Informed Dialysis Modality Selection Among Veterans With Advanced CKD: A Community-Level Needs Assessment.

Rationale & Objective: The Advancing Americans Kidney Health Executive order has directed substantial increases in home dialysis use for incident kidney replacement therapy (KRT). Clinical guidelines recommend patients' self-selection of KRT modality through a shared decision-making process, which, at the minimum, requires predialysis nephrology care and KRT-directed comprehensive prekidney failure patient education (CoPE). The current state of these essential services among Americans with advanced (stages 4 and 5) chronic kidney disease (CKD) and their informed preferences for home dialysis are unknown. Study Design: We conducted a community-based, cross-sectional, observational cohort study across a large regional Veteran Healthcare System from October 1, 2020, to September 30, 2021. Setting & Participants: Of the 928 Veterans with advanced CKD, 287 (30.9%) were invited for needs assessment evaluations. Of the 218 (76% of invited cohort) responding, 178 (81.6%) were receiving nephrology care, with approximately half of those (43.6%) receiving such care from non-Veterans Affairs providers. Outcomes: The study was targeted to assess the prevalent state of ongoing nephrology care and KRT-directed pre-kidney failure education among Veterans with advanced CKD. The secondary outcome included evaluation of dialysis decision-making state among Veterans with advanced CKD. Analytical Approach: Veterans with advanced CKD with 2 sustained estimated glomerular filtration rates <30 mL/min/1.73 m2 were identified through an electronic database query, and a randomly selected cohort was invited for their current state of and outstanding needs for predialysis nephrology care and CoPE, essential for informed KRT selection. Results: Basic awareness of kidney disease was high (92.2%) among Veterans with advanced CKD, although only 38.5% were aware of the severity of their CKD. KRT-directed education during clinical care was reported by 46.8% of Veterans, of which 21.1% reported having received targeted CoPE classes. Three-quarters (74.3%) of Veterans expressed interest in receiving CoPE services. Overall, awareness of CKD and its severity and receipt of KRT-directed education were significantly higher among Veterans with nephrology care than among those without. Of the 61 Veterans providing their KRT preferences, overall decision making was poor, with three-quarters (73.8%) of the cohort unable to choose any KRT modality, irrespective of ongoing nephrology care. Only 8 (13%) felt confident choosing home KRT modalities. Limitations: The study results are primarily applicable to the Veterans with advanced CKD. Furthermore, a limited numbers of respondents provided data on their KRT decision-making state, prohibiting broad generalizations. Conclusions: In a first-of-its-kind community-based needs assessment evaluation among Veterans with advanced CKD, we found that awareness of kidney disease is positively associated with nephrology care; however, the informed KRT selection capabilities are universally poor, irrespective of nephrology care. Our results demonstrate a critical gap between the recommended and prevalent nephrology practices such as KRT-directed education and targeted CoPE classes required for informed patient-centered home dialysis selection in advanced CKD.

The Advancing American Kidney Health Executive Order recommended substantial, potentially unrealistic increases in societal home dialysis use. Unfortunately, we have not examined patient preferences for these targets to guide health care policies. Conducting a community-level needs assessment study among Veterans with advanced kidney disease, we found significant deficits in basic clinical care, namely the specialty nephrology care and dialysis-directed patient education services essential for informed patient-centered dialysis selection. This was expectedly associated with a suboptimal state of dialysis decision making, with about three-quarters of those surveyed being unable to select any dialysis modality. Our results show a critical need for provider and system-level efforts to ensure universal availability of specialty kidney care and targeted education for all patients with advanced chronic kidney disease.

Comparative Safety of Long-Acting vs. Short-Acting Erythropoiesis-Stimulating Agents Among Patients Undergoing Hemodialysis.

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.

Tremor Induced by Cyclosporine, Tacrolimus, Sirolimus, or Everolimus: A Review of the Literature.

Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.

Electronic Phenotype for Advanced Chronic Kidney Disease in a Veteran Health Care System Clinical Database: Systems-Based Strategy for Model Development and Evaluation.

BACKGROUND: Identifying advanced (stages 4 and 5) chronic kidney disease (CKD) cohorts in clinical databases is complicated and often unreliable. Accurately identifying these patients can allow targeting this population for their specialized clinical and research needs. OBJECTIVE: This study was conducted as a system-based strategy to identify all prevalent Veterans with advanced CKD for subsequent enrollment in a clinical trial. We aimed to examine the prevalence and accuracy of conventionally used diagnosis codes and estimated glomerular filtration rate (eGFR)-based phenotypes for advanced CKD in an electronic health record (EHR) database. We sought to develop a pragmatic EHR phenotype capable of improving the real-time identification of advanced CKD cohorts in a regional Veterans health care system. METHODS: Using the Veterans Affairs Informatics and Computing Infrastructure services, we extracted the source cohort of Veterans with advanced CKD based on a combination of the latest eGFR value ≤30 ml·min-1·1.73 m-2 or existing International Classification of Diseases (ICD)-10 diagnosis codes for advanced CKD (N18.4 and N18.5) in the last 12 months. We estimated the prevalence of advanced CKD using various prior published EHR phenotypes (ie, advanced CKD diagnosis codes, using the latest single eGFR <30 ml·min-1·1.73 m-2, utilizing two eGFR values) and our operational EHR phenotypes of a high-, intermediate-, and low-risk advanced CKD cohort. We evaluated the accuracy of these phenotypes by examining the likelihood of a sustained reduction of eGFR <30 ml·min-1·1.73 m-2 over a 6-month follow-up period. RESULTS: Of the 133,756 active Veteran enrollees at North Florida/South Georgia Veterans Health System (NF/SG VHS), we identified a source cohort of 1759 Veterans with advanced nondialysis CKD. Among these, 1102 (62.9%) Veterans had diagnosis codes for advanced CKD; 1391(79.1%) had the index eGFR <30 ml·min-1·1.73 m-2; and 928 (52.7%), 480 (27.2%), and 315 (17.9%) Veterans had high-, intermediate-, and low-risk advanced CKD, respectively. The prevalence of advanced CKD among Veterans at NF/SG VHS varied between 1% and 1.5% depending on the EHR phenotype. At the 6-month follow-up, the probability of Veterans remaining in the advanced CKD stage was 65.3% in the group defined by the ICD-10 codes and 90% in the groups defined by eGFR values. Based on our phenotype, 94.2% of high-risk, 71% of intermediate-risk, and 16.1% of low-risk groups remained in the advanced CKD category. CONCLUSIONS: While the prevalence of advanced CKD has limited variation between different EHR phenotypes, the accuracy can be improved by utilizing two eGFR values in a stratified manner. We report the development of a pragmatic EHR-based model to identify advanced CKD within a regional Veterans health care system in real time with a tiered approach that allows targeting the needs of the groups at risk of progression to end-stage kidney disease.

Needs and Considerations for Standardization of Kidney Disease Education in Patients with Advanced CKD.

Kidney health advocacy organizations and leaders in the nephrology community have repeatedly emphasized the need to increase home dialysis utilization in the United States. Limited awareness and understanding of options for the management of kidney failure among patients living with advanced CKD is a significant barrier to increasing the selection and use of home dialysis. Studies have shown that providing targeted comprehensive patient education before the onset of kidney failure can improve patients' awareness of kidney disease and substantially increase the informed utilization of home dialysis. Unfortunately, in the absence of validated evidence-based education protocols, outcomes associated with home dialysis use vary widely among published studies, potentially affecting the routine implementation and reporting of these services among patients with advanced CKD. This review provides pragmatic guidance on establishing effective patient-centered education programs to empower patients to make informed decisions about their KRT and, in turn, increase home dialysis use.

VA-Based Peritoneal Dialysis Program Feasibility Considerations and Process Outline.

Background: Home dialysis utilization is lower among veterans than in the general US population. Several sociodemographic factors and comorbidities contribute to peritoneal dialysis (PD) underutilization. In 2019, the Veterans Health Administration (VHA) Kidney Disease Program Office convened a PD workgroup to address this concern. Observations: The PD workgroup was explicitly concerned by the limited availability of PD within the VHA, which frequently requires veterans to transition kidney disease care from US Department of Veterans Affairs medical centers (VAMCs) to non-VHA facilities when they progress from chronic kidney disease to end-stage kidney disease, causing fragmentation of care. Since the administrative requirements and infrastructure of VAMCs vary, the workgroup focused its deliberations on synthesizing a standard process for evaluating the feasibility and establishing a new PD program within any individual VAMC. A 3-phased approach was envisioned, beginning with ascertainment of prerequisites, leading to an examination of the clinical and financial feasibility through the process of data gathering and synthesis, culminating in a business plan that translates the previous 2 steps into an administrative document necessary for obtaining VHA approvals. Conclusions: VAMCs can use the guide presented here to improve therapeutic options for veterans with kidney failure by establishing a new or restructured PD program.

Phenomenology and Physiology of Tacrolimus Induced Tremor.

Background: Tacrolimus is a potent immunosuppressant drug commonly used after solid organ transplant surgery. The use of this drug is frequently associated with the emergence of tremors. There is little information on the clinical and physiological characteristics of tacrolimus-induced tremors. Characterizing these tremors is essential as they can promote the development of specific therapies. Methods: We describe four patients placed on tacrolimus immunosuppressant therapy following kidney transplant surgery and who developed tremors impacting their daily functional activities. We describe the clinical and physiological characteristics of the tremor and the response generated after a limb cooling test. Results: A postural and kinetic tremor mainly involving the distal hands was observed in our cohort. In the accelerometer-based assessment, the tremor amplitude was noted to be mild to moderate, and the frequency was 5-6 Hz. Cooling the forearm and the hand led to a temporary albeit significant reduction of tremor amplitude (p = 0.03). Limb cooling lowered the tremor frequency by 1 Hz in two patients with no change in the other two patients, and the statistical comparison was not significant (p > 0.05). Conclusions: Limb cooling may be pursued as a therapeutic option for addressing tacrolimus-induced tremor, as the patients in our cohort benefitted from temporary tremor suppression.

Kidney impairment and outcomes in acute ischaemic stroke.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of stroke and mortality. AIMS: To evaluate the clinical and imaging features and outcomes of patients with and without kidney impairment among t admitted for acute ischaemic stroke (AIS). METHODS: AIS patients with brain magnetic resonance imaging (MRI) were included in the study. Kidney impairment was defined by an admission estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) were evaluated using the Microbleed Anatomical Rating Scale and Fazekas scales, respectively. Primary outcomes were defined by modified Rankin Scale (mRS) and discharge disposition. Multivariate logistic regression analysis was performed to evaluate factors associated with the presence of kidney impairment and poor discharge outcomes. RESULTS: Of the 285 patients with AIS, 80 had kidney impairment on admission. Patients with kidney impairment were older (mean age ± standard deviation: 74.7 ± 12.9 vs 64.4 ± 13.8 years, P < 0.0001) and had more neurological deficits on National Institutes of Health Stroke Scale (NIHSS) score (median 8.5 vs 5, P = 0.02). In unadjusted analysis, patients with kidney impairment were less likely to have a good functional outcome (mRS 0-2: 36% vs 57%, P = 0.002) and good discharge outcome (home or inpatient rehabilitation: 68% vs 82%, P = 0.008). On multivariate analysis, kidney impairment was associated with higher NIHSS score (odds ratio (OR) = 1.04; 95% confidence interval (CI) = 1.002-1.08) and severe WMH (OR = 1.99; 95% CI = 1.06-3.77) suggestive of small vessel disease, but kidney impairment was not associated with poor discharge outcome (OR = 1.62; 95% CI = 0.75-3.53). CONCLUSION: Presence of kidney impairment at the time of stroke presentation, regardless of previous renal function, is associated with more neurological deficits and severe WMH on MRI.

Supporting Shared Decision-Making and Home Dialysis in End-Stage Kidney Disease.

It has been widely demonstrated that patient education and empowerment, especially involving shared treatment decisions, improve patient outcomes in chronic medical conditions, including chronic kidney disease requiring kidney replacement therapies. Accordingly, regulatory agencies in the US and worldwide recommend shared decision-making for finalizing one's choice of kidney replacement therapy. It is also recognized that the US needs to substantially increase home dialysis utilization to leverage its positive impacts on patient and healthcare cost-related outcomes. This perspective highlights how the routine clinical use of the recommended practice of shared decision-making can exist in synergy with the system's goal for increased home dialysis use. It introduces a pragmatic provider checklist, The Nephrologist's Shared Decision-Making Checklist, grounded in the relevant theories of shared decision-making, and, unlike some research assessments and extant tools, is easy to understand and implement in clinical practice. This qualitative Checklist can help providers ensure that they have co-constructed an SDM experience with the patient and involved caretakers, helping them benefit from the improved outcomes associated with SDM.

Development and validation of an end stage kidney disease awareness survey: Item difficulty and discrimination indices.

INTRODUCTION: Lack of awareness for chronic kidney disease (CKD), including end stage kidney disease (ESKD) and their management options is a major impediment to patients being able to select and use home dialysis therapies. While some instruments have been developed to measure CKD awareness, we lack validated instruments to evaluate patients' awareness of ESKD and dialysis modalities. This study is part of multipart project for developing and validating an ESKD-centric disease awareness questionnaire. METHODS: A team of specialty renal care experts developed a 45-items questionnaire encompassing the subdomains of General Kidney Knowledge, CKD Knowledge, and ESKD Knowledge. Item reduction analysis-specifically, calculation of item difficulty and item discrimination index scores-was used to items for further review and potential removal. RESULTS: Index scores were reviewed in conjunction with consideration of theoretical and substantive item content to reduce the number of items in the questionnaire, resulting in a 32-item questionnaire, retaining 5/10 items in the general kidney knowledge subdomain, 14/21 items in the CKD knowledge subdomain, and 13/14 items in the ESKD knowledge subdomain. Retained items ranged from 0.19 to 0.79 on the difficulty index, and from 0.31 to 0.81 on the discrimination index. Scores for percent correct on the reduced questionnaire spanned 0% to 87.5% correct on the full scale, 0% to 100% correct on the General Knowledge subdomain, 0% to 100% on the CKD Knowledge subdomain, and 0% to 92.3% on ESKD Knowledge subdomain. CONCLUSIONS: The questionnaire developed and refined in this study constitutes a patient disease awareness instrument that spans a range of difficulty, and yet shows strong ability to distinguish between patients with varying levels of disease awareness. This study is the first in part of a multistep project to addresses a gap in measuring ESKD specific knowledge. Accurate assessment of patients' disease awareness through a validated instrument can allow identification of knowledge domains leading to positive impacts on their healthcare decisions and improve targeted patient education efforts.

Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis Patients.

Background: Pre-ESKD Kidney Disease Education (KDE) has been shown to improve multiple CKD outcomes, but its effect on vascular access outcomes is not well studied. In 2010, Medicare launched KDE reimbursements policy for patients with advanced CKD. Methods: In this retrospective USRDS analysis, we identified all adult patients on incident hemodialysis with ≥6 months of pre-ESKD Medicare coverage during the first 5 years of CMS-KDE policy and divided them into CMS-KDE services recipients (KDE cohort) and nonrecipients (non-KDE cohort). The primary outcome was incident arteriovenous fistula (AVF) and the composite of incident AVF or arteriovenous graft (AVG) utilization. Secondary outcomes were central venous catheter (CVC) with maturing AVF/AVG and pure CVC utilizations. Step-wise multivariate analyses were performed in four progressive models (model 1, KDE alone; model 2, multivariate model encompassing model 1 with sociodemographics; model 3, model 2 with comorbidity and functional status; and model 4, model 3 with pre-ESKD nephrology care). Results: Of the 211,990 qualifying patients on incident hemodialysis during the study period, 2887 (1%) received KDE services before dialysis initiation. The rates of incident AVF and composite AVF/AVG were more than double (30% and 35%, respectively, compared with 14% and 17%), and pure catheter use about a third lower (40% compared with 65%) in the KDE cohort compared with the non-KDE cohort. The maximally adjusted odds ratios in model 4 for study outcomes were incident AVF use, 1.78, 99% confidence interval, 1.55 to 2.05; incident AVF/AVG use, 1.78, 99% confidence interval, 1.56 to 2.03; incident CVC with maturing AVF/AVG, 1.69, 99% confidence interval, 1.44 to 1.97; and pure CVC without any AVF/AVG, 0.51, 99% confidence interval, 0.45 to 0.58. The benefits of the KDE service were maintained even after accounting for the presence, duration, and facility of ESKD care. Conclusion: The occurrence of pre-ESRD KDE service is associated with significantly improved incident vascular access outcomes. Targeted studies are needed to examine the effect of KDE on patient engagement and self-efficacy as a cause for improvement in vascular access outcomes.

A randomized controlled trial to evaluate and assess the effect of comprehensive pre-end stage kidney disease education on home dialysis use in veterans, rationale and design.

BACKGROUND: Informed dialysis selection and greater home dialysis use are the two long-desired, underachieved targets of advanced chronic kidney disease (CKD) care in the US healthcare system. Observational institutional studies have shown that comprehensive pre-kidney failure, conventionally referred to as end stage kidney disease education (CPE) can improve both these outcomes. However, lack of validated protocols, well-controlled studies, and systemic models have limited wide-spread adoption of CPE in the US. We hypothesized that a universal CPE and patient-centered initiation of kidney replacement therapy can improve multiple clinical, patient-centered and health service outcomes in advanced CKD and kidney failure requiring dialysis therapy. METHODS: Trial to Evaluate and Assess the effects of CPE on Home dialysis in Veterans (TEACH-VET) is a multi-method randomized controlled trial aimed to evaluate the effects of a system-based approach for providing CPE to all Veterans with advanced CKD across a regional healthcare System. The study will randomize 544 Veterans with non-dialysis stage 4 and 5 CKD in a 1:1 allocation stratified by their annual family income and the stage of CKD to an intervention (CPE) arm or control arm. Intervention arm will receive a two-phase CPE in an intent-to-teach manner. Control arm will receive usual clinical care supplemented by resources for the freely-available kidney disease information. Participants will be followed after intervention/control for the duration of the study or until 90-days post-kidney failure, whichever occurs earlier. RESULTS: The primary outcome will assess the proportion of Veterans using home dialysis at 90-days post-kidney failure, and secondary outcomes will include post-intervention/control CKD knowledge, confidence in dialysis decision and home dialysis selection. Qualitative arm of the study will use semi-structured interviews to in-depth assess Veterans' satisfaction with the intervention, preference for delivery, and barriers and facilitators to home dialysis selection and use. Several post-kidney failure clinical, patient-centered and health services outcomes will be assessed 90-days post-kidney failure as additional secondary outcomes. CONCLUSION: The results will provide evidence regarding the need and efficacy of a system-based, patient-centered approach towards universal CPE for all patients with advanced CKD. If successful, this may provide a blueprint for developing such programs across the similar healthcare infrastructures throughout the country. TRIAL REGISTRATION: NCT04064086 .

Simultaneous catheter removal and reinsertion, is it acceptable in M. abscessus exit site infection?

In recent times, increasing reports of exit site infections (ESI) in peritoneal dialysis (PD) patients related to environmentally acquired atypical organisms, such as nontuberculous mycobacterium (NTM), have been reported in the literature. Among these NTM, Mycobacterium abscessus (M. abscessus) is unique and is associated with high morbidity and treatment failure rates. The international society of PD guidelines suggests individualizing therapeutic options for NTM-related ESI. Moreover, the guidelines encourage simultaneous catheter removal and reinsertion (SCRR) in isolated ESI, not responding to antimicrobial therapy to avoid PD interruptions. Physicians should be aware of the limitations of such approaches as delay in appropriate PD catheter intervention can be fraught with complications in patients with M. abscessus ESI. We report an M. abscessus ESI in a PD patient who underwent SCRR in conjunction with targeted antimicrobial therapy, and developed M. abscessus peritonitis requiring PD catheter removal and conversion to hemodialysis. The patient also developed ESI at the new exit site long after the PD catheter was removed, requiring prolonged antimicrobial therapy. Our case, taken together with available published case reports, highlights the futility of the SCRR approach towards the M. abscessus ESI and makes the cases for early PD catheter removal in these patients.

Association of early initiation of dialysis with all-cause and cardiovascular mortality: A propensity score weighted analysis of the United States Renal Data System.

BACKGROUND: Early initiation of maintenance hemodialysis has been associated with excess mortality in some studies, but the effects on cardiovascular (CV) mortality has not been studied. Moreover, whether the increased mortality is due to co-morbidities or early initiation of dialysis is unclear. We used a propensity score weighted analysis of the United States Renal Data System (USRDS) to examine how the estimated glomerular filtration rate (eGFR) at initiation of dialysis affects total and CV mortality. METHODS: Association between tertiles of eGFR at initiation of hemodialysis and all-cause and CV mortality were assessed in 676,196 adult patients who initiated hemodialysis between 2006 and 2014, using inverse probability of treatment weighting (IPTW) weighted multivariable regression models. RESULTS: The intermediate (eGFR 8.7 to <13.0 mL/min) and early start groups (eGFR ≥13.0 mL/min) had a 42% and 93% increased all-cause mortality, respectively compared to late (eGFR < 8.7), start group (unadjusted hazard ratio (HR) = 1.42; 95% CI, 1.41-1.43 and HR = 1.93; 95%CI, 1.91-1.94, respectively). This association was attenuated but remained significant in propensity weighted multivariable analysis (adjusted HR = 1.13; 95%CI, 1.12-1.14 for intermediate and HR = 1.37; 95%CI, 1.36-1.39, for early start, respectively). The CV mortality was similarly increased (adjusted HR = 1.08; 95%CI, 1.07-1.10 and HR = 1.23; 95%CI, 1.21-1.24, for intermediate and early start, respectively). In patients with cystic kidney disease, all-cause mortality was increased with early start, but there were no differences in CV mortality between groups. CONCLUSIONS: Early initiation of dialysis is associated with increased all-cause and CV mortality. Our observations support delaying hemodialysis according to the eGFR values.

Management of Cardiovascular Disease in Kidney Disease Study: Rationale and Design.

INTRODUCTION: Atherosclerosis, inflammation, and vascular stiffness are prominent interrelated risk factors contributing to the high incidence of cardiovascular disease (CVD) in patients with CKD. Conventional CVD management strategies in CKD largely target atherosclerotic CVD and have had a limited impact on the cardiovascular mortality in this population. Multiple in vivo and in vitro studies and epidemiological evidence from the rheumatologic cohorts have shown that low-dose hydroxychloroquine has beneficial effects on inflammation, endothelial function, insulin sensitivity, and metabolic syndrome. Our recent proof-of-concept animal study showed that hydroxychloroquine has marked protection against atherosclerosis and vascular stiffness. We hypothesize that hydroxychloroquine has the potential to provide significant cardiovascular benefits in patients with CKD. METHODS: The Management of Cardiovascular disease in Kidney disease study (NCT03636152) is a phase 2B, randomized, double-blind, placebo-controlled trial evaluating the effects of low-dose hydroxychloroquine therapy on the parameters of atherosclerosis, inflammation, and vascular stiffness in patients with CKD. The study plans to enroll 100 CKD patients estimated to be at high cardiovascular risk by a combination of low estimated glomerular filtration rate and albuminuria and treat them for 18 months with hydroxychloroquine or placebo in 1:1 allocation. RESULTS: The study will assess the change in the total carotid plaque volume as measured by serial noncontrast carotid MRI as the primary outcome and the serial changes in plasma inflammation markers, vascular stiffness, renal function, and the composition characteristics of the carotid plaque as secondary outcome measures. DISCUSSION/CONCLUSION: The results of this trial will provide the proof-of-applicability for hydroxychloroquine in the CVD in CKD. If positive, this trial should lead to phase-3 trials with clinical end points for this potentially transformative, novel, and inexpensive therapy for CVD in CKD.

Utilization of CMS pre-ESRD Kidney Disease Education services and its associations with the home dialysis therapies.

BACKGROUND: Kidney Disease Education (KDE) has been shown to improve informed dialysis selection and home dialysis use, two long-held but underachieved goals of US nephrology community. In 2010, the Center for Medicare and Medicaid Services launched a policy of KDE reimbursements for all Medicare beneficiaries with advanced chronic kidney disease. However, the incorporation of KDE service in real-world practice and its association with the home dialysis utilization has not been examined. METHODS: Using the 2016 US Renal Data System linked to end-stage renal disease (ESRD) and pre-ESRD Medicare claim data, we identified all adult incident ESRD patients with active Medicare benefits at their first-ever dialysis during the study period (1 January 2010 to 31 December 2014). From these, we identified those who had at least one KDE service code before their dialysis initiation (KDE cohort) and compared them to a parsimoniously matched non-KDE control cohort in 1:4 proportions for age, gender, ESRD network, and the year of dialysis initiation. The primary outcome was home dialysis use at dialysis initiation, and secondary outcomes were home dialysis use at day 90 and anytime through the course of ESRD. RESULTS: Of the 369,968 qualifying incident ESRD Medicare beneficiaries with their first-ever dialysis during the study period, 3469 (0.9%) received KDE services before dialysis initiation. African American race, Hispanic ethnicity, and the presence of congestive heart failure and hypoalbuminemia were associated with significantly lower odds of receiving KDE services. Multivariate analyses showed that KDE recipients had twice the odds of initiating dialysis with home modalities (15.0% vs. 6.9%; adjusted odds ratio (aOR):95% confidence interval (CI) 2.0:1.7-2.4) and had significantly higher odds using home dialysis throughout the course of ESRD (home dialysis use at day 90 (17.6% vs. 9.9%, aOR:CI 1.7:1.4-1.9) and cumulatively (24.7% vs. 15.1%, aOR:CI 1.7:1.5-1.9)). CONCLUSIONS: Utilization of pre-ESRD KDE services is associated with significantly greater home dialysis utilization in the incident ESRD Medicare beneficiaries. The very low rates of utilization of these services suggest the need for focused systemic evaluations to identify and address the barriers and facilitators of this important patient-centered endeavor.

Circulating endothelial cells as predictor of long-term mortality and adverse cardiovascular outcomes in hemodialysis patients.

Circulating endothelial cells (CEC) are thought to be markers of endothelial injury. We hypothesized that the numbers of CEC may provide a novel means for predicting long-term survival and cardiovascular events in hemodialysis patients. 54 hemodialysis patients underwent enumeration of their CEC number. We retrospectively analyzed their survival and incidence of adverse cardiovascular events. 22 deaths (41%) were noted over the median follow up period of 3.56 years (IQR 1.43-12) and 6 were attributed to cardiovascular deaths (11%) of which 1 (4%) was in the low CEC (CEC<20 cells/ml) and 5 (19%) in the high CEC (CEC≥20 cells/ml) group. High CEC was associated with worse cardiovascular survival (p = 0.05) and adverse cardiac events (p = 0.01). In multivariate analysis, CEC >20 cells/ml was associated with a 4-fold increased risk of adverse cardiac events (OR, 4.16 [95% CI,1.38-12.54],p = 0.01) while all-cause mortality and cardiovascular mortality were not statistically different. In this hemodialysis population, a single measurement of CEC was a strong predictor of long term future adverse cardiovascular events. We propose that CEC may be a novel biomarker for assessing cardiovascular risk in dialysis patients.

Mycobacterium abscessus exit-site infection in peritoneal dialysis patients: should we ever aim to salvage the catheter?

Improvements in the exit-site care for peritoneal dialysis (PD) patients have uncovered a trend for increasing incidence of rapidly growing nontuberculous mycobacterium exit-site infections (ESI). Among these, Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates. The international society of PD guidelines encourage PD catheter removal in patients with M. abscessus peritonitis but, do not have evidence-based recommendations for the management of ESIs related to this organism. We report an unusual case in which an asymptomatic end-stage renal disease patient with multiple favorable clinical characteristics, i.e., no apparent immunodeficiency, sensitivity pattern showing possibility of treatment with multiple antibiotics, no evidence of peritonitis, and early clinical response, was treated with a 9-month combination antimicrobial regimen administered orally and intraperitoneally. Despite excellent clinical response with a resolution of the ESI, our patient relapsed quickly, within 30 days of stopping antimicrobial therapy and required PD catheter removal. Our case, taken together with available published case reports, highlights the futility of the conservative approach towards the M. abscessus ESI and makes the cases for early PD catheter removal in these patients.