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Introduction: Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN., Materials and Methods: A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)., Results: The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup., Conclusions: eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN., Competing Interests: Potential conflict of interest: None declared.

Background: Elevated depressive symptoms that do not reach criteria for a clinical diagnosis of depression are highly prevalent in persons with diabetes. This study was aimed at determining the efficacy of psychoeducation and physical exercise compared with enhanced treatment as usual on 1-year changes in depressive symptoms, diabetes distress and self-management, and quality of life and metabolic control in type 2 diabetes patients with subsyndromal depression., Methods: Adult type 2 diabetes patients who screened positively for depression and expressed a need for professional help with mood-related issues were eligible. Exclusion criteria were clinical depression, current psychiatric treatment and advanced diabetes complications. Out of 365 eligible patients 209 consented to either 6 weekly sessions of psychoeducation (A) and physical exercise (B), or to enhanced treatment as usual (C). Computer-generated sequences for block randomisation stratified by gender were used. Depressive symptoms (primary outcome) and diabetes distress, diabetes self-care, metabolic control and health-related quality of life (secondary outcomes) were analysed at 6-month and 12-month follow-up using repeated-measures ANOVAs., Results: Out of the 74 patients randomised into group A, 66 into B and 69 into group C, 203 completed the interventions, and 179 patients with all 3 assessments were analysed. Depressive symptoms in participants from the psychoeducational, physical exercise and the enhanced treatment as usual groups improved equally from baseline to 12-month follow-up (time versus time x group effect; F = 12.51, p < 0.001, η(2) = 0.07 and F = 0.609, p = 0.656, η(2) = 0.007 respectively), as did diabetes distress and quality of life (all p < 0.001), diabetes self-care (p < 0.001 to < 0.05), triglycerides, and total cholesterol and LDL-cholesterol (p < 0.001)., Conclusions: The employed interventions had comparable positive effects on 12-month psychological and diabetes-related outcomes suggesting that even minimal intervention addressing patients' diabetes-related problems and concerns had favourable clinical implications and might be sufficient to treat subsyndromal depression. Further investigation is warranted to clarify possible mechanisms of improvement., Trial Registration: Current Controlled Trials ISRCTN05673017. The message on assigning the above mentioned ISRCTN was received on 11 August 2010.

The role of adiponectin in hypertension is still a matter of debate. Obtained conflicting results could be mostly explained with diversity of subjects included in different studies. Our aim was to analyze association of adiponectin with blood pressure (BP) in a group of normotensive and untreated hypertensive subjects. Participants (N=257) were selected from a random sample of 2487 subjects enrolled in an observational cross-sectional study. Subjects with diabetes and chronic kidney diseases were excluded. BP was measured using Omron M6 device following ESH/ESC guidelines. Adiponectin concentration was determined by ELISA. There were no differences in adiponectin values (mg/L) between hypertensives and normotensives (median 9.75; iqr: 7.44-17.88 vs 11.35; iqr: 7.43-12.63; P=0.17). On univariate linear regression adiponectin was not associated with systolic or diastolic BP (P>0.05). Furthermore, multivariate analysis did not show significant contribution of log-transformed adiponectin either to systolic (β=-0.040; P=0.43) or diastolic BP (β=0.066; P=0.33). In our group of normotensives and untreated hypertensives with normal kidney function adiponectin was not associated with BP even after adjustment for other risk factors. Our results and conclusions should not be extrapolated to subjects with other characteristics.

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., (Copyright © 2012 S. Karger AG, Basel.)

Background: Tubular proteinuria and enzymuria are hallmarks of endemic nephropathy (EN). The role of I/D angiotensin convertase (ACE) gene polymorphism has not yet been elucidated in this peculiar chronic tubulointerstitial nephritis, and our aim was to investigate the role of this polymorphism in EN focusing on the urinary N-acetyl-β-D-glucosaminidase (NAG) excretion, a biomarker of proximal tubular damage., Methods: ACE genotype and allele frequencies were determined in 229 farmers (147 women and 82 men) from an endemic Croatian village. The farmers were stratified according to the WHO criteria into the following subgroups: those 'at risk' for EN (n = 37), 'suspected of having EN' (n = 57), and 'others' (n = 135)., Results: There were 74 (32.3%) subjects homozygous for the D allele, 99 (43.2%) heterozygous (ID genotype) and 56 (24.4%) homozygous for the I allele. No differences in allele frequency were found between the established WHO subgroups (p > 0.05). In the whole group, DD subjects had significantly higher values of diastolic blood pressure (p = 0.003) and urinary NAG than subjects with ID and II genotype (5.5 ± 1.2 vs. 4.0 ± 3.0 vs. 3.8 ± 4.2, respectively; p = 0.023). The highest values of serum creatinine (p = 0.02), proteinuria (p = 0.03) and urinary NAG (6.0 ± 3.7 vs. 3.7 ± 2.1 vs. 3.0 ± 1.6, respectively; p = 0.008) were observed in those suspected of having EN group with the DD genotype., Conclusion: ACE gene polymorphism is not a risk factor for EN. However, it might influence the clinical course of EN, and increased excretion of NAG might be a prognostic marker of this chronic tubulointerstitial nephritis., (2011 S. Karger AG, Basel.)

Poor control of blood pressure (BP) is one of the main reasons for high cardiovascular mortality and morbidity. The aim of this study was to analyse control of BP in outpatient settings in four biggest towns in Croatia. The study included 412 medical doctors (GP) and 7031 middle-aged patients (62.9 +/- 11.5 years). Mean BP in treated patients was 162.9 +/- 16.8/95.6 +/- 9.9 mmHg. There were no statistically significant differences in systolic (p = 0.173) and diastolic (p = 0.561) BP between men and women. In this group of patients only 8% achieved target BP values. In contrast, and surprisingly, 44.5% of medical doctors and 72% of patients were satisfied with obtained BP control. Higher percentage of male patients vs. female were satisfied with blood pressure control (81.9%:66.9%). BMI < 25 was registered in 22.9% of hypertensive patients, and there was statistically significant difference in BMI between men and women (chi2 = 56.769, p < 0.001). In this study we found a statistically significant difference of hypertension in regard to BMI in both sexes (chi2 = 46.339, p < 0.001; chi(z)2 = 45.992, p = 0.024). BMI was in correlation with severity of hypertension as well as with obtained treatment result. BMI was in correlation with the number of prescribed drugs. According to this, patients with BMI < 25 were prescribed less drugs than those with BMI > 30 (1.4:1,6 p = 0.001). BP control in Croatia is, according to this study, very poor. The main reason for such situation is, beside obesity which determines the stage of hypertension and BP control in both sexes, insufficiently developed conscience in patients and doctors about the importance of stronger blood pressure control. The results indicate the necessity for the more intensive education of the population.

Aim: To explore the hypothesis that chronic dietary poisoning by aristolochic acid could account for the unique geographical distribution, specific pattern of tubulointerstitial fibrosis, occurrence of chronic renal insufficiency, and an increased risk of developing upper urothelial cancer, all of which are associated with endemic nephropathy., Methods: This case-controlled epidemiologic study consisted of three groups of subjects residing in an endemic region of Croatia: (a) patients meeting WHO criteria for endemic nephropathy (n=28), (b) individuals who have been treated for renal insufficiency secondary to other forms of renal disease (n=30), and (c) apparently healthy residents of the endemic village (n= 30). A detailed questionnaire, designed to collect information on demographics, exposure to potentially toxic substances, diet, agricultural practices, and other factors potentially impacting endemic nephropathy was administered to the three study groups. The seeds of Aristolochia clematitis, obtained from plants growing in the endemic region, were extracted with ethanol and analyzed by high-performance liquid chromatography for their aristolochic acid content., Results: The majority of subjects, including 90% of endemic nephropathy patients, recall that the plant Aristolochia clematitis (birthwort, vucja stopa in Croatian) was frequently found in local meadows and wheat fields between 20 and 30 years ago. At that time, endemic nephropathy patients encountered Aristolochia clematitis significantly more frequently than controls (P=0.035). Since then, all three study groups reported a significant increase in the use of herbicides (P<0.001) and reduction in the prevalence of Aristolochia clematitis (P<0.001). Chemical analysis established that the seeds of A. clematitis contain 0.65% aristolochic acid. It is likely that the harvesting process used by local farmers permitted the seeds of A. clematitis to mingle with the wheat grain., Conclusion: Flour used to bake bread, a dietary staple in the endemic region of Croatia, is derived from wheat grain which, in the past, is likely to have been contaminated with seeds of A. clematitis during harvesting. This observation supports the hypothesis that aristolochic acid, a major constituent of the seeds, plays a central role in the development of endemic nephropathy.