Bicarbonate-Based Solution for the Management of Established Acute Kidney Injury: A Pilot Open-Label Observation Study.

Background Administration of intravenous (IV) solutions constitutes a key component of acute kidney injury (AKI) management. However, the optimal IV fluid solution in the setting of AKI remains uncertain. In this study, we assessed whether the use of bicarbonate-containing solution in patients with established AKI is associated with early renal recovery as compared to bicarbonate-free solutions. Methods We performed an open-label observational pilot study in 59 patients with established AKI. IV fluid solutions that were used include bicarbonate-based solution with low chloride content (80 mEq/L of 8% sodium bicarbonate in a solution that contains 77 mEq/L of sodium, 77 mEq/L of chloride and 25 g/L of glucose) or solutions without bicarbonate with high chloride content (0.9% normal saline, 0.45% half-saline, normal ringer, or 4% succinylated gelatine). We evaluated the association of IV fluids type with renal recovery. Results The median age of study participants was 66 years (inter-quartile range (IQR) 37-85), and 59% (n=35) were men. The prevalence of diabetes and chronic kidney disease (CKD) stages 1-3 were 34% (n=20) and 39% (n=23), respectively. Patients who received bicarbonate-based IV solutions had a greater reduction of serum creatinine (sCr) per day (delta sCr) as compared with patients who received bicarbonate-free solutions (-0.29±0.47 vs. 0.07±0.42; p=0.007). The renal recovery was faster in patients who received bicarbonate-based solutions as compared to the bicarbonate-free group (days from peak sCr to baseline sCr: 5.6±2.1 vs. 7.6±2.8; p < 0.001, respectively). Conclusions We observed faster renal recovery in patients with established AKI who received the bicarbonate-based solution with low chloride content. Our study findings require confirmation in larger cohorts.

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.

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.

Pathways to improve nephrologist comfort in managing patients on in-center or home self-care dialysis.

In end-stage kidney disease (ESKD), patient engagement and empowerment are associated with improved survival and complications. However, patients lack education and confidence to participate in self-care. The development of in center self-care hemodialysis can enable motivated patients to allocate autonomy, increase satisfaction and engagement, reduce human resource intensiveness, and cultivate a curiosity about home dialysis. In this review, we emphasize the role of education to overcome barriers to home dialysis, strategies of improving home dialysis utilization in the COVID 19 era, the significance of in-center self-care dialysis (e.g., cost containment and empowering patients), and implementation of an in-center self-care dialysis as a bridge to home hemodialysis (HHD).

Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Longitudinal Blood Pressure Change in Middle-Aged Adults: The CARDIA Study.

BACKGROUND: Urine biomarkers of kidney tubule injury associate with incident hypertension in older adults with comorbidities, but less is known about these associations in younger adults. METHODS: In 1170 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults; mean age, 45 years; 40% Black people; 56% women) without hypertension, cardiovascular disease, or kidney disease at baseline, we examined associations of urine MCP-1 (monocyte chemoattractant protein-1), α1m (alpha-1-microglobulin), KIM-1 (kidney injury molecule-1), EGF (epidermal growth factor), IL (interleukin)-18, YKL-40 (chitinase-3-like protein 1), and UMOD (uromodulin) with incident hypertension (onset of systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg or initiation of hypertension medications) and longitudinal BP change in models adjusted for hypertension risk factors, estimated glomerular filtration rate, and albuminuria. RESULTS: After a median 9.9 (interquartile range, 5.9-10.2) years, 376 participants developed incident hypertension. In demographic-adjusted analyses, higher tertiles of EGF associated with lower risk of incident hypertension in both Black and White participants. After multivariable adjustment, the risk of incident hypertension remained lower in tertile 2 (hazard ratio, 0.70 [95% CI, 0.50-0.97]) and tertile 3 (hazard ratio, 0.58 [0.39-0.85]) of EGF versus tertile 1. In fully adjusted models, participants in EGF tertile 3 had smaller 10-year increases in systolic (-3.4 [95% CI, -6.1 to -0.7] mm Hg) and diastolic BP (-2.6 [95% CI, -4.6 to -0.6] mm Hg) than tertile 1. Other biomarkers showed inconsistent associations with incident hypertension and BP change. CONCLUSIONS: In middle-aged adults without hypertension, cardiovascular disease, or kidney disease, higher urine EGF associated with lower risk of incident hypertension and lower 10-year BP elevations.

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.

Biphasic Dynamics of Inflammatory Markers Following Hemodialysis Initiation: Results From the International MONitoring Dialysis Outcome Initiative.

Introduction: Inflammation is highly prevalent among patients with end-stage kidney disease and is associated with adverse outcomes. We aimed to investigate longitudinal changes in inflammatory markers in a diverse international incident hemodialysis patient population. Methods: The MONitoring Dialysis Outcomes (MONDO) Consortium encompasses hemodialysis databases from 31 countries in Europe, North America, South America, and Asia. The MONDO database was queried for inflammatory markers (total white blood cell count [WBC], neutrophil count, lymphocyte count, serum albumin, and C-reactive protein [CRP]) and hemoglobin levels in incident hemodialysis patients. Laboratory parameters were measured every month. Patients were stratified by survival time (≤6 months, >6 to 12 months, >12 to 18 months, >18 to 24 months, >24 to 30 months, >30 to 36 months, and >36 months) following dialysis initiation. We used cubic B-spline basis function to evaluate temporal changes in inflammatory parameters in relationship with patient survival. Results: We studied 18,726 incident hemodialysis patients. Their age at dialysis initiation was 71.3 ± 11.9 years; 10,802 (58%) were males. Within the first 6 months, 2068 (11%) patients died, and 12,295 patients (67%) survived >36 months (survivor cohort). Hemodialysis patients who died showed a distinct biphasic pattern of change in inflammatory markers where an initial decline of inflammation was followed by a rapid rise that was consistently evident approximately 6 months before death. This pattern was similar in all patients who died and was consistent across the survival time intervals. In contrast, in the survivor cohort, we observed initial decline of inflammation followed by sustained low levels of inflammatory biomarkers. Conclusion: Our international study of incident hemodialysis patients highlights a temporal relationship between serial measurements of inflammatory markers and patient survival. This finding may inform the development of prognostic models, such as the integration of dynamic changes in inflammatory markers for individual risk profiling and guiding preventive and therapeutic interventions.

A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. METHODS: In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge. RESULTS: From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median [IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care alone). No clinically significant differences were found between those who received adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, 4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: 0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose levels, and larger increase in creatinine and sodium levels within the first 7 days of hospital admission were each independent predictors of 28-day mortality (p < 0.05). CONCLUSION: In this study of hospitalized patients with COVID-19, while the outcomes of COVID illness severity, odds of mortality, and chance of respiratory failure were better in the Aggrenox group compared to standard of care alone, the data did not reach statistical significance to support the standard use of adjuvant Aggrenox in such patients.

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.

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.

Physical activity in hemodialysis patients on nondialysis and dialysis days: Prospective observational study.

INTRODUCTION: The physical decline in patients with end-stage kidney disease (ESKD) is associated with morbidity and mortality. Prior studies have attempted to promote physical activity at the time of dialysis; however, physical activity patterns on the nondialysis days are unknown. This study aimed to quantify physical activity on dialysis and nondialysis days in hemodialysis patients using a wearable actigraph. METHODS: In this prospective study, subjects receiving hemodialysis were recruited from two outpatient dialysis units in urban San Diego and rural Imperial County, CA, between March 2018 and April 2019. Key inclusion criteria included: (1) receiving thrice weekly hemodialysis for ≥3 months, (2) age ≥ 18 years, and (3) able to walk with or without assistive devices. All participants wore a Fitbit Charge 2 tracker for a minimum of 4 weeks. The primary outcome was the number of steps per day. Each participant completed the Physical Activity Questionnaire, the Patient Health Questionnaire (PHQ)-9, the PROMIS Short form Fatigue Questionnaire at baseline, and the Participant Technology Experience Questionnaire at day 7 after study enrolment. FINDINGS: Of the 52 recruited, 45 participants (urban = 25; rural = 20) completed the study. The mean age was 61 ± 15 years, 42% were women, 64% were Hispanic, and the mean dialysis vintage was 4.4 ± 3.0 years. For those with valid Fitbit data (defined as ≥10 hours of wear per day) for 28 days (n = 45), participants walked an average of 3688 steps per day, and 73% of participants were sedentary (<5000 steps/day). Participants aged >80 years were less active than younger (age < 65 years) participants (1232 vs. 4529 steps, P = 0.01). There were no statistical differences between the groups when stratified by gender (women vs. men [2817 vs. 4324 steps, respectively]), urbanicity (rural vs. urban dialysis unit [3141 vs. 4123 steps, respectively]), and dialysis/nondialysis day (3177 vs. 4133 steps, respectively). Due to the small sample size, we also calculated effect sizes. The effect size was medium for the gender differences (cohen's d = 0.57) and small to medium for urbanicity and dialysis/nondialysis day (d = 0.37 and d = 0.33, respectively). We found no association between physical activity and self-reported depression and fatigue scale. The majority of participants (62%, 28/45) found the Fitbit tracker easy to wear and comfortable. DISCUSSION: ESKD participants receiving hemodialysis are frequently sedentary, and differences appear more pronounced in older patients. These findings may assist in designing patient-centered interventions to increase physical activity among hemodialysis patients.

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%.

Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline in SPRINT Trial Participants with CKD.

BACKGROUND AND OBJECTIVES: eGFR and albuminuria primarily reflect glomerular function and injury, whereas tubule cell atrophy and interstitial fibrosis on kidney biopsy are important risk markers for CKD progression. Kidney tubule injury markers have primarily been studied in hospitalized AKI. Here, we examined the association between urinary kidney tubule injury markers at baseline with subsequent loss of kidney function in persons with nondiabetic CKD who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 2428 SPRINT participants with CKD (eGFR<60 ml/min per 1.73 m2) at baseline, we measured urine markers of tubule injury (IL-18, kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL]), inflammation (monocyte chemoattractant protein-1 [MCP-1]), and repair (human cartilage glycoprotein-40 [YKL-40]). Cox proportional hazards models evaluated associations of these markers with the kidney composite outcome of 50% eGFR decline or ESKD requiring dialysis or kidney transplantation, and linear mixed models evaluated annualized change in eGFR. RESULTS: Mean participant age was 73±9 (SD) years, 60% were men, 66% were white, and mean baseline eGFR was 46±11 ml/min per 1.73 m2. There were 87 kidney composite outcome events during a median follow-up of 3.8 years. Relative to the respective lowest quartiles, the highest quartiles of urinary KIM-1 (hazard ratio, 2.84; 95% confidence interval [95% CI], 1.31 to 6.17), MCP-1 (hazard ratio, 2.43; 95% CI, 1.13 to 5.23), and YKL-40 (hazard ratio, 1.95; 95% CI, 1.08 to 3.51) were associated with higher risk of the kidney composite outcome in fully adjusted models including baseline eGFR and urine albumin. In linear analysis, urinary IL-18 was the only marker associated with eGFR decline (-0.91 ml/min per 1.73 m2 per year for highest versus lowest quartile; 95% CI, -1.44 to -0.38), a finding that was stronger in the standard arm of SPRINT. CONCLUSIONS: Urine markers of tubule cell injury provide information about risk of subsequent loss of kidney function, beyond the eGFR and urine albumin.