CHRONIC KIDNEY DISEASE IN RURAL POPULATION.

The aims of the study were to provide data on chronic kidney disease (CKD) prevalence in rural population and to analyze the association with cardiovascular risk factors and aging. A random sample of 2193 farmers (1333 female (F) and 860 male (M), mean age 50.61±17.12) were enrolled. Questionnaire and clinical examination were conducted. Participants provided a spot urine and fasting blood sample. Estimated glomerular filtration rate (eGFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Subjects were classified according to the KDIGO guidelines. The overall prevalence of CKD (eGFR <60 mL/min/1.73 m2) was 8.83% (F vs. M 9.9% vs. 6.3%; p<0.001). Albuminuria (albumin-to-creatinine ratio >30 mg/g) was found in 8.45% (F vs. M p>0.05). Sharp increase in CKD prevalence was found to begin after the sixth decade (29.44% in subjects older than 65 years; F vs. M 30.9% vs. 26.8%; p<0.01). The strongest predictor factors for CKD were age >65 years (OR 22.12), hypertension (OR 6.53), albuminuria (OR 5.71), fasting blood glucose >7 mmol/L (OR 5.49), diabetes (OR 3.07), abdominal obesity (OR 2.05) and non-smoking (OR 0.41). In multivariate analysis, age (OR 1.13), female gender (OR 0.60) and diabetes (OR 1.75) were the independent predictor factors for CKD. In conclusion, CKD prevalence is high in rural population, being higher in women than in men. In both genders, eGFR significantly decreased with aging. Aging is a significant independent predictor of CKD.

Arterial Stiffness in Balkan Endemic Nephropathy, an Environmental Form of Aristolochic Acid Nephropathy.

Balkan endemic nephropathy (BEN), an environmental form of aristolochic acid nephropathy is characterized with later onset and milder forms of hypertension (HT). Thus, we hypothesized that arterial stiffness progresses slower in BEN patients resulting in lower CV mortality. A total of 186 hemodialysed (HD) patients (90 BEN, 96 non-BEN; 67.3 + 13.0 years) were enrolled and followed-up for 25 months. Brachial blood pressure (BP) and pulse wave velocity (PWV) were determined before mid-week dialysis. BEN patients were older (72.1 ± 37.1 vs. 62.8 ± 15.1; p < 0.001), had shorter duration of HT prior commencement of HD than non-BEN patients (36 vs. 84 months; p < 0.001). There were no differences in BP, but BEN patients were treated with less antihypertensive drugs (p < 0.01). BEN patients had lower PWV values at baseline and at the end of follow-up period despite being chronologically older (p < 0.001). Baseline PWV > 10 m/s was associated with higher risk for CV mortality (aHR 1.8 [1.4, 2.4]). In multivariate analyses BEN was predictor of lower PWV. During the follow-up period significantly less CV deaths were observed in BEN vs. on-BEN patients (12 vs. 31; p = 0.001). CV mortality adjusted for other risk factors was significantly lower in BEN group (aHR 0.2 [0.1, 0.5]). Overall BEN patients had longer mean survival time on HD (22.3 vs. 18.2 months; p < 0.001). Observed slower vascular aging (i.e., lower PWV) in BEN patients compared to other ESRD patients is related to the later onset of HT and milder stages of HT during predialytic clinical course and better control of BP and phosphate during HD.

The impact of education and cooking methods on serum phosphate levels in patients on hemodialysis: 1-year study.

INTRODUCTION: Control of serum phosphate is important for patients on hemodialysis. The aim of the study was to determine if education based on phosphorus-reducing techniques in food preparation and thermal processing, and accordingly prepared and applied diets, will lead to better outcomes than a standard education program to improve phosphate control in patients on hemodialysis. METHODS: Forty-seven patients on hemodialysis were divided between an intervention and a control group. All subjects received training about nutrition for hemodialysis patients by trained dietitian. In addition, subjects in the intervention group received additional training in phosphorus-reducing techniques in food preparation and received two hospital meals prepared using suggested cooking methods to reduce the phosphate content of food during dialysis treatment. Serum phosphate, serum albumin, and anthropometric parameters were measured, while nPCR was calculated, at the baseline and during the 1-year study. FINDINGS: No differences in serum phosphate levels were observed between intervention (1.68 mmol/L [1.48-2.03]) and control group (1.88 mmol/L [1.57-2.2]) at baseline (P = 0.130). Although not statistically significant between groups the mean reduction was more apparent in the intervention group (-0.3 mmol/L (-0.4 to 0.1) vs. -0.2 (-0.5 to 0.1)), and lead to significantly reduction of phosphate binder therapy. During the study, the nPCR and anthropometric status of the patients did not change significantly. DISCUSSION: Providing additional education to hemodialysis patients on the specific cooking methods and accordingly prepared meals may decrease serum phosphate levels without significantly affecting nutritional status which may be useful in helping to prevent and treat hyperphosphatemia.

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.

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Angiotensin-converting enzyme gene polymorphism and N-Acetyl-ß-D-glucosaminidase excretion in endemic nephropathy.

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-ß-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.

[Epidemiologic characteristics of endemic nephropathy in Croatia in 2005]. / Epidemioloske osobitosti endemske nefropatije u Hrvatskoj 2005. Godine.

INTRODUCTION: Endemic nephropathy (EN) is chronic renal disease of unknown etiology, characterized with ominous onset and progressive clinical course. It occurs in rural areas in values of tributaries of the river Danube. According to the census from 2001, 10865 farmers live in Croatian endemic focus, i. e. 14 villages in Brod Posavina County. Apart from kidney impairment, high incidence of urothelial cancers is a hallmark of EN. Due to this, most agents that have been investigated were nephrotoxic and carcinogen. PARTICIPANTS AND METHODS: In the last 25 years approximately 70% of 13 Croatian endemic villages' inhabitants were examined following WHO criteria. In spring 2005, 1081 inhabitants of 3 endemic villages (Kaniza, Bebrina, Banovci) and control village of Klakar were examined using the same criteria, and persons were divided as follows: diseased of EN, suspect of having EN, at risk for EN and others. RESULTS: In the group of 1081 persons, we found 25 diseased of EN (12 men and 13 women): Bebrina 11, Banovci 9, Kaniza 5 (chi2 = 8.06; p < 0.05). Prevalence of EN in Kaniza was 0.6%, Bebrina 2.1% and Banovci 2.3%, while prevalence of suspect of EN was 1.7%, 6%, 6%, respectively. One fifth of inhabitants were at risk of having EN. CONCLUSION: This epidemiologic survey that was conducted in spring 2005 found out that prevalence of EN in Croatia is approximately the same as it was in the last decades. Apart from renal impairment, high incidence of urothelial cancers is characteristic of EN in this region. In addition to medical and scientific, we will need social and political help in elucidating the etiology of EN as well as in improving treatment and cure of this poor rural population.

Efficacy of interferon-alpha in the treatment of chronic hepatitis C in dialysis patients: two therapeutic protocols compared.

BACKGROUND: Data on the efficacy of particular therapeutic protocols of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. AIM: To compare the efficacy of two different therapeutic protocols for HD patients. PATIENTS AND METHODS: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-alpha 3 x 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-alpha 3 x 5 MU/week for 3 months, then 1 x 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. RESULTS: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). CONCLUSION: Therapy with IFN-alpha 3 x 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.