There's no place like home: 35-year patient survival on home hemodialysis.

The vast majority of maintenance dialysis patients suffer from poor long-term survival rates and lower levels of health-related quality of life. However, home hemodialysis is a historically significant dialysis modality that has been associated with favorable outcomes as well as greater patient autonomy and control, yet only represents a small minority of the total dialysis performed in the United States. Some potential disadvantages of home hemodialysis include vascular access complications, infection-related hospitalizations, patient fatigue, and attrition. In addition, current barriers and challenges in expanding the utilization of this modality include limited patient and provider education and technical expertise. Here we report a 65-year old male with end-stage renal disease due to Alport's syndrome who has undergone 35 years of uninterrupted thrice-weekly home hemodialysis (ie, every Sunday, Tuesday, and Thursday evening, each session lasting 3 to 3¼ hours in length) using a conventional hemodialysis machine who has maintained a high functional status allowing him to work 6-8 hours per day. The patient has been able to liberalize his dietary and fluid intake while only requiring 3-4 liters of ultrafiltration per treatment, despite having absence of residual kidney function. Through this case of extraordinary longevity and outcomes after 35 years of dialysis and a review of the literature, we illustrate the history of home hemodialysis, its significant clinical and psychosocial advantages, as well as the barriers that hinder its widespread adaptation

LIVES for families psychological first aid training programme to address COVID-19 psychological distress: a mixed methods acceptability and feasibility protocol

IntroductionBest practice approaches for addressing COVID-19-related psychological distress among young people (&lt;25 years) and their families remain unclear. Psychological first aid (PFA) is promoted by public health authorities to provide psychological support in the context of extreme events; however, there is limited evidence for its effectiveness. As a prerequisite to conducting a randomised controlled trial to examine programme effectiveness, this project is evaluating the acceptability and feasibility of implementing and evaluating a PFA training programme (‘LIVES for Families’) for mental health (MH) practitioners to improve their ability to recognise and respond to COVID-19-related psychological distress among their clients.Methods and analysisWe are using a triangulation mixed methods research design; complementary strands of quantitative and qualitative data are being collected in parallel and will be merged at the interpretation phase of the project. The quantitative strand uses a repeated measures design; a consecutive sample of MH practitioners (n=80) providing MH support to young people or their families are being recruited to participate in the LIVES for Families PFA training programme and complete quantitative measures at baseline (pretraining), 2-week and 6-month follow-up time points. The qualitative strand uses fundamental description and semistructured interviews with a subset of practitioners (n=30), as well as managers of MH agencies (n=20). A mixed methods joint display and associated narrative will generate a comprehensive understanding regarding acceptability and feasibility.Ethics and disseminationThe Hamilton Integrated Research Ethics Board approved the study (project number: 11295). Results will be shared broadly with the policy and practice community through publications, presentations and public webinars. As a brief, evidence-informed intervention, the LIVES for Families PFA training programme is suitable in its mode of delivery across care settings. The outcomes of this study could have international implications for mitigating the MH impacts of viral pandemics.</jats:sec

Postdialysis blood pressure rise predicts long-term outcomes in chronic hemodialysis patients: a four-year prospective observational cohort study

<p>Abstract</p> <p>Background</p> <p>The blood pressure (BP) of a proportion of chronic hemodialysis (HD) patients rises after HD. We investigated the influence of postdialysis BP rise on long-term outcomes.</p> <p>Methods</p> <p>A total of 115 prevalent HD patients were enrolled. Because of the fluctuating nature of predialysis and postdialysis BP, systolic BP (SBP) and diastolic BP before and after HD were recorded from 25 consecutive HD sessions during a 2-month period. Patients were followed for 4 years or until death or withdrawal.</p> <p>Results</p> <p>Kaplan-Meier estimates revealed that patients with average postdialysis SBP rise of more than 5 mmHg were at the highest risk of both cardiovascular and all-cause mortality as compared to those with an average postdialysis SBP change between -5 to 5 mmHg and those with an average postdialysis SBP drop of more than 5 mmHg. Furthermore, multivariate Cox regression analysis indicated that both postdialysis SBP rise of more than 5 mmHg (HR, 3.925 [95% CI, 1.410-10.846], <it>p </it>= 0.008) and high cardiothoracic (CT) ratio of more than 50% (HR, 7.560 [95% CI, 2.048-27.912], <it>p </it>= 0.002) independently predicted all-cause mortality. We also found that patients with an average postdialysis SBP rise were associated with subclinical volume overload, as evidenced by the significantly higher CT ratio (<it>p </it>= 0.008).</p> <p>Conclusions</p> <p>A postdialysis SBP rise in HD patients independently predicted 4-year cardiovascular and all-cause mortality. Considering postdialysis SBP rise was associated with higher CT ratio, intensive evaluation of cardiac and volume status should be performed in patients with postdialysis SBP rise.</p

Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension

Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors

<p>Abstract</p> <p>Background</p> <p>High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).</p> <p>Methods</p> <p>A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥1 μg/kg/week)).</p> <p>Results</p> <p>Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week) vs usual-dose (0.5 μg/kg/week) ESA.</p> <p>In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (r_s= 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per μcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05).</p> <p>Conclusion</p> <p>High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted.</p> <p>Trial registration</p> <p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00526747">NCT00526747</a></p

Association of Glomerular Filtration Rate with High-Sensitivity Cardiac Troponin T in a Community-Based Population Study in Beijing

BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT) is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT) and evaluated the association of estimated glomerular filtration rate (eGFR) with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs-cTnT levels were measured in 1365 community dwelling population aged ≥45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD) equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (≥3pg/mL) in 744 subjects (54.5%). The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P<0.001). After adjustment for the high predicted Framingham Coronary Heart Disease (CHD) risk (10-year risk >20%) and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs-cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function

(Clinical) trial and error in diabetic nephropathy

Patients with diabetes and nephropathy face a high risk of end-stage renal disease (ESRD) and cardiovascular disease. Trials in the past decades of nephrology research have shown the importance of lowering glucose, blood pressure, and albuminuria as a mean to lower renal and cardiovascular risk in these patients. However, despite the promising and successful results from RAAS inhibition with angiotensin receptor blockers in combination with tight glycemic and blood pressure control, many patients with diabetes and nephropathy are left with a high residual risk and still progress to ESRD. The high residual risk highlights the urgent need for additional therapies. This chapter reviews the clinical trial landscape in diabetic nephropathy and draws lessons for future clinical trials in this area.In order to improve outcome of patients with diabetic nephropathy, novel drugs have been tested in the last decades. After numerous large and expensive trials, unfortunately only a few interventions have been shown to reduce the risk of ESRD. One of the potential explanations why many of the conducted trials failed to prove ultimate efficacy is that all interventions focused on the effect of the drug in the overall population without taking into account how the individual patient responded to the drug. In the past trials, individual patients showed a large variation in drug response: some patients benefitted, and others did not or even experienced an increased risk. Because of this variation, no benefit could be detected in the overall population. The drug response variation may thus play a much bigger and more important role than originally anticipated in clinical trial design.The important lesson learned from a decade of clinical trial failures in nephrology is that more emphasis should be placed on the individual and how the individual responses to the drug rather than evaluating drug effects on a population level. This personalized medicine concept should be integrated in the design of future clinical trials as there are still promising therapies at the horizon for diabetic nephropathy and their potential efficacy should be tested in an appropriate fashion

Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis