa Mujbegović 109-123



Ako nema biomarkera postoje biohemijski parametre za dijagnozu bolesti i odredjivanje stepena renalnei nsuficijencije

If there are no biomarkers biochemical tests can help with diagnosis and determination of the degree of renal insufficiency

Pašić ISušić H Halilbašić AMartinović K Naša iskustva u liječenju bolesnika od endemske nefropatije uključujući i dijalizu Acta medica saliniana Tuzla decembar 1976Regionalni medicinski centar Dr Mustafa Mujbegović 153-160

AHalilbašićMartinović KPavličević AMehikić S Nakičević MPašić R Selesković H Pašić i Neki poremećaji biohemizma krvi kao mogući indikator lezije bubrega kod stanovnika sela Pisari Acta medica saliniana Tuzla decembar 1976Regionalni medicinski centar Dr Mustafa Mujbegović 163-169



Dugo vremena je dosta istraživača a posebno akademik Jakov Gaon su smatrali da je uzrok BEN u vodi ( analize vode endemskih i neendemskih sela se nisu razlikovale)

Takodje je isptivano zemljište endemskih područja bez posebnih zaključaka

Academician Jakov Gaon and many other researcers believed taht the couse of BEN was in the water (The analyses showed no difference between water in endemic and non endemic area)

The soil of endemic area was also analysed but without significant results

Gaon J Pokrajčić B EDurić Uticaj nekih faktora spoljne sredine na održavanje endemske nefropatijei proijedlog za

primjenu preventivnih mjera Acta medica saliniana Tuzla decembar 1976Regionalni medicinski centar Dr Mustafa Mujbegović 109-118

OsmićI I sar Ispitivanje zemljišta i vode kao mogućih nosilaca uzročnika endemske nefropatije u selu Bosanski Miloševac Etiology of endemic (Balkan) nephropathy Prosveta 1987 35-41



I najmlađi su bili predmet ispitivanja jer se pretpostavljalo da bolest počinje još u djetinjstvu (ispitivanja 3705 djece od 7 do 15 godina iz endemskih žarišta Semberije (BiH) pojava signifikantne patološke i proteiurije i mikrohematurije kod školske djece ukazuju da je početak endemskog glomerulonefritisa unajvećem procentu u dječijem uzrastu)

Children were also included in the study because it was believed that disease begins in childhood (3705 children from 7-15 years who were living in the endemic area) Positive proteinuria and microhematuria found in young population indicate taht endemic glomerulonephritis bigins at an early age

SimojlovićVSušaS I saradnici 1981 Učestalost proteinurije u dece u regionu SemberijeZbornik radova I kongresa nefrologa

Jugoslavije 72-79



U vremenu od 1986 godine do pred rat 1992 istraživanje rade grupe iz Tuzle

Ljubljane i Beograda koje traže patohistološku osnovu BENa posebno ranih

faza kliničku sliku biomarkereRadovi ove grupe su objavljeni u Kindney 1991 godine

Nadjena je patohistološka osnova bolesti Dominira acelularna skleroza koja počinju oko proksimalnih tubula u koriklinička slika je nespecifična od biomakrera postoji i beta2 mikrolglobulin ali je u l00 urinima nadjen alfa 1 mikroglobulin kao marekr tubulske proteinurije

From 1986-1992 research was conducted by the research group from Tuzla Ljubljana Belgrade The group was seeking for the histopathological basis of BEN its clinical manifestation significant biomarkers The results were published in Kidney 1991

The histopathological basis of BEN was found (acellular sclerosis taht begins around proximal tubules in the cortex) Clinical manifestation is not specific Beta 2 microglobulin was found as biomarker but alfa 1 microglobulin was 100 positive in the urine samples of patientes with BEN



Balkanska endemska nefropatija u Bosni i Hercegovini 50 godina istraživanja

Prvi patohistološki znaci BENa acelularna skleroza i kolapsna atrofija proksimalnih tubula

The histopathological basis of BEN (acellular sclerosis and collapsing atrophy around proximal

tubules)

Prodiranje acelularne skleroze u dublje slojeve korteksa sa edemom intersticijuma glomeruli normalni

Spreading the acellular sclerosis in the deeper layers of the cortex with interstitial edema glomerulus remains normal

Terminalni stadijum BENa potpuna acelularna skleroza u intersticijumu i fibroza izvijuganost aferentne arteriole

The terminal stage of BEN complete acellular sclerosis and fibrosis afferent arterioles are tortuous

Nakon rata 1992-1995godine

After the War



Administrativno uredjenje Bosne i Hercegovine nakon 1995godine

The administrative organization of Bosnia and Herzegovina after 1995

Okružene opštine gdje postoji BEN

The municipalities in the endemic area



Ali šta je sa BENom

koliki je broj bolesnika

ima li novih žarišta

koliki je broj raseljenih bolesnika

koliko se stanovnika doselilo

šta će se desiti sa raseljenim osobama i useljenim hoće li i kada dobiti BEN

prirodni ratom uslovljen eksperiment

But what happened to BEN

bull How many patients with BEN

bull Are there new endemic area

bull How many displaced patients

bull How many residents moved in the endemic area

bull What will happen with emigrants and immigrants in the endemic area

bull Do we have a natural war-conditioned experiment

Nakon rata postoje pokušaji da se prikupi i analizira broj bolesnika od BENa u BiH da se evidentirajuprikaže trend ove bolesti ali su to radile istraživačke grupe preko Udruženja nefrologa u BiH ili u okviru istraživaćčkih projekata Akademija nauka i umjetnosti BiH ili ISN

After the war there are attempts to collect and analyze the number of patients with BEN organized by the research group supported by The Association for Nephrology Dialysis and Transpalntation of Bosnia and Herzegovina and The Academy of Arts and Sciences



Association for Nephrology Dialysis and Transplantation of Bosnia and Herzegovina

Prof dr Senaid Trnacevic President

Prof dr Enisa Mesic Project Coordinator

Application for Non-communicable Chronic Disease PreventionPrograms in Developing Countrie ISN Research Committee

Regional Coordinator Dick de Zeeuw (The Netherlands)ddezeeuwmedumcgnl

Program of early detection of chronic kidney disease in high-risk population of Bosnia and Herzegovin(EDCKD-BH)

Section A General Project Information1 Country Bosnia and Herzegovina South-East Europe2 Project title bdquoProgram of early detection of chronic kidney disease in highriskpopulation of Bosnia and Herzegovinaldquo3 Name and address of the coordinating Institution (Aplicant)1048707 Legal name Association for Nephrology Dialysis and Transplantation

of Bosnia and Herzegovina1048707 Address University Clinical Center Tuzla Trnovac bb 75000 Tuzla

BampH1048707 Head of the Association Prof Senaid Trnačević PhD MD

4 Name of the local coordinator of the project Prof Enisa Mešić PhD MD1048707 ISN member ID 606351048707 Position Chief of Nephrology and Dialysis Dept Clinic for Internal

Diseases University Clinical Centre Tuzla1048707 Contact Address Trnovac bb Nephrology and Dialysis Dept Clinic

for Internal Diseases

Trnačević S Halilbašić A Imamović G Mešić E Balkan endemic nephropathy in Bosnia and Herzegovina Facta universitatis 2002 Series Medicine and Biology Vol9 No 1 University of Niš

Imamovic G Batuman V Sinanovic O et al Microalbuminuria as a possible marker of risk of Balkan endemic nephropathy Nephrology 2008 13

Mešić E Early detection of Balkan endemic nephropathyin Bosanska Posavina Bosnian Journal of basic scintient 2010 10 (Suplement 1) S 84-S 90

Alecković M Mesić E Trnacević S et al Glomerular filtrationrate in examined population of Bosnian Posavinamdashregion of Balkan Endemic Nephropathy Bosn J Basic Med Sci 2010 10S68ndashS72

Mirna Aleckovic-Halilovic Enisa Mesic Senaid Trnacevic Emir Hodzic Vildana Habul Mirza Atic Maida Dugonjic and Evlijana Hasanovic 2014Values of Alpha 1 Microglobulin Does Not Differ between Individuals with and without Family History of Balkan Endemic Nephropathy International Journal of NephrologyVolume 2014 (2014) Article ID 284293 5 pageshttpdxdoiorg1011552014284293



Arthur Grollman 2010 Aristolochic acidan environmental and yatrogenic disease Abstract booktrećeg kongresa nefrologa Bosne i Hercegovine sa medjunarodnim učeščem 6

Grollman AP Scarborough J Jelaković B Aristolochic acid nephropathy an environmental and iatrogenic disease In Fishbein J ed Advances in Molecular Toxicology 3 Elsevier Amsterdam 2009211ndash222

Jelaković B 2010 The role of Aristolochic acid in endemic nephropathy Abstract booktrećeg kongresa nefrologa Bosne i Hercegovine sa medjunarodnim učeščem 6



Rad Cosynsa i saradnika nakon epizode trovanja žena koje su uzimale susptance sa sastojcima kineskog bilja

Pisoning with ingredients of Chinese herbs for the purpose of weight loss(Cosynsa)

Nigdje toliko korova kao u pšenici endesmkih terena u odnosu na druge regione

Seljaci su koristili pšenicu sa svoje zemlje samo za svoje potrebe

Nisu davali nikakvu važnost toksičnosti korova

Kruh tih seljaka je bio otrovanMilenko Ivić u Liječničkom vijesnku 91(12) 1273-1281 (1969)

Weed is most common in the endemic area

Farmers have used wheat from their land only for their own purposes

They did not pay any attention to the toxicity of weed

Their bread was poisoned

Milenko Ivić u Liječničkom vijesnku 91(12) 1273-1281 (1969)



Analogija BENa i Aristolohijskom kiselinom uslovljenom nefropatijom(AAN)

Klinička slika

Patološko histološki nalazi

Incidenca

Pojava papilarnih tumora

Eksperimenti sa Aristolihijskom kiselinom na eksperimenatlnim životinjama dokazali su istovjetne patološko histološke promejene koje se vidjaju u BENu

Samo je različit famijarni karakter u BEN postoji a u AAN ne postoji

The analogy between Ben and Nephropaty caused by aristolochic acid (AAN)

Clinical manifestations

Histologically

Incidence

The appearance of papillary tumors

Experiments with the laboratory animals that were exposed to aristolochic acid showed the same patohistological changes in kidney like those one found in BEN patints

Differs only family history





Više od 40 svih dijaliznih bolesnika u BIH su u regionu opština sjerevoistočne BiH gdje je najveća koncentracija dijaliznih cenatara i endemska žarišta BENa



More than 40 of all dialysis patients in BiH are in the endemic area where is the largest number of dialysis centers

Od cjelokupne dijalizne populacije u BiH na BEN populaciju pripada 10 što predstavlja medicinski naučni finansijski socijalni i organizacijski problem zdravstvene zaštitie stanovništa



From the entire dialysis population in BiH 10 are patients with BEN This is the medical scientific financial social and organizational problem

Broj stanovnika u Bosni i Hercegovini u popisima stanovništva 19711991 i 2013 godine

Sa decembrom 2013 godine u BIH ima ukupno 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

Sa decembrom 1971 godine 3 746 111




The population of Bosnia and Herzegovina in the censuses in 1971 in 1991 and 2013

December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033

Agencija za statistiku Bosne i HercegovinePrvo saopštenjeGodina 2013Sarajevo 5112013Broj 1 Preliminarni rezultatti Popisa stanovništva domaćinastva i stanova u Bosni i Hercegovini 2013

podaci Bijeljina Brčko Šamac Orašje Odžak Modriča Domaljevac

Broj stanovnika od 1978god

92800 87000 32000 27806 27895 32 800 4208

Broj stanovnika 2013god

114663 93028 19041 21584 21289 27799 5216

Broj gradskog stanivništva 2013

56600 46 000 5000 3796 9182 7 000 5216

Broj seoskog stanovništva 2013

58000 52 000 14 600 17788 12 107 25 000 5216

Broj seoskog stanovništva

1978god

52800 52 000 27 000 23896 20261 25 800 4208

Broj gradskog stanivništva

1978god

40 000 43 900 5000 3910 7634 7 000 4208

Ukupan broj BEN bolesnka

2013god

300 36 90 44 53 80 55

Ukupan broj bolesnika na

hemodijaliziHD

290 62 40 27 22 34 13

Ukupan broj BEN na HD

190 8 26 19 14 10 14

Ukupan broj tumora i BEN

30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1

Ukupan brojizbjeglica

2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno

Broj stanovnika sa registrovanim broj endemskih nefropatija hemodijaliznih bolesnika tumora i BENa broj transplantiranih i BENa u opština sjeveroistočne Bosne i HercegovineNumber of patients with BEN number of patients who are dialyzed number of patients with BEN and tumors

transplanted patients with BEN in th endemic area

BEN ( Balkanska endemska nefropatija )

Agencija za statistiku Bosne i HercegovinePrvo saopštenjeGodina 2013Sarajevo 5112013Broj 1

Preliminarni rezultatti Popisa stanovništva domaćinastva i stanova u Bosni i Hercegovini 2013

broj stanovnika u 6 opština 1978 304 509

broj stanovnika u 6 opština 2013 302620

Sa decembrom 2014godine ukupno BENa 1007Sa decembrom 1977 godine 1730

population in six municipalities in 1978 304 509


number of patients with BEN december 2013 1016number of patients with BEN december 1977 1730

Zavod za statistiku Bosne i Hercegovinegodina 1977Sarajevo




Osnovni cilj je ispitati ranih faza BENa u jednom mikroregionu- sa ostvrtom na

dijagnostičke kriterijume

Hipoteze

da žive na endemskom terenu preko 15 (20) godina

postojanje bolesti u porodici

povišena vrijednosti mikroalbumina i alfa1mikroglobulina u urinu

anemija

smanjene dimenzije bubrega su pokazatelji ranih faza BEN

The main goal is to detect the early stages of Ben in one micro region- paying

attention to diagnostic criteria

The main hypothesis is that the indicators of the early stages of BEN are

Living in an endemic area over 15 (20) years

Family history

Increased microalbumin and alpha 1-microglobulin in urine

Anemia

Reduced kidney dimensions



Metodologija je uniformna prema prekorukama eksperata za BEN izvornih od 2008godine i dogradjenih kasnije u 2013godini

The methodology is unified according to experts recommendations for BENoriginal from 2008 and later annexed in 2013

Consensus statemant on sceeningdiagnosis classification and tretmant of endemic (Balkan) nephropathy NDT Advance

Access published October 282013



Consensus statemant on sceeningdiagnosis classification and tretmant of endemic (Balkan) nephropathy NDT Advance Access published October 282013

Osnovni kriteriji uključenja ispitanika u ovu studiju su bili življenje u Domaljevcu više od 15 (20)godina patološki nalaz mikroalbuminurije (MA) postojanje ili odsustvo pozitivne porodične anamneze BEN

Dok su kriteriji isključenja prema Konsenzusu (2008) bili postojanje hiperlipidemije hipertenzije dijabetes melitusa mikrohematurije i leukociturije (Anonymous 1999)

Basic criteria for inclusion were living in Domaljevac more than 15 (20) years microalbuminiria family histroy (relative)

While exclusion criteria according to Consensus (2008) were the existence of hyperlipidemia hypertension diabetes mellitus microhaematuria and leukocyturia (Anonymous 1999)



Istraživanje se odvijalo u dvije faze

U I fazi ispitanicima Uzimana je anamnezaklinički poregled laboratorijumski nalazi urina iispunjavani formulari pregleda i anketni list

U obje faze ispitivanja MA određivana je stiks metodom a imunoeseji su je detektovali u koncentracijama od 50 do 100 mgL urina

Izdvojeni su MA pozitivni iz I faze Ponovo je u II fazi odredjivana MA Urin odgovarajuće specifične težine uz pozitivan nalaz mikroalbuminurije ostavljen je za određivanje alfa 1 mikroglobulina (A1M) i kreatinina

Ispitanicima u drugoj fazi ispitivanja uzeta je krv za određivanje kompletne krvne slike kreatinina na osnovu formula određivan je klirens kreatinina-GFR željezo te su vršena morfometrijska mjerenja ultrazvučnim pregledom bubrega

The research was conducted in two phases

In the phase one family history was taken participants were examined urin was tested questionnaries were filled

In both phases of the study MA was tested by styx and was detected at concentrations of 50 to 100 mg L of urine MA positive participants were separated Test was repeated

Urin was tested (detecting alpha 1 microglobulin and creatinine)



Funkcionalno stanje bubrega procjenjivano na osnovu klirensa kreatinina odnosno JGF (MDRD formula) prema preporukama KDIGO- Kidney Internatinal Suplements smjernicama [19] Dimenzije bubrega prema spolu i dobu mjerene su prema standardima preporukama Spiegela i saradnika i sar [20]

Statistička obrada podataka je uradjena prema Altmanu i saradnicima [21]

In the second phase blood sample was taken (blood count creatinine Fe) participants were underwent ultrasound of the kidneys Renal function was evaluated by creatinine clearance (recommended by KDIGO- Kidney Internatinal Suplements guidelines) [19] Kidney dimensions were measured according to standard recommendations (Spiegel )

Statistical analysis was performed according to Altman [21]



Pregledano je ukupno 360 ispitanika u Domaljevcu a od toga 131 je imao patološki nalaz MA

Od tih 131 ispitanika 59 ispitanika imalo je samo patološki nalaz MA bez hiperlipidemije dijabetes melitusa hipertenzije leukociturije i mikrohematurije dok 72 ispitnika su uz MA imali i jedan od drugih navednih patoloških nalaza te su zbog toga isključeni dalje iz studije

The study included 360 participants in Domaljevac 131 had microalbuminuria detected

59 participants had microalbuminuria without hyperlipidemia diabetes mellitus hypertension leukocituria and microhaematuria while 72 patients had microalbuminuria along with some of the exclusionary factors



Ispitanici Godine (XplusmnSD) t P

Grupa I 470plusmn155 121 023

Grupa II 521plusmn159

Životna dob u ispitivaim grupama

Bez statističke značajnosti



The age

No statistical significance

gender Group I (N=36) Group II (N=23) Ukupno

Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186

Demografski podaci u isptivanim grupama

Preko 55 ispitanika su u životnoj dobi od 35 do 55 godina



Demographic data

Over 55 of participants were between 35-55 years old

Parameter Group I (N36=) Group II (N23=) t-test p

Min-Max Mean SD Min-Max Mean SD

Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321

N number of patients

Klirens krea- klirens kreatinina A1M ndash alfa 1 mikroglobulin Cr urin- kreatinin u urinu A1MCr urin- odnos alfa1

mikroglobulina i kreatinina urina

Laboratorijumski nalazi u ispitivanim grupama

Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)

Right Left Right Left Right Le

ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)

Ultrazvučni nalazi bubrega u ispitivanim grupama BENa

Bez statističke značajnosti u dimenzijama bubrega u ispoitivanim grupamaI u odnosu na normalne referentne vrijednosti

Ultrasound of the kidneys

No statistical significance in kidney size in the examined groups compared to the normal reference values

Zaključci Nema bitnih razlika u obolijevanju među spolovima na endemskom terenu u isitanika opeterećenih BENom i bez

BEN opeterećenja u porodici

Rane faze BEN počinju poslije 40 godine života i protiču bez akutnog početka i hipertenzije

Prvi znaci bolesti mogu biti povišena koncentracija mikroalbulbumina u urinu U starijim grupama je u većim koncentracijama alfa1mikroglobulina u urinu što je znak duže izloženosti agensu

U ranima fazama bolesti normalna je bubrežna funkcija

Anemija nije rani znak BEN

Ultrazvučne dimenzije bubrega su normalne u ranim fazama BENa

Patohistološki je acelularna skleroza u intersticijumu i počinje u kori bubrega

Conclusions No significant differences in morbidity rates between the sexes in participants with positive and negative family

history

The early stages of BEN begin after the age of 40 without acute reaction and hypertension

The first sign of the disease can be microalbuminuria The elderly participants have increased concentration of alpha 1-microglobulin in the urine awhich is a sign of longer exposure to agent In the early stages of the disease renal function is normal

Anemia is not an early sign of BEN

Ultrasonic kidney dimensions are normal in the early stages of Ben

Histopathology indicates acellular interstitial sclerosis and begins in the renal cortex



Početak bolesti se pomjera prema starijim životnim dobima

Nema novih žarišta

Bitnije je ekspozicija i dužina ekspozicije na terenu za nastanak BEN jer to objašnjava da imigranti poslije 20 godina obole

Jer i grupe koje u porodici nemaju BEN poslije dugo godina življenja na terenu dobiju bolest

Posebno kako neki od članova pojedinih porodica obole a neko ne ( jer neko je više izložen agensu a neko nije i to je osnovni razlog)

Start of disease is shifting towards older ages

There are no new endemic areas

More important is the exposure to the agent because it explains that immigrants after 20 years show the sympthoms

Some of the family members get sick and others do not depending on how much they are exposed to agent



Novija saznanja i istraživanja BENa

Aristolohijska kiselina ili njeni adukti su razlog bolesti jeste

Da li je to jedan osnovni razlog a ostalo su uticajni činioci mislim da jeste

da li će BEN nestati - hoće ALI BAR ZNAMO ETIOLOGIJU ( ILI MISLIMO DA ZNAMO )

Prethodi li BEN papilarnim karcinomima urotelijuma-prethodi

Je li razlog tumora i BENa isti - jeste -Arisholohijska kiselina i njeni adukti

Napraviti nove sveobuhvatna

Epidemiološka istraživanja

Tražiti adukte Arisholohijske kiseline u tkivu

Markere tumorogeneze

Future research

Aristolochic acid or its adducts are the cause of disease Yes

Is it the main reason and the rest are influential factors I think it is

Whether BEN desapear It will But at least we know the etiology ( or we think we know)

Whether BEN precededs papillary urothelial carcinoma-precedes

Is the cause of tumors and Ben the same ndash yes it is - Aristolochic acid

New comprehensive research

epidemiological research

Searching for adducts of Aristolochic acid in the tissue

Searching for tumor markers





Kako je i zašto BEN progresivna ireverzibilna bolest i vodi u terminačlnu bubrežnu slabost jer ako je toksin razlog zašto ako se otkloni ili prestane djejstvo toksina bolest napreduje i ne ostaje na odredjenom stepenu renalne slabosti

How and why BEN is progressive reversible disease that leads to the terminal renal failure If the toxin is the cause of BEN why when we eliminate exposure to toxin disease still makes a progress and does not remain at a certain stage of renal failure


Koatori rada

Enisa Mešić Evlijana Hasanović

Goran Imamović Amra Šakušić

Mirna Alečković Halilović Dinka Begić

Jasminka Mustedanagić Jugoslav Stahov

Ljiljana Lukić Emir Hodžić

Zlatko Maksimović Denijal Tulumović

Nenad Petković

Besim Prnjavorac

Emir Trnačević




endemski

porodično

hronično




Endemic

Family

Chronically


















































































Jugoslavije 72-79














tubules)






After the War

































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research


















endemski

porodično

hronično




Endemic

Family

Chronically


















































































Jugoslavije 72-79














tubules)






After the War

































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research


































































































Jugoslavije 72-79














tubules)






After the War

































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research




























tubules)






After the War

































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research






















After the War

































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research















































































Klinička slika


Incidenca






Histologically

Incidence


















F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research





























F BiH 2 371 603

RS 1 326 991

Brčko 93 028






December 2013 3 791 622

F BiH 2 371 603

RS 1 326 991

Brčko 93 028

December 1971 3 746 111

December 1991 4 377 033




92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research



















92800 87000 32000 27806 27895 32 800 4208


114663 93028 19041 21584 21289 27799 5216


56600 46 000 5000 3796 9182 7 000 5216


58000 52 000 14 600 17788 12 107 25 000 5216


1978god

52800 52 000 27 000 23896 20261 25 800 4208


1978god

40 000 43 900 5000 3910 7634 7 000 4208


2013god

300 36 90 44 53 80 55


hemodijaliziHD

290 62 40 27 22 34 13


190 8 26 19 14 10 14


30 2 30 2 3 0 3

Broj BEN na

transplantaciji

0 0 0 0 1 1


2013god

20 000 5000 0 0 oko 7000 0

Primjedbe

Ukupno


















Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research





























Hipoteze




anemija






Family history


Anemia















































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research




























































The age



Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research


















Male 556 391 492

Female 444 609 508

Dob (godine) N=36

ispitanika

N=23

ispitanika

Ukupno

N= ispitanika

le25 3 83 0 00 3 51

26-35 5 139 5 217 10 169

36-45 11 306 4 174 15 254

46-55 6 167 3 130 9 152

56-65 6 177 5 217 11 186

gt65 5 139 6 261 11 186





Demographic data




Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research



















Eritrociti 30-56 460 049 322-508 439 049 1552 0127

Hemoglobin 96-169 1376 144 102-162 1345 145 0734 0467

Hematokrit 29-49 4097 40 31-46 3973 382 1117 0269

Željezo 26-475 1924 755 42-316 1617 633 1595 0116

Creatinine 55-132 8036 1783 49-119 7739 155 0656 0515

Klirens

krea

48-126 9114 1948 39-130 867 196 0851 0398

A1M 522-40 108 80 522-667 1622 158 -1524 0138

Cr urin 221-40 1538 1021 265-347 1398 787 0561 0577

A1MCr

urin

020-39 113 091 020-103 153 211 -1001 0321





Laboratory findings



Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research

















Kidney size

measurements

Group I (N=36)

Kidney

Group II (N=23)

Kidney

t-test

(p)


ft

Length in mm

(SD)

1039 (988) 1062 (90) 1038 (80) 1038 (99) 065

(0949)

0925

(035

9)

Parenhim in

mm (SD)

1429 (262) 1483(224) 139 (239) 1387(290) 0548

(0586)

1437

(015

6)

Width in mm

(SD)

4731(636) 4764(473) 4556(516) 4622(513) 1046

(0300)

1090

(028

0)

Kosi in mm

(SD)

4766(791) 4678(682) 447(924) 4648(720) 1304

(0198)

0161

(087

3)














history





























Future research


























history





























Future research






































Future research

















balcan endemic nephropathy in bosnia and herzegovina 50...

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