Vedran Premužić

Reduced telomere length is not associated with early signs of vascular aging in young men born after intrauterine growth restriction: a paradox?

Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early signs of vascular aging and whether telomere length could be a biomarker of this pathway. Methods: One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams, including blood pressure (BP) measurement routine laboratory analyses, and carotid intima–media thickness (cIMT). Leukocyte telomere length (LTL) was assessed by quantitative PCR. Birth data were obtained from medical records. Results: The SGA group had significantly higher pulse pressure and cIMT, and a trend to increased SBP and heart rate in comparison to the AGA group. Interestingly, SGA men exhibited a 42% longer LTL than the AGA group. LTL was inversely associated with age, BMI, BP and birth parameters. In multiple regression analysis, BMI was the key determinant of SBP and cIMT. Conclusion: Young men born SGA show early signs of vascular aging. Unexpectedly, in our cohort, the SGA group had longer telomeres than the normal controls. Although longer telomeres are predictive of better health in the future, our findings could indicate a faster telomere attrition rate and probable early onset of cardiovascular risk in SGA participants. Follow-up of this cohort will clarify hypothesis and validate telomere dynamics as indicators of future health risks.

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.

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.

Adiponectin is Not Associated With Blood Pressure in Normotensives and Untreated Hypertensives With Normal Kidney Function

AbstractThe 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 (&bgr; = −0.040; P = 0.43) or diastolic BP (&bgr; = 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.

HYPERTENSION IN PRIMARY GLOMERULONEPHRITIS - REPORT FROM THE CROATIAN REFERRAL CENTRE FOR GLOMERULAR DISEASES

Objective: Hypertension (HT) is an important prognostic factor for renal impairment and it accelerates progression of chronic kidney disease (CKD) and vice versa CKD increases blood pressure (BP) and HT prevalence. There are scarce data on prevalence and characteristics of HT in patients with primary glomerulonephritis (PGN) and our aim was to analyse data on HT in this heterogeneous group of patients with renal impairment. Design and method: In these analyses we included 708 subjects with PGN from the Croatian referral centre registry: 195 membranous glomerulopathy (MGN), 136 mesangioproliferative GN (MSGN), 167 IgAnephropathy (IgAN), 154 focal-segmental-glomerolosclerosis (FSGS) and 56 membranoproliferative GN (MPGN). Data were collected from medical records. Results: Prevalence of HT was 44.1%, 60.5%, 63.5%, 66.2% and 81.2% in MSGN, IgAN, MGN, FSGS and MPGN, respectively (p < 0.001). MSGN were the youngest, had less CKD > 3, and had the shortest duration of HT and kidney impairment before the kidney biopsy. MPGN had the highest prevalence of CKD > 3, and the longest duration of HT before the kidney biopsy. In all PGN HT were older, had more CKD > 3 and longer duration of HT before the kidney biopsy. There was no difference between HT and normotension (NT) in prevalence of obesity and duration of kidney impairment before the kidney biopsy. Significant difference in HT prevalence between patients with CKD < 3 and > 3 was observed in MGN, MSGN, IgAN, FSGS and MPGN (54.8% vs.72.2%; 38.6% vs.65.5%; 43% vs.82.2%; 54.7% vs.77.3%;66.6% vs.82.8%). We failed to find differences in HT prevalence among PGN when we analyzed only PGN with CKD > 3 (p > 0.05). However, in the subgroup with CKD < 3 HT prevalence was significantly lower in IgAN an MSGN compared to MGN, FSGS and MPGN (p = 0.01). Conclusions: Age, CKD > 3 and duration of HT before kidney biopsy are the most important determinants of HT in PGN at the time of kidney biopsy. In the subgroup of patients with CKD < 3 observed higher prevalence of HT in MGN, FSGS and MPGN vs. IgAN and MSGN could be explained with differences in pathology and pathophysiology.

Acute Kidney Failure as a Single Complication of Varicella Virus Infection in an Adult Patient

Background: Varicella zoster virus (VZV) is distributed worldwide and is highly contagious. In adults and immunosuppressed patients of any age, the clinical course is much more severe. The most severe complications are pneumonia (the main cause of lethal outcomes in this infection), encephalitis, and very rarely Reye syndrome and hepatitis. Case Presentation: We present a 59-year-old man who came to the emergency department due to varicella and diarrhea. During initial evaluation acute kidney failure (AKF) was diagnosed, and the patient was admitted to the intensive care unit. Continuous renal replacement therapy was applied, and the patient was treated with acyclovir in adjusted doses; renal biopsy revealed acute tubular necrosis. Complete renal function recovery was established after 12 days. Conclusion: VZV infection occurs in a range of clinical scenarios, sometimes presenting only with mild symptoms, but in some other setting it can result in severe AKF even in healthy kidneys. Acute VZV infection can lead to isolated, clinically significant kidney failure. The administration of continuous renal replacement therapy and adjusted doses of acyclovir has a favorable effect on the course of the infection, with complete recovery of kidney function.

Sexual dysfunction as a determinant of cardiovascular outcome in patients undergoing chronic hemodialysis

Sexual dysfunction (SD) is common in men and women with chronic kidney disease (CKD) and is considered as an early marker for cardiovascular (CV) disease. We hypothesized that patients with SD have higher risk for vascular damage of the large arteries, accelerated vascular aging, and consequently higher CV mortality than other end-stage renal disease (ESRD) patients. In this study, the International Index of Erectile Function (IIEF) questionnaire and the Female Sexual Function Index (FSFI) questionnaire were applied in men and women, respectively. Ambulatory blood pressure monitoring (ABPM), arterial stiffness, and ankle-brachial index (ABI) were performed in all patients. Pulse wave velocity (PWV) was significantly slower in non-SD patients (10.5 vs. 8.8 m/s; p < 0.001) with significantly lower number of non-SD patients with PWV > 10 m/s compared to SD patients (p < 0.001). Only 57% of the patients with prior CV event had PWV > 10 m/s. No difference in AIx was observed. Non-SD patients had better values of ABI (0.83 vs. 1.09; p < 0.05) with significantly lower number of non-SD patients with ABI < 0.9 compared to SD patients (p = 0.001) as well as smaller percentage of LVH (57.5% vs. 80.7%; p = 0.01). There were no differences in hemodynamic parameters when patients with SD were divided by sex. Pulse wave velocity was the strongest predictor of lower IIEF and FSFI scores. Mean survival time was longer in non-SD patients than in SD patients (11.6 vs. 10.5 months, p = 0.019). The higher incidence of prior CV events and CV mortality found in SD patients on hemodialysis (HD) is a consequence of accelerated vascular aging. Sexual dysfunction in HD patients should also be considered a marker of subclinical organ damage and future CV events. Our study confirms the predictive role of PWV in HD 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.

OBESITY IS AN IMPORTANT DETERMINANT OF SYSTOLIC BLOOD PRESSURE IN YOUNG MEN BORN SMALL FOR GESTATION AGE: PP.26.329

Objective: Recent reports have shown that concurrent obesity influences blood pressure (BP) phenotype in children born small for gestational age (SGA). Our aim was to investigate the impact of obesity and birth weight on blood pressure (BP) values in young adult men. Subjects and Methods: Young, healthy, normotensive non-treated adult men (N = 185 ; mean age 21.29 + 0.9) years were enrolled. Birth parameters were obtained from medical records. SGA was defined as birth weight (BW) under 10th percentile for gestational age and obesity as BMI > 25 kg/m2. According to the presence or absence of obesity and BW the subjects were divided into four groups: (1) non- obese with normal BW (N = 50), (2) obese with normal BW (N = 40), (3) non-obese SGA (N = 67), (4) obese SGA (N = 28). BP was measured using oscillometric manometer (Omron M6) and Spacelab 90207 device following the ESH/ESC guidelines, and the average 24-hour, daytime and nighttime systolic and diastolic BP values, blood pressure load (BPL), dipper vs. non-dipper status, BP variability (estimated as standard deviation), heart rate and pulse pressure (PP) values were analysed. Results: Systolic BP, 24-hour BP variability and pulse pressure were significantly higher in subjects with SGA than in those born with normal BW (p 0.05). Conclusion: In addition to birth weight and shorter pregnancy duration obesity concurrently and significantly determines systolic BP in young normotensive men and may contribute to the early vascular ageing. Our findings are in agreement with the results obtained in children and point to a need for aggressive implementation of healthy lifestyle as early as possible in the population subset particularly prone to develop hypertension.