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.

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.

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.

Nonatherosclerotic Vascular Abnormalities Associated with Chronic Kidney Disease.

Nonatherosclerotic vascular diseases are manifested by endothelial dysfunction, hypertension, vascular calcification, coronary microvascular dysfunction, and calciphylaxis. Unfortunately, there are no definitive treatments for many of these disorders other than hypertension. In addition, although hypertension is more difficult to treat in the chronic kidney disease population, it is necessary to try and target a blood pressure of less than 130/80 mm Hg through the use of aggressive angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, and other antihypertensive medications. New therapies are being actively investigated in an attempt to treat nonatherosclerotic vascular diseases in the chronic kidney disease population.

Pro Re Nata Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity-Matched Cohort Study.

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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.

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.

Collapsing glomerulopathy in a patient with mixed connective tissue disease.

Collapsing glomerulopathy (CG) is a distinct podocytopathy characterized by the global or segmental collapse of glomerular capillary tuft with overlying podocyte hypertrophy and hyperplasia. CG has been associated with numerous etiologies, including infections, autoimmune disorders, drugs, and malignancies. Anecdotal reports of CG in patients with mixed connective tissue disease (MCTD) have been reported in the literature. We report a case of a 53-year-old female who presented to us with acute kidney injury and proteinuria. The patient underwent renal biopsy for further evaluation of her proteinuria, and was diagnosed to have collapsing glomerulopathy. The patient was subsequently diagnosed with MCTD, given her constellation of symptoms and serology titers. The patient was started on prednisone with subsequent stabilization of renal function and reduction of proteinuria and continues to be in remission. We report our case to highlight the association between collapsing glomerulopathy and MCTD and the potential role of steroids as first-line therapy in such cases.

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.

Venous Thromboembolism in Hospitalized COVID-19 Patients.

BACKGROUND: Venous thromboembolism (VTE) is increasingly reported in seriously ill patients with COVID-19 infection. Incidence of VTE has been reported before and results varied widely in study cohorts. AREA OF UNCERTAINTY: Incidence of major VTE (segmental pulmonary embolism and above and proximal deep vein thrombosis) which is a contributor to mortality and morbidity is not known. Also, data is unclear on the optimal anticoagulation regimen to prevent VTE. DATA SOURCES: Multiple databases including PubMed were searched until May 12, 2020, to include studies reporting VTE in hospitalized COVID-19 adult patients. MOOSE guidelines were followed in selection, and 11 studies were included. We conducted a systematic review and meta-analysis to quantitatively assess the VTE burden in hospitalized COVID-19 patients and potential benefits of therapeutic dosing of anticoagulation compared with prophylaxis dosing for VTE prevention. THERAPEUTIC ADVANCES: Many societies and experts recommend routine prophylactic anticoagulation with heparin for VTE prevention in hospitalized COVID-19 patients. In this meta-analysis, the pooled rate of major VTE was 12.5% in hospitalized patients and 17.2% in intensive care unit patients. When therapeutic anticoagulation dosing was compared with prophylactic anticoagulation, the pooled odds ratio of VTE was 0.33 (95% confidence interval 0.14-0.75; P = 0.008, I = 0%) suggesting statistical significance with therapeutic dosing of anticoagulation for primary prevention of VTE in all hospitalized patients. However, this should be interpreted with caution as the bleeding events and safety profile could not be ascertained because of lack of adequate information. We recommend applying this finding to hospitalized COVID 19 patients only after carefully weighing individual bleeding risks and benefits. CONCLUSION: Major VTE events, especially pulmonary embolism, seem to be high in COVID-19 patients admitted to the intensive care unit. Therapeutic anticoagulation dosing seems to significantly benefit the odds of preventing any VTE when compared with prophylactic dosing in all hospitalized patients.

The journey of remdesivir: from Ebola to COVID-19.

Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.

Infection-related Glomerulonephritis and C3 Glomerulonephritis - Similar Yet Dissimilar: A Case Report and Brief Review of Current Literature.

Infection-related glomerulonephritis (IRGN) is an immune complex-mediated glomerulonephritis (GN), often preceded by infection with subsequent recovery of renal function after the resolution of the infection. C3 deposition in the absence of immune complex deposits can be seen in patients with IRGN, but with the emergence of C3 glomerulonephritis (C3GN), the distinction is difficult as the clinical and pathological presentation may be similar. However, their treatment and clinical course vary significantly. A 64-year-old man with a history of hypertension and bioprosthetic aortic valve presented to the Emergency Department with left upper quadrant (LUQ) pain and a purpuric rash on bilateral lower extremities. The patient became septic, and further workup during the hospitalization revealed endocarditis secondary to Streptococcus viridans. On admission, the patient had acute kidney injury (AKI) with a serum creatinine of 3.79 mg/dl, which peaked at 5.72 mg/dl during the hospitalization. Renal biopsy demonstrated segmental necrotizing glomerulonephritis on light microscopy, predominant C3 deposition on immunofluorescence (IF) staining, and mesangial and paramesangial deposits on electron microscopy. This histologic picture can be seen both in IRGN and C3GN. The patient was treated with intravenous ceftriaxone for six weeks for endocarditis and the kidney injury was managed with supportive care. The patient's renal function improved and complement levels normalized, supporting the diagnosis of IRGN retrospectively. IRGN can mimic C3GN, and evaluation for alternate pathways of the complement system may be warranted in patients with atypical presentation of IRGN.

Point-of-Care Ultrasonography for Objective Volume Management in End-Stage Renal Disease.

Focused ultrasonography or point-of-care ultrasonography (POCUS) is increasingly considered as an essential bedside diagnostic tool. In patients with end-stage renal disease (ESRD) treated with hemodialysis, it can be used as an adjunct to physical examination to objectively assess the volume status and guide the rate and amount of ultrafiltration. Herein, we describe the case of an ESRD patient presenting with hypertensive urgency where POCUS disclosed the presence of hypervolemia despite unremarkable physical examination. The sonographic findings of the inferior vena cava, heart, and lungs guided fluid extraction during hemodialysis therapy, and the actual ultrafiltration volume was significantly higher than what was anticipated based on clinical findings. This case highlights the importance of using -POCUS as a tool for objective and precise assessment of volume status in patients with ESRD.

Methamphetamine-induced renal pseudovasculitis: Suspicion is the key.

It is important to recognize drug-induced vasculitis as patients with true vasculitis often require immunosuppressive therapy and delay in treatment can result in significant mortality. Illicit drug use (specifically methamphetamine and cocaine) should be in the differential diagnosis of vasculitis as it typically resolves with cessation of the drug.

Point-of-care renal ultrasound: Interpret with care.

Renal vascular malformations may mimic hydronephrosis on gray-scale ultrasound and can be easily differentiated using color doppler imaging. Non-radiology physicians performing point-of-care renal ultrasound should be aware of this finding to avoid mismanagement.

An uncommon cause of loss of vision in a dialysis patient with lupus.

Optic neuropathy is an uncommon finding in dialysis patients and has been associated with uremia, ischemia (arteritic and nonarteritic), drugs (isoniazid, ethambutol), infections (tuberculosis), and intracranial hypertension. Inflammatory optic neuritis associated with lupus is relatively rare, but clinicians need to be aware of this condition and obtain urgent ophthalmology consultation.