Utilization and Outcomes of Clinically Indicated Invasive Cardiac Care in Veterans with Acute Coronary Syndrome and Chronic Kidney Disease.

SIGNIFICANCE STATEMENT: Of studies reporting an association of CKD with lower use of invasive cardiac care to treat acute coronary syndrome (ACS), just one accounted for the appropriateness of such care. However, its findings in patients hospitalized nearly 30 years ago may not apply to current practice. In a more recent cohort of 64,695 veterans hospitalized with ACS, CKD was associated with a 32% lower likelihood of receiving invasive care determined to be clinically indicated. Among patients with CKD, not receiving such care was associated with a 1.39-fold higher risk of 6-month mortality. Efforts to elucidate the reasons for this disparity in invasive care in patients with ACS and CKD and implement tailored interventions to enhance its use in this population may offer the potential to improve clinical outcomes. BACKGROUND: Previous studies have shown that patients with CKD are less likely than those without CKD to receive invasive care to treat acute coronary syndrome (ACS). However, few studies have accounted for whether such care was clinically indicated or assessed whether nonuse of such care was associated with adverse health outcomes. METHODS: We conducted a retrospective cohort study of US veterans who were hospitalized at Veterans Affairs Medical Centers from January 2013 through December 2017 and received a discharge diagnosis of ACS. We used multivariable logistic regression to investigate the association of CKD with use of invasive care (coronary angiography, with or without revascularization; coronary artery bypass graft surgery; or both) deemed clinically indicated based on Global Registry of Acute Coronary Events 2.0 risk scores that denoted a 6-month predicted all-cause mortality ≥5%. Using propensity scoring and inverse probability weighting, we examined the association of nonuse of clinically indicated invasive care with 6-month all-cause mortality. RESULTS: Among 34,430 patients with a clinical indication for invasive care, the 18,780 patients with CKD were less likely than the 15,650 without CKD to receive such care (adjusted odds ratio, 0.68; 95% confidence interval, 0.65 to 0.72). Among patients with CKD, nonuse of invasive care was associated with higher risk of 6-month all-cause mortality (absolute risk, 21.5% versus 15.5%; absolute risk difference 6.0%; adjusted risk ratio, 1.39; 95% confidence interval, 1.29 to 1.49). Findings were consistent across multiple sensitivity analyses. CONCLUSIONS: In contemporary practice, veterans with CKD who experience ACS are less likely than those without CKD to receive clinically indicated invasive cardiac care. Nonuse of such care is associated with increased mortality.

Soluble Urokinase Receptor and Acute Kidney Injury.

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).

Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

BACKGROUND: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. METHODS: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. RESULTS: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. CONCLUSIONS: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners.

OBJECTIVES: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. DESIGN: Multinational internet-assisted survey. SETTING: Critical care practitioners involved with 14 societies in 80 countries. SUBJECTS: Intervention: MEASUREMENT AND MAIN RESULTS:: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2-22.0 yr). Two third of practitioners (71.0%; regional range, 55.0-95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0-111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0-365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7-47.8%) assessed hourly net fluid balance during continuous renal replacement therapy. Hemodynamic instability was reported in 20% (range, 20-38%) of patients and practitioners decreased the rate of fluid removal (70.3%); started or increased the dose of a vasopressor (51.5%); completely stopped fluid removal (35.8%); and administered a fluid bolus (31.6%), with significant regional variation. Compared with physicians, nurses were most likely to report patient intolerance to net ultrafiltration (73.4% vs 81.3%; p = 0.002), frequent interruptions (40.4% vs 54.5%; p < 0.001), and unavailability of trained staff (11.9% vs 15.6%; p = 0.04), whereas physicians reported unavailability of dialysis machines (14.3% vs 6.1%; p < 0.001) and costs associated with treatment as barriers (12.1% vs 3.0%; p < 0.001) with significant regional variation. CONCLUSIONS: Our study provides new knowledge about the presence and extent of international practice variation in net ultrafiltration. We also identified barriers and specific targets for quality improvement initiatives. Our data reflect the need for evidence-based practice guidelines for net ultrafiltration.

Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial.

RATIONALE & OBJECTIVE: The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design. STUDY DESIGN: Longitudinal analysis. SETTING & PARTICIPANTS: A subset of participants from the PRESERVE trial. EXPOSURES: Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography. OUTCOMES: MAKE-D and CA-AKI. ANALYTICAL APPROACH: We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com. RESULTS: We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants). LIMITATIONS: Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings. CONCLUSIONS: Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.

A Simple Equation to Estimate Urinary Flow Rate Using Urine Creatinine.

BACKGROUND: Accurate assessment of urine flow remains challenging in both inpatient and outpatient settings. We hypothesized we could derive an equation that would accurately estimate urine flow rate (eV) through derivation from other existing equations commonly used in nephrology clinical practice. METHODS: The eV equation was derived using the Cockcroft-Gault and the measured creatinine clearance (CrCl = UCrV/PCr) equations. Within the African American Study of Kidney Disease and Hypertension (AASK; n = 570) and COMBINE (n = 133) clinical trials, we identified participants with concordant estimated and measured creatinine excretion rates to define a subset with highly accurate 24-h urine collections, to assure a reliable gold standard. We then compared eV to measured 24-h urine flow rates in these trials. RESULTS: In AASK, we found a high correlation between eV and measured urine flow rate (V; r = 0.91, p < 0.001); however, Bland-Altman plots showed that eV was 9.5 mL/h lower than V, on average. Thus, we added a correction factor to the eV equation and externally validated the new equation in COMBINE. eV and V were again highly correlated (r = 0.91, p < 0.001), and bias was improved (mean difference 5.3 mL/h). Overall, 80% of individuals had eV that was within 20% of V. CONCLUSIONS: A simple equation using urine creatinine, demographics, and body weight can accurately predict urine flow rate and may have clinical utility in situations where it is difficult to accurately measure the urine flow rate.

Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial.

Background: Although depression is common among patients receiving maintenance hemodialysis, data on their acceptance of treatment and on the comparative efficacy of various therapies are limited. Objective: To determine the effect of an engagement interview on treatment acceptance (phase 1) and to compare the efficacy of cognitive behavioral therapy (CBT) versus sertraline (phase 2) for treating depression in patients receiving hemodialysis. Design: Multicenter, parallel-group, open-label, randomized controlled trial. (ClinicalTrials.gov: NCT02358343). Setting: 41 dialysis facilities in 3 U.S. metropolitan areas. Participants: Patients who had been receiving hemodialysis for at least 3 months and had a Beck Depression Inventory-II score of 15 or greater; 184 patients participated in phase 1, and 120 subsequently participated in phase 2. Intervention: Engagement interview versus control visit (phase 1) and 12 weeks of CBT delivered in the dialysis facility versus sertraline treatment (phase 2). Measurements: The primary outcome for phase 1 was the proportion of participants who started depression treatment within 28 days. For phase 2, the primary outcome was depressive symptoms measured by the Quick Inventory of Depressive Symptoms-Clinician-Rated (QIDS-C) at 12 weeks. Results: The proportion of participants who initiated treatment after the engagement or control visit did not differ (66% vs. 64%, respectively; P = 0.77; estimated risk difference, 2.1 [95% CI, -12.1 to 16.4]). Compared with CBT, sertraline treatment resulted in lower QIDS-C depression scores at 12 weeks (effect estimate, -1.84 [CI, -3.54 to -0.13]; P = 0.035). Adverse events were more frequent in the sertraline than the CBT group. Limitation: No randomized comparison was made with no treatment, and persistence of treatment effect was not assessed. Conclusion: An engagement interview with patients receiving maintenance hemodialysis had no effect on their acceptance of treatment for depression. After 12 weeks of treatment, depression scores were modestly better with sertraline treatment than with CBT. Primary Funding Source: Patient-Centered Outcomes Research Institute, Dialysis Clinic, Kidney Research Institute, and National Institute of Diabetes and Digestive and Kidney Diseases.

Intravascular Iodinated Contrast Is an Independent Cause of Acute Kidney Injury Following Coronary Angiography.

OBJECTIVES: Recent studies have questioned whether intravascular iodinated contrast remains an independent cause of acute kidney injury (AKI). We sought to assess whether iodinated contrast administered during coronary angiography is an independent cause of AKI. METHODS: We identified all of the patients who underwent coronary angiography between July 1, 2015 and June 30, 2017 with a discharge diagnosis of AKI that developed within 7 days following angiography. Using chart review, we categorized patients as having multifactorial AKI if ≥1 insults other than intravascular contrast potentially contributed to kidney injury or contrast-induced AKI (CI-AKI) if the only insult was contrast administration. We compared the severity of AKI and renal function upon discharge between patients with CI-AKI and multifactorial AKI. RESULTS: We identified 78 patients who experienced AKI within 7 days following angiography, 10 (13%) of whom had CI-AKI and 68 of whom (87%) experienced multifactorial AKI. Nine (90%) patients with CI-AKI manifested stage 1 disease, 1 (10%) had stage 2 disease, and 9 (90%) experienced full recovery of kidney function. More patients with multifactorial AKI developed stage 2 or 3 disease (42% vs 10%, χ2 = 3.73, P = 0.05) and experienced either partial recovery of kidney function or persistent kidney impairment compared with patients with CI-AKI (25% vs 10%, χ2 = 1.9, P = 0.17), although the latter comparison was not statistically significant. CONCLUSIONS: The intravascular administration of iodinated contrast remains an independent cause of AKI. Compared with those with multifactorial AKI, patients with CI-AKI appear to be more likely to experience mild decrements in kidney function that recover completely.

The associations of hemodialysis access type and access satisfaction with health-related quality of life.

OBJECTIVE: In addition to age and comorbidities, health-related quality of life (HRQOL) is known to predict mortality in hemodialysis (HD) patients. Understanding the association of vascular access type with HRQOL can help surgeons to provide patient-centered dialysis access recommendations. We sought to understand the impact of HD access type on HRQOL. METHODS: We conducted a cross-sectional prospective study of community-dwelling prevalent HD patients in Pittsburgh, Pennsylvania. We assessed patient satisfaction with their access using the Vascular Access Questionnaire (VAQ) and HRQOL with the Short Form Health Survey. We compared access satisfaction and HRQOL across access types. We used logistic regression modeling to evaluate the association of access type with satisfaction and multivariate analysis of variance to evaluate the association of both of these variables on HRQOL. RESULTS: We surveyed 77 patients. The mean age was 61.8 ± 15.9 years. Arteriovenous fistula (AVF) was used by 62.3%, tunneled dialysis catheter (TDC) by 23.4%, and arteriovenous graft (AVG) by 14.3%. There was a significant difference in satisfaction by access type with lowest median VAQ score (indicating highest satisfaction) in patients with AVF followed by TDC and AVG (4.5 vs 6.5 vs 7.0; P = .013). Defining a VAQ score of <7 to denote satisfaction, AVF patients were more likely to be satisfied with their access, compared with TDC or AVG (77% vs 56% vs 55%; P = NS). Multivariate regression analysis yielded a model that predicted 46% of the variance of VAQ score; important predictors of dissatisfaction included <1 year on dialysis (ß = 3.36; P < .001), increasing number of access-related hospital admissions in the last year (ß = 1.69; P < .001), and AVG (ß = 1.72; P = .04) or TDC (ß = 1.67; P = .02) access. Mean physical and mental QOL scores (the composite scores of Short Form Health Survey) were not different by access type (P = .49; P = .41). In an additive multivariate analysis of variance with the two composite QOL scores as dependent variables, 25.8% of the generalized variance in HRQOL (effect size) was accounted for by access satisfaction with only an additional 3% accounted for by access type. CONCLUSIONS: HD patients experience greatest satisfaction with fistula, and access satisfaction is significantly associated with better HRQOL. Controlling for access satisfaction, there is no significant independent association of access type on HRQOL. Future research should investigate the relationship between access satisfaction, adherence to dialysis regimens, mortality, and the consequent implications for patient-centered care.

Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced Chronic Kidney Disease.

Each year approximately 13,000 Veterans transition to maintenance dialysis, mostly in the traditional form of thrice-weekly hemodialysis from the start. Among >6000 dialysis units nationwide, there are currently approximately 70 Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers and their limited capacity, only 10% of all incident dialysis Veterans initiate treatment in a VA center. Evidence suggests that, among Veterans, the receipt of care within the VA system is associated with favorable outcomes, potentially because of the enhanced access to healthcare resources. Data from the United States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest that Veterans who receive dialysis in a VA unit exhibit greater survival compared with the non-VA centers. Substantial financial expenditures arise from the high volume of outsourced care and higher dialysis reimbursement paid by the VA than by Medicare to outsourced providers. Given the exceedingly high mortality and abrupt decline in residual kidney function (RKF) in the first dialysis year, it is possible that incremental transition to dialysis through an initial twice-weekly hemodialysis regimen might preserve RKF, prolong vascular access longevity, improve patients' quality of life, and be a more patient-centered approach, more consistent with "personalized" dialysis. Broad implementation of incremental dialysis might also result in more Veterans receiving care within a VA dialysis unit. Controlled trials are needed to examine the safety and efficacy of incremental hemodialysis in Veterans and other populations; the administrative and health care as well as provider structure within the VA system would facilitate the performance of such trials.

Patient-Centered Dialysis Care: Depression, Pain, and Quality of Life.

Remarkable advancements have been made in the provision of chronic dialysis therapy since its inception decades ago. A series of studies inform current dialysis dosing recommendations, while advancements in strategies to treat mineral and bone disease, acid-base and electrolyte disturbances, and anemia have facilitated the management of these well-recognized complications of ESRD. The collective result has been a model of chronic dialysis care focused principally on the achievement of metabolic and dialysis-related targets. In fact, guidelines such as the Kidney Disease Outcomes Quality Initiative put forth by the National Kidney Foundation recommend metrics that characterize successful dialysis care, including the attainment of specific solute clearance targets; maintenance of hemoglobin, calcium, phosphorous, and parathyroid hormone levels within target ranges; and the preferred use of primary arteriovenous fistulae for vascular access. This focus on serologic and dialysis-specific outcomes has helped renal providers manage the biochemical effects related to the loss of kidney function and has reduced ESRD-related morbidity and mortality. Yet, absent from this model of care is an emphasis on the treatment of bothersome symptoms and the impact of such treatment on quality of life (QOL). Among the many symptoms that affect patients on chronic dialysis, depression and pain are particularly common, strongly associated with decrements in QOL, and potentially treatable. This review discusses key research findings and unanswered questions pertaining to the prevalence, significance, and treatment of depression and pain and the effect of such treatment on QOL in patients dependent on chronic dialysis, with the broad goal of incorporating symptom management strategies into a paradigm of patient-centered dialysis care.

Evaluation of a single-item screening question to detect limited health literacy in peritoneal dialysis patients.

Studies have shown that a single-item question might be useful in identifying patients with limited health literacy. However, the utility of the approach has not been studied in patients receiving maintenance peritoneal dialysis (PD). We assessed health literacy in a cohort of 31 PD patients by administering the Rapid Estimate of Adult Literacy in Medicine (REALM) and a single-item health literacy (SHL) screening question "How confident are you filling out medical forms by yourself?" (Extremely, Quite a bit, Somewhat, A little bit, or Not at all). To determine the accuracy of the single-item question for detecting limited health literacy, we performed sensitivity and specificity analyses of the SHL and plotted the area under the receiver operating characteristic (AUROC) curve using the REALM as a reference standard. Using a cut-off of "Somewhat" or less confident, the sensitivity of the SHL for detecting limited health literacy was 80%, and the specificity was 88%. The positive likelihood ratio was 6.9. The SHL had an AUROC of 0.79 (95% confidence interval: 0.52 to 1.00). Our results show that the SHL could be effective in detecting limited health literacy in PD patients.

Association of Symptoms and Collaborative Care Intervention (TACcare) with Systemic Inflammation Biomarkers in End-Stage Kidney Disease.

BACKGROUND: Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TACcare) intervention on these biomarkers. METHODS: In the TACcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- and between-group differences after adjusting for age, sex, race, and comorbidities. RESULTS: Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue or depression at baseline. Both intervention and control group demonstrated reductions in IL-10 and IL-1RA over 6 months (ß range=-1.22 to -0.40, p range=<0.001 to 0.02) At 3 months, the treatment group exhibited decreases in TNF-α (ß=-0.22, p<0.001) and IL-2 (ß=-0.71, p<0.001), whereas the control group showed increases in IL-6/IL-10 ratio (ß=0.33, p=0.03). At 6 months, both groups exhibited decreases in IL-2 (ß range=-0.66 to -0.57,p<0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (ß=0.75,p<0.001) and decrease in TNF-α (ß=-0.16, p=0.02). Compared to controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (ß=-0.53, p<0.001). Significant interaction effects of treatment were observed on the association between changes in pro-inflammatory biomarkers (TNF-α and hs-CRP) levels and changes in symptom scores from baseline to 6 months. CONCLUSIONS: The TACcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine if these biomarkers mediate the link between symptoms and disease progression.

Associations of health literacy with dialysis adherence and health resource utilization in patients receiving maintenance hemodialysis.

BACKGROUND: Although limited health literacy is common in hemodialysis patients, its effects on clinical outcomes are not well understood. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 260 maintenance hemodialysis patients enrolled in a randomized clinical trial of symptom management strategies from January 2009 through April 2011. PREDICTOR: Limited health literacy. OUTCOMES: Dialysis adherence (missed and abbreviated treatments) and health resource utilization (emergency department visits and end-stage renal disease [ESRD]-related hospitalizations). MEASUREMENTS: We assessed health literacy using the Rapid Estimate of Adult Literacy in Medicine (REALM) and used negative binomial regression to analyze the independent associations of limited health literacy with dialysis adherence and health resource utilization over 12-24 months. RESULTS: 41 of 260 (16%) patients showed limited health literacy (REALM score, ≤60). There were 1,152 missed treatments, 5,127 abbreviated treatments, 552 emergency department visits, and 463 ESRD-related hospitalizations. Limited health literacy was associated independently with an increased incidence of missed dialysis treatments (missed, 0.6% vs 0.3%; adjusted incidence rate ratio [IRR], 2.14; 95% CI, 1.10-4.17), emergency department visits (annual visits, 1.7 vs 1.0; adjusted IRR, 1.37; 95% CI, 1.01-1.86), and hospitalizations related to ESRD (annual hospitalizations, 0.9 vs 0.5; adjusted IRR, 1.55; 95% CI, 1.03-2.34). LIMITATIONS: Generalizability and potential for residual confounding. CONCLUSIONS: Patients receiving maintenance hemodialysis who have limited health literacy are more likely to miss dialysis treatments, use emergency care, and be hospitalized related to their kidney disease. These findings have important clinical practice and cost implications.

KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.