Bubrežno oštećenje u dvjema različitim populacijama endemskoga žarišta [Kidney damage in two different population of endemic focus]

Vuković Lela, Ivana (2015) Bubrežno oštećenje u dvjema različitim populacijama endemskoga žarišta [Kidney damage in two different population of endemic focus]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Background and objectives: Improvements in agricultural practices in Croatia have reduced exposure to aristolochic acid viacontaminated flour and risk for development of endemic (Balkan) nephropathy. Therefore, due to reduced exposure to aristolochic acid, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15 – 30 years ago would be at lower risk of developing endemic nephropathy. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. ----- Participants, and methods: In this cross-sectional observational study conducted from 2005 to 2010, overall 2822 inhabitans of the villages were enrolled, and 2161 eligible farmers were divided into groups: indigenous inhabitants from endemic nephropathy and non – endemic nephropathy villages and Bosnian immigrants; α1 microglobuline to creatinine ratio 31.5 mg/g and eGFR < 60 ml/min per 1.73m2 were considered to be abnormal. ----- Results: CKD and proximal tubule damage prevalences were significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.9%; p<0.001; 2.0% versus 6.2%; p=0.007, respectively); 20 years ago, Bosnian immigrants observed less Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and less seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, p=0.001). Currently, both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15–30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (OR, 1.64; 95% CI, 1.05 to 2.58; p=0.03), whereas present exposure was not (OR, 1.50; 95% CI, 0.93 to 2.41; p=0.98). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (OR, 0.41; 95% CI, 0.19 to 0.87; p=0.02). ----- Conclusions: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.

Abstract in Croatian

Uvod: Tehnološki napredak agrikulturnih djelatnosti je smanjio kontaminaciju kruha aristolohičnom kiselinom, a time i razvoj endemske nefropatije. Stoga bi imigranti iz ne – endemskih sela Bosne koji su naselili endemska sela hrvatskog žarista unatrag 30 do 15 godina trebali biti pod manjim rizikom razvoja endemske nefropatije. S ciljem testiranja smanjenja izloženosti aristolohičnoj kiselini, analizirali smo prošlu i sadašnju izloženost aristolohičnoj kiselini, oštećenje proksimalnog tubula kao ranog znaka endemske nefropatije, te prevalenciju kronične bubrežne bolesti u starosjedioca endemskih i ne – endemskih sela, te imigranata endemskih sela. ----- Ispitanici i metode: U ovom opservacijskom, presječnom istraživanju od 2005. do 2010. godine je uključeno ukupno 2822 stanovnika ispitivanih sela, od čega je 2161 zadovoljilo kriterije za daljnju analizu i podjeljeno u tri skupine; starosjedioci endemskih i ne – endemskih sela, imigranti koji su se u endemska sela naselili unatrag 30 do 15 godina. Oštećenje proksimalnog tubula je definirano omjerom α1 mikroglobulina i kreatinina u urinu većim od 31,5 mg/g, a kronična bubrežna bolest procijenjenom glomerularnom filtracijom nižom od 60 ml/min/1,73m2. ----- Rezultati: Prevalencija kronične bubrežne bolesti i oštećenja proksimalnog tubula je značajno niža u imigranata nego u starosjedioca endemskih sela (6,9% versus 16,9%; p<0,001; 2,0% versus 6,2%; p=0,007). Unatrag 20-tak godina imigranti endemskih sela su rijeđe viđali biljku Aristolochiae clematitis na svojim poljima (41,9% vs. 67,8%), njene sjemenke među sjemenkama žita namjenjenim za brašno (6,1% vs. 35,6%) nego starosjedioci endemskih sela. Također su imigranti, u odnosu na starosjedioce endemskih sela, češće jeli kupovni nego domaći kruh (38,5% vs. 14,8%, p=0,001). Danas i starosjedioci i imigranti endemskih sela značajno manje viđaju biljku Aristolochiae clematitis i njene sjemenke među sjemenkama žita. Izloženost aristolohičnoj kiselini u prošlosti je povezana s oštećenjem proksimalnog tubula (OR, 1,64; 95% CI, 1,05 do 2,58; p=0,03), dok sadašnja izloženost aristolohičnoj kiselini nije povezana s oštećenjem proksimalnog tubula (OR, 1,50; 95% CI, 0,93 do 2,41; p=0,98). Nadalje, status imigranta je nezavisni negativni prediktor postojanja oštećenja proksimalnog tubula (OR, 0,41; 95% CI, 0,19 do 0,87; p=0,02). ----- Zaključak: Imigranti i starosjedioci endemskih sela su značajno manje izloženi ingestiji aristolohične kiseline u odnosu na prošlost i za očekivati je daljnje smanjenje prevalencije endemske nefropatije i pridruženih karcinoma gornjeg dijela urotela.

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