The Impact of Frailty on Technique Failure and Mortality in Patients on Home Dialysis.

Background:Patients on home dialysis therapies experience technique failure, which is associated with morbidity and mortality. Reasons for technique failure are complex, and often related to functional decline in the patient or caregiver. Frailty is associated with an increased risk of adverse health outcomes. We investigated the impact of frailty on technique failure and mortality in a prospective cohort of patients on home dialysis therapies.Methods:We collected objective (Fried criteria and Short Physical Performance Battery [SPPB]), and subjective (physician and nurse impression) measures of frailty from 109 prevalent home dialysis patients. Our primary outcome was a composite of technique failure, defined as a permanent unplanned transition (> 30 days in duration) to facility-based hemodialysis or all-cause death. The association between different frailty assessment tools and the primary composite outcome was evaluated using Cox models.Results:Fried criteria and physician impression was associated with a greater than 2-fold increase in risk of our composite outcome (HR: 2.10 [95% CI 1.09 - 3.99], 2.15 [95% CI 1.15 - 4.00, respectively] in adjusted analyses. Weakness and weight loss subdomains of the Fried criteria were both associated with an increased risk of our composite outcome in adjusted analyses (HR: 2.16 [95% CI 1.23 - 3.78], 2.69 [95% CI 1.39 - 5.40], respectively).Conclusions:Objective and subjective measures of frailty are associated with a more than 2-fold higher risk of technique failure or death in patients undergoing home dialysis. Assessing frailty as part of the clinical evaluation for home dialysis therapies may be useful for prognostication and clinical management.

Treatment of Uremic Pruritus: A Systematic Review.

BACKGROUND: Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. STUDY DESIGN: Systematic review. SETTING & POPULATION: Adult patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. SELECTION CRITERIA FOR STUDIES: PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. INTERVENTION: Any intervention for the treatment of uremic pruritus was included. OUTCOMES: A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale. RESULTS: 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high. LIMITATIONS: Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis. CONCLUSIONS: Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.

Risk Prediction Models in CKD.

Chronic kidney disease (CKD) currently affects 20 million Americans and is associated with increased morbidity and mortality. Resource-efficient and appropriate treatment of CKD benefits the patient and provides improved resource allocation for the health care system. Prediction models can be useful in efficiently allocating resources, and currently are being used at the bedside for several important clinical decisions. There is a paucity of prediction models in use in nephrology, but one such model, the Kidney Failure Risk Equation, uses routinely collected laboratory values and can inform clinical decisions related to the following: (1) triage of nephrology referrals, (2) evaluating the need for more intensive interdisciplinary clinic care, (3) determining the timing of modality education, and (4) dialysis access planning. The development of new models that predict survival and quality of life on dialysis, success on home modalities, failure of arteriovenous fistulas, and risk of cardiovascular disease in patients with CKD is needed.

A retrospective review of the two-step tuberculin skin test in dialysis patients.

BACKGROUND: Reactivation of latent Mycobacterium tuberculosis infection (LTBI) is a health concern for patients on dialysis or receiving a kidney transplant, as these patients are often immunosuppressed. The most frequently used test for LTBI screening in this population is the tuberculin skin test (TST). The diagnostic accuracy (sensitivity and specificity) of the TST in a contemporary North American or Western European dialysis population is unknown. OBJECTIVES: Our objective was to determine the diagnostic accuracy and clinical utility of the two-step TST in patients receiving dialysis. DESIGN: This is a retrospective cohort study. SETTING: This study is set at four tertiary dialysis units across Winnipeg, Manitoba. PATIENTS: There are 483 chronic hemodialysis and peritoneal dialysis patients in the study. MEASUREMENTS: The measurements are sensitivity and specificity of the TST with respect to abnormal chest X-ray. METHODS: All patients received a two-step TST and assessment of risk factors for prior tuberculosis (TB) infection between February 2008 and December 2008. This cohort was retrospectively linked to our tuberculosis registry to ascertain if prophylaxis was received for LTBI. RESULTS: At an induration cutoff of 5 mm, 62 (13 %) patients had a positive two-step TST. Patients with a known Bacillus Calmette-Guérin (BCG) vaccination were more likely to test positive (50 % of those with a positive TST had a BCG versus 34 % with a negative TST, p = 0.05). Using a diagnostic gold standard of an abnormal chest X-ray as a proxy for LTBI, the sensitivity of the TST was only 14 % and the specificity was 88 %. Only 8 of 62 patients with a positive TST (13 %) received prophylaxis for LTBI. None of the patients who tested negative were treated. LIMITATIONS: There is a lack of a truly accurate gold standard for LTBI. CONCLUSIONS: The TST has limited diagnostic and clinical utility for LTBI screening in patients on dialysis. Further research into the diagnostic accuracy of interferon-gamma release assays and a revision of LTBI screening guidelines in patients on dialysis should be considered.

MISE EN CONTEXTE: La réactivation d'une infection latente à Mycobacterium Tuberculosis demeure une préoccupation constante pour la santé des patients recevant des traitements de dialyse de même que pour les receveurs d'une greffe puisque ces patients sont souvent immunodéprimés. Le test le plus fréquemment utilisé pour le dépistage des infections tuberculeuses latentes (ITL) chez cette population est le test cutané à la tuberculine (TCT). Néanmoins, l'exactitude du diagnostic (sensibilité et spécificité) du TCT demeure inconnue pour les populations de patients actuellement sous dialyse en Amérique du nord et en Europe de l'ouest. OBJECTIF DE L'ÉTUDE: Cette étude visait à évaluer la précision diagnostique et la pertinence clinique de ce test de dépistage en deux étapes chez les patients recevant des traitements de dialyse. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective qui s'est tenue dans quatre unités de dialyse en centre de soins tertiaires à Winnipeg, au Manitoba. PATIENTS: La cohorte était constituée de 483 patients sous hémodialyse chronique ou sous hémodialyse péritonéale. MESURES: La sensibilité et la spécificité du TCT ont été évaluées sur la base d'une radiographie pulmonaire anormale. MÉTHODOLOGIE: Au cours de la période comprise entre février et décembre 2008, tous les participants avaient subi les deux étapes du TCT et fait l'objet d'une évaluation de leurs facteurs de risque attribuables à des antécédents d'infection tuberculeuse. La cohorte a été reliée de façon rétrospective aux registres actuels de la tuberculose afin de vérifier si les mesures de prophylaxie avaient été suivies. RÉSULTATS: À la valeur seuil d'induration de 5 mm, 62 patients (13 %) ont obtenu un résultat positif au TCT réalisé en deux étapes. Les patients qui avaient été vaccinés contre le BCG (bacille de Calmette et Guérin) par le passé étaient plus susceptibles d'obtenir un résultat positif. La moitié (50 %) des patients présentant un résultat positif au TCT avaient reçu le vaccin alors que cette proportion était de seulement 34 % parmi les patients qui avaient eu un résultat négatif (p = 0,05). À titre d'indicateur de la présence d'une ITL, le recours à une radiographie pulmonaire anormale a permis d'établir la sensibilité du TCT à 14 % alors que la spécificité s'est élevée à 88 %. Seuls huit des 62 patients ayant obtenu un résultat positif au TCT avaient suivi les mesures prophylactiques adéquates et aucun des patients ayant obtenu un résultat négatif au TCT n'a été traité. LIMITES DE L'ÉTUDE: Il n'existe aucune norme de référence véritablement précise en ce qui concerne les ITL. CONCLUSIONS: Le test cutané à la tuberculine s'avère d'une pertinence diagnostique et clinique limitée pour le dépistage des infections tuberculeuses latentes chez les patients sous dialyse. La fiabilité diagnostique de mesures telles que le test de libération d'interféron gamma devrait être davantage explorée. De plus, une révision des lignes directrices en matière de dépistage des ITL chez les patients sous dialyse devrait être prise en considération.

The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. PURPOSE: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. DATA SOURCES: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. DATA SYNTHESIS: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. LIMITATION: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias. CONCLUSION: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. PRIMARY FUNDING SOURCE: KRESCENT and Manitoba Health Research Council Establishment.

The cost effectiveness of erythropoietin-stimulating agents for treating anemia in patients on dialysis: a systematic review.

BACKGROUND: Anemia is a common complication associated with kidney failure and is marked by poor health and increased risk of morbidity and mortality. There are ongoing concerns with the use of Erythropoietin Stimulating Agents (ESAs) to treat anemia in patients with kidney failure on dialysis. Questions as to their benefits, harms and overall effect on quality of life are still relevant today. Our objective was to systematically review studies evaluating the cost-effectiveness of ESAs in patients with kidney failure on dialysis. METHODS: We performed a systematic review of studies determining the cost-effectiveness of ESAs in adult patients on dialysis. Databases, including PubMed, EMBASE, and Cochrane Database of Systematic Reviews, were searched from their establishment until June 2013. Studies that reported an incremental cost-effectiveness ratio of hemoglobin correction strategies based on ESA treatments in comparison to red blood cell transfusions, lower hemoglobin targets, or no ESA treatment were included. RESULTS: Seven studies met inclusion criteria. Reported cost/quality-adjusted life-year (QALY) ratios ranged from USD 931-677,749/QALY across five studies comparing ESAs to red blood cell transfusions. There was heterogeneity in results when considering higher hemoglobin targets, with studies finding higher targets to be both dominant and dominated. Mortality, hospitalization, and utility estimates were major drivers. CONCLUSIONS: There is substantial variability in the estimates of the cost-effectiveness of using ESAs in the dialysis population. New models incorporating recent meta-analyses for estimates of utility, mortality, and hospitalization changes would allow for a more comprehensive answer to this question.

The diagnostic accuracy of tests for latent tuberculosis infection in hemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Reactivation of latent Mycobacterium tuberculosis infection is an important health concern for patients on hemodialysis because of their immunosuppressed state and in kidney transplant patients receiving immunosuppressive therapy to prevent organ rejection. There are several tests available to determine the presence of latent tuberculosis infection: the tuberculin skin test (TST), QuantiFERON-TB Gold (QFT-G), and T-SPOT.TB. The objective of this study is to evaluate the diagnostic accuracy of these tests in determining latent tuberculosis infection in the hemodialysis population. METHODS: The study design was a systematic review. We selected studies with adequate information to ascertain test sensitivity or specificity of the TST, QFT-G, and TSPOT.TB with regards to determining latent tuberculosis infection in the hemodialysis population. RESULTS: One hundred two articles were selected for full review, and 17 were included in the meta-analysis. The TST had a pooled sensitivity of 31% (26%-36%, 95% confidence interval) and specificity of 63% (60%-65%) across eight studies. The QFT-G test had a pooled sensitivity of 53% (46%-59%) and specificity of 69% (65%-72%) across nine studies. The T-SPOT.TB test had a pooled sensitivity of 50% (42%-59%) and specificity of 67% (61%-73%) across three studies. CONCLUSION: The QFT-G and the T-SPOT.TB tests were more sensitive than the TST for diagnosis of latent tuberculosis infection in patients on hemodialysis while offering a comparable level of specificity. This systematic review calls into question the practice of using the TST to screen in this population, especially in patients considered for kidney transplantation.

Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review and meta-analysis to understand the role of flow-mediated dilatation (FMD) of the brachial artery (BA) and peripheral arterial tonometry (PAT) in predicting adverse events, including cardiovascular (CV) events and all-cause mortality. BACKGROUND: FMD of the BA and PAT are non-invasive measures of endothelial function. Impairment of endothelial function is associated with increased CV events. While FMD is the more widely used and studied technique, PAT offers several advantages. The purpose of this systematic review and meta-analysis is to determine whether brachial FMD and PAT are independent risk factors for future CV events and mortality. METHODS: Multiple electronic databases were searched for articles relating FMD or PAT to CV events. Data were extracted on study characteristics, study quality, and study outcomes. Relative risks (RRs) from individual studies were combined and a pooled multivariate RR was calculated. RESULTS: Thirty-six studies for FMD were included in the systematic review, of which 32 studies consisting of 15, 191 individuals were meta-analysed. The pooled RR of CV events and all-cause mortality per 1% increase in brachial FMD, adjusting for potential confounders, was 0.90 (0.88-0.92). In contrast, only three studies evaluated the prognostic value of PAT for CV events, and the pooled RR per 0.1 increase in reactive hyperaemia index was 0.85 (0.78-0.93). CONCLUSION: Brachial FMD and PAT are independent predictors of CV events and all-cause mortality. Further research to evaluate the prognostic utility of PAT is necessary to compare it with FMD as a non-invasive endothelial function test in clinical practice.