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.

Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19.

Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.

Corrigendum to "The Association of TNF-Alpha Inhibitors and Development of IgA Nephropathy in Patients with Rheumatoid Arthritis and Diabetes".

[This corrects the article DOI: 10.1155/2020/9480860.].

The Association of TNF-Alpha Inhibitors and Development of IgA Nephropathy in Patients with Rheumatoid Arthritis and Diabetes.

IgA nephropathy (IgAN) is a rather uncommon complication of TNF-alpha inhibition with a range of findings such as asymptomatic microscopic/macroscopic hematuria or different degrees of proteinuria and could progress to end-stage renal disease. We are reporting three patients with longstanding rheumatoid arthritis (RA), which developed IgAN while receiving TNF-alpha inhibitors. All off our three patients had RA, which lasted 2-4 years, and none of them had a prior history of chronic kidney disease. Two patients were treated with adalimumab while one patient was treated with golimumab. Discontinuation of anti-TNF-alpha therapy and initiation of immunosuppressive therapy led to improvement in serologic abnormalities and renal function in two patients, while the third patient's 24-hour proteinuria was only partially reduced, which supports previous reports on TNF-alpha inhibitor induced autoimmunity. Two of our patients had previously been diagnosed with type 2 diabetes mellitus while the third patient developed diabetes years after the onset of IgAN. This is in line with the previously described association of IgAN and diabetes mellitus. To our best knowledge, this is the first report to analyze the development of IgAN as a potential consequence of anti-TNF-alpha therapy and its possible association with pretreatment or posttreatment diabetes.

Reliability of CKD-EPI predictive equation in estimating chronic kidney disease prevalence in the Croatian endemic nephropathy area.

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.

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.

Adiponectin is not associated with blood pressure in normotensives and untreated hypertensives with normal kidney function.

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 (ß=-0.040; P=0.43) or diastolic BP (ß=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.

[Classification of glomerulopathies]. / Klasifikacija glomerulopatija.

Glomerular diseases may be classified as acute or chronic, primary or secondary, hereditary or acquired, proliferative or non-proliferative etc. The most commonly used is the classification according to the histopathological finding. For certain types of glomerulonephritides histopathological image, as well as clinical presentation, may vary widely. A while ago there was no classification based on the pathogenesis of certain types of glomerular diseases. However, as scientists ellucidate the underlying pathogenetic mechanism, current classifications change. The latter is best shown at the example of membranoproliferative glomerulonephritis.

[Treatment of resistant primary glomerulopathies]. / Lijecenje rezistentnih primarnih glomerulopatija.

Considerable progress in understanding of the pathogenesis of a number of primary glomerular diseases is evident. Scientific achievements in this field led to reclassification of certain types of glomerulonephritides, development of new diagnostic tests, as well as new therapeutic approaches. These new findings will enable us to treat primary glomerulopathies more efficiently thus reducing incidence of resistant disease. Novelties in diagnostics, treatment algorithm, characteristics of the resistant disease and the possibilities of specific treatment are shown in this review.

Evaluation of diagnostic criteria for endemic nephropathy.

Diagnosis of endemic nephropathy (EN) is based on the combination of several clinical and laboratory criteria. Despite extensive research no specific diagnostic biomarker for EN has yet been identified. The aim of the study was to evaluate the diagnostic significance of the variables previously proposed as diagnostic criteria, but also new ones. After an extended questionnaire, the clinical and laboratory examination population in EN villages was classified according to the modified WHO criteria. The urinary active form of TGF-ß was measured with a bioassay using a cell line which expresses luciferase activity. In the study we used ROC analysis to examine the predictive value of the tested variables. In the study there was no difference in haemoglobin level between the study subgroups. Leucine aminopeptidase (LAP) in urine and active urinary TGF-ß levels were increased in the EN diseased group when compared to other subgroups, but they did not fulfil the statistical criteria needed for differentiating a diseased form from other study subgroups. Both kidney length and parenchima thickness, alfa1-microglobulinuria, and kidney function assessed by MDRD formula were the variables that differentiated the study subgroups well. Based on our results the cut-off value of alfa1-microglobulin for screening should be 23.5 mg/g creatinine instead of 15 mg/g creatinine in the present criteria, and for making a diagnosis of EN 31,5 mg/g creatinine. Persons with a positive family history for EN had a 5.8 times greater risk of developing EN when compared to a negative one. Taken together, the above-mentioned variables should be implemented in new uniform diagnostic criteria for EN.

[Blood pressure measurement--do not sweat the small stuff and it is all small stuff?! Position paper of the Croatian national referral center for hypertension, center of excellence of the European Society of Hypertension]. / Mjerenje arterijskoga tlaka--ne mari za male stvari i ostat ce male stvari?! Preporuke Hrvatskoga referalnog centra za hipertenziju centra izvrsnosti Europskog drustva za hipertenziju.

Office blood pressure measurement using mercury sphygmomanometer is the gold standard for making diagnoses of hypertension, evaluation of cardiovascular risk and estimation of obtained control of treated hypertensives. The vast majority of epidemiologic data are based on this method. However, the importance of blood pressure variability, white coat effect as well as availability of simple devices, home and ambulatory blood pressure measurements became routine parts in routine clinical work. As mercury will be soon forbidden in clinical work such devices and methodology will be even more important. In everyday clinical practice all three techniques should be implemented and in this paper advantages and drawbacks of all techniques are discussed. In the end, based on recent data and recommendations of international societies, diagnostic algorithm was proposed. Additionally, we described the technique of non-invasive central blood pressure measurement, determination of pulse wave velocity and calculation of augmentation index, new proposed risk factors.

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.

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.

[Treatment and control of hypertension in Croatia. The BEL-AH study]. / Lijecenje i kontrola arterijske hipertenzije u hrvatskoj. BEL-AH istrazivanje.

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.

[Antihypertensive agents and the risk of new onset diabetes mellitus]. / Antihipertenzivni lijekovi i rizik od novonastale secerne bolesti.

Arterial hypertension is frequently associated with type 2 diabetes mellitus, and both of these diseases are the major risk factors for cardiovascular complications. During the past few years, a number of large randomized clinical trials examined the frequency of new onset diabetes mellitus during administration of antihypertensive drugs. Application of ACE inhibitors or angiotensin receptor blockers reduces the risk for the onset of diabetes mellitus by 20-27%, and calcium channel blockers by 16%. Despite some uncertainties, novel studies have demonstrated an increased risk for cardiovascular complications related to new onset diabetes mellitus. The duration of patient monitoring is also an important factor, as the onset of diabetes-related complications is closely associated with the duration of this disease. Considering all above, the aim of preventing the onset of diabetes is to recognize patients with an increased risk. The risk factors include basal glycemia, positive family history for diabetes mellitus, obesity, metabolic syndrome, and some ethnic groups (South Asia, the Caribbeans). Therefore, increased-risk patients should be subjected to therapy with ACE inhibitor, angiotensin receptor blocker, or calcium channel blocker as the first drug of choice. For these patients, application of thiazides and beta blockers or the combination of these two drugs is not advantageous. However, such a view poses a dilemma whether thiazide diuretics should be the first choice in the treatment of hypertension.

[Influence of visceral obesity on blood pressure values in patients with essential hypertension]. / Utjecaj abdominalne debljine na vrijednosti tlaka u bolesnika s esencijalnom hipertenzijom.

Obesity significantly increases the risk for the occurrence of cardiovascular disease in patients with essential hypertension. The aim of the study was to assess the frequency of obesity, measured by different methods, in patients with essential hypertension, its effect on arterial pressure, and to determine the best correlation between indicators of obesity and arterial pressure. The study included 88 patients with essential hypertension, 32 males, mean age 59.4 (+/- 10.4) years, and 56 females, mean age 62.9 (+/- 8.8) years. Body weight (BW) and height (BH), waist circumference (WC), and body mass index (BMI) were measured for each subject. Arterial pressure was determined using mercury sphygmomanometer. Overweight patients were defined as those with BMI 25-29.9 kg/m2, while obese as those with > or = 30 kg/m2. Abdominal obesity was assessed by WC. WC values exceeding 102 cm for men and 88 cm for women indicated obesity. Body measures of male patients were higher than those for women (BW 92.5 (+/- 14.5) vs 76.7 (+/- 11.5) p < 0.001; BH 175.4 (+/- 7.4) vs 163.4 (+/- 5.8) p < 0.001), significantly higher waist circumference values (102.4 (+/- 12.2) vs 94.1 (+/- 13.9) p = 0.006), with no differences in age, BMI, and arterial pressure values (p > 0.05). Also, no differences were observed in the number of uncontrolled hypertensive patients or number of overweight or obese patients (p > 0.05). The number of obese patients did not differ significantly with regard to the various measurement methods employed (BMI: M 50%, F 37%; waist measurement: M 51%, F 54%). A significant difference was noted in arterial pressure values only in the male patient group on comparing patients with normal BW and obese patients (systolic blood pressure (SBP) 156 (+/- 22.5) vs 142 (+/- 6.4) p = 0.04; diastolic blood pressure (DBP) 94 (+/- 11.6) vs 82.5 (+/- 6.4) p = 0.05). The correlation between obesity indicators and arterial pressure was significant for WC only in the male group (SBP r = 0.33, DBP r = 0.35, p < 0.05). The frequency of obesity does not differ with regard to the determined obesity indicators. Obese men have higher risk for increased arterial pressure values. WC values correlate better with arterial pressure values as it is a more accurate indicator of abdominal obesity.

Endemic nephropathy: the case for chronic poisoning by aristolochia.

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.