Search

Introduction: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated. Methods: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model. Results: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41–50, 31–40, 21–30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis. Conclusion: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated.

Introduction: Metabolomics could offer novel prognostic biomarkers and elucidate mechanisms of diabetic kidney disease (DKD) progression. Via metabolomic analysis of urine samples from 995 CRIC participants with diabetes and state-of-the-art statistical modeling, we aimed to identify metabolites prognostic to DKD progression. Methods: Urine samples (N = 995) were assayed for relative metabolite abundance by untargeted flow-injection mass spectrometry, and stringent statistical criteria were used to eliminate noisy compounds, resulting in 698 annotated metabolite ions. Utilizing the 698 metabolites' ion abundance along with clinical data (demographics, blood pressure, HbA1c, eGFR, and albuminuria), we developed univariate and multivariate models for the eGFR slope using penalized (lasso) and random forest models. Final models were tested on time-to-ESKD (end-stage kidney disease) via cross-validated C-statistics. We also conducted pathway enrichment analysis and a targeted analysis of a subset of metabolites. Results: Six eGFR slope models selected 9-30 variables. In the adjusted ESKD model with highest C-statistic, valine (or betaine) and 3-(4-methyl-3-pentenyl)thiophene were associated (p < 0.05) with 44% and 65% higher hazard of ESKD per doubling of metabolite abundance, respectively. Also, 13 (of 15) prognostic amino acids, including valine and betaine, were confirmed in the targeted analysis. Enrichment analysis revealed pathways implicated in kidney and cardiometabolic disease. Conclusions: Using the diverse CRIC sample, a high-throughput untargeted assay, followed by targeted analysis, and rigorous statistical analysis to reduce false discovery, we identified several novel metabolites implicated in DKD progression. If replicated in independent cohorts, our findings could inform risk stratification and treatment strategies for patients with DKD., American Journal of Nephrology, 53 (2-3), ISSN:0250-8095, ISSN:1421-9670

Rationale & Objective The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. Study Design Retrospective analysis nested in a cohort study. Setting & Participants Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). Exposure Years before ESKD. Outcomes Serial FGF-23, PTH, serum phosphate, and serum calcium levels. Analytical Approach To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. Results Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. Limitations Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Conclusions Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

Rationale and Objective: Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. beta 2-Microglobulin (B2M) and beta-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.Study Design: Study of diagnostic test accuracy.Setting and Participants: Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants. Tests Compared: Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race. Outcomes: GFRmeasured as the urinary clearance of iothalamate, plasmaclearanceof iohexol, orplasma clearance of [Cr-51]EDTA.Results: Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m(2), and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1-P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1-P-30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups.Limitations: No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe.Conclusions: The 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Rationale & Objective Social support in older adults with chronic kidney disease (CKD) is a potentially modifiable factor that may affect important clinical outcomes such as health-related quality of life, cognitive function, and frailty. However, limited data about the effects of social support in older patients with non–dialysis-dependent CKD exist. Our objective was to evaluate the association of social support with health-related quality of life, cognitive function, and frailty in older adults with CKD. Study Design Cross-sectional analysis of a prospective cohort study. Setting & Population 1,851 participants older than 65 years with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure Social support (Lubben Social Network Scale [LSNS]). Outcomes(s) Health-related quality of life (Kidney Disease Quality of Life-36), cognitive function (Modified Mini-Mental State Examination, Trail Making Test A & B, and Buschke Selective Reminder Tests), and frailty (modified Fried frailty criteria). Analytic Approach Multivariable, linear, and logistic regression to determine the association between social support and health-related quality of life, cognitive function, and frailty. Results Low social support, defined as LSNS score, Graphical abstract

Author(s): Hsu, Raymond K; Hsu, Chi-Yuan; McCulloch, Charles E; Yang, Jingrong; Anderson, Amanda H; Chen, Jing; Feldman, Harold I; He, Jiang; Liu, Kathleen D; Navaneethan, Sankar D; Porter, Anna C; Rahman, Mahboob; Tan, Thida C; Wilson, F Perry; Xie, Dawei; Zhang, Xiaoming; Go, Alan S; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators | Abstract: Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73nm2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73nm2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria.

Rationale & Objective Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list. Study Design Prospective cohort study. Setting & Population 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up. Exposures HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory. Outcomes Time to kidney transplant wait-listing and time to pre-emptive wait-listing. Analytic Approach Time-to-event analysis using Cox proportional hazards regression. Results During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P, Visual abstract

Rationale & Objective The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain. Study Design A multicenter, prospective, cohort study. Setting & Participants We evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study. Exposures Baseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Outcomes Incident heart failure, myocardial infarction, and stroke events. Analytical Approach We used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders. Results Participants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR. Limitations Exclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances. Conclusions In a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

Background People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making. Study Design Prospective research cohort. Setting & Participants 1,798 participants with estimated glomerular filtration rates (eGFRs) 2 in the CRIC Study were followed up for a median of 5.5 years. Predictors Age, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history. Outcomes ESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death. Results Baseline age of the cohort was 60 years, 46% were women, and 46% were African American. Although 52.3% of participants progressed to ESRD during follow-up, the path by which this occurred was variable. For example, predicted 1-year probabilities for a hypothetical 60-year-old white woman with eGFR of 30mL/min/1.73m 2 , urine protein excretion of 1.8g/d, and no diabetes or CVD (risk characteristics similar to the average participant) were 3.3%, 4.1%, and 0.3%, for first developing CVD, ESRD, and death, respectively. For a 40-year-old African American man with similar characteristics but higher systolic blood pressure, the corresponding 1-year probabilities were 2.4%, 13.2%, and 0.1%. For all participants, the development of ESRD or CVD increased the risk for subsequent mortality, with no differences by patient race or body mass index. Limitations The CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist. Conclusions The prognosis and timing of adverse outcomes in chronic kidney disease vary by patient characteristics. These results may help guide the development of personalized approaches for managing patients with advanced CKD.

Background Chronic kidney disease (CKD) and arterial stiffness are associated with increased cardiovascular morbidity and mortality. Inflammation is proposed to have a role in the development of arterial stiffness, and CKD is recognized as a proinflammatory state. Arterial stiffness is increased in CKD, and cross-sectional data has suggested a link between increased inflammatory markers in CKD and higher measures of arterial stiffness. However, no large scale investigations have examined the impact of inflammation on the progression of arterial stiffness in CKD. Methods We performed baseline assessments of 5 inflammatory markers in 3,939 participants from the chronic renal insufficiency cohort (CRIC), along with serial measurements of arterial stiffness at 0, 2, and 4 years of follow-up. Results A total of 2,933 participants completed each of the follow-up stiffness measures. In cross-sectional analysis at enrollment, significant associations with at least 2 measures of stiffness were observed for fibrinogen, interleukin-6, high-sensitivity C-reactive protein, proteinuria, and composite inflammation score after adjustment for confounders. In longitudinal analyses, there were few meaningful correlations between baseline levels of inflammation and changes in metrics of arterial stiffness over time. Conclusion In a large cohort of CKD participants, we observed multiple significant correlations between initial markers of inflammation and metrics of arterial stiffness, but baseline inflammation did not predict changes in arterial stiffness over time. While well-described biologic mechanisms provide the basis for our understanding of the cross-sectional results, continued efforts to design longitudinal studies are necessary to fully elucidate the relationship between chronic inflammation and arterial stiffening.

Low health-related quality of life is associated with increased mortality in patients with ESRD. However, little is known about demographic and clinical factors associated with health-related quality of life or its effect on outcomes in adults with CKD.Data from 3837 adult participants with mild to severe CKD enrolled in the prospective observational Chronic Renal Insufficiency Cohort and Hispanic Chronic Renal Insufficiency Cohort Studies were analyzed. Health-related quality of life was assessed at baseline with the Kidney Disease Quality of Life-36 and its five subscales: mental component summary, physical component summary, burden of kidney disease (burden), effects of kidney disease (effects), and symptoms and problems of kidney disease (symptoms). Low health-related quality of life was defined as baseline score1 SD below the mean. Using Cox proportional hazards analysis, the relationships between low health-related quality of life and the following outcomes were examined: (1) CKD progression (50% eGFR loss or incident ESRD), (2) incident cardiovascular events, and (3) all-cause death.Younger age, women, low education, diabetes, vascular disease, congestive heart failure, obesity, and lower eGFR were associated with low baseline health-related quality of life (P0.05). During a median follow-up of 6.2 years, there were 1055 CKD progression events, 841 cardiovascular events, and 694 deaths. Significantly higher crude rates of CKD progression, incident cardiovascular events, and all-cause death were observed among participants with low health-related quality of life in all subscales (P0.05). In fully adjusted models, low physical component summary, effects, and symptoms subscales were independently associated with a higher risk of incident cardiovascular events and death, whereas low mental component summary was independently associated with a higher risk of death (P0.05). Low health-related quality of life was not associated with CKD progression.Low health-related quality of life across several subscales was independently associated with a higher risk of incident cardiovascular events and death but not associated with CKD progression.

Including target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is “Patient Centered-Research”, in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases.

BACKGROUND: Integrating primary care has been proposed to reduce fragmented care delivery for patients with complex medical needs. Because of their high rates of morbidity, healthcare use, and mortality, patients with end-stage kidney disease (ESKD) may benefit from increased access to a primary care medical home. OBJECTIVE: To evaluate the effect of integrating a primary care medical home on health-related quality of life (HRQOL) for patients with ESKD receiving chronic hemodialysis. DESIGN: Before–after intervention trial with repeated measures at two Chicago dialysis centers. PARTICIPANTS: Patients receiving hemodialysis at either of the two centers. INTERVENTION: To the standard hemodialysis team (nephrologist, nurse, social worker, dietitian), we added a primary care physician, a pharmacist, a nurse coordinator, and a community health worker. The intervention took place from January 2015 through August 2016. MAIN MEASURES: Health-related quality of life, using the Kidney Disease Quality of Life (KDQOL) measures. KEY RESULTS: Of 247 eligible patients, 175 (71%) consented and participated; mean age was 54 years; 55% were men and 97% were African American or Hispanic. In regression analysis adjusted for individual visits with the medical home providers and other factors, there were significant improvements in four of five KDQOL domains: at 12 and 18 months, the Mental Component Score improved from baseline (adjusted mean 49.0) by 2.64 (p = 0.01) and 2.96 (p = 0.007) points, respectively. At 6 and 12 months, the Symptoms domain improved from baseline (adjusted mean = 77.0) by 2.61 (p = 0.02) and 2.35 points (p = 0.05) respectively. The Kidney Disease Effects domain improved from baseline (adjusted mean = 72.7), to 6, 12, and 18 months by 4.36 (p = 0.003), 6.95 (p

Motivation Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological ‘concepts’ that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression. Results We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks ‘triacylglycerols’ and ‘cardiolipins-phosphatidylethanolamines (CL-PE)’ characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years. Availability and implementation A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi.org/netgsa/12345-022118/cric_cprobe/022118/results_cric_cprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape.org. Supplementary information Supplementary data are available at Bioinformatics online.

Patients with chronic kidney disease have a high disease burden may benefit from primary care services and care coordination. A medical home model with direct access to primary care services is one approach that may address this need, yet has not been examined. As a substudy of the Patient-Centered Outcomes Research Institute (PCORI) patient-centered medical home for kidney disease (PCMH-KD) health system intervention study, we examined the uptake of free primary care physician (PCP) services. The PCORI PCMH-KD study was an initial step toward integrating PCPs, a nurse coordinator, a pharmacist, and community health workers (CHWs) within the health care delivery team. Adult chronic hemodialysis (CHD) at two urban dialysis centers were enrolled in the intervention. We examined trends and factors associated with the use of the PCMH-KD PCP among two groups of patients based on their report of having a regular physician for at least six months (established-PCP) or not (no-PCP). Of the 173 enrolled patients, 91 (53%) patients had at least one visit with the PCMH-KD PCP. The rate of visits was higher in those in the no-PCP group compared with those in the established-PCP group (62% vs. 41%, respectively). Having more visits with the CHW was positively associated with having a visit with the PCMH-KD PCPs for both groups. Embedded CHWs within the care team played a role in facilitating the uptake of PCMH-KD PCP. Lessons from this health system intervention can inform future approaches on the integration of PCPs and care coordination for CHD patients.

In the U.S., more than 400,000 individuals with end-stage renal disease (ESRD) require hemodialysis (HD) for renal replacement therapy. ESRD patients experience a high burden of morbidity, mortality, resource utilization, and poor quality of life (QOL). Under current care models, ESRD patients receive fragmented care from multiple providers at multiple locations. The Patient-Centered Medical Home (PCMH) is a team approach, providing coordinated care across the healthcare continuum. While this model has shown some early benefits for complex chronic diseases such as diabetes, it has not been applied to HD patients. This study is a non-randomized quasi-experimental intervention trial implementing a Patient-Centered Medical Home for Kidney Disease (PCMH-KD). The PCMH-KD extends the existing dialysis care team (comprised of a nephrologist, dialysis nurse, dialysis technician, social worker, and dietitian) by adding a general internist, pharmacist, nurse coordinator, and a community health worker, all of whom will see the patients together, and separately, as needed. The primary goal is to implement a comprehensive, multidisciplinary care team to improve care coordination, quality of life, and healthcare use for HD patients. Approximately 240 patients will be recruited from two sites; a non-profit university-affiliated dialysis center and an independent for-profit dialysis center. Outcomes include (i) patient-reported outcomes, including QOL and satisfaction; (ii) clinical outcomes, including blood pressure and diet; (iii) healthcare use, including emergency room visits and hospitalizations; and (iv) staff perceptions. Given the significant burden that patients with ESRD on HD experience, enhanced care coordination provides an opportunity to reduce this burden and improve QOL.

Background In general populations, healthy lifestyle is associated with fewer adverse outcomes. We estimated the degree to which adherence to a healthy lifestyle decreases the risk of renal and cardiovascular events among adults with chronic kidney disease (CKD). Study Design Prospective cohort. Setting & Participants 3,006 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictors 4 lifestyle factors (regular physical activity, body mass index [BMI] of 20- 2 , nonsmoking, and "healthy diet"), individually and in combination. Outcomes CKD progression (50% decrease in estimated glomerular filtration rate or end-stage renal disease), atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease), and all-cause mortality. Measurements Multivariable-adjusted Cox proportional hazards. Results During a median follow-up of 4 years, we observed 726 CKD progression events, 355 atherosclerotic events, and 437 deaths. BMI≥25kg/m 2 and nonsmoking were associated with reduced risk of CKD progression (HRs of 0.75 [95% CI, 0.58-0.97] and 0.61 [95% CI, 0.45-0.82] for BMIs of 25 to 2 , respectively, versus 20 to 2 ; HR for nonsmoking of 0.68 [95% CI, 0.55-0.84] compared to the current smoker reference group) and reduced risk of atherosclerotic events (HRs of 0.67 [95% CI, 0.46-0.96] for BMI of 25- 2 and 0.55 [95% CI, 0.40-0.75] vs current smoker). Factors associated with reduced all-cause mortality were regular physical activity (HR, 0.64 [95% CI, 0.52-0.79] vs inactive), BMI≥30kg/m 2 (HR, 0.64 [95% CI, 0.43-0.96] vs 20- 2 ), and nonsmoking (HR, 0.45 [95% CI, 0.34-0.60] vs current smoker). BMI 2 was associated with increased all-cause mortality risk (HR, 2.11 [95% CI, 1.13-3.93] vs 20- 2 ). Adherence to all 4 lifestyle factors was associated with a 68% lower risk of all-cause mortality compared to adherence to no lifestyle factors (HR, 0.32; 95% CI, 0.11-0.89). Limitations Lifestyle factors were measured only once. Conclusions Regular physical activity, nonsmoking, and BMI≥25kg/m 2 were associated with lower risk of adverse outcomes in this cohort of individuals with CKD.

BACKGROUND: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN: Data on AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: 9361 participants aged 50 or older with one or more risk factors for cardiovascular disease. INTERVENTIONS: Participants were randomly assigned to a systolic BP target of

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.

Depression is a common psychological disorder among adults receiving maintenance hemodialysis. Up to 30% of these patients either report symptoms or have a clinical diagnosis of depression.1 Similarly, mental health and, more broadly, health-related quality of life (HRQoL) are well below general population averages in maintenance hemodialysis patients.2 Depression and poor mental health are associated with a higher risk of hospitalization and death in this population.3-10 Moreover, depressed hemodialysis patients are more likely to not adhere to dietary and fluid restrictions, to withdraw from dialysis therapy, and to commit suicide.11-13 With improvements in health care treatment and delivery, care goals for hemodialysis patients have evolved beyond just survival to include patients’ overall well-being.14 Hence, it is incumbent upon nephrologists to be vigilant in managing depression and poor mental health in hemodialysis patients.

Background/Aims: Optimal dosing regimens for 25-OH vitamin D (VitD) deficiency are unknown in hemodialysis (HD) patients. Our aim was to evaluate the efficacy of prescribing ergocalciferol supplementation based on KDOQI guidelines for chronic kidney disease (CKD) stages III-IV in HD patients. Methods: We conducted a retrospective study of 96 urban, predominately African-American HD patients at a single-center dialysis unit with VitD insufficiency or deficiency treated with ergocalciferol. Patients were classified as either compliant or non-compliant with supplementation as determined by review of pharmacy records. The primary outcome was VitD levels 6 months after initiation of treatment and secondary outcomes were VitD levels at 11 months, bone/mineral and anemia parameters. Results: The population was predominately African-American (69%) and Hispanic (28%). There were 61 individuals in the compliant group and 35 individuals in the non-compliant group. The compliant group was older but otherwise similar in demographics and co-morbid conditions to the non-compliant group. After 6 months of treatment, the compliant group had a significant increase in VitD level (14.7 ± 6.0 to 28.7 ± 10.0 ng/ml, p < 0.0001) compared to the non-compliant group (14.7 ± 5.5 to 14.8 ± 7.1 ng/ml, p = 0.95). There were no differences in the incidence of hypercalcemia between the two groups. Except for a decrease in phosphorus in the compliant group (5.6 ± 1.6 to 4.9 ± 1.7 mg/dl, p = 0.004), there were no significant difference in bone/mineral or anemia parameters including dosing of darbepoetin. Conclusion: An ergocalciferol-prescribing strategy using the KDOQI guidelines for stage III-IV kidney disease in HD patients with VitD deficiency or insufficiency is inadequate to achieve repletion or maintenance of normal VitD levels.

Introduction Using a quasi-experimental design, we implemented the Patient-Centered Medical Home for Kidney Disease (PCMH-KD), a comprehensive, multidisciplinary care team to improve quality of life and healthcare coordination for adult chronic hemodialysis (CHD) patients. This paper highlights our experience in the first two years of the study. We focus on the process dimensions of Reach , Adoption , and Implementation within the context of the RE-AIM framework. Materials and methods We established a new PCMH-KD model at two outpatient dialysis centers. During the intervention phase, adult patients were recruited for participation and data collection. We monitored RE-AIM measures to identify areas for potential adaptation of the care model. Results During the start-up phase, we engaged patients and stakeholders in planning the intervention, established the new PCMH-KD team, and trained new and continuing clinicians and staff at two dialysis centers. In the intervention phase we recruited 155 patients to participate. Patients had individual visits with the PCP (40%) and the CHWs (92%) ( Reach ). Patient feedback informed procedures for appointment scheduling ( Adoption ). The new PCMH-KD team members were consistent in their roles. With staff changes, some responsibilities were adapted for cross coverage ( Implementation ). Implications After one year of start-up and one year of intervention, active monitoring of Reach, Implementation and Adoption measures have facilitated necessary adaptions in the planned intervention to accommodate scheduling demands and patient feedback in the PCMH-KD model. Insights from this trial may inform care of CHD patients more broadly.

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.

CKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (

Background and Purpose— Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors. Methods— The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates. Results— In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin–angiotensin system did not decrease stroke risk in individuals with albuminuria. Conclusions— Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.

Coronary artery calcification (CAC) is highly prevalent in dialysis-naive patients with chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease and all-cause mortality in this population.To study the prospective association of CAC with risk of cardiovascular disease and all-cause mortality among dialysis-naive patients with CKD.The prospective Chronic Renal Insufficiency Cohort study recruited adults with an estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m2 from 7 clinical centers in the United States. There were 1541 participants without cardiovascular disease at baseline who had CAC scores.Coronary artery calcification was assessed using electron-beam or multidetector computed tomography.Incidence of cardiovascular disease (including myocardial infarction, heart failure, and stroke) and all-cause mortality were reported every 6 months and confirmed by medical record adjudication.During an average follow-up of 5.9 years in 1541 participants aged 21 to 74 years, there were 188 cardiovascular disease events (60 cases of myocardial infarction, 120 heart failures, and 27 strokes; patients may have had1 event) and 137 all-cause deaths. In Cox proportional hazards models adjusted for age, sex, race, clinical site, education level, physical activity, total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, use of antihypertensive treatment, current cigarette smoking, diabetes status, body mass index, C-reactive protein level, hemoglobin A1c level, phosphorus level, troponin T level, log N-terminal pro-B-type natriuretic peptide level, fibroblast growth factor 23 level, estimated glomerular filtration rate, and proteinuria, the hazard ratios associated with per 1 SD log of CAC were 1.40 (95% CI, 1.16-1.69; P .001) for cardiovascular disease, 1.44 (95% CI, 1.02-2.02; P = .04) for myocardial infarction, 1.39 (95% CI, 1.10-1.76; P = .006) for heart failure, and 1.19 (95% CI, 0.94-1.51; P = .15) for all-cause mortality. In addition, inclusion of CAC score led to an increase in the C statistic of 0.02 (95% CI, 0-0.09; P .001) for predicting cardiovascular disease over use of all the above-mentioned established and novel cardiovascular disease risk factors.Coronary artery calcification is independently and significantly related to the risks of cardiovascular disease, myocardial infarction, and heart failure in patients with CKD. In addition, CAC improves risk prediction for cardiovascular disease, myocardial infarction, and heart failure over use of established and novel cardiovascular disease risk factors among patients with CKD; however, the changes in the C statistic are small.

Previous studies in chronic disease states have demonstrated an association between lower urinary creatinine excretion (UCr) and increased mortality, a finding presumed to reflect the effect of low muscle mass on clinical outcomes. Little is known about the relationship between UCr and other measures of body composition in terms of the ability to predict outcomes of interest.Using data from the Chronic Renal Insufficiency Cohort (CRIC), the relationship between UCr, fat free mass (FFM) as estimated by bioelectrical impedance analysis, and (in a subpopulation) whole-body dual-energy x-ray absorptiometry assessment of appendicular lean mass were characterized. The associations of UCr and FFM with mortality and ESRD were compared using Cox proportional hazards models.A total of 3604 CRIC participants (91% of the full CRIC cohort) with both a baseline UCr and FFM measurement were included; of these, 232 had contemporaneous dual-energy x-ray absorptiometry measurements. Participants were recruited between July 2003 and March 2007. UCr and FFM were modestly correlated (rho=0.50; P0.001), while FFM and appendicular lean mass were highly correlated (rho=0.91; P0.001). Higher urinary urea nitrogen, black race, younger age, and lower serum cystatin C level were all significantly associated with higher UCr. Over a median (interquartile range) of 4.2 (3.1-5.0) years of follow-up, 336 (9.3%) participants died and 510 (14.2%) reached ESRD. Lower UCr was associated with death and ESRD even after adjustment for FFM (adjusted hazard ratio for death per 1 SD higher level of UCr, 0.63 [95% confidence interval, 0.56 to 0.72]; adjusted hazard ratio for ESRD per 1 SD higher level of UCr, 0.70 [95% confidence interval, 0.63 to 0.75]).Among a cohort of individuals with CKD, lower UCr is associated with death and ESRD independent of FFM as assessed by bioelectrical impedance analysis.

Accurate assessment of kidney function by measurement of glomerular filtration rate (GFR) is essential to the risk assessment of prospective living kidney donors. We evaluated the performance of various estimating equations for creatinine clearance (Cockcroft-Gault), GFR (Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration), and 24-hour urine collections for creatinine clearance in obese potential kidney donors. We evaluated 164 potential kidney donors including 49 with a BMI of 30–35 and 32 with a BMI >35 that have completed a routine living donor evaluation with a measured GFR. All the estimating equations performed poorly in obese donors. While 24-hour urine collections performed better, only 15% had an adequate 24-hour urine collection. Since obese kidney donors may be at higher than average risk for kidney failure, accurate assessment of kidney function in these donors is crucial to ensure their long-term health postdonation.

With the increasing prevalence of hypertension, there has been a growing interest in understanding the health-related quality of life (HRQOL) of patients with hypertension. Although hypertension is often perceived as asymptomatic, it is associated with impaired HRQOL because of complications or comorbidities, awareness of the diagnosis, and adverse effects from antihypertensive medications. This article focuses on the literature published since 2000, on HRQOL in elderly hypertensive individuals as well as hypertensives with co-existent diseases, including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Most of the studies found that hypertensive individuals with co-existent co-morbidities tend to have lower HRQOL than those with hypertension alone, and identified the number of co-morbid illnesses as an independent determinant of HRQOL. The most pronounced effect was noted in the physical function domains of HRQOL. Studies have also examined the effects on HRQOL of specific classes of antihypertensive drugs without specific demonstration of superiority of one drug class over another in terms of HRQOL measures. Although there is evidence in favor of angiotensin-converting enzyme-inhibition for improving renal and cardiovascular outcomes in hypertensive patients, its role in ameliorating HRQOL outcomes remains to be established.

Health-related quality of life (HRQOL) is an important patient-reported outcome that has gained attention in research and clinical practice. In recent years, reports of chronic kidney disease (CKD) have increased. However, not much information is available for Hispanics with CKD, a group whose rates of incidents are on the rise. This review discusses the measurement of HRQOL in CKD, with a particular focus on issues pertaining to Hispanics. Future research directions also are discussed.

Background Protein from plant, as opposed to animal, sources may be preferred in chronic kidney disease (CKD) because of the lower bioavailability of phosphate and lower nonvolatile acid load. Study Design Observational cross-sectional study. Setting and Participants A total of 2,938 participants with CKD and information on their dietary intake at the baseline visit in the Chronic Renal Insufficiency Cohort Study. Predictors Percentage of total protein intake from plant sources (percent plant protein) was determined by scoring individual food items using the National Cancer Institute Diet History Questionnaire (DHQ). Outcomes Metabolic parameters, including serum phosphate, bicarbonate (HCO 3 ), potassium, and albumin, plasma fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH), and hemoglobin levels. Measurements We modeled the association between percent plant protein and metabolic parameters using linear regression. Models were adjusted for age, sex, race, diabetes status, body mass index, estimated glomerular filtration rate, income, smoking status, total energy intake, total protein intake, 24-hour urinary sodium concentration, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and use of diuretics. Results Higher percent plant protein was associated with lower FGF-23 ( P = .05) and higher HCO 3 ( P = .01) levels, but not with serum phosphate or parathyroid hormone concentrations ( P = .9 and P = .5, respectively). Higher percent plant protein was not associated with higher serum potassium ( P = .2), lower serum albumin ( P = .2), or lower hemoglobin ( P = .3) levels. The associations of percent plant protein with FGF-23 and HCO 3 levels did not differ by diabetes status, sex, race, CKD stage (2/3 vs. 4/5), or total protein intake (≤0.8 g/kg/day vs. >0.8 g/kg/day; P -interaction >.10 for each). Limitations This is a cross-sectional study; determination of percent plant protein using the Diet History Questionnaire has not been validated. Conclusions Consumption of a higher percentage of protein from plant sources may lower FGF-23 and raise HCO 3 levels in patients with CKD.