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This chapter describes the Israeli health system, kidney disease epidemiology in adult and pediatric populations, the major causes of chronic kidney disease, renal replacement therapies, and strategies to improve the quality of medical practices provided to kidney patients. We also portray the history and highlights of Israeli nephrology.

Background The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries. Methods Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated. Results In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.m.p.), 62% of patients were men, 51% were ≥65 years of age and 20% had diabetes mellitus as cause of kidney failure. Treatment modality at the onset of KRT was haemodialysis (HD) for 84%, peritoneal dialysis (PD) for 11% and pre-emptive kidney transplantation for 5% of patients. On 31 December 2018, the prevalence of KRT was 897 p.m.p., with 57% of patients on HD, 5% on PD and 38% living with a kidney transplant. The transplant rate in 2018 was 35 p.m.p.: 68% received a kidney from a deceased donor, 30% from a living donor and for 2% the donor source was unknown. For patients commencing dialysis during 2009–13, the unadjusted 5-year survival probability was 42.6%. For patients receiving a kidney transplant within this period, the unadjusted 5-year survival probability was 86.6% for recipients of deceased donor grafts and 93.9% for recipients of living donor grafts.

WOS:000577244700025 PubMed ID: 32897277 Background. This article presents a summary of the 2017 Annual Report of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 37 countries. Methods. The ERA-EDTA Registry received individual patient data on patients undergoing RRT for ESRD in 2017 from 32 national or regional renal registries and aggregated data from 21 registries. The incidence and prevalence of RRT, kidney transplantation activity and survival probabilities of these patients were calculated. Results. In 2017, the ERA-EDTA Registry covered a general population of 694 million people. The incidence of RRT for ESRD was 127 per million population (pmp), ranging from 37 pmp in Ukraine to 252 pmp in Greece. A total of 62% of patients were men, 52% were >= 65 years of age and 23% had diabetes mellitus as the primary renal disease. The treatment modality at the onset of RRT was haemodialysis for 85% of patients. On 31 December 2017, the prevalence of RRT was 854 pmp, ranging from 210 pmp in Ukraine to 1965 pmp in Portugal. The transplant rate in 2017 was 33 pmp, ranging from 3 pmp in Ukraine to 103 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2008-12, the unadjusted 5-year patient survival probability for all RRT modalities combined was 50.8%. ERA-EDTA The ERA-EDTA Registry is funded by the ERA-EDTA. This article was written by Kramer et al. on behalf of the ERAEDTA Registry, which is an official body of the ERA-EDTA. In addition, M.F.S.R. reports personal fees from NxStage outside the submitted work and K.J.J. reports grants from the ERA-EDTA during the conduct of the study and a speaker fee from Fresenius Medical Care outside the submitted work.

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure. European UnionEuropean Commission [PP-01-2016]; ERAEDTA This study was funded by the European Union (grant PP-01-2016) and ERAEDTA.

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease.We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease.During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults40 years of age, 10.40 [95% CI, 7.96 to 13.59]).A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

BACKGROUND The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. METHODS Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. RESULTS Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, P

Publisher's version (útgefin grein), Background: This article summarizes the ERA-EDTA Registry's 2016 Annual Report, by describing the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2016 within 36 countries. Methods: In 2017 and 2018, the ERA-EDTA Registry received data on patients undergoing RRT for ESRD in 2016 from 52 national or regional renal registries. In all, 32 registries provided individual patient data and 20 provided aggregated data. The incidence and prevalence of RRT and the survival probabilities of these patients were determined. Results: In 2016, the incidence of RRT for ESRD was 121 per million population (pmp), ranging from 29 pmp in Ukraine to 251 pmp in Greece. Almost two-thirds of patients were men, over half were aged ≥65 years and almost a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 84% of patients. On 31 December 2016, the prevalence of RRT was 823 pmp, ranging from 188 pmp in Ukraine to 1906 pmp in Portugal. In 2016, the transplant rate was 32 pmp, varying from 3 pmp in Ukraine to 94 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2007-11, the 5-year unadjusted patient survival probability on all RRT modalities combined was 50.5%. For 2016, the incidence and prevalence of RRT were higher among men (187 and 1381 pmp) than women (101 and 827 pmp), and men had a higher rate of kidney transplantation (59 pmp) compared with women (33 pmp). For patients starting dialysis and for patients receiving a kidney transplant during 2007-11, the adjusted patient survival probabilities appeared to be higher for women than for men., The ERA-EDTA Registry is funded by the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). This article was written by Anneke Kramer et al. on behalf of the ERA-EDTA Registry, which is an official body of the ERA-EDTA. In addition, Dr. Caskey reports funding from the National Health Service during the conduct of the study. Dr. Finne reports personal fees from Baxter, outside the submitted work and Dr. Slon Roblero reports personal fees from NxStage, outside the submitted work.

Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists.To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (500 ng/ml) ferritin levels.In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation.Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period.Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.

BACKGROUND Patients with end-stage renal disease who undergo chronic renal replacement therapy (RRT) have a higher incidence of cancer. A limited number of studies addressed the risk for cancer in children exposed to RRT. The purpose of the present study was to examine whether children undergoing RRT in Israel are at increased risk for all-site and specific cancers. SUBJECTS AND METHODS The study population comprised 674 children 0 to 19 years of age who were registered between January 1990 and December 2012 in the Israel National Renal Replacement Therapy Registry. The Registry database was linked with the Israel National Cancer Registry to trace cancer incidence. Variables associated with malignancy were estimated by univariate analysis. Standardized incidence ratios for cancer were calculated using the general Israel population 0 to 15 years of age, for the corresponding years 1990-2012, as a reference. RESULTS Seventeen children developed cancer during the follow-up period. Younger age at RRT initiation was the only variable associated with malignancy in the univariate analysis (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99; P=0.03). Cancer incidence was 6.7-fold higher among children undergoing RRT than the general population. CONCLUSIONS Children treated by chronic RRT have a higher incidence of cancer than their peers, and therefore should be followed closely.

Publisher's version (útgefin grein), Background This article summarizes the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry’s 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. Methods In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. Results In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006–10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9–50.1)., The ERA-EDTA Registry is funded by the ERA-EDTA. This article was written by Anneke Kramer et al. on behalf of the ERA-EDTA Registry, which is an official body of the ERA-EDTA.

Higher health-related quality of life (HRQOL) in dialysis patients has been associated with fewer hospitalizations and lower mortality. Since Arab patients on dialysis have better survival rates than Jewish patients, we hypothesized that they would have higher HRQOL. We also studied the impact of several risk factors on HRQOL in each population. Based on a national dialysis registry, patients from 64 hemodialysis units were recruited to participate. Patients who consented were interviewed face-to-face, using the Kidney Disease Quality of Life Short Form (KDQOL-SF36) questionnaire. Five hundred and fifty-eight (50.6%) Jewish and 544 (49.4%) Arab patients participated in the study. For Arab patients mean crude scores for the “mental component summary” and KDQOL scores were significantly lower than for Jewish patients [31.6 (95% Cl 30.0–33.3) vs. 38.0 (95% Cl 36.1–39.9), p

Objective Persistent hypertension in adulthood is a leading cause of end-stage renal disease (ESRD). Whether lower blood pressure (BP) values, in the range of prehypertension, are also associated with future occurrence of ESRD is unclear. Even less clear is the potential risk of early prehypertension appearing in adolescence. To address this question, we examined whether BP measurements in the prehypertensive range at age 16-19 years predict adult ESRD. Methods Medical data on 2194 635 16-19-year-old adolescents examined for medical fitness prior to military service from 1977 to 2013 were linked to the Israeli ESRD registry in this nationwide population-based cohort study. Incident cases of ESRD were recorded. Survival models were applied. Results During 35 007 506 person-years of follow-up (median follow-up 16.8 years), there were 690 ESRD cases, with an overall incidence rate of 1.97 cases per 100 000 person-years. Examinees with elevated BP readings in the prehypertensive range (BP between the 90th and 95th percentiles or between 120 and 139/80-89 mmHg) had increased incidence of ESRD with a hazard ratio of 1.32 (95% confidence interval, 1.11-1.58) adjusted for year of birth, age at examination, sex, BMI, education, socioeconomic status, and country of origin. Hypertension (BP above the 95th percentile or above 140/90 mmHg) was associated with a hazard ratio of 1.44 (95% confidence interval, 1.17-1.79). A spline model demonstrated a nadir of risk at SBP values as low as 94 mmHg. Conclusion Asymptomatic, healthy adolescents with prehypertension have a 32% increased risk for subsequent ESRD, compared with adolescents with optimal BP.

Background This article provides a summary of the 2011 ERA–EDTA Registry Annual Report (available at www.era-edta-reg.org). Methods Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were calculated for those registries providing individual patient data. Results The overall unadjusted incidence rate of RRT in 2011 among all registries reporting to the ERA–EDTA Registry was 117 per million population (pmp) (n = 71.631). Incidence rates varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall transplant rate was reported from Spain, Cantabria (81 pmp), whereas the highest rate of living donor transplants was reported from Turkey (39 pmp). For patients who started RRT between 2002 and 2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence interval (CI) 46.6–47.0], and on dialysis 39.3% (95% CI 39.2–39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2–87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6–95.0) for kidneys from living donors.

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

High blood and tissue concentrations of glucose and advanced glycation end products (AGEs) are thought to play an important role in the development of diabetic vascular complications. Thioredoxin interacting protein (TXNIP) is up-regulated in response to high levels of glucose and is an endogenous inhibitor of thioredoxin (TRX), and may play a contributory role in the occurrence of diabetic-related vascular diseases. Vitamin D inhibits endothelial proliferation and is a cardiovascular protective agent. The present study evaluated the impact of paricalcitol and calcitriol on the endothelial inflammatory and TXNIP pathways in cultured endothelial cells exposed to a diabetic-like environment. Fresh human umbilical vein cord endothelial cells (HUVEC) were treated for 24 h with 200 μg/ml AGE-HSA and 250 mg/dl glucose concentrations, with paricalcitol or calcitriol. IL6, IL8, NFκB (p50/p65), receptor of AGE (RAGE), TXNIP, and TRX expressions were evaluated at the levels of mRNA, protein, and TRX activity. Calcitriol and paricalcitol significantly down-regulated the markers involved in the inflammatory responses. Only paricalcitol induced a significant decrease in TXNIP mRNA and protein expressions. Neither paricalcitol nor calcitriol affected TRX reductase activity or TRX mRNA and protein expressions. Our findings indicate that in an endothelial diabetic-like environment, paricalcitol and calcitriol significantly decreased the expression of genes involved in the inflammatory pathway. In this in vitro study, it seems that the TRX antioxidant system was not involved. The different effects found between paricalcitol and calcitriol might reflect the selectivity of vitamin D receptor (VDR) activation.

There are counterintuitive but consistent observations that African American maintenance dialysis patients have greater survival despite their less favorable socioeconomic status, high burden of cardiovascular risks including hypertension and diabetes, and excessively high chronic kidney disease prevalence. The fact that such individuals have a number of risk factors for lower survival and yet live longer when undergoing dialysis treatment is puzzling. Similar findings have been made among Israeli maintenance dialysis patients, in that those who are ethnically Arab have higher end-stage renal disease but exhibit greater survival than Jewish Israelis. The juxtaposition of these two situations may provide valuable insights into racial/ethnic-based mechanisms of survival in chronic diseases. Survival advantages of African American dialysis patients may be explained by differences in nutritional status, inflammatory profile, dietary intake habits, body composition, bone and mineral disorders, mental health and coping status, dialysis treatment differences, and genetic differences among other factors. Prospective studies are needed to examine similar models in other countries and to investigate the potential causes of these paradoxes in these societies. Better understanding the roots of racial/ethnic survival differences may help improve outcomes in both patients with chronic kidney disease and other individuals with chronic disease states.

Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era- edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9- 51.2) for patients with DM as the cause of ESRD.

Background Current blood pressure (BP) classification is based on the recent recommendations of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) and the 2003 European Society of Hypertension–European Society of Cardiology Guidelines for the Management of Arterial Hypertension. The JNC-7 introduced a new concept, prehypertension, and recommended health-promoting lifestyle modifications for these individuals. Obesity is also recognized as a major risk factor for the development of hypertension. We aimed to determine the prevalence of hypertension and obesity in a large cohort of adolescents and to assess whether prehypertension and body mass index (BMI) increase with increasing age. Methods A cross-sectional population-based study was performed using data collected during 1996 to 2002 in an army recruitment examination of 560,588 Israeli individuals 16.5 to 19 years of age. The subjects were divided according to gender and stratified by increasing 6-month intervals into five groups. Prehypertension was defined as BP 120 to 139 / 80 to 89 mm Hg. Overweight was defined as BMI 25 to ≤30 and obesity as BMI >30 kg/m2. Results Mean systolic BP (SBP) and diastolic BP (DBP) were significantly higher in male subjects for all groups. By applying the JNC-7 criteria, 56.8% of male subjects and 35.8% of female subjects would be considered prehypertensive. There was a statistically significant increase in the mean SBP and DBP with age and BMI. Among male subjects 10.9% were overweight and 3.3% were obese; among female subjects, 11.1% were overweight and 3.2% were obese. The BMI did not increase with increasing age. The prevalence of prehypertension was significantly higher in obese subjects. Conclusions Prehypertension is very common among Israeli adolescents. A substantial number of adolescents exhibit a BMI greater than normal. As both of these factors are known to be asssociated with increased cardiovascular risk, early institution of healthful lifestyle changes in a large proportion of this age group is recommended.

Contains fulltext : 155733.pdf (Publisher’s version ) (Open Access) BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as >/=65 years). METHODS: Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients >/=75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients >/=75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients >/=65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3-60.0) which fell to 39.3% (95% CI: 38.7-39.9) in patients 65-74 years and 21.3% (95% CI: 20.8-21.9) in patients >/=75 years.

Apart from seeking target organ damage, the investigation of hypertension is primarily aimed at finding a treatable cause of the hypertension. The finding of one such cause is usually construed as being the sole culprit responsible for the patient's elevated blood pressure. The existence of multiple aetiologies of secondary hypertension in one patient is infrequent. In this report, we describe such a patient in whom secondary hypertension due to Cushing's disease, renovascular and finally baroreflex failure was successively documented.

Objective There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. Methods We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16–20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. Results During 30 years of follow-up, death rates were 8.73/10 4 versus 4.32/10 4 person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. Conclusions FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.

Background. The extent of involvement of the subcutaneous Tenckhoff catheter tract in CAPD peritonitis and catheter-related infections is of major therapeutic importance. By definition. both peritonitis and exit-site infections do not involve the catheter tract. However, diagnosis of these infections as well as the more sinister tunnel infection is based mainly on clinical signs. Methods. We examined the usefulness of ultrasound examination (US) of the catheter tract in delineating catheter-related (exit-site and tunnel) infections, and their relationship to each other and to peritonitis. CAPD patients with no evidence of peritonitis or catheter-related infections for 6 months prior to examination served as controls. US were performed by one of two experienced radiologists using the Acuson 128XP/10 scanner with a 7-MHz linear transducer. A positive US was defined as an area of hypoechogenicity (indicative of fluid collection) >2 mm in width along any portion of the catheter tract. Findings were localized into segments (S) as follows : S1, limited to external cuff ; S2, intercuff segment adjacent to the external cuff : S3, intercuff segment adjacent to the internal cuff ; S4, limited to the internal cuff ; and S5, involvement extending throughout the catheter tract. Results. Between March 1993 and January 1995, 39 CAPD patients, all with a double-cuff straight Tenckhoff catheter with the exit site situated above the point of entry into the peritoneum were studied. A total of 56 US were performed divided among 26 episodes of peritonitis, four tunnel infections, 13 exit-site infections, and 13 controls. There were 30 positive US distributed among 16 peritonitis, four tunnel, eight exit site infections and two control patients. The two positive controls went on to develop peritonitis within 1 month of the US. The majority of the US findings (13/16 in episodes of peritonitis and 5/8 exit site infections) were localized to segment 4, that is, to the internal cuff region. Apart from a significant increase in width in all infected segments versus a normal tunnel, no differences in size were seen between peritonitis, exit-site, or tunnel infections, nor were there any differences in size and localization in these infections when comparing the offending organism (Gram-positive, negative, or culture negative). Conclusions. We conclude that peritonitis and exit-site infections are frequently accompanied by involvement of the catheter tract. The localization of infection to the internal cuff region in cases of exit-site infection probably occurred as a result of downward migration along the catheter tract. This supports the notion that ideally the exit site should be pointing caudally or that the peritoneal catheter have a swan-neck configuration. With regard to peritonitis, infection within the peritoneal cavity appears to extend and involve the internal cuff region. Thus both the internal and external cuffs do not seem to pose an effective barrier against the spread of infection. Based on our data, we recommend that US be performed as a routine investigation in all cases of exit-site infection and in cases of refractory or relapsing peritonitis.

Background The relationship between adolescent body mass index (BMI) and future risk for end-stage renal disease (ESRD) is not fully understood, nor is it known the extent to which this association is limited to diabetic ESRD. We evaluated the association between BMI in adolescence and the risk for all-cause, diabetic, and nondiabetic ESRD. Methods Medical data about 1 194 704 adolescents aged 17 years who had been examined for fitness for military service between January 1, 1967, and December 31, 1997, were linked to the Israeli ESRD registry in this nationwide population-based retrospective cohort study. Incident cases of treated ESRD between January 1, 1980, and May 31, 2010, were included. Cox proportional hazards models were used to estimate the hazard ratio (HR) for treated ESRD among study participants for their BMI at age 17 years, defined in accord with the US Centers for Disease Control and Prevention BMI for age and sex classification. Results During 30 478 675 follow-up person-years (mean [SD], 25.51 [8.77] person-years), 874 participants (713 male and 161 female) developed treated ESRD, for an overall incidence rate of 2.87 cases per 100 000 person-years. Compared with adolescents of normal weight, overweight adolescents (85th to 95th percentiles of BMI) and obese adolescents (≥95th percentile of BMI) had an increased future risk for treated ESRD, with incidence rates of 6.08 and 13.40 cases per 100 000 person-years, respectively. In a multivariate model adjusted for sex, country of origin, systolic blood pressure, and period of enrollment in the study, overweight was associated with an HR of 3.00 (95% CI, 2.50-3.60) and obesity with an HR of 6.89 (95% CI, 5.52-8.59) for all-cause treated ESRD. Overweight (HR, 5.96; 95% CI, 4.41-8.06) and obesity (HR, 19.37; 95% CI, 14.13-26.55) were strong and independent risk factors for diabetic ESRD. Positive associations of overweight (HR, 2.17; 95% CI, 1.71-2.74) and obesity (HR, 3.41; 95% CI, 2.42-4.79) with nondiabetic ESRD were also documented. Conclusions Overweight and obesity in adolescents were associated with significantly increased risk for all-cause treated ESRD during a 25-year period. Elevated BMI constitutes a substantial risk factor for diabetic and nondiabetic ESRD.

Context Few data are available on long-term outcomes among adolescents and young adults with persistent asymptomatic isolated microscopic hematuria. Objective To evaluate the risk of end-stage renal disease (ESRD) in adolescents and young adults with persistent asymptomatic isolated microscopic hematuria. Design, Setting, and Participants Nationwide, population-based, retrospective cohort study using medical data from 1 203 626 persons aged 16 through 25 years (60% male) examined for fitness for military service between 1975 and 1997 were linked to the Israeli treated ESRD registry. Incident cases of treated ESRD from January 1, 1980, to May 31, 2010, were included. Cox proportional hazards models were used to estimate the hazard ratio (HR) of treated ESRD among those diagnosed as having persistent asymptomatic isolated microscopic hematuria. Main Outcome Measures Treated ESRD onset, defined as the date of initiation of dialysis treatment or the date of renal transplantation, whichever came first. Results Persistent asymptomatic isolated microscopic hematuria was diagnosed in 3690 of 1 203 626 eligible individuals (0.3%). During 21.88 (SD, 6.74) years of follow-up, treated ESRD developed in 26 individuals (0.70%) with and 539 (0.045%) without persistent asymptomatic isolated microscopic hematuria, yielding incidence rates of 34.0 and 2.05 per 100 000 person-years, respectively, and a crude HR of 19.5 (95% confidence interval [CI], 13.1-28.9). A multivariate model adjusted for age, sex, paternal country of origin, year of enrollment, body mass index, and blood pressure at baseline did not substantially alter the risk associated with persistent asymptomatic isolated microscopic hematuria (HR, 18.5 [95% CI, 12.4-27.6]). A substantially increased risk for treated ESRD attributed to primary glomerular disease was found for individuals with persistent asymptomatic isolated microscopic hematuria compared with those without the condition (incidence rates, 19.6 vs 0.55 per 100 000 person-years, respectively; HR, 32.4 [95% CI, 18.9-55.7]). The fraction of treated ESRD attributed to microscopic hematuria was 4.3% (95% CI, 2.9%-6.4%). Conclusion Presence of persistent asymptomatic isolated microscopic hematuria in persons aged 16 through 25 years was associated with significantly increased risk of treated ESRD for a period of 22 years, although the incidence and absolute risk remain quite low.

Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions, and calcitriol may improve the cardiovascular complications. Therefore, we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor-kappaB in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-human serum albumin (HSA). AGE-HSA induced a decrease in endothelial nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA-treated endothelial cells improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of interleukin-6 mRNA in the presence of AGE-HSA was also blunted by calcitriol. The NF-kappaB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kappaBalpha (IkappaBalpha) and an increase in phosphorylated (p)-IkappaBalpha levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-kappaB-p65 DNA binding activity, a phenomenon related to an increased expression of IkappaBalpha. This increase was correlated to declined p-IkappaBalpha levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities.

It is estimated that by 2025,1.5 billion adults worldwide will be hypertensive. Early identification of the population at risk would lead to improved utilization of preventive measures. We aimed to evaluate whether baseline body mass index (BMI) and blood-pressure (BP) values during adolescence (categorized according to the guidelines of the European Society of Hypertension-European Society of Cardiology) are of use in predicting the development of hypertension in young adulthood.The study population consisted of 18,513 male regular army personnel who were initially recruited at 16.5 and 19 years of age between 1976 and 1996. The main outcome was the percentage of subjects who developed hypertension (or =140 systolic andor =90 diastolic) at ages 26 to 45 years.At baseline, BP categories were: optimal, 5961 (32.2%); normal, 7998 (43.2%); and high normal, 4554 (24.6%). Moreover, 1377 (7.4%) were overweight (BMI 25-30 kg/m(2)), and 199 (1.1%) were obese (BMI30 kg/m(2)). At follow-up, 2277 (12.3%) subjects developed hypertension. The percentages progressing to hypertension were 9.46%, 11.99%, and 16.56% for optimal, normal, and high-normal categories, respectively (P.01). Odds ratios (OR) for the development of hypertension in the normal and high-normal categories versus optimal were 1.30 (95% confidence interval [CI], 1.22-1.39) and 1.79 (95% CI, 1.67-1.93), respectively, adjusted for age and BMI. The ORs for hypertension in overweight and obese versus normal BMI were 1.75 (95% CI, 1.66-1.86) and 3.75 (95% CI, 3.45-4.07), adjusted for age and BP. Of 9762 remaining at ideal BMI at follow-up, the percentages progressing to hypertension were 5.3%, 6.4%, and 9.5% for optimal, normal, and high normal (at baseline) (P.01).The risk of developing hypertension in young adulthood may be predicted by BP categories and BMI at adolescence.

Background. The prevalence of hepatitis C (HCV) antibodies in dialysis patients is considerably higher than that found among healthy blood donors. This increased seroprevalence has been correlated to increased duration of dialysis, mode of dialysis and to the number of blood transfusions administered. However, factors other than nosocomial ones also seem to play a part in disease transmission. The role of the patient's ethnic origin, possibly reflecting on his/her genetic makeup has received scant attention. In this study, HCV seroprevalence in our dialysis population, which consists of three major ethnic subgroups (Ashkenazi Jews, Sephardi Jews and Arabs), was examined. Methods and results. Altogether HCV seropositivity was determined in 120 dialysed patients-65 males/55 females (76 hemodialysis, 44 CAPD), using second generation ELISA confirmed by RIBA-2. Mean age was 59.7±15.7 (range 16-86 years). Patients had to have been on dialysis for a minimum of 3 months (mean duration 45.2±44.5 months). Patients whose end-stage renal disease was due to diabetic nephropathy (DN) or those who had previously been transplanted (TP) were considered as separate groups and compared to the group as a whole. Of the 120 patients, there were 49 Ashkenazi Jews (40.8%), 57 Sephardi Jews (47.5%) and 14 Arabs (11.7%). Overall HCV prevalence was 21.7%, (26/120) with a significantly greater prevalence in HD compared to CAPD (30.3 vs. 6.8%, P

Multiple factors are involved in the pathogenesis of hypertension in the obese individualTo evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.We evaluated three groups: 25 obese hypertensive patients (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50 mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76, SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5, MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin (radio-immunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.Obese hypertensive patients had significantly higher basal RMR and plasma NE levels insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and plasma NE and insulin. Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.A reduction in sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

Diffuse Proliferative Glomerulonephritis (DPGN) is the most ominous form of lupus nephritis. Treatment according to the "NIH Protocol" is considered by many physicians to be the treatment of choice for this form of disease, but this is not accepted exclusively. OUR AIM: To evaluate the outcome of SLE patients with biopsy proven DPGN diagnosed and treated in our department, between the years 1976-1996, and to compare the results achieved by using the "NIH Protocol" as opposed to other forms of treatment.The archive of the Department of Pathology was screened for patients with SLE and DPGN. The specimens were re-examined to confirm the diagnosis and calculate the activity and chronicity scores. The pertinent data was extracted from the patients medical records.Twenty-six patients fulfilled the inclusion criteria, 22 females and 4 males. We followed-up on these patients for an average period of 89 +/- 74 months (range 9-255). More than 80% of the patients achieved remission, about a third experienced at least one relapse. Only one patient died during the follow-up period and 4 others developed end stage renal failure necessitating chronic renal replacement therapy. Sixteen patients were treated according to the NIH protocol, the other 10 were treated with high dose Prednisone, either alone or in combination with oral immunosuppressive drugs. At time of diagnosis there was no statistically significant difference between the two groups regarding the age and gender distribution, blood levels of creatinine and C3 and the level of proteinuria. We were unable to demonstrate any statistically significant difference between the two groups in any of the evaluated parameters, regarding neither patient and kidney survival nor the type and rate of complications.Following treatment, patient and kidney survival is good. The NIH protocol is the treatment of choice, but the use of high dose steroids for six months with or without oral immunosuppressive drugs may yield comparable results in selected cases.

Using a gas mask (GM) may involve considerable inconvenience, impairment of respiration and communication, and serious psychological reactions. The medical literature is primarily focused on the occupational aspects of using the GM by young and healthy workers. In contrast, there is hardly any information concerning the use of GMs by large, unselected populations, including children, the elderly, and the sick. Issuing GMs to all residents of Israel prior to Operation Desert Storm created an urgent need to define the populations whose health might be jeopardized by using the standard GM. Adding an active air supply system (AASS) to a standard GM may ease the burden on this high-risk group. We evaluated the physiological aspects of breathing with a GM, with and without AASS, in respect to pathophysiology of diseases, and reached a set of criteria for identifying those who may be endangered by a GM and are expected to benefit from the AASS. The method used to sort and identify those entitled to the AASS is described.

Background. Recently we observed a unique clinical phenomenon, namely, orthostatic or postural hypoxaemia in a 72-year-old female adult polycystic kidney disease (APKD) patient, maintained on CAPD. Extensive investigations failed to yield a satisfactory explanation for her ambulatory hypoxaemia. Methods. To validate our observation, 15 dialysed patients underwent blood gases analyses in both the supine and ambulatory positions (SpO 2 and ApO 2 respectively). Patients were divided into two groups: group 1 (n-7) whose end-stage renal failure (ESRF) was due to APKD and group 2 (n-8) in whom ESRF was due to other causes. Both haemodialysed (HD) and CAPD patients were included. ApO 2 was determined as the pO 2 immediately upon standing up. Readings in HD patients were taken at the end of the dialysis session, that is, at the patients' dry weight. Results. Respective SpO 2 and ApO 2 of the two groups were 85±17.1 and 78±20.5 vs 85.8±19 and 91±21 mmHg. Delta change in pO 2 defined as the mean decrease (negative value) or mean increase (positive value) of ApO 2 in relation to SpO 2 was -7.85 (group 1) vs + 5.2mmHg (group 2), P

Background. Pefloxacin, a fluorinated 4-quinolone, has recently been advocated as a first-line treatment for minimal-change nephropathy (MCN) or focal segmental glomerulosclerosis ( FSGS ). To further evaluate this issue we have utilized an animal model resembling human MCN, namely adriamycin-induced nephrotic syndrome in Wistar male rats. Methods. Adriamycin at a dose of 7 mg/kg was injected intravenously to all rats at day zero. Rats were divided into two groups: group A (n = 20) given only water served as the control group while group B (n = 19) was administered pefloxacin at 150 mg/kg. At days 7, 14, 21 and 28, the rats were placed in metabolic cages and daily proteinuria determined. Results. The nephrotic syndrome developed in all rats within 7 days of adriamycin administration. At day 7, proteinuria in group B was 173 ± 78 vs 423 ± 626 mg/day in group A, P

Background High blood and tissue concentrations of glucose and advanced glycation end-products are believed to play an important role in the development of vascular complications in patients with diabetes mellitus (DM) and chronic kidney disease. MicroRNAs (miRNA) are non-coding RNAs that regulate gene expression in a sequence specific manner. MiRNA are involved in various biological processes and become novel biomarkers, modulators and therapeutic targets for diseases such as cancer, atherosclerosis, and DM. Calcitriol (the active form of vitamin D) may inhibit endothelial proliferation, blunt angiogenesis, and be a cardioprotective agent. Calcitriol deficiency is a risk factor for DM and hypertension. The aim of this project was to study the miRNA microarray expression changes in human umbilical vein endothelial cells (HUVEC) treated in a diabetic-like environment with the addition of calcitriol. Methods HUVEC were treated for 24 h with 200 μg/ml human serum albumin (HSA) and 100 mg/dl glucose (control group) or 200 μg/ml AGE-HSA, and 250 mg/dl glucose (diabetic-like environment), and physiological concentrations (10-10 mol/l) of calcitriol. miRNA microarray analysis and real time PCR to validate the miRNA expression profile and mRNA target gene expression were carried out. Results Compared to control, 31 mature human miRNA were differentially expressed in the presence of a diabetic-like environment. Addition of physiological concentrations of calcitriol revealed 39 differentially expressed mature human miRNA. MiR-181c, miR-15a, miR-20b, miR-411, miR-659, miR-126 and miR-510 were selected for further analysis because they are known to be modified in DM and in other biological disorders. The predicted targets of these miRNA (such as KLF6, KLF9, KLF10, TXNIP and IL8) correspond to molecular and biological processes such as immune and defense responses, signal transduction and regulation of RNA. Conclusion This study identified novel miRNA in the field of diabetic vasculopathy and might provide new information about the effect of vitamin D on gene regulation induced by a diabetic-like environment. New gene targets that are part of the molecular mechanism and the therapeutic treatment in diabetic vasculopathy are highlighted.