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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2006.01.015 Byline: Aimee S. Dunlap, Bonnie B. Chen, Peter A. Bednekoff, Tom M. Greene, Russell P. Balda Abstract: Based on differing roles during the breeding season, male pinyon jays are predicted to be more accurate than females in recovering cached seeds over long retention intervals. We additionally predicted that males should be able to accurately recover caches made by their mates over short and long retention intervals. We conducted four experiments to test these predictions. During experiment 1, we tested the accuracies of the jays' spatial memory at a short retention interval of 5-7 days. We tested their recovery of their own caches and caches made in their presence by their mate and a nonmate of the opposite sex. While females and males found their own caches with similar accuracy, males were more accurate in finding caches made by their mates. Experiment 2 used the same design for caching, but longer retention intervals of 1, 2 and 4 months. Males were more accurate than females in the longer month intervals. To test whether differences found indicated a broad difference in spatial cognition, in experiment 3 we tested nonmated male and female jays in an open-field analogue to the radial arm maze. There were no significant effects of sex for task acquisition, accuracies across retention intervals, or patterns of adjacent holes or errors chosen. In experiment 4, we compared nonmated males and females in cache recovery at long internals and found no sex difference in accuracy. In addition, neither sex was affected by opportunities for memory rehearsal. We conclude that spatial memory in pinyon jays may be a state-dependent trait: females tend to be less accurate after longer intervals when mated than when not mated. Author Affiliation: (a) Avian Cognition Laboratory, Northern Arizona University, Flagstaff, AZ, U.S.A. (a ) Department of Ecology, Evolution and Behavior, University of Minnesota-Twin Cities, MN, U.S.A. (a ) Department of Biology, Eastern Michigan University, Ypsilanti, MI, U.S.A. Article History: Received 19 July 2005; Revised 8 September 2005; Accepted 10 January 2006 Article Note: (miscellaneous) MS. number: A10210

Background: Atrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice.Methods and Results: We used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P < .001), more likely to have prior stroke (29% vs 17%, P < .001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference -3.45, 95% confidence interval [CI] -6.24 to -0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference -1.63, 95% CI -2.59 to -0.67). The difference in visual analog scale general health was borderline (adjusted mean difference -2.01, 95% CI -4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI -0.48 to 1.57).Conclusions: AF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further. [ABSTRACT FROM AUTHOR]

Background: Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients.Objectives: The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment.Methods: This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment.Results: Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality.Conclusions: SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062). [ABSTRACT FROM AUTHOR]

We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure. [ABSTRACT FROM AUTHOR]

Mechanical unloading and circulatory support with left ventricular assist devices (LVADs) leads to significant structural and functional myocardial improvement in a subset of advanced heart failure (HF) patients, but the interplay between clinical parameters and underlying biological phenomena driving these changes is not well understood. By applying novel machine learning (ML) techniques, we sought to identify transcriptomics and clinical characteristics before the LVAD intervention that associate with subsequent structural and functional cardiac improvement. In a multicenter collaboration, baseline clinical variables and left ventricular apical tissue were collected from HF patients at the time of LVAD implantation (n=208). RNA was isolated from the apical tissue and mRNA transcripts were identified through RNA sequencing. Next, we used ML based on 59 clinical variables and 22,373 mRNA transcripts for the prediction of combined structural and functional myocardial improvement using a cutoff for left ventricular ejection fraction (LVEF) ≥40% and left ventricular end-diastolic diameter (LVEDD) ≤5.9cm. We also independently assessed LVEF and LVEDD as continuous variables representative of functional and structural myocardial improvement respectively, within the year post-LVAD implant. Combining the RNA and clinical data resulted in a support vector machine (SVM) model with 80 variables achieving an AUC of 0.73±0.15 for predicting LVAD-mediated myocardial recovery (Figure). Clinical factors associated with myocardial recovery included HF symptoms duration, pre-LVAD LVEF, LVEDD, and HF pharmacologic therapy, as well as LVAD configuration (axial vs. centrifugal). Transcriptomics associated with myocardial recovery included expression of CYREN (DNA repair), ATF3 (cellular stress), DUSP5 (cellular proliferation), and LRRN4C (ligand binding and programmed cell death). Using ML, we revealed specific clinical and molecular drivers of LVAD-mediated myocardial recovery. We also identified mechanistic pathways that may have diagnostic, prognostic, and therapeutic implications for the entire spectrum of HF. [ABSTRACT FROM AUTHOR]

Purpose Postoperative management of pediatric patients with non-ruptured appendicitis is highly variable and often includes an overnight stay in the hospital. We implemented a criteria-based postoperative protocol designed to eliminate postoperative antibiotics and facilitate timely discharge by utilizing the bedside nurse to evaluate for readiness for discharge. Methods We collected data on all patients with non-ruptured appendicitis at our institution following protocol implementation (May 1, 2012 to April 30, 2013) and compared them to a control group. Results 580 patients were treated for non-ruptured appendicitis (285 prior protocol, 295 new protocol). Following implementation of our protocol, there was an overall reduction in length of stay from 40.1 (SD 27.5) to 23.5 (SD 20.8) h, and total cost of care per patient also decreased from $5783 (SD $2501) to $4499 (SD $1983) (p < 0.001). There was no change in hospital readmission rate (1.1% prior protocol, 1.4% new protocol) or postoperative abscess rate (0.8% prior protocol, 0.3% new protocol). Conclusion Our new protocol reveals the value of eliminating postoperative antibiotics and leveraging the continuous availability of the bedside nurse in the determination of readiness for discharge. [ABSTRACT FROM AUTHOR]

Purpose We examined the effectiveness of a postoperative ruptured appendicitis protocol that eliminated Pseudomonas coverage and based the duration of IV antibiotic treatment and length of hospital stay on the patient’s clinical response. Methods In our new protocol, IV antibiotics were administered until the patient met discharge criteria: adequate oral intake, pain control with oral medications, and afebrile for 24 h. We collected data on all patients with ruptured appendicitis at our institution following protocol implementation (May 1, 2012, to April 30, 2013) and compared them to a control group. Results 306 patients were treated (154 prior protocol, 152 new protocol). The new clinical response-based protocol led to a decrease in hospital stay from 134 h (SD 66.1) to 94.5 h (SD 61.7) (p < 0.001) and total cost of care per patient also decreased from $13,610 (SD $6859) to $9870 (SD $5670) (p < 0.001). Conclusion Our clinical response-based protocol for pediatric patients with ruptured appendicitis decreased LOS, cost, and IV antibiotics use without significant changes in adverse events. [ABSTRACT FROM AUTHOR]

Amyloidosis cardiomyopathy is a systemic disease with high risk of disability and death. Patient-reported outcomes (PROs) are validated tools that measure health-related quality of life (HRQoL) and provide prognostic information in patients with heart failure. However, data on HRQoL profile and prognostic value of PROs in patients with cardiac amyloidosis are limited. This is an observational study of patients with transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL) who completed Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at the time of clinic visit. We examined KCCQ-12 scores and their relationship to HF hospitalization or death in both amyloidosis groups. A total of 81 patients were included in the study, 48 with ATTR and 33 with AL with a mean age of 78±7 years and 65±10 years, respectively. KCCQ-12 results were similar in both groups and showed significant HRQoL limitation - median summary score of 38 (IQR 24-60) for ATTR and 51 (IQR 31-73) for AL, p = 0.128. Compared to AL, patients with ATTR had more impairment in the physical limitation domain (Table). Over a median follow-up of 343 days, HF hospitalization or death occurred in 23 (48%) patients with ATTR and 17 (51%) patients with AL. KCCQ score was associated with the risk of HF hospitalization or death with a correlation ratio of 0.9 for ATTR (p=0.025) and 1.0 for AL (p=0.03). ROC AUC for KCCQ-12 ability to predict HF hospitalization or death was 0.7 (95% CI, 0.54-0.84, p = 0.026) for ATTR and 0.8 (95% CI, 0.62-0.95, p = 0.006) for AL. In ATTR, the rate of HF hospitalization or death increased proportionally with decreasing KCCQ-12 scores while in patients with AL high events rates were seen for KCCQ-12 scores 60 or lower. (Figure). Patients with ATTR and AL amyloidosis cardiomyopathy suffer from poor HRQoL and high burden of events. Our study shows that KCCQ provides important prognostic information in these patients. Routine KCCQ assessments could be used to identify high-risk patients in need of close monitoring. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We performed a pilot trial to compare reduced dose versus standard soybean lipid emulsion in neonates at risk for parenteral nutrition-associated liver disease. Methods: A prospective randomized controlled trial was performed (2009–2011) enrolling surgical patients ≥26weeks' gestation anticipated to require >50% of daily caloric intake from parenteral nutrition (PN) for at least 4weeks. Randomization occurred into either reduced (1.0g/kg/day) or standard (3 g/kg/day) groups. Co-primary outcomes for interpretation of the results were conjugated bilirubin and total bile acids. Additional outcomes included ALT, AST, GGT, alkaline phosphatase, growth, and essential fatty acid levels. Outcomes were compared between treatment groups using Wilcoxon rank sums tests. Results: Twenty-eight patients (47% enrollment rate) were included in the study with an average treatment duration of 5.4weeks. Groups had similar PN calories and protein intake throughout the study. Total increase from baseline was smaller in the reduced vs. standard group for conjugated bilirubin (p =0.04) and total bile acids (p =0.02). Weight z-score increased more in the standard group, and no patient experienced essential fatty acid deficiency. Conclusion: Markers of cholestasis rose at a slower rate using reduced lipid doses. This pilot study demonstrates feasibility and need for a larger study evaluating the effects of reduced lipids in patients at risk for developing parenteral nutrition-associated liver disease. [Copyright &y& Elsevier]

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined. [ABSTRACT FROM AUTHOR]

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5±0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3±0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition. [ABSTRACT FROM AUTHOR]

Abstract: Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m2.7 in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease. [Copyright &y& Elsevier]

Health-related quality of life (HRQOL) is poorly understood in patients with chronic kidney disease (CKD) prior to end-stage renal disease. The association between psychosocial measures and HRQOL has not been fully explored in CKD, especially in African Americans. We performed a cross-sectional analysis of HRQOL and its association with sociodemographic and psychosocial factors in African Americans with hypertensive CKD. There were 639 participants in the African American Study of Kidney Disease and Hypertension Cohort Study. The Short Form-36 was used to measure HRQOL. The Diener Satisfaction with Life Scale measured life satisfaction, the Beck Depression Inventory-II assessed depression, the Coping Skills Inventory-Short Form measured coping, and the Interpersonal Support Evaluation List-16 was used to measure social support. The mean participant age was 60 years at enrollment, and men comprised 61% of participants. Forty-two percent reported a household income less than $15,000/year. Higher levels of social support, coping skills, and life satisfaction were associated with higher HRQOL, whereas unemployment and depression were associated with lower HRQOL (P < 0.05). A significant positive association between higher estimated glomerular filtration rate (eGFR) was observed with the Physical Health Composite (PHC) score (P = 0.004) but not in the Mental Health Composite (MHC) score (P = 0.24). Unemployment was associated with lower HRQOL, and lower eGFR was associated with lower PHC. African Americans with hypertensive CKD with better social support and coping skills had higher HRQOL. This study demonstrates an association between CKD and low HRQOL, and it highlights the need for longitudinal studies to examine this association in the future. [Copyright &y& Elsevier]

Background: A low serum bicarbonate level is prevalent in chronic kidney disease (CKD); however, its relationship to long-term outcomes is unclear. Study Design: Cohort study. Setting & Participants: The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and blood pressure control on progression of kidney disease. This analysis includes 942 screened but non-randomized individuals and 839 randomized participants with baseline serum bicarbonate measurements with stage 2-4 CKD. Factor: Serum bicarbonate level categorized into quartiles. Outcomes: Kidney failure, all-cause mortality, and a composite outcome of mortality and kidney failure. Measurements: Local laboratories at each participating site measured bicarbonate in fasting serum samples. Kidney failure outcomes were obtained from the US Renal Data System, and mortality data, from the National Death Index. Results: Mean glomerular filtration rate (GFR) was 39 ± 21 (SD) mL/min/1.73 m² and serum bicarbonate level was 23.3 ± 3.8 mEq/L. Kidney failure rates were 72%, 64%, 50%, and 41%; mortality rates were 31%, 25%, 21%, and 25%, and rates of the composite outcome were 78%, 71%, 58%, and 54% in bicarbonate quartiles 1, 2, 3, and 4, respectively. In analyses adjusted for demographic and cardiovascular disease factors, serum albumin level, proteinuria, and cause of kidney disease, compared with quartile 4, quartile 1 was associated with a 2.22 HR (95% CI, 1.83-2.68) of kidney failure; 1.39 HR (95% CI, 1.07-1.18) of all-cause mortality; and 1.36 HR (95% CI, 1.15-1.62) of the composite outcome. These associations were rendered nonsignificant with adjustment for GFR (kidney failure HR, 1.05 [95% CI, 0.87-1.28]; all-cause mortality HR, 0.99 [95% CI, 0.75-1.13]; composite HR, 1.04 [95% CI, 0.87-1.24]). Limitations: Single baseline measurement of serum bicarbonate. Conclusions: Low serum bicarbonate level was associated with increased risk of long-term outcomes in nondiabetic patients with CKD. However, this risk is not independent of baseline GFR. Clinical trials are necessary to evaluate whether bicarbonate supplementation slows the progression of CKD. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the association between obesity and markers of kidney injury in a chronic kidney disease population. We hypothesized that obesity is independently associated with proteinuria, a marker of chronic kidney disease progression. Study Design: Observational cross-sectional analysis. Setting & Participants: Post hoc analysis of baseline data for 652 participants in the African American Study of Kidney Disease (AASK). Predictors: Obesity, determined using body mass index (BMI). Measurements & Outcomes: Urine total protein-creatinine ratio and albumin-creatinine ratio measured in 24-hour urine collections. Results: AASK participants had a mean age of 60.2 ± 10.2 years and serum creatinine level of 2.3 ± 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 ± 7.0 kg/m². Approximately 70% of participants had a daily urine total protein excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2-kg/m² increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4% (95% CI, 4.9-14.1) increase in urine total protein-creatinine and urine albumin-creatinine ratios, respectively. In multivariable models adjusting for age, sex, systolic blood pressure, serum glucose level, uric acid level, and creatinine level, each 2-kg/m² increase in BMI was associated with a 3.5% (95% CI, 0.4-6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria, respectively. The interaction between older age and BMI was statistically significant, indicating that this relationship was driven by younger AASK participants. Limitations: May not generalize to other populations; cross-sectional analysis precludes statements regarding causality. Conclusions: BMI is associated independently with urine total protein and albumin excretion in African Americans with hypertensive nephrosclerosis, particularly in younger patients. [ABSTRACT FROM AUTHOR]

Background: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics.Study Design: Test of diagnostic accuracy.Setting& Participants: Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index.Index Tests: eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine.Reference Test: Measured GFR using urinary or plasma clearance of exogenous filtration markers.Results: Mean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR<30 mL/min/1.73 m2, both equations have similar bias (median difference compared with measured GFR). For eGFR of 30-59 mL/min/1.73 m2, bias was decreased from 4.9 to 2.1 mL/min/1.73 m2 (57% improvement). For eGFR of 60-89 mL/min/1.73 m2, bias was decreased from 11.9 to 4.2 mL/min/1.73 m2 (61% improvement). For eGFR of 90-119 mL/min/1.73 m2, bias was decreased from 10.0 to 1.9 mL/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR<90 mL/min/1.73 m2, other than body mass index<20 kg/m2, with greater variation noted for some subgroups with eGFR>or=90 mL/min/1.73 m2.Limitations: Limited number of elderly people and racial and ethnic minorities with measured GFR.Conclusions: The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation. [ABSTRACT FROM AUTHOR]

Background: Evaluating the accuracy of estimated glomerular filtration rate (eGFR) derived from serum creatinine (SCr) and serum cystatin C (SCysC) equations requires gold-standard measures of GFR. However, the influence of imprecise measured GFRs (mGFRs) on estimates of equation error is unknown.Study Design: Diagnostic test study.Setting& Participants: 1,995 participants from the Modification of Diet in Renal Disease (MDRD) Study and African American Study of Kidney Disease and Hypertension (AASK) with at least 2 baseline mGFRs from iodine 125-iothalamate urinary clearances, 1 standardized SCr value, and 1 SCysC value.Index Tests: eGFRs calculated using the 4-variable isotope-dilution mass spectrometry (IDMS)-traceable MDRD Study equation, the Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) SCysC equation, the CKD-EPI SCr-SCysC equation, and mGFRs collected from another prerandomization visit.Reference Tests: A single reference mGFR, average of 2, and average of 3 mGFRs; additional analysis limited to consistent mGFRs (difference Results: We found that mGFRs had stable mean values, but substantial variability across visits. Of all mGFRs collected a mean of 62 days apart from the reference visit, 8.0% were outside 30% of the single reference mGFR (1 - P(30)). Estimation equations were less accurate because 12.1%, 17.1%, and 8.3% of eGFRs from the MDRD Study, CKD-EPI SCysC, and CKD-EPI SCr-SCysC equations were outside 30% of the same gold standard (1 - P(30)). However, improving the precision of the reference test from a single mGFR to the average of 3 consistent mGFRs decreased these error estimates (1 - P(30)) to 8.0%, 12.5%, and 3.9%, respectively.Limitations: Study population limited to those with CKD.Conclusions: Imprecision in gold-standard measures of GFR contribute to an appreciable proportion of the cases in which eGFR and mGFR differ by >30%. Reducing and quantifying errors in gold-standard measurements of GFR is critical to fully estimating the accuracy of GFR estimates. [ABSTRACT FROM AUTHOR]

Background Evaluating the accuracy of estimated glomerular filtration rate (eGFR) derived from serum creatinine (SCr) and serum cystatin C (SCysC) equations requires gold-standard measures of GFR. However, the influence of imprecise measured GFRs (mGFRs) on estimates of equation error is unknown. Study Design Diagnostic test study. Setting & Participants 1,995 participants from the Modification of Diet in Renal Disease (MDRD) Study and African American Study of Kidney Disease and Hypertension (AASK) with at least 2 baseline mGFRs from iodine 125-iothalamate urinary clearances, 1 standardized SCr value, and 1 SCysC value. Index Tests eGFRs calculated using the 4-variable isotope-dilution mass spectrometry (IDMS)-traceable MDRD Study equation, the Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) SCysC equation, the CKD-EPI SCr-SCysC equation, and mGFRs collected from another prerandomization visit. Reference Tests A single reference mGFR, average of 2, and average of 3 mGFRs; additional analysis limited to consistent mGFRs (difference ⩽25% from reference mGFR). Results We found that mGFRs had stable mean values, but substantial variability across visits. Of all mGFRs collected a mean of 62 days apart from the reference visit, 8.0% were outside 30% of the single reference mGFR (1 - P30). Estimation equations were less accurate because 12.1%, 17.1%, and 8.3% of eGFRs from the MDRD Study, CKD-EPI SCysC, and CKD-EPI SCr-SCysC equations were outside 30% of the same gold standard (1 - P30). However, improving the precision of the reference test from a single mGFR to the average of 3 consistent mGFRs decreased these error estimates (1 - P30) to 8.0%, 12.5%, and 3.9%, respectively. Limitations Study population limited to those with CKD. Conclusions Imprecision in gold-standard measures of GFR contribute to an appreciable proportion of the cases in which eGFR and mGFR differ by >30%. Reducing and quantifying errors in gold-standard measurements of GFR is critical to fully estimating the accuracy of GFR estimates. [ABSTRACT FROM AUTHOR]

Background: The Frequent Hemodialysis Network (FHN) is conducting 2 randomized clinical trials, a daytime in-center trial ("daily") comparing 6 versus 3 treatments/wk, and a home nocturnal trial comparing 6 nocturnal treatments versus 3 conventional treatments/wk. The goal of this study was to project separation between the treatment and control arms of these studies for measures of dialysis dose by using simulations based on 2-compartment variable-volume models.Setting& Participants: Data from the most recent hemodialysis treatment in 100 patients dialyzed 3 times/wk at facilities of the Renal Research Institute in New York and from 2 data sets (n = 154 and 115 patients) from the Hemodialysis (HEMO) trial.Design: Observational study.Predictor: Dialysis prescriptions for the treatment and control arms in the FHN trials. DIALYSIS REGIMEN OUTCOMES: Treatment time, ultrafiltration rate, standard Kt/V/wk for urea (stdKt/V(urea)), and continuous clearance estimates based on ratios of urea, creatinine, and normalized beta(2)-microglobulin generation rates (denoted by Gn) to time-averaged concentrations (TACs) of these solutes during 1 treatment week.Results: The expected differences between median values in the experimental and control groups were weekly treatment time: daily trial, 29%; nocturnal trial, 234%; ultrafiltration rate: daily, -20%; nocturnal, -69%; stdKt/V(urea): daily, 52%; nocturnal, 133%; Gn(urea)/TAC(urea): daily, 34%; nocturnal, 130%; Gn(cr)/TAC(cr): daily, 31%; nocturnal, 135%; and Gn(beta2)/TAC(beta2): daily, 8%; nocturnal, 67%.Limitations: Use of simulated data and assumption of equivalent volumes and ultrafiltration rates between treatment arms.Conclusions: The nocturnal 6-times-weekly regimen produces substantially greater separation between the treatment and control arms than the daytime 6-times-weekly regimen for a wide range of treatment parameters. However, the 6-times-weekly interventions in both FHN trials will produce substantially greater separation than in the HEMO trial, where separations in median weekly treatment time and stdKt/V(urea) between the 3-times-weekly high- and standard-dose groups were 18% and 17%, respectively. The FHN trials will test whether substantial increases in solute clearance and other effects of frequent hemodialysis materially influence selected intermediate outcome measures. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is prevalent in patients with chronic kidney disease (CKD); however, data are limited about the relationship of uric acid levels with long-term outcomes in this patient population.Study Design: Cohort study.Setting& Participants: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial (N = 840) conducted from 1989 to 1993 to examine the effects of strict blood pressure control and dietary protein restriction on progression of stages 3 to 4 CKD. This analysis included 838 patients.Predictor: Uric acid level.Outcomes& Measurements: The study evaluated the association of baseline uric acid levels with all-cause mortality, cardiovascular disease (CVD) mortality, and kidney failure.Results: Mean age was 52 +/- 12 (SD) years, glomerular filtration rate was 33 +/- 12 mL/min/1.73 m(2), and uric acid level was 7.63 +/- 1.66 mg/dL. During a median follow-up of 10 years, 208 (25%) participants died of any cause, 127 (15%) died of CVD, and 553 (66%) reached kidney failure. In multivariate models, the highest tertile of uric acid was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.07 to 2.32), a trend toward CVD mortality (HR, 1.47; 95% CI, 0.90 to 2.39), and no association with kidney failure (HR, 1.20; 95% CI, 0.95 to 1.51) compared with the lowest tertile. In continuous analyses, a 1-mg/dL greater uric acid level was associated with 17% increased risk of all-cause mortality (HR, 1.17; 95% CI, 1.05 to 1.30) and 16% increased risk of CVD mortality (HR, 1.16; 95% CI, 1.01 to 1.33), but was not associated with kidney failure (HR, 1.02; 95% CI, 0.97 to 1.07).Limitations: Primary analyses were based on a single measurement of uric acid. Results are generalizable primarily to relatively young white patients with predominantly nondiabetic CKD.Conclusions: In patients with stages 3 to 4 CKD, hyperuricemia appears to be an independent risk factor for all-cause and CVD mortality, but not kidney failure. [ABSTRACT FROM AUTHOR]

C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. Background. High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. Methods. The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP ≥3.0 mg/L ( N= 414) versus low CRP<3.0 mg/L ( N= 283)], and serum albumin, with all-cause and cardiovascular mortality. Results. Median follow-up time was 125 months, all-cause mortality was 20% ( N= 138) and cardiovascular mortality was 10% ( N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07–2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13–3.31), but not serum albumin (HR 0.94, 95% CI 0.87–1.02), was an independent predictor of cardiovascular mortality. Conclusion. Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD. [ABSTRACT FROM AUTHOR]

The intent-to-treat analyses of all patients in the HEMO trial suggested that increases in dose of dialysis as measured by urea Kt/V were of marginal or no benefit when dialysis was provided in a 3 times/wk schedule. The as-treated analysis in the HEMO trial pointed to markedly increased mortality when the delivered dose decreased even slightly below the targeted dose, evidence of a dose-targeting bias. The intent-to-treat HEMO study results suggested a potential interaction between sex and the dose-mortality relationship, and this also has been found in some cross-sectional studies, the cause of which remains unexplained. Whether dialysis dose should continue to be targeted based on urea distribution volume (V), or targeted to a body size measure that is a lower power of body weight (such as body surface area), remains an open question. The lack of benefit of increasing the dialysis dose in a 3 times/wk setting is more understandable if one looks at measures of equivalent continuous solute removal, such as the standard Kt/V. Differences in standard Kt/V in the 2 dose arms of the HEMO trial, for example, were only about 15%. Without going into removal of very large solutes (eg, beta-2-microglobulin), which is discussed elsewhere in this issue, or protein-bound uremic solutes, the only way to provide significantly more dialysis dose may be to move to more frequent dialysis schedules and/or to very long session lengths. Here, benefit may be related as much to better control of salt and water balance as to better removal of uremic toxins. [ABSTRACT FROM AUTHOR]

Prescribing an equilibrated intermittent hemodialysis dose in intensive care unit acute renal failure. Background. Prospective, formal, blood-side, urea kinetic modeling (UKM) has yet to be applied in intermittent hemodialysis for acute renal failure (ARF). Methods for prescribing a target, equilibrated Kt/V (eKt/V) are described for this setting. Methods. Serial sessions were studied in 28 intensive care unit ARF patients. eKt/V was derived using delayed posthemodialyis urea samples and formal, double-pool UKM (eKt/Vref), and by applying the Daugirdas-Schneditz venous rate equation to pre- and posthemodialysis samples (eKt/Vrate). Individual components of prescribed and delivered dose were compared. Prescribed eKt/V values were determined using in vivo dialyzer clearance estimates and anthropometric (Watson and adjusted Chertow) and modeled urea volumes. Results. was well-approximated by . Modeled V exceeded Watson V by and Adjusted Chertow V by , although the degree of overestimation diminished over time. This difference was influenced by access recirculation (AR) and use of saline flushes. The median % difference between Vdprate and Watson V was reduced to 1% after adjusting for AR for the 22 sessions with ≤1 saline flush. The median coefficients of variation for serial determinations of Adjusted Chertow V, modeled V, urea generation rate, and eKt/Vref were 2.7%, 12.2%, 30.1%, and 16.4%, respectively. Because of comparatively higher modeled urea Vs, delivered eKt/Vref was lower than prescribed eKt/V, based on Watson V or Adjusted Chertow V, by 0.13 and 0.08 Kt/V units. The median absolute errors of prescribed eKt/V vs. delivered therapy (eKt/Vref) were not large and were similar in prescriptions based on the Adjusted Chertow V (0.127) vs. those based on various double-pool modeled urea volumes (∼0.127). Conclusion. Equilibrated Kt/V can be derived using formal, double-pool UKM in intensive care unit ARF patients, with the venous rate equation providing a practical alternative. A target eKt/V can be prescribed to within a median absolute error of less than 0.14 Kt/V units using practical prescription algorithms. The causes of the increased apparent volume of urea distribution appear to be multifactorial and deserve further investigation. [ABSTRACT FROM AUTHOR]

Anthropometrically estimated total body water volumes are larger than modeled urea volume in chronic hemodialysis patients: Effects of age, race, and gender. Background. The modeled volume of urea distribution (Vm) in intermittently hemodialyzed patients is often compared with total body water (TBW) volume predicted from population studies of patient anthropometrics (Vant). Methods. Using data from the HEMO Study, we compared Vm determined by both blood-side and dialysate-side urea kinetic models with Vant as calculated by the Watson, Hume-Weyers, and Chertow anthropometric equations. Results. Median levels of dialysate-based Vm and blood-based Vm agreed (43% and 44% of body weight, respectively). These volumes were lower than anthropometric estimates of TBW, which had median values of 52% to 55% of body weight for the three formulas evaluated. The difference between the Watson equation for TBW and modeled urea volume was greater in Caucasians (19%) than in African Americans (13%). Correlations between Vm and Vant determined by each of the three anthropometric estimation equations were similar; but Vant derived from the Watson formula had a slightly higher correlation with Vm. The difference between Vm and the anthropometric formulas was greatest with the Chertow equation, less with the Hume-Weyers formula, and least with the Watson estimate. The age term in the Watson equation for men that adjusts Vant downward with increasing age reduced an age effect on the difference between Vant and Vm in men. Conclusion. The findings show that kinetically derived values for V from blood-side and dialysate-side modeling are similar, and that these modeled urea volumes are lower by a substantial amount than anthropometric estimates of TBW. The higher values for anthropometry-derived TBW in hemodialyzed patients could be due to measurement errors. However, the possibility exists that TBW space is contracted in patients with end-stage renal disease (ESRD) or that the TBW space and the urea distribution space are not identical. [ABSTRACT FROM AUTHOR]

Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD Study. Background. The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean ± SD glomerular filtration rate (GFR) was 39.8 ± 21.1 mL/min/1.73 m2. Methods. The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. Results. The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. Conclusions. These cross-sectional findings suggest that in patients with... [ABSTRACT FROM AUTHOR]

Relationship between apparent (single-pool) and true (double-pool) urea distribution volume. Background. The volume of urea distribution (V) is usually derived from single-pool variable volume urea kinetics. A theoretical analysis has shown that modeled single-pool V (Vsp) is overestimated when the urea reduction ratio (URR) is greater than 65 to 70% and is underestimated when the URR is less than 65%. The “true” volume derived from double-pool kinetics (Vdp) does not exhibit this effect. An equation has been derived to adjust Vsp to the expected Vdp. Methods. To validate these theoretical predictions, we examined data from the Hemodialysis (HEMO) Study to assess the performance of Vdp as estimated from Vsp using the previously published prediction equation. For increased precision, both Vsp and Vdp were factored by anthropometric volume (Va). Patients were first dialyzed with a target equilibrated dialysis dose (eKt/V) of 1.45 during a baseline period and were then randomly assigned to eKt/V targets of either 1.05 (a URR of approximately 67%) or 1.45 (a URR of approximately 75%). A blood sample was obtained one hour after starting dialysis during one dialysis in each patient. Results. Vsp/Va was (mean ±sd) 1.014 ± 0.127 in 795 patients during the baseline period when the URR was approximately 1.45. During the first modeled dialysis after randomization, the Vsp/Va fell to 0.961 ± 0.138 in the group with an eKt/V target of 1.05, but did not change significantly under the high eKt/V goal. The correction of Vsp to Vdp using the prediction equation resulted in a Vdp/Va ratio of 0.96 to 0.98 in all three circumstances without significant differences. When a blood sample was drawn one hour after starting dialysis, the apparent Vsp/Va ratio at one hour was much lower at 0.708 ± 0.139. However, the mean Vdp/Va ratio, computed using the correction equation, was 0.968 ± 0.322, which was similar to the Vdp/Va ratio calculated from the... [ABSTRACT FROM AUTHOR]

Imprecision of the hemodialysis dose when measured directly from urea removal. Background. The postdialysis blood urea nitrogen (BUN; Ct) is a pivotal parameter for assessing hemodialysis adequacy by conventional blood-side methods, but Ct is relatively unstable because of hemodialysis-induced disequilibrium. The uncertainty associated with this method is potentially reduced or eliminated by measuring urea removed on the dialysate side, a more direct approach that can determine adequacy from the fraction of urea removed and by substituting an estimate of the equilibrated postdialysis BUN (Ceq) for Ct. For a patient with a known urea volume (V), Ceq, the equilibrated Kt/V (eKt/V), and the solute removal index (SRI) can be calculated from the predialysis BUN (C0), total urea nitrogen removed (A), and V from simple mass balance calculations (dialysate/volume method). However, a theoretical error analysis showed that relatively small errors in A, C0, or V are magnified when SRI or eKt/V is calculated using this method, especially at higher eKt/V values (for example, if eKt/V = 1.4 per dialysis, a 7% dialysate collection error causes a 20% error in eKt/V). Methods. During three to four baseline dialyses in each of 39 patients enrolled in the pilot phase of the HEMO Study, “A” was measured using an instrument that sampled dialysate frequently (Biostat®), and V was calculated from A, C0, and Ceq (median CV for V = 5.6%). The mean V was then applied to the dialysate/volume method to estimate eKt/V and SRI during two to five subsequent dialyses per patient (comparison dialyses). The accuracy and precision of these estimates were assessed by comparing them with eKt/V and SRI derived from a direct measurement of Ceq drawn 30 minutes after dialysis (reference method), from mathematical curve-fitting of sequential dialysate urea... [ABSTRACT FROM AUTHOR]

Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial.Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial.Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups.Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40).Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791). [ABSTRACT FROM AUTHOR]

There is need for interventions that can assist with long-term maintenance of healthy body weight and be sustainably integrated into existing primary care teams. The goal of MAINTAIN PRIME (Promoting Real (World) IMplEmentation) is to evaluate whether a successful electronic health record (EHR)-based weight maintenance intervention can be adapted to a new clinical setting with primary care staff serving as coaches. EHR tools include tracking tools, standardized surveys, and standardized "SmartPhrases" for coaching. Inclusion criteria were age 18–75 years, voluntary 5% weight loss in the past 2 years with prior BMI ≥ 25 kg/m2, and no bariatric procedures in past 2 years. Participants were randomized 1:1 to tailored online coaching with EHR tracking tools (coaching) or EHR tracking tools alone (tracking). We screened 405 individuals between September 2021 and April 2023; 269 participants enrolled (134 coaching; 135 tracking). The most common reason for not enrolling was ineligibility (55%). At baseline, participants were 50.3 (SD 15.02) years old, 66.4% female, and 84% White; 83.7% reported moderate physical activity. Average weight and BMI at baseline were 205.0 (SD 48.9) lbs. and 33.2 (6.8) kg/m2, respectively. Participants lost an average of 10.7% (SD 5.2) of their body weight before enrolling. We recruited 39 primary care coaches over the same period. Conclusion The study successfully identified and recruited primary care patients with recent intentional weight loss for participation in a weight maintenance program that uses EHR-based tools. We also successfully recruited and trained primary care staff as coaches. [ABSTRACT FROM AUTHOR]

This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. [ABSTRACT FROM AUTHOR]

Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50–60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups. [ABSTRACT FROM AUTHOR]

Standard Kt/Vurea (stdKt/V) is a hypothetical continuous clearance in patients treated with intermittent hemodialysis based on the generation rate of urea nitrogen and the average predialysis urea nitrogen. Previous equations to estimate stdKt/V were derived using a fixed-volume model. To determine the impact of fluid removal as well as residual urea clearance on stdKt/V, we modeled 245 hemodialysis sessions (including conventional 3/week, in-center 6/week, and at-home nocturnal 6/week) in 210 patients enrolled in the Frequent Hemodialysis Network Daily and Nocturnal clinical trials. To examine the role of fluid removal, modeled stdKt/V was compared to stdKt/V estimated from a previously published simplified equation. In a subgroup of 45 sessions with residual urea clearance over 1.5 ml/min, the contribution of residual urea clearance to stdKt/V was measured. For all dialysis schedules, the fixed-volume equation predicted stdKt/V well when both fluid removal and residual urea clearance were set to zero. When fluid removal was included, modeled stdKt/V was slightly underestimated for all three modes of hemodialysis. The shortfall correlated directly with weekly fluid removal and inversely with modeled urea volume. Modeled stdKt/V compressed residual urea clearance to about 70% of its measured value and the fractional downsizing significantly correlated inversely with treatment Kt/V. Our new equation predicted modeled stdKt/V with a high level of accuracy, even when substantial fluid removal and residual urea clearance were present. [ABSTRACT FROM AUTHOR]

Certain clinical characteristics affect brain natriuretic peptide (BNP) levels independently of clinical heart failure (HF). However, it is unclear how to adjust the diagnostic cutoffs of BNP for these variables. We hypothesized that adjusting for important covariates would improve the diagnostic accuracy of BNP for HF in the emergency room setting. We included patients presenting with dyspnea at the Salt Lake City Veterans Affairs Medical Center. Physicians unaware of the BNP values adjudicated the outcome as dyspnea due to HF or noncardiac dyspnea. Subgroup analyses and logistic regression analysis were used to adjust the BNP cutoffs. The mean age of the study population (n = 335) was 72 ± 11 years. A BNP of 100 pg/ml had a sensitivity of 91%, and a BNP of 400 pg/ml had a specificity of 92%. The covariates age, history of atrial fibrillation, creatinine, and body mass index affected BNP levels independently of HF. The subgroup-specific BNP cutoff that maintained 91% sensitivity was 184 pg/ml for patients ≥75 years, 150 pg/ml for those with atrial fibrillation, and 449 pg/ml for patients with a creatinine ≥2 mg/dl. These subgroup-specific cutoffs improved specificity compared to a cutoff of 100 pg/ml. The regression model that adjusted BNP improved the reclassification of patients as having cardiac or noncardiac dyspnea compared to the conventional BNP cutoffs. Of the patients without HF, 11% were correctly reclassified as having noncardiac dyspnea (p = 0.003). In conclusion, adjusting BNP levels for clinical covariates improves its diagnostic performance. [Copyright &y& Elsevier]

Cystatin C is an endogenous glomerular filtration marker hence its serum level is affected by the glomerular filtration rate (GFR). To study what other factors might affect it blood level we performed a cross-sectional analysis of 3418 patients which included a pooled dataset of clinical trial participants and a clinical population with chronic kidney disease. The serum cystatin C and creatinine levels were related to clinical and biochemical parameters and errors-in-variables models were used to account for errors in GFR measurements. The GFR was measured as the urinary clearance of 125I-iothalamate and 51Cr-EDTA. Cystatin C was determined at a single laboratory while creatinine was standardized to reference methods and these were 2.1+/−1.1 mg/dL and 1.8+/−0.8 mg/L, respectively. After adjustment for GFR, cystatin C was 4.3% lower for every 20 years of age, 9.2% lower for female gender but only 1.9% lower in blacks. Diabetes was associated with 8.5% higher levels of cystatin C and 3.9% lower levels of creatinine. Higher C-reactive protein and white blood cell count and lower serum albumin were associated with higher levels of cystatin C and lower levels of creatinine. Adjustment for age, gender and race had a greater effect on the association of factors with creatinine than cystatin C. Hence, we found that cystatin C is affected by factors other than GFR which should be considered when the GFR is estimated using serum levels of cystatin C.Kidney International (2009) 75, 652–660; doi:10.1038/ki.2008.638; published online 31 December 2008 [ABSTRACT FROM AUTHOR]

Abstract: The Bcr-Abl kinase inhibitor, STI571, is the first line treatment for chronic myeloid leukaemia (CML), but the recent emergence of STI571 resistance has led to the examination of combination therapies. In this report, we describe how a novel non-toxic G1-arresting compound, pyrrolo-1,5-benzoxazepine (PBOX)-21, potentiates the apoptotic ability of STI571 in Bcr-Abl-positive CML cells. Co-treatment of CML cells with PBOX-21 and STI571 induced more apoptosis than either drug alone in parental (K562S and LAMA84) and STI571-resistant cells lines (K562R). This potentiation of apoptosis was specific to Bcr-Abl-positive leukaemia cells with no effect observed on Bcr-Abl-negative HL-60 acute myeloid leukaemia cells. Apoptosis induced by PBOX-21/STI571 resulted in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl. Repression of proteins involved in Bcr-Abl transformation, the anti-apoptotic proteins Mcl-1 and Bcl-XL was also observed. The combined lack of an early change in mitochondrial membrane potential, release of cytochrome c and cleavage of pro-caspase-9 suggests that this pathway is not involved in the initiation of apoptosis by PBOX-21/STI571. Apoptosis was significantly reduced following pre-treatment with either the general caspase inhibitor Boc-FMK or the chymotrypsin-like serine protease inhibitor TPCK, but was completely abrogated following pre-treatment with a combination of these inhibitors. This demonstrates the important role for each of these protease families in this apoptotic pathway. In conclusion, our data highlights the potential of PBOX-21 in combination with STI571 as an effective therapy against CML. [Copyright &y& Elsevier]

Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins.Background.Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD).Methods.Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study[study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m2 and study B GFR 13 to 24 mL/min/1.73 m2]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5′-phosphate (PLP) and 6μg of vitamin B12. Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year.Results.The prevalence of hyperhomocysteinemia (tHcy>15μmol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B12, and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to≤15μmol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10).Conclusion.Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population. [ABSTRACT FROM AUTHOR]

Effects of hemodialysis dose and membrane flux on health-related quality of life in the HEMO Study. Background. It has been widely supposed that high dose and high flux hemodialysis would affect the quality as well as the length of life of patients treated by maintenance hemodialysis. The HEMO Study examined changes in health-related quality of life as a secondary study outcome. Specific hypotheses were that study interventions would affect physical functioning, vitality, Short Form-36 Health Survey (SF-36) physical and mental component summary scores, symptoms and problems associated with kidney disease, and sleep quality. Methods. At baseline and annually, subjects responded to both the Index of Well-Being and the Kidney Disease Quality of Life-Long Form questionnaires. The interventions were assessed on the basis of their average effects over 3 years. Results. At baseline, the SF-36 physical component summary score was lower than in healthy populations, but the mental component score was nearly normal. Over 3-year follow-up, physical health continued to decline; mental health and kidney disease-targeted scores remained relatively stable. The high dose hemodialysis intervention was associated with significantly less pain (4.49 points, P < 0.001) and higher physical component scores (1.23 points P= 0.007), but these effects were small compared to the natural variability in scores. High flux membranes were not associated with statistically significant differences in health-related quality of life. Conclusion. The HEMO Study results demonstrate the marked burden of chronic kidney failure and hemodialysis treatment on daily life. In this trial among patients undergoing maintenance three times a week hemodialysis, the SF-36 physical component summary score and pain scale showed significant but very small clinical effects favoring the higher dialysis dose. No clinically meaningful benefits or either the dose or flux interventions were observed for other indices of health-related quality of life. [ABSTRACT FROM AUTHOR]

Dialysis dose and the effect of gender and body size on outcome in the HEMO Study. Background. Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial. Methods. The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States. We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients. Results. Adjusting for age only, overall mortality was lower in patients with higher body weight ( P < 0.001), higher body mass index ( P < 0.001), and higher body water content determined by the Watson formula (Vw) ( P < 0.001), but was not associated with gender ( P= 0.27). The RR of mortality comparing the high dose with the standard dose group was related to gender ( P= 0.014). Women randomized to the high dose had a lower mortality rate than women randomized to the standard dose (RR = 0.81, P= 0.02), while men randomized to the high dose had a nonsignificant trend for a higher mortality rate than men randomized to the standard dose (RR = 1.16, P= 0.16). Analysis of both genders combined showed no overall dose effect (R = 0.96, P= 0.52), as reported previously. Vw was greater than 35 L in 84% of men compared with 17% of women. However, the RR of mortality for the high versus standard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters, including weight and body mass index. Conversely, the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender. Conclusion. The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current standard in women but not in men. This effect was not explained by differences between men and women in age, race, or in several indices of body size. Because multiple comparisons were considered in this analysis, the role of gender on the effect of dialysis dose is suggestive and invites further study. [ABSTRACT FROM AUTHOR]

Objective: Elevated rates of epilepsy and motor impairments including cerebral palsy are observed in children who were born prematurely. Maternal antenatal magnesium supplementation has been associated with decreased rates of cerebral palsy in infants born prematurely. Our objective was to determine whether the neonatal serum magnesium level between 24 and 48 hours after birth is associated with better long-term neurodevelopmental outcomes (epilepsy, motor impairment) in premature infants.Methods: We performed a retrospective cohort analysis in infants born less than 37-weeks gestation over a ten-year period. Prenatal, perinatal, and postnatal clinical and demographic information was collected. Crude and adjusted odds ratios were estimated under generalized linear models with generalized estimating equations to examine the association of the neonatal serum magnesium level between 24 and 48 hours after birth with the risk of epilepsy and/or motor impairment (spasticity; hypotonia; cerebral palsy).Results: The final cohort included 5461 infants born less than 37-weeks gestation from 2002 to 2011. The adjusted relative risk ratio for the combined outcomes of epilepsy and/or motor impairment, controlling for gestational age, current age, maternal magnesium supplementation, maternal steroid administration, five-minute Apgar score, neonatal infection, need for vasopressor use, and birth weight and with serum magnesium level as the main independent variable, was 0.85 (P = 0.24). Stratified analyses by gestational age less than 32 or greater than 32 weeks were not significantly associated with adverse neurodevelopmental outcome (risk ratio = 0.79 and 1.2, P = 0.12 and 0.49, respectively). A multivariate analysis for the risk of motor impairment alone had a risk ratio of 0.94 (P = 0.72).Conclusion: This study demostrates that the neonatal magnesium level between 24 and 48 hours of life in premature infants is not significantly associated with the risk for developing epilepsy or motor impairment. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343 ), A Trial of S ertraline vs . C ognitive Behavioral Therapy (CBT) for En d-stage Renal Disease Patients with D epression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m2) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease. [ABSTRACT FROM AUTHOR]

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome. [ABSTRACT FROM AUTHOR]

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect. [ABSTRACT FROM AUTHOR]

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m2 lower eGFR below a threshold of 45 ml/min per 1.73 m2 was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD. [ABSTRACT FROM AUTHOR]