Genetic Markers Among the Israeli Druze Minority Population With End-Stage Kidney Disease.

RATIONALE & OBJECTIVE: Genetic etiologies have been identified among approximately 10% of adults with chronic kidney disease (CKD). However, data are lacking regarding the prevalence of monogenic etiologies especially among members of minority groups. This study characterized the genetic markers among members of an Israeli minority group with end-stage kidney disease (ESKD). STUDY DESIGN: A national-multicenter cross-sectional study of Israeli Druze patients (an Arabic-speaking Near-Eastern transnational population isolate) who are receiving maintenance dialysis for ESKD. All study participants underwent exome sequencing. SETTING & PARTICIPANTS: We recruited 94 adults with ESKD, comprising 97% of the total 97 Druze individuals throughout Israel being treated with dialysis during the study period. PREDICTORS: Demographics and clinical characteristics of kidney disease. OUTCOME: Genetic markers. ANALYTICAL APPROACH: Whole-exome sequencing and the relationship of markers to clinical phenotypes. RESULTS: We identified genetic etiologies in 17 of 94 participants (18%). None had a previous molecular diagnosis. A novel, population-specific, WDR19 homozygous pathogenic variant (p.Cys293Tyr) was the most common genetic finding. Other monogenic etiologies included PKD1, PKD2, type IV collagen mutations, and monogenic forms of noncommunicable diseases. The pre-exome clinical diagnosis corresponded to the final molecular diagnosis in fewer than half of the participants. LIMITATIONS: This study was limited to Druze individuals, so its generalizability may be limited. CONCLUSIONS: Exome sequencing identified a genetic diagnosis in approximately 18% of Druze individuals with ESKD. These results support conducting genetic analyses in minority populations with high rates of CKD and for whom phenotypic disease specificity may be low. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects many people worldwide and has multiple genetic causes. However, there is limited information on the prevalence of genetic etiologies, especially among minority populations. Our national-multicenter study focused on Israeli Druze patients. Using exome-sequencing, we identified previously undetected genetic causes in nearly 20% of patients, including a new and population-specific WDR19 homozygous pathogenic variant. This mutation has not been previously described; it is extremely rare globally but is common among the Druze, which highlights the importance of studying minority populations with high rates of CKD. Our findings provide insights into the genetic basis of end-stage kidney disease in the Israeli Druze, expand the WDR19 phenotypic spectrum, and emphasize the potential value of genetic testing in such populations.

The Association of Urolithiasis with Uricosuria, Uricemia and their Combination.

BACKGROUND: There are conflicting data on the significance of hyperuricemia or hyperuricosuria in urolithiasis formation and on the need for medical treatment. OBJECTIVES: To assess the significance of hyperuricemia or hyperuricosuria in urolithiasis formation, particularly when hyperuricemia occurs with normal uricosuria. METHODS: The electronic medical records of patients treated in Haifa and the Western Galilee district of Clalit Health Services, Israel, were retrospectively screened for diagnosis of nephrolithiasis or renal or urinary tract/bladder calculi between February 2014 and April 2019. The diagnosis was confirmed by ultrasonography or computed tomography. The study group included patients with one of these diagnoses. Patients in the control group did not have these diagnoses. The inclusion criterion for all patients was the presence of both serum and urinary uric acid levels. RESULTS: The study group included 359 patients and the control group 267. After adjustment by logistic regression, we found no significant differences in the prevalence of hyperuricosuria in the study group (14.8%) compared to the control group (9.7%), odds ratio (OR) 1.54 (95% confidence interval [95%CI] 0.74-3.2, P = 0.245). No significant differences between the groups were observed for hyperuricemia prevalence (45.4% vs. 55.1%, respectively, OR 0.82, 95%CI 0.54-1.25, P = 0.355), nor among those without hyperuricosuria (OR 0.83, 95%CI 0.52-1.33, P = 0.438) and after propensity score matching (OR 0.93, 95%CI 0.66-1.3, P = 0.655). CONCLUSIONS: There were no significant differences in hyperuricemia or hyperuricosuria between the two groups of patients or in hyperuricemia among participants without hyperuricosuria.

Oral Health-Related Quality of Life in the Elderly in Israel--Results from the National Health and Nutrition Survey of the Elderly 2005-2006.

PURPOSE: To assess the oral health-related quality of life of the Israeli elderly. MATERIALS AND METHODS: Data were collected from a subsample of those interviewed for the cross-sectional Mabat Zahav National Health and Nutrition Survey of the Elderly, carried out in 2005 and 2006 by the Ministry of Health in Israel. In-person interviews were conducted in the interviewees' homes using a structured questionnaire which included 7 questions on subjective dental health status and the 14 questions of the Oral Health Impact Profile 14 (OHIP-14). Statistical significance of continuous variables was assessed with the Student t-test; categorical variables with normal distribution were analysed using the chi-square test and those with non-normal distribution with the Wilcoxon Mann-Whitney two-sample test. RESULTS: 828 Jews and 159 Arabs from the total survey population of 1852 elderly (1536 Jews and 316 Arabs) completed the OHIP-14 questionnaire. An impact of oral health on the quality of life was reported by 16.6% of the respondents, 19.2% of females and 13.9% of males (p<0.05). There were statistically significant differences in impact prevalence by gender, place of birth and economic status. No such differences were found by age group, population group or education. Significant statistical correlation was found between subjective assessment of general and dental health and OHIP impact prevalence, with poorer assessment correlated with increased prevalence of impact. CONCLUSIONS: The quality of life of 17% of Israeli elderly is affected by oral health. The OHIP-14 findings emphasise the importance of including basic dental treatment (treatment of dental pain and infections) in the range of services covered by the National Health Insurance Law.

Validation of a Hebrew version of the child-OIDP index, an oral health-related quality of life measure for children.

PURPOSE: Sociodental indicators assess to what extent oral conditions interfere with normal social functions and alter behaviour such as attending work or school, parenting or home chores. The child OIDP (oral impact on daily performance), a sociodental indicator developed by Adulyan and Sheiham, is easy to apply and has a scoring system that quantifies the effect both by extent and frequency. The purpose of this study was to adapt the child OIDP into Hebrew and evaluate its validity and reliability. MATERIALS AND METHODS: The questionnaire was translated from English into Hebrew and back again. After receiving permission from parents and from the children attending the consultation clinic of the Department of Children's Dentistry at the Hebrew University-Hadassah Dental School, we examined their dental condition and asked them to answer the questions. According to the results, we analysed the reliability and the validity of the questionnaire. RESULTS: 179 children aged 6-11 years answered the questions. 88.8% of the children that attended the dental clinic experienced an oral or dental problem and 52.5% of them experienced interference in at least one of 8 everyday activities because of oral or dental problems in the 3 months prior to the interview. The OIDP was found valid in the aspects of Face, Content and Construct validity and with good internal reliability. CONCLUSIONS: The validity and the reliability of the Hebrew child OIDP found in the present study enables its use in future studies to assess the impact of oral health on children's quality of life.

Nontuberculous mycobacteria infections of peritoneal dialysis patients: A multicenter study.

OBJECTIVES: Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients. METHODS: All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed. RESULTS: Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52-76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD. CONCLUSIONS: Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

Sustainability of Supervised Toothbrushing in Israeli Nurseries - Teachers' Perspective.

PURPOSE: The national supervised toothbrushing programme was implemented in 2015-2016 among 3- to 4-year-old children attending 600 nurseries in Israel. The objectives of this study were to assess factors associated with sustainability of programme implementation, based on nursery teachers' attitudes towards the programme, beliefs in its success and willingness to continue it in in the future. MATERIALS AND METHODS: A phone survey was conducted among nursery teachers participating in the programme. Study objectives were assessed using a 19-item structured questionnaire. A linear regression model was built to identify factors which contributed to the positive attitude of the teachers towards programme sustainability. RESULTS: Some 300 teachers were interviewed over the telephone. The programme was implemented daily or several times a week in 66% of the nurseries. Around 70% of teachers reported willingness to continue the programme in the future. Teachers' confidence in programme success (r = 0.73), acknowledgment of their role in teaching children to brush their teeth (r = 0.53), tendency to like teaching toothbrushing (r = 0.59) were positively associated with their willingness to continue the programme. Teachers who anticipated more problems were less willing to implement the programme in the future (r = -0.34). Statistically significant differences in frequency of programme implementation were found according to teachers' attitudes towards the programme. A strong relationship (adjusted r2 = 0.71) was found between the teacher's positive perception of programme sustainability and the attribute variables. The degree of interest in continuing a programme and the belief in their ability to operate it attributed most to teachers' positive perception of programme sustainability. CONCLUSION: A high percentage of teachers expressed a positive attitude towards the programme. Factors contributing to the positive attitude of teachers towards programme sustainability were identified. The survey's results may help in the implementation of similar programmes and contribute to their future success.

The ideal position of the peritoneal dialysis catheter is not always ideal.

PURPOSE: Peritoneal catheter dysfunction is a frequent complication of peritoneal dialysis (PD). Traditionally, dysfunction has been attributed to catheter malposition, but whether the location of the catheter tip in the small pelvis really determines proper function is unclear. METHODS: We reviewed 900 abdominal X-ray images of PD patients from a 7-year period in two PD units that use different catheter types (straight and Swan Neck Curled). RESULTS: In 52% of the images, the dialysis catheter tip was located in the ideal position in the small pelvis and in 48% in other sites. Peritoneal catheter function was normal at the time of imaging in 87% of those with ideal catheter tip position, and in 74% of those with other than ideal position. The tip was located in small pelvis in 35% of images performed during catheter dysfunction and in 56% of those performed during normal catheter function. There were no differences between two catheter types. The positive predictive value of abdominal X-ray images to predict catheter function was 26%, and the negative predictive value 87%. We also found a significant positive correlation between polycystic kidney disease and normal catheter function. In contrast, obese patients were more likely to have catheter malfunction. Previous abdominal surgery was not associated with catheter dysfunction. CONCLUSION: Our data showed a higher probability of normal function of peritoneal catheters whose tips were located in the small pelvis. However, also malpositioned catheters generally functioned well, and malpositioning of the PD catheter did not in itself explain its malfunction.

Validation of a Hebrew version of the Oral Health Impact Profile 14.

OBJECTIVE: This study determined the validity of a Hebrew version of the Oral Health Impact Profile in a cross-sectional study of a general dental practice in Israel. METHODS: The original English version of a short-form oral health impact profile (OHIP-14) was translated into Hebrew using the back-translation technique. Participants were interviewed and examined clinically by a calibrated dentist. Information on the subjects' sociodemographic background and oral health conditions was collected. RESULTS: A total of 142 persons were interviewed and clinically examined. The Cronbach's alpha and the standardized item alpha for OHIP-14 were both 0.88. Cronbach's alpha of the translated OHIP-14 subscales ranged from 0.48 to 0.76. Construct validity of the translated Hebrew version was supported by the finding that the total OHIP score correlated with the number of decayed teeth, missing teeth, need for prosthodontic treatment, and pattern of dental attendance. Participants with oral pain were more likely to report impact on one of the OHIP subscales and to have more impacts than participants who were pain free. CONCLUSIONS: The Hebrew version of OHIP-14 presented acceptable validity and reliability. Further research is needed to assess the value of this measure in Israel.

Acute effects of peritoneal dialysis solutions in the mesenteric microcirculation.

Long-term peritoneal dialysis induces morphological changes that may lead to gradual functional impairment of the peritoneal membrane. These changes are characterized by progressive reduction in solute transport or ultrafiltration failure. The mechanism of the peritoneal response to dialysis fluids has not yet been fully elucidated. We used video-microscopy for in vivo evaluation of microhemodynamics and peritoneal microvascular inflammatory response, after a single intraperitoneal exposure of rats to commercial PD fluids: (1) glucose 1.5 % PD solution; (2) lactate buffered glucose 4.25% PD solution; (3) Icodextrin 7%; (4) bicarbonate buffered glucose 3.86% PD fluid; and 5) Hanks solution. Sham-control groups were not injected. A 5-h exposure of the peritoneal membrane to glucose 1.5% PD solution or to Hanks solution did not induce a significant change in leukocyte rolling and adhesion. In contrast, PD solutions containing glucose 4.25% or Icodextrin 7.5% caused a significant 2-3-fold increase in leukocyte rolling (P < 0.001) and adhesion (P < 0.001) and a significant increase in venular blood flow velocity (P < 0.01) and shear rates (P < 0.05 for glucose 4.25%, and P < 0.01 for Icodextrin). Exposure to glucose 3.86% bicarbonate buffered (Physioneal) solution was associated with the lowest values of leukocyte rolling and adhesion among the PD solutions and with extremely higher venular flow velocities and shear rates. A single exposure to conventional PD solutions with a high concentration of glucose (4.25%) or polyglucose (Icodextrin 7.5%) induces changes consistent with an early peritoneal inflammatory response that may be attenuated by the use of bicarbonate-based fluids.

Peritoneal transport after long-term exposure to Icodextrin in rats.

BACKGROUND: Icodextrin, an effective osmotic substance that has been proposed as an alternative agent for peritoneal dialysis induces ultrafiltration over long dwells. This study examines the peritoneal transport after exposure to Icodextrin in rats. METHODS: Animals were divided in 4 groups and injected daily for 30 days with Icodextrin 7.5 % (n = 14), Glucose 4.25 % (n = 19) or glucose 4.25% plus Icodextrin 7.5 % (n = 13). Rats of the control group (n = 15) were not exposed. A 4-hour permeability study was performed using glucose at days 1, 30 and 60. At days 2, 31 and 61 the same animals were injected with Icodextrin. RESULTS: Slopes of effluent sodium at day 30 were significantly higher (p < 0.001) in the glucose (0.006 +/- 0.016), Icodextrin (0.013 +/- 0.014) and mixed groups (0.012 +/- 0.017) than in the control group (-0.041 +/- 0.021). Urea D/P ratio was not significantly different in the 4 groups. After 30 days, glucose effluent levels were significantly lower (p < 0.001) in the glucose (701 +/- 278 mg/dl), Icodextrin (552 +/- 209 mg/dl) and mixed groups (587 +/- 344 mg/dl) than in control rats (1519 +/- 413 mg/dl). Effluent protein (mg/l) in the mixed group (1,555 +/- 357) was significantly higher (p < 0.001) than control (376 +/- 33), glucose (1,015 +/- 232) and Icodextrin (765 +/- 75) groups at day 30. CONCLUSION: The long-term use of Icodextrin does not affect small molecule transport, but induces changes in the peritoneal protein excretion, especially when Icodextrin and glucose are injected together.