Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants.

BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, 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 because of reduced exposure to aristolochic acid. 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer 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). 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 (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; 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.

The assessment of arterial stiffness in endemic (Balkan) nephropathy patients undergoing haemodialysis.

Cardiovascular (CV) complications are the most important cause of morbidity and mortality in patients with advanced chronic kidney disease (CKD). Arterial stiffness (AS) has been recognized as a strong and independent predictor for CV events in CKD. Our aim was to assess indices of AS in a group of Endemic (Balkan) Nephropathy (EN) patients undergoing haemodialysis (HD). Hypertenison was not considered an importnat feauture in earlier stages of the disease, and therefore we presumed that those patients would have lower AS. Interestingly, we found AS to be even higher in this group of EN patients. This result should be confirmed in a larger cohort of EN patients.

Prevalence, treatment and control of hypertension in a Croatian endemic nephropathy area.

BACKGROUND: Hypertension is not considered to be a characteristic of endemic nephropathy (EN). Recent observations suggested that it might be more prevalent than it was reported before. AIM: The aim of our study was to analyze prevalence, treatment and control of hypertension in a Croatian endemic area. METHODS: In the present cross-sectional study, 1,602 farmers were enrolled, 1,246 from EN and 356 from control villages. Epidemiological and medical histories were taken and clinical and laboratory examinations performed for kidney function. Blood pressure was measured following the ESH/ESC guidelines. RESULTS: The prevalence of hypertension in EN villages was higher than in control (50.8 vs. 46.5%, p = 0.005). There was no difference in overall treatment, control of all and treated hypertensives between the villages. In all villages, women were treated more than men (EN 41.6 vs. 28.4%, p < 0.001; control 46.4 vs. 27.3%, p < 0.001), but better control of treated was achieved in men (EN 24.7 vs. 17.4%, p = 0.002; control 29.6 vs. 15.5%, p = 0.002). Women had lower income and level of education than men (p < 0.01). CONCLUSION: Hypertension is highly prevalent in endemic villages. In all villages, men had better blood pressure control despite being treated less. This finding could be explained by poorer education and income in women.

[Diabetic nephropathy and prevention of diabetic nephropathy caused chronic renal insufficiency]. / Dijabeticka nefropatija i prevencija kronicnog bubreznog zatajenja uzrokovanog dijabetickom nefropatijom.

There is an ongoing trend of a rapid increment in the frequency of diabetes mellitus, expecially the non-insulin dependent form. By the end of the 2nd millenium 150 million cases were recorded worldwide, while the estimations predicted doubling the number by the year 2030. Numerous chronic complications accompany the disease, among them micro-, as well as macrovascular prevail, affecting small and large blood vessels. This paper provides a literature review on the topic of diabetic nephropathy, the main microvascular complication of diabetic disease. Microalbuminuria is the earliest sign of the diabetic renal involvement, with more than 30 mg and less than 300 mg of albumins in 24 h urine sample. The reduction of renal function begins with albuminuria leaving microalbuminuria level and entering the pathologic proteinuria range. Renal failure advances through the 5 stages, the final fifth occurring fortunately only in a minor proportion of the patients. The final stage ensues in 232 of 100 000 diabetic patients, according to the US data. However, in many developed countries there are 30-40% of new patients entering chronic dialysis treatment for diabetic nephropathy. Pathogenesis of diabetic nephropathy is based on hyperglycemia and distinct hemodynamic changes, glomerular hyperfiltration and high intraglomerular pressure. The important role have oxidative stress, advanced glycation end products, some cytokines, growth factors and sorbitol pathway. Nevertheless, genetic influence is considered by far the most important risk factor for diabetic nephropathy. Heritage determines the susceptibility in one and the protection in another diabetic patient. At the moment of pathologic proteinuria occurrence, glomerular filtration rate begins to decline for 1.2 ml/min/monthly in some patients, making the annual reduction of 7-14 ml/min/1.73 m2 of body surface area. Improving glycemia, blood pressure control, renal anemia correction with rHu-Epo, dyslipidemia control, reduction in protein intake, i.e. management of the nongenetic factors, could slower the renal function loss in some of the patients. Hence, these measures could reduce the proportion of the patients reaching end-stage renal disease, having in mind that morphological and functional changes are reversible only within certain limits. Therefore, the success of kidney protection is better if commenced earlier.