LONGTERM RISK OF DYSGLYCEMIA AFTER SYMPTOMATIC GASTROENTERITIS DUE TO BACTERIAL WATER CONTAMINATION: THE WALKERTON HEALTH STUDY

In May 2000, the Walkerton Ontario municipal water supply was contaminated with Escherichia coli O157:H7 and Campylobacter, causing widespread gastroenteritis and hemolytic uremic syndrome (HUS). Previous studies indicate HUS may be complicated by insulin deficiency. We performed a retrospective cohort study with prospective follow-up to examine whether individuals who developed gastroenteritis without overt HUS during the outbreak are at increased risk of diabetes mellitus, impaired fasting glucose or impaired glucose tolerance. From 2002-2005, 3259 residents of Walkerton and surrounding areas who were \u3e10 years old with no known history of diabetes or impaired fasting glucose completed annual questionnaires and fasting plasma glucose and oral glucose tolerance tests. Participants were categorized regarding presence of gastroenteritis during the outbreak using data from multiple sources. After a mean follow-up of 4.5+1.0 years, there were no significant differences between groups in age- and sex-standardized rates of the primary composite outcome (asymptomatic: 11.0% [95% CI 8.8-13.2%]; possible gastroenteritis: 11.6% [95% CI 9.0-14.4%]; confirmed gastroenteritis: 10.9% [95% CI 9.4-12.5%]; (trend p=0.944). Gastroenteritis without HUS does not result in an increased risk of abnormal glucose homeostasis up to 5 years after the initial infection

The risk of hospitalization and modality failure with home dialysis

While home dialysis is being promoted, there are few comparative effectiveness studies of home-based modalities to guide patient decisions. To address this, we matched 1116 daily home hemodialysis (DHD) patients by propensity scores to 2784 contemporaneous USRDS patients receiving home peritoneal dialysis (PD), and compared hospitalization rates from cardiovascular, infectious, access-related or bleeding causes (prespecified composite), and modality failure risk. We performed similar analyses for 1187 DHD patients matched to 3173 USRDS patients receiving in-center conventional hemodialysis (CHD). The composite hospitalization rate was significantly lower with DHD than with PD (0.93 vs. 1.35/patient-year, hazard ratio=0.73 (95% CI=0.67–0.79)). DHD patients spent significantly fewer days in hospital than PD patients (5.2 vs. 9.2 days/patient-year), and significantly more DHD patients remained admission-free (52% DHD vs. 32% PD). In contrast, there was no significant difference in hospitalizations between DHD and CHD (DHD vs. CHD: 0.93 vs. 1.10/patient-year, hazard ratio 0.92 (0.85–1.00)). Cardiovascular hospitalizations were lower with DHD than with CHD (0.68 (0.61–0.77)), while infectious and access hospitalizations were higher (1.15 (1.04–1.29) and 1.25 (1.08–1.43), respectively). Significantly more PD than DHD patients switched back to in-center HD (44% vs. 15%; 3.4 (2.9–4.0)). In this prevalent cohort, home DHD was associated with fewer admissions and hospital days than PD, and a substantially lower risk of modality failure

Risk of pregnancy-related hypertension within 5 years of exposure to drinking water contaminated with Escherichia coli O157:H7

The authors evaluated the risk for pregnancy-related hypertension among previously healthy women who conceived within 5 years of exposure to drinking water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000). Chronic hypertension was defined as systolic/diastolic blood pressure ≥140/90 mm Hg before 20 weeks gestation; gestational hypertension was defined as new onset systolic/diastolic blood pressure ≥140/90 mm Hg ≥20 weeks gestation. The incidence of hypertension was compared between women who were asymptomatic during the outbreak to those who experienced acute gastroenteritis. Blood pressure data were available for 135 of 148 eligible pregnancies. The adjusted relative risks for chronic and gestational hypertension were 1.5 (95% confidence interval [CI]: 0.3-7.7) and 1.0 (95% CI: 0.4-2.5), respectively. Mean arterial pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute gastroenteritis (95% CI: 0.05-5.4). A trend toward higher chronic hypertension and mean arterial pressure in early pregnancy was observed among women who experienced gastroenteritis after exposure to bacterially-contaminated drinking water. © 2010 Wiley Periodicals, Inc

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Further delineation of Malan syndrome

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall–Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only

Comparative Effectiveness of Home Dialysis Therapies: A Matched Cohort Study

Background: Home dialysis is being increasingly promoted among patients with end-stage renal disease, but the comparative effectiveness of home hemodialysis and peritoneal dialysis is unknown. Objective: To determine whether patients receiving home daily hemodialysis have reduced mortality risk compared with matched patients receiving home peritoneal dialysis. Design: This study is an observational, propensity-matched, new-user cohort study. Setting: Linked electronic data were from the United States Renal Data System (USRDS) and a large dialysis provider's database. Patients: The patients were adults receiving in-center hemodialysis in the USA between 2004 and 2011 and registered in the USRDS. Measurements: Baseline comorbidities, demographics, and outcomes for both groups were ascertained from the United States Renal Data System. Methods: We identified 3142 consecutive adult patients initiating home daily hemodialysis (≥5 days/week for ≥1.5 h/day) and matched 2688 of them by propensity score to 2688 contemporaneous US patients initiating home peritoneal dialysis. We used Cox regression to compare all-cause mortality between groups. Results: After matching, the two groups were well balanced on all baseline characteristics. Mean age was 51 years, 66 % were male, 72 % were white, and 29 % had diabetes. During 10,221 patient-years of follow-up, 1493/5336 patients died. There were significantly fewer deaths among patients receiving home daily hemodialysis than those receiving peritoneal dialysis (12.7 vs 16.7 deaths per 100 patient-years, respectively; hazard ratio (HR) 0.75; 95 % CI 0.68–0.82; p < 0.001). Similar results were noted with several different analytic methods and for all pre-specified subgroups. Limitations: We cannot exclude residual confounding in this observational study. Conclusions: Home daily hemodialysis was associated with lower mortality risk than home peritoneal dialysis

Transition From Pediatric to Adult Nephrology Care: Program Report of a Single-Center Experience

Purpose of program: Adolescents and young adults with chronic disease face many personal and systemic barriers that may impede their successful transition from pediatric to adult care, putting them at risk for treatment nonadherence, loss to follow-up, and poor health outcomes. Such barriers include impaired socioemotional functioning, overreliance on adult caregivers, lack of disease-specific knowledge, and poor coordination between pediatric and adult health care services. In 2007, we established a specialized youth to adult nephrology transition clinic at a tertiary care center to address these barriers and provide adolescents and young adults with renal disease followed at the affiliated children’s hospital with a seamless transition to adult care. Sources of information: The attending clinic nephrologist collected data prospectively for this quality improvement report. Methods: The features of this specialized clinic included (1) single point of entry and single triage adult nephrologist, (2) ongoing follow-up with a single adult nephrologist who communicated with the pediatric nephrologists, and (3) a single specialized clinic nurse who provided disease-specific education and helped to ensure ongoing patient engagement and follow-up. Importantly, the transition patients were booked into regular appointment slots in the adult nephrologist’s general clinic, which facilitated regular follow-up without additional resources. The salary of the transition clinic nurse was covered by an unrestricted grant. Patient visits were in-person, except between 2020 and 2021 when visits were by telephone due to the pandemic. Key findings: A total of 213 patients were referred and assessed in the transition clinic from February 2007 until October 2022. Most referrals were from pediatric nephrologists. Among the patients, 29% had a hereditary kidney disease; in 71%, the disease was acquired. The most common disease was glomerulonephritis and ~30% of the patients suffered from a “rare” disease. Of the 213 patients, 123 (58%) continue to be followed up (mean follow-up: 4.8 years), 27 (13%) were transferred to other physicians, in part to accommodate treatment closer to patients’ homes, and 29 (14%) without ongoing care needs were discharged. Only 33 (15%) were lost to follow-up. There were several advantages to the clinic, including the maintenance of accurate records, a process to minimize loss to follow-up, and a “critical mass” of patients with rare diseases, which facilitated development of special expertise in rare disease pathogenesis, diagnosis, treatment, and management of complications. Patients with glomerulonephritis demonstrated a stable serum creatinine over 3 to 15 years, and morbidity (as reflected by emergency room visits and hospitalizations) was low. Limitations: Due to the relatively small numbers of patients in the disease categories, it was not possible to determine conclusively whether attendance of patients in the transition clinic reduced the rate of progression of kidney disease or morbidity. Implications: A dedicated referral, triage, and follow-up process post-transition with only modest financial resources and personnel can result in accurate tracking of clinic data, as well as consistent and reliable follow-up and expert patient care

Volume status assessment by lung ultrasound in end-stage kidney disease : a systematic review

Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. Sources of information: We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. Methods: From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooledrcorrelation coefficient of .57 and .36, respectively. Among echocardiographic parameters, left ventricular ejection fraction and inferior vena cava index had the strongest correlation with the number of B-lines, with a pooledrcoefficient of .35 and .31, respectively. Three randomized studies compared a lung ultrasound-guided approach with standard of care on hard clinical endpoints. Although patients in the lung ultrasound group achieved better decongestion and blood pressure control, there was no difference between the 2 management strategies with respect to death from any cause or major adverse cardiovascular events. Key findings: Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. Limitations: The included studies were heterogeneous and of relatively limited quality.L’échographie pulmonaire est une technique non-invasive réalisée au chevet du patient qui permet d’évaluer avec précision la congestion pulmonaire en mesurant l’eau pulmonaire extravasculaire. Cette technique facilement accessible est de plus en plus utilisée. Notre principal critère de jugement était de comparer l’efficacité de l’évaluation de la volémie par échographie pulmonaire avec l’évaluation clinique, l’échocardiographie, la bio-impédance ou les biomarqueurs. Les critères d’évaluation secondaires étaient la mortalité toutes causes confondues et les événements cardiovasculaires.Nous avons recherché sur MEDLINE les études observationnelles et les essais randomisés où une échographie pulmonaire avait été réalisée chez des patients sous dialyse d’entretien.Sur un total de 2 363 articles, nous avons retenu 28 études (25 observationnelles et 3 randomisées). Les coefficients de corrélation ont été regroupés pour chaque variable d’intérêt en utilisant la méthode générique de variance inverse avec un modèle à effets aléatoires. Les paramètres cliniques qui avaient montré les corrélations les plus élevées avec le nombre de lignes B à l’échographie étaient le statut de l’insuffisance cardiaque selon la classification de la New York Heart Association et l’auscultation pulmonaire, avec des coefficients de corrélation r regroupés respectifs de 0,57 et de 0,36. Les paramètres de l’échocardiographie qui avaient montré les plus fortes corrélations avec le nombre de lignes B étaient la fraction d’éjection du ventricule gauche et l’indice de la veine cave inférieure, avec des coefficients r regroupés respectifs de 0,35 et de 0,31. Trois essais randomisés avaient comparé une approche guidée par échographie pulmonaire aux normes de soins selon des critères cliniques stricts. Bien que les patients du groupe avec échographie pulmonaire aient montré une décongestion plus efficace et un meilleur contrôle de la pression artérielle, aucune différence n’a été observée entre les deux stratégies de prise en charge en ce qui concerne les décès de toutes causes confondues ou les événements cardiovasculaires indésirables majeurs.L’échographie pulmonaire pourrait être envisagée pour identifier les patients qui présentent une surcharge volumique subclinique. Les essais inclus n’ont pas montré de différences dans les résultats cliniquement pertinents. Le nombre d’études incluses était faible et plusieurs étaient de qualité sous-optimale.Les études incluses étaient hétérogènes et de qualité relativement limitée

Sodium-glucose co-transporter 2 inhibitors in patients with chronic kidney disease

Diabetes drives an increasing burden of cardiovascular and renal disease worldwide, motivating the search for new hypoglycemic agents that confer cardiac and renal protective effects. Although initially developed as hypoglycemic agents, sodium-glucose co-transporter 2 (SGLT-2) inhibitors have since been studied in patients with and without diabetes for the management of heart failure and chronic kidney disease. A growing body of evidence supports the efficacy and safety of SGLT-2 inhibitors in patients with chronic kidney disease (CKD), based on complex mechanisms of action that extend far beyond glucosuria and that confer beneficial effects on cardiovascular and renal hemodynamics, fibrosis, inflammation, and end-organ protection. This review focuses on the pharmacology and pathophysiology of SGLT-2 inhibitors in patients with CKD, as well as their cardiovascular and renal effects in this population. We are focusing on the five agents that have been tested in cardiovascular outcome trials and that have been approved either in Europe or in North America: empagliflozin, dapagliflozin, canagliflozin, ertugliglozin, and sotagliflozin