The Impact of a Wearable Activity Tracker and Structured Feedback Program on Physical Activity in Hemodialysis Patients: The Step4Life Pilot Randomized Controlled Trial.

RATIONALE & OBJECTIVE: People with end-stage kidney disease (ESKD) have very low physical activity, and the degree of inactivity is strongly associated with morbidity and mortality. We assessed the feasibility and effectiveness of a 12-week intervention coupling a wearable activity tracker (FitBit) and structured feedback coaching versus wearable activity tracker alone on changes in physical activity in hemodialysis patients. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 55 participants with ESKD receiving hemodialysis who were able to walk with or without assistive devices recruited from a single academic hemodialysis unit between January 2019 and April 2020. INTERVENTIONS: All participants wore a Fitbit Charge 2 tracker for a minimum of 12 weeks. Participants were randomly assigned 1:1 to a wearable activity tracker plus a structured feedback intervention versus the wearable activity tracker alone. The structured feedback group was counseled weekly on steps achieved after randomization. OUTCOME: The outcome was step count, and the main parameter of interest was the absolute change in daily step count, averaged per week, from baseline to completion of 12 weeks intervention. In the intention-to-treat analysis, mixed-effect linear regression analysis was used to evaluate change in daily step count from baseline to 12-weeks in both arms. RESULTS: Out of 55 participants, 46 participants completed the 12-week intervention (23 per arm). The mean age was 62 (± 14 SD) years; 44% were Black, and 36% were Hispanic. At baseline, step count (structured feedback intervention: 3,704 [1,594] vs wearable activity tracker alone: 3,808 [1,890]) and other participant characteristics were balanced between the arms. We observed a larger change in daily step count in the structured feedback arm at 12 weeks relative to use of the wearable activity tracker alone arm (Δ 920 [±580 SD] versus Δ 281 [±186 SD] steps; between-group difference Δ 639 [±538 SD] steps; P<0.05). LIMITATIONS: Single-center study and small sample size. CONCLUSION: This pilot randomized controlled trial demonstrated that structured feedback coupled with a wearable activity tracker led to a greater daily step count that was sustained over 12 weeks relative to a wearable activity tracker alone. Future studies are required to determine longer-term sustainability of the intervention and potential health benefits in hemodialysis patients. FUNDING: Grants from industry (Satellite Healthcare) and government (National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT05241171.

Risk of de novo proteinuria following hospitalization with acute kidney injury.

BACKGROUND: Acute Kidney Injury (AKI) incidence has continued to rise and is recognized as a major risk factor for kidney disease progression and cardiovascular complications. Early recognition of factors associated with post-AKI complications is fundamental to stratifying patients that could benefit from closer follow-up and management after an episode of AKI. Recent studies have shown that proteinuria is a prevalent sequela after AKI and a strong predictor of complications post-AKI. This study aims to evaluate the frequency and timing of the development of de-novo proteinuria after an AKI episode in patients with known kidney function and no prior history of proteinuria. METHODS: We retrospectively analyzed data from adult AKI patients with pre- and post-kidney function information between Jan 2014 and March 2019. The presence of proteinuria determined before and after index AKI encounter was based on ICD-10 code and/or urine dipstick and UPCR during the follow-up period. RESULTS: Of 9697 admissions with AKI diagnoses between Jan 2014 and March 2019, 2120 eligible patients with at least one assessment of Scr and proteinuria before AKI index admission were included in the analysis. The median age was 64 (IQR 54-75) years, and 57% were male. 58% (n-1712) patients had stage 1 AKI, 19% (n = 567) stage 2 AKI, and 22% (n = 650) developed stage 3 AKI. De novo proteinúria was found in 62% (n = 472) of patients and was already present by 90 days post-AKI in 59% (209/354). After adjusting for age and comorbidities, severe AKI (stage 2/3 AKI) and diabetes, were independently associated with increased risk for De novo proteinuria. CONCLUSION: Severe AKI is an independent risk factor for subsequent de novo proteinuria post-hospitalization. Further prospective studies are needed to determine whether strategies to detect AKI patients at risk of proteinuria and early therapeutics to modify proteinuria can delay the progression of kidney disease.

Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD.

BACKGROUND: Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment. METHODS: Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR <60 ml/min per 1.73 m2, we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia). RESULTS: Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups. CONCLUSION: Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.

Violence Within Food Deserts: A Block-Group Examination of Food Access, Racial Composition, and Violent Crime.

While there is substantial public health literature that documents the negative impacts of living in "food deserts" (e.g., obesity and diabetes), little is known regarding whether living in a food desert is associated with increased criminal victimization. With the block group as the unit of analysis, the present study examines whether there is a relationship between food deserts and elevated crime counts, and whether this relationship varies by racial composition. Results from multiple count models suggest that living in a food desert is not associated with higher levels of violent or property crime. But multiplicative models interacting percent Black with food deserts revealed statistically significant associations with violent crime but not property crime. Alternatively, multiplicative models interacting percent White with food deserts revealed statistically significant associational reductions in violent crimes. Several policy and research implications are discussed.

Kidney tubule health, mineral metabolism and adverse events in persons with CKD in SPRINT.

BACKGROUND: Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown. METHODS: Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia). RESULTS: At baseline, the mean age was 73 ± 9 years and mean estimated glomerular filtration rate (eGFR) was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.8 years, 716 (30%) participants experienced the composite AE. Higher urine interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1), lower urine uromodulin (UMOD) and higher serum fibroblast growth factor-23 were individually associated with higher risk of the composite AE outcome in multivariable-adjusted models including eGFR and albuminuria. When modeling biomarkers in combination, higher NGAL [hazard ratio (HR) = 1.08 per 2-fold higher biomarker level, 95% confidence interval (CI) 1.03-1.13], higher MCP-1 (HR = 1.11, 95% CI 1.03-1.19) and lower UMOD (HR = 0.91, 95% CI 0.85-0.97) were each associated with higher composite AE risk. Biomarker associations did not vary by intervention arm (P > 0.10 for all interactions). CONCLUSIONS: Among persons with CKD, several kidney tubule biomarkers are associated with higher risk of AEs during hypertension treatment, independent of eGFR and albuminuria.

Estimated GFR Variability and Risk of Cardiovascular Events and Mortality in SPRINT (Systolic Blood Pressure Intervention Trial).

RATIONALE AND OBJECTIVE: Although low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality. STUDY DESIGN: Longitudinal analysis of clinical trial participants. SETTINGS AND PARTICIPANTS: 7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors. PREDICTORS: eGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits. OUTCOMES: The SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up. ANALYTICAL APPROACH: Cox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18. RESULTS: Mean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up. LIMITATIONS: Persons with diabetes and proteinuria > 1 g/d were excluded. CONCLUSIONS: In trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Tubular Biomarkers and Chronic Kidney Disease Progression in SPRINT Participants.

BACKGROUND: Kidney tubular atrophy on biopsy is a strong predictor of chronic kidney disease (CKD) progression, but tubular health is poorly quantified by traditional measures including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of impaired tubule function would be associated with faster eGFR declines in persons with CKD. METHODS: We measured baseline urine concentrations of uromodulin, ß2-microglobulin (ß2m), and α1-microglobulin (α1m) among 2,428 participants of the Systolic Blood Pressure Intervention Trial with an eGFR <60 mL/min/1.73 m2. We used linear mixed models to evaluate biomarker associations with annualized relative change in eGFR, stratified by randomization arm. RESULTS: At baseline, the mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. In the standard blood pressure treatment arm, each 2-fold higher urinary uromodulin was associated with slower % annual eGFR decline (0.34 [95% CI: 0.08, 0.60]), whereas higher urinary ß2m was associated with faster % annual eGFR decline (-0.10 [95% CI: -0.18, -0.02]) in multivariable-adjusted models including baseline eGFR and albuminuria. Associations were weaker and did not reach statistical significance in the intensive blood pressure treatment arm for either uromodulin (0.11 [-0.13, 0.35], p value for interaction by treatment arm = 0.045) or ß2m (-0.01 [-0.08, 0.08], p value for interaction = 0.001). Urinary α1m was not independently associated with eGFR decline in the standard (0.01 [-0.22, 0.23]) or intensive (0.03 [-0.20, 0.25]) arm. CONCLUSIONS: Among trial participants with hypertension and CKD, baseline measures of tubular function were associated with subsequent declines in kidney function, although these associations were diminished by intensive blood pressure control.

Identifying Informal Settlements Using Contourlet Assisted Deep Learning.

As the global urban population grows due to the influx of migrants from rural areas, many cities in developing countries face the emergence and proliferation of unplanned and informal settlements. However, even though the rise of unplanned development influences planning and management of residential land-use, reliable and detailed information about these areas is often scarce. While formal settlements in urban areas are easily mapped due to their distinct features, this does not hold true for informal settlements because of their microstructure, instability, and variability of shape and texture. Therefore, detecting and mapping these areas remains a challenging task. This research will contribute to the development of tools to identify such informal built-up areas by using an integrated approach of multiscale deep learning. The authors propose a composite architecture for semantic segmentation using the U-net architecture aided by information obtained from a multiscale contourlet transform. This work also analyzes the effects of wavelet and contourlet decompositions in the U-net architecture. The performance was evaluated in terms of precision, recall, F-score, mean intersection over union, and overall accuracy. It was found that the proposed method has better class-discriminating power as compared to existing methods and has an overall classification accuracy of 94.9-95.7%.

The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury.

Urine markers can quantify tubular function including reabsorption (α-1 microglobulin [α1m]) and ß-2-microglobulin [ß2m]) and protein synthesis (uromodulin). Individuals with tubular dysfunction may be less able to compensate to insults than those without, despite similar estimated glomerular filtration rate (eGFR) and albuminuria. Among Systolic Blood Pressure Intervention Trial (SPRINT) participants with an eGFR under 60 ml/min/1.73m2, we measured urine markers of tubular function and injury (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], interleukin-18 [IL-18], monocyte chemoattractant protein-1, and chitinase-3-like protein [YKL-40]) at baseline. Cox models evaluated associations with subsequent acute kidney injury (AKI) risk, adjusting for clinical risk factors, baseline eGFR and albuminuria, and the tubular function and injury markers. In a random subset, we remeasured biomarkers after four years, and compared changes in biomarkers in those with and without intervening AKI. Among 2351 participants, 184 experienced AKI during 3.8 years mean follow-up. Lower uromodulin (hazard ratio per two-fold higher (0.68, 95% confidence interval [0.56, 0.83]) and higher α1m (1.20; [1.01, 1.44]) were associated with subsequent AKI, independent of eGFR and albuminuria. None of the five injury markers were associated with eventual AKI. In the random subset of 947 patients with repeated measurements, the 59 patients with intervening AKI versus without had longitudinal increases in urine NGAL, IL-19, and YKL-40 and only 1 marker of tubule function (α1m). Thus, joint evaluation of tubule function and injury provided novel insights to factors predisposing to AKI, and responses to kidney injury.

Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT.

BACKGROUND: Random assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown. STUDY DESIGN: Longitudinal subgroup analysis of clinical trial participants. SETTINGS & PARTICIPANTS: Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline. OUTCOMES & MEASUREMENTS: Urine biomarkers of tubule function (ß2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. RESULTS: 978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively. LIMITATIONS: Exclusion of persons with diabetes, and few participants had advanced CKD. CONCLUSIONS: Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease.

BACKGROUND: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. METHODS: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. RESULTS: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01-1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02-1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. CONCLUSIONS: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

Kidney Damage Biomarkers and Incident Chronic Kidney Disease During Blood Pressure Reduction: A Case-Control Study.

Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown. Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial). Design: Nested case-control study within SPRINT. Setting: Adults with hypertension without baseline kidney disease. Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group. Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes. Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95% CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti-chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, ß2-microglobulin, α1-microglobulin, YKL-40, and uromodulin. Limitation: Biomarker measurements were available only at baseline and 1 year. Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury. Primary Funding Source: National Institute for Diabetes and Digestive and Kidney Diseases.

Protein Intake and Long-term Change in Glomerular Filtration Rate in the Jackson Heart Study.

OBJECTIVE: Dietary protein intake could have deleterious renal effects in populations at risk for chronic kidney disease. Here, we examined whether higher protein intake (≥80th percentile of energy from protein) is associated with decline in kidney function and whether this decline varies by diabetes status. DESIGN: Observational cohort study. SUBJECTS AND SETTINGS: Participants were African-Americans (n = 5,301), who enrolled in the Jackson Heart Study between 2000 and 2004. METHODS: Dietary intake was assessed using a validated food-frequency questionnaire at baseline, and serum creatinine was measured at baseline (visit 1) and 8 years later (visit 3). Estimated glomerular filtration rates (eGFRs) at baseline and follow-up were computed using the chronic kidney disease epidemiology collaboration equation. MAIN OUTCOME MEASURE: The change in eGFR was computed by subtracting eGFR at visit 1 from that at visit 3. RESULTS: Of 3,165 participants with complete data, 64% were women, 57% had hypertension, and 19% had diabetes. The median (25th, 75th percentile) percent energy intake from protein was 14.3 (12.4, 16.4), comparable to that reported for the general US population (15% of energy). During a median (25th, 75th percentile) follow-up of 8.0 (7.4, 8.3) years, eGFR declined by 10.5% from a mean (SD) of 97.4 (17.5) to 86.9 (21.3) mL/min/1.73 m2. In the fully adjusted model, consumption of protein as percent of energy intake in lowest and highest quintiles was associated with decline in eGFR among diabetic subjects. The analysis of variance with a robust variance estimator was used to determine whether long-term change in eGFR significantly varies by protein intake. CONCLUSIONS: Our results show that, among African-Americans with diabetes, higher protein intake as a percent of total energy intake is positively associated with greater decline in eGFR in analyses that accounted for risk factors for kidney disease.

Reliability and Utility of the Surprise Question in CKD Stages 4 to 5.

BACKGROUND: Prognostic uncertainty is one barrier to engaging in goals-of-care discussions in chronic kidney disease (CKD). The surprise question ("Would you be surprised if this patient died in the next 12 months?") is a tool to assist in prognostication. However, it has not been studied in non-dialysis-dependent CKD and its reliability is unknown. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 388 patients at least 60 years of age with non-dialysis-dependent CKD stages 4 to 5 who were seen at an outpatient nephrology clinic. PREDICTOR: Trinary (ie, Yes, Neutral, or No) and binary (Yes or No) surprise question response. OUTCOMES: Mortality, test-retest reliability, and blinded inter-rater reliability. MEASUREMENTS: Baseline comorbid conditions, Charlson Comorbidity Index, cause of CKD, and baseline laboratory values (ie, serum creatinine/estimated glomerular filtration rate, serum albumin, and hemoglobin). RESULTS: Median patient age was 71 years with median follow-up of 1.4 years, during which time 52 (13%) patients died. Using the trinary surprise question, providers responded Yes, Neutral, and No for 202 (52%), 80 (21%), and 106 (27%) patients, respectively. About 5%, 15%, and 27% of Yes, Neutral, and No patients died, respectively (P<0.001). Trinary surprise question inter-rater reliability was 0.58 (95% CI, 0.42-0.72), and test-retest reliability was 0.63 (95% CI, 0.54-0.72). The trinary surprise question No response had sensitivity and specificity of 55% and 76%, respectively (95% CIs, 38%-71% and 71%-80%, respectively). The binary surprise question had sensitivity of 66% (95% CI, 49%-80%; P=0.3 vs trinary), but lower specificity of 68% (95% CI, 63%-73%; P=0.02 vs trinary). LIMITATIONS: Single center, small number of deaths. CONCLUSIONS: The surprise question associates with mortality in CKD stages 4 to 5 and demonstrates moderate to good reliability. Future studies should examine how best to deploy the surprise question to facilitate advance care planning in advanced non-dialysis-dependent CKD.

Performance of the Surprise Question Compared to Prediction Models in Hemodialysis Patients: A Prospective Study.

BACKGROUND: The surprise question (SQ) ("Would you be surprised if this patient were still alive in 6 or 12 months?") is used as a mortality prognostication tool in hemodialysis (HD) patients. We compared the performance of the SQ with that of prediction models (PMs) for 6- and 12-month mortality prediction. METHODS: Demographic, clinical, laboratory, and dialysis treatment indicators were used to model 6- and 12-month mortality probability in a HD patients training cohort (n = 6,633) using generalized linear models (GLMs). A total of 10 nephrologists from 5 HD clinics responded to the SQ in 215 patients followed prospectively for 12 months. The performance of PM was evaluated in the validation (n = 6,634) and SQ cohorts (n = 215) using the areas under receiver operating characteristics curves. We compared sensitivities and specificities of PM and SQ. RESULTS: The PM and SQ cohorts comprised 13,267 (mean age 61 years, 55% men, 54% whites) and 215 (mean age 62 years, 59% men, 50% whites) patients, respectively. During the 12-month follow-up, 1,313 patients died in the prediction model cohort and 22 in the SQ cohort. For 6-month mortality prediction, the GLM had areas under the curve of 0.77 in the validation cohort and 0.77 in the SQ cohort. As for 12-month mortality, areas under the curve were 0.77 and 0.80 in the validation and SQ cohorts, respectively. The 6- and 12-month PMs had sensitivities of 0.62 (95% CI 0.35-0.88) and 0.75 (95% CI 0.56-0.94), respectively. The 6- and 12-month SQ sensitivities were 0.23 (95% CI 0.002-0.46) and 0.35 (95% CI 0.14-0.56), respectively. CONCLUSION: PMs exhibit superior sensitivity compared to the SQ for mortality prognostication in HD patients.

A risk prediction score for acute kidney injury in the intensive care unit.

BACKGROUND: Acute kidney injury (AKI) is common in critically ill patients and is associated with high morbidity and mortality. Early identification of high-risk patients provides an opportunity to develop strategies for prevention, early diagnosis and treatment of AKI. METHODS: We undertook this multicenter prospective cohort study to develop and validate a risk score for predicting AKI in patients admitted to an intensive care unit (ICU). Patients were screened for predictor variables within 48 h of ICU admission. Baseline and acute risk factors were recorded at the time of screening and serum creatinine was measured daily for up to 7 days. A risk score model for AKI was developed with multivariate regression analysis combining baseline and acute risk factors in the development cohort (573 patients) and the model was further evaluated on a test cohort (144 patients). Validation was performed on an independent prospective cohort of 1300 patients. The discriminative ability of the risk model was assessed by the area under the receiver operating characteristic curve (AUROC) and model calibration was evaluated by Hosmer-Lemeshow statistic. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria (absolute change of 0.3 mg/dL or relative change of 50% from baseline serum creatinine in 48 h to 7 days, respectively). RESULTS: AKI developed in 754 (37.2%) patients. In the multivariate model, chronic kidney disease, chronic liver disease, congestive heart failure, hypertension, atherosclerotic coronary vascular disease, pH ≤ 7.30, nephrotoxin exposure, sepsis, mechanical ventilation and anemia were identified as independent predictors of AKI and the AUROC for the model in the test cohort was 0.79 [95% confidence interval (CI) 0.70-0.89]. On the external validation cohort, the AUROC value was 0.81 (95% CI 0.78-0.83). The risk model demonstrated good calibration in both cohorts. Positive and negative predictive values for the optimal cutoff value of ≥ 5 points in test and validation cohorts were 22.7 and 96.1% and 31.8 and 95.4%, respectively. CONCLUSIONS: A risk score model integrating chronic comorbidities and acute events at ICU admission can identify patients at high risk to develop AKI. This risk assessment tool could help clinicians to stratify patients for primary prevention, surveillance and early therapeutic intervention to improve care and outcomes of ICU patients.

Sarcopenic Obesity Definitions by Body Composition and Mortality in the Hemodialysis Patients.

OBJECTIVE: Sarcopenic obesity (SO), a combination of low muscle mass and high fat mass, is considered as risk factor for mortality in general population. It is unclear if SO affects mortality in maintenance hemodialysis (MHD) patients. In this study, we aimed to determine whether body composition as assessed by currently available SO definitions is related to all-cause mortality in MHD subjects. We also examined the impact of applying different definitions on the prevalence of SO in our MHD database. DESIGN: Retrospective analysis. SUBJECTS: Adult patients on MHD for at least 3 months with no acute illness studied in the clinical research center between 2003 and 2011. INTERVENTION: Assessment of body composition was performed using dual energy x-ray absorptiometry. SO (appendicular skeletal mass: arm lean mass + leg lean mass and fat mass) was defined according to Baumgartner definition, Janssen criteria 1, and Janssen criteria 2. MAIN OUTCOME MEASURE: All-cause mortality and prevalence of SO. Patient deaths were ascertained from medical records and United States social security death index. RESULTS: Of 122 participants, 62% were male; mean age was 46 years (interquartile range: 40, 54) in men and 50 years (44, 61) in women. Prevalence of SO ranged from 12% to 62% in men and 2% to 74% in female according to different definitions. SO prevalence was lowest using the Baumgartner criteria (all: 8%, men 12%, women: 2%) and highest according to the Janssen criteria 2 (all: 57%, men 46%, women 74%). There were 45 deaths during a median follow-up period of 44 (20, 76) months. SO by any definition was not statistically significantly associated with mortality during follow-up. CONCLUSIONS: The current SO definitions are not applicable to predict increased risk of death in MHD patients. We found high degree of variation in the rates of SO when using different definitions. Future studies should focus on establishing MHD population-specific thresholds of muscle mass and adiposity for accurate prognostication.

Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients.

OBJECTIVE: Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. SUBJECTS: Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. INTERVENTION: Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. MAIN OUTCOME MEASURE: Sleep, fatigue, and depression as assessed by subjective questionnaire. RESULTS: TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 µmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 µmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores (r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. CONCLUSIONS: Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.

Higher defibrillation threshold in methamphetamine cardiomyopathy patients with implantable cardioverter-defibrillator.

INTRODUCTION: Identification of patients with an increased risk of high defibrillation thresholds (DFTs) is important in planning implantable cardioverter-defibrillator (ICD) procedures. Clinical observations have suggested that patients with methamphetamine cardiomyopathy (MACMP) have significantly elevated defibrillation thresholds. We hypothesized that MACMP patients would have higher DFT thresholds than controls and would require procedural changes during ICD implantation to accommodate higher thresholds. METHODS: We identified consecutive patients with MACMP undergoing ICD implantation at the academic center from 2003 to 2007. We then compared DFTs against age-and sex-matched controls. RESULTS: The MACMP (n = 10) group showed significantly increased DFT thresholds (23.7 ± 6.7 J) compared with age and sex-matched controls (14.5 ± 4.6 J, p < 0.005). Additionally, patients with MACMP had evidence of more severe congestive heart failure, with increased B-type natrieutic protein (BNP) levels (1173 ± 784 vs 260 ± 349, p = 0.02) and decreased left ventricular ejection fraction (LVEF) (17.8 ± 9.4 vs 35.9 ± 15.2, p = 0.02). MACMP patients required high output devices than controls (50% versus 0%, p = 0.03). Differences between groups remained significant despite adjusting for LVEF. CONCLUSIONS: Planning for ICD implantation should take into consideration a history of methamphetamine abuse, mandating DFT testing and empiric consideration of high output devices for such patients.