Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. METHODS: The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. RESULTS: Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. CONCLUSION: In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Cerebral blood flow characteristics following hemodialysis initiation in older adults: A prospective longitudinal pilot study using arterial spin labeling imaging.

PURPOSE: To investigate cerebral blood flow (CBF) characteristics before and after hemodialysis initiation and their longitudinal associations with global cognitive function in older adults. METHODS: A cohort of 17 older end-stage renal disease patients anticipating standard thrice-weekly hemodialysis and a group of 11 age- and sex-matched healthy control volunteers were recruited for brain perfusion imaging studies using arterial spin labeling. Hemodialysis patients participated in a prospective longitudinal study using brain magnetic resonance imaging and global cognitive assessment using the Modified Mini-Mental State Examination (3MS) at two time points: baseline, 2.9 ± 0.9 months before, and follow-up, 6.4 ± 2.4 months after hemodialysis initiation. Healthy controls were imaged once using the same protocol. CBF analyses were performed globally in grey and white matter and regionally in the hippocampus and orbitofrontal cortex. Covariate-adjusted linear mixed-effects models were used for statistical analyses (significance: p < 0.05; marginal significance: p < 0.1). RESULTS: At baseline, global and regional CBF was significantly higher in hemodialysis patients than in healthy controls. However, after approximately 6 months of hemodialysis, CBF declined substantially in hemodialysis patients, and became comparable to those in healthy controls. Specifically, in the hemodialysis patients, CBF declined non-significantly globally for grey and white matter and significantly regionally in the hippocampus and orbitofrontal cortex. Marginally significant associations were observed between 3MS scores and regional CBF measurements in the hippocampus and orbitofrontal cortex at baseline and follow-up, and between longitudinal changes. CONCLUSION: The significant decline in CBF after hemodialysis initiation and the observed association between longitudinal changes in regional CBF and 3MS scores suggest that decreased brain perfusion may contribute to the observed cognitive decline.

Ultrafiltration rate in conventional hemodialysis: Where are the limits and what are the consequences?

BACKGROUND: Ultrafiltration rate (UFR) has attracted attention as a modifiable aspect of volume management. OBJECTIVE: The objective of this review is to summarize the evidence that links UFR to patient outcomes and discuss UFR cut-offs proposed, and discuss possible consequences of adapting UFR as a quality metric. RESULTS: Higher UFRs has been associated with younger age, longer dialysis vintage, greater prevalence of comorbidities, higher Kt/V, lower weight, greater interdialytic weight gain, lower residual renal function, and shorter treatment times. Many of the characteristics associated with high UFRs have also been independently associated with poor patient outcomes. Four observational studies have assessed the association between UFR and patient mortality. All of them reported an association between higher UFR and greater patient mortality, though the studies differed in their definition of UFR, follow-up, and adjustment for confounding. Evidence for the association between higher UFR and potential mediations of the mortality association, such as interdialytic hypotension, cardiac remodeling, and cardiovascular events was less consistent. There was a graded association between higher UFRs and all-cause mortality; no definitive cut-off for acceptable UFR can be established based on the current evidence. Targeting UFR in isolation might result in volume expansion and worsening patient outcomes. Residual confounding likely contributed to the findings of the observational studies. No randomized controlled trials addressed the questions. CONCLUSION: Evidence supporting UFR limits is weak and confounded. Randomized controlled trials are needed before UFR can be used as a quality of care indicator.

Serum phosphate and cognitive function in older men.

OBJECTIVE: Determine whether serum phosphate is associated with concurrent cognitive impairment and subsequent cognitive decline in older men independent of demographic covariates and atherosclerotic risk factors. METHODS: In a prospective study of 5529 men enrolled in the Osteoporotic Fractures in Men study, we measured baseline serum phosphate, baseline cognitive function, and change in cognitive function between baseline and follow-up exams an average of 4.6 years later using the Modified Mini-Mental State (3MS) Examination and Trails B. RESULTS: There was no association between serum phosphate and odds of cognitive impairment as assessed by baseline 3MS score or risk of cognitive decline as assessed by longitudinal change in 3MS score. Higher baseline serum phosphate was associated with higher odds of poor executive function as assessed by Trails B with fully adjusted odds ratios 1.12 (95% confidence interval: 0.83-1.52), 1.31 (0.97-1.77), and 1.45 (1.08-1.94) for men in the second, third, and fourth versus the bottom quartile (referent group) of serum phosphate (p-trend 0.007). However, higher phosphate level was not associated with risk of decline in executive function as assessed by longitudinal change in Trails B score with fully adjusted odds ratios 0.94 (95% confidence interval 0.69-1.28), 0.96 (0.70-1.32), and 1.21 (0.89-1.66) for men in the second, third, and fourth versus the bottom quartile (referent group) of serum phosphate (p-trend 0.22). CONCLUSIONS: Higher serum phosphate in older men was associated with a higher likelihood of poor executive function, but not with impaired global cognitive function or decline in executive or global cognition. Copyright © 2017 John Wiley & Sons, Ltd.

Prevalence and Risk of Severe Cognitive Impairment in Advanced Chronic Kidney Disease.

Background: Our primary goal is to describe the prevalence, severity, and risk of cognitive impairment (CI) by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) in a cohort enriched for advanced chronic kidney disease (CKD; eGFR < 45), adjusting for albuminuria, as measured by urine albumin-to-creatinine ratio (UACR, in mg/g). As both eGFR and albuminuria are associated with CI risk in CKD, we also seek to determine the extent that eGFR remains a useful biomarker for risk of CI in those with CKD and concomitant albuminuria. Methods: Chi-square tests measured the prevalence of severe CI and mild cognitive impairment (MCI) by eGFR level. Logistic regression models and generalized linear models measured risk of CI by eGFR, adjusted for UACR. Results: Participants were 574 adults with a mean age of 69; 433 with CKD (eGFR < 60, nondialysis) and 141 controls (eGFR ≥ 60). Forty-eight percent of participants with CKD had severe CI or MCI. The prevalence of severe CI was highest (25%) in those with eGFR < 30. eGFR < 30 was only associated with severe CI in those without albuminuria (UACR < 30; OR = 3.3; p = .02) and was not associated with MCI in similar models. Conclusions: One quarter of those with eGFR < 30 had severe CI. eGFR < 30 was associated with over threefold increased odds of severe CI in those with UACR < 30, but not with UACR > 30, suggesting that eGFR < 30 is a valid biomarker for increased risk of severe CI in those without concomitant albuminuria.

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. STUDY DESIGN: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). PREDICTORS: Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). OUTCOMES: Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging. RESULTS: Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. LIMITATIONS: Cross-sectional only, no patients with diabetes were included. CONCLUSIONS: In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.

Effect of Intensive Versus Standard Clinic-Based Hypertension Management on Ambulatory Blood Pressure: Results From the SPRINT (Systolic Blood Pressure Intervention Trial) Ambulatory Blood Pressure Study.

The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary study was to evaluate the effect of intensive versus standard clinic-based BP targets on ambulatory BP. Ambulatory BP was obtained within 3 weeks of the 27-month study visit in 897 SPRINT participants. Intensive treatment resulted in lower clinic systolic BP (mean difference between groups=16.0 mm Hg; 95% confidence interval, 14.1-17.8 mm Hg), nighttime systolic BP (mean difference=9.6 mm Hg; 95% confidence interval, 7.7-11.5 mm Hg), daytime systolic BP (mean difference=12.3 mm Hg; 95% confidence interval, 10.6-13.9 mm Hg), and 24-hour systolic BP (mean difference=11.2 mm Hg; 95% confidence interval, 9.7-12.8 mm Hg). The night/day systolic BP ratio was similar between the intensive (0.92±0.09) and standard-treatment groups (0.91±0.09). There was considerable lack of agreement within participants between clinic systolic BP and daytime ambulatory systolic BP with wide limits of agreement on Bland-Altman plots. In conclusion, targeting a systolic BP of <120 mm Hg, when compared with <140 mm Hg, resulted in lower nighttime, daytime, and 24-hour systolic BP, but did not change the night/day systolic BP ratio. Ambulatory BP monitoring may be required to assess the effect of targeted hypertension therapy on out of office BP. Further studies are needed to assess whether targeting hypertension therapy based on ambulatory BP improves clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835249.

Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

BACKGROUND: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. OBJECTIVE: To measure the association between kidney function biomarkers and brain MRI findings in CKD. METHODS: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. RESULTS: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: eGFR 45-59; 74 controls: eGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. CONCLUSIONS: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

Cystatin C and Objectively Measured Mobility 10 Years Later in Older Women.

BACKGROUND: Serum biomarkers predicting physical performance in late life are uncertain. We tested the hypotheses that lower serum cystatin C (cysC) in older women is associated with good mobility 10 years later. METHODS: We conducted a longitudinal analysis of a prospective cohort of 1,384 women attending Year 10 and Year 20 examinations of the Study of Osteoporotic Fractures. Serum cysC was measured using Year 10 frozen serum specimens. Year 20 mobility was ascertained by the Short Physical Performance Battery; scores of 10-12 indicated good mobility. RESULTS: At Year 20, mean age was 87.5 years and 364 women (26.3%) had good mobility. After adjustment for age, race, education, health status, diabetes, cardiovascular disease, and body mass index, lower cysC at Year 10 was associated with a higher likelihood of good mobility at Year 20. Compared with quartile (Q) 4 of cysC (referent group), odds ratios (95% confidence interval) were 1.52 (1.02-2.25) for Q3, 1.93 (1.32-2.84) for Q2 and 1.80 (1.21-2.67) for Q1 (p trend across Qs .003). The association was only modestly attenuated after further adjustment for mobility as assessed by a modified Short Physical Performance Battery at Year 10 (p trend .02) or consideration of potential biologic mediators including Year 10 levels of serum 25-hydroxyvitamin D, interleukin 6, and cytokine soluble receptors (p trend .04). CONCLUSIONS: Lower cysC in older women is independently associated with good mobility 10 years later and may be a biomarker for successful aging as manifested by preservation of lower extremity performance in late life.

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

BACKGROUND: The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. STUDY DESIGN: Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2). SETTING & PARTICIPANTS: Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR≥60 mL/min/1.73 m(2). PREDICTOR: eGFR group. OUTCOMES: Performance on cognitive function tests and structural brain magnetic resonance imaging. MEASUREMENTS: Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. RESULTS: Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ≥60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs≥30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. LIMITATIONS: Healthy cohort bias, competing risk for death versus cognitive decline. CONCLUSIONS: Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

Long-term Outcomes of Living Kidney Donation.

BACKGROUND: In an effort to improve outcomes associated with living kidney donation, the Kidney Diseases Improving Global Outcomes (KDIGO) assembled a Work Group to develop comprehensive guidelines addressing the evaluation and care of living kidney donors. We conducted this systematic review to inform guideline development. METHODS: We searched Ovid Medline, Ovid Embase, and the Cochrane Library to identify systematic reviews, randomized controlled trials, and observational studies published through September of 2014 and consulted the KDIGO Expert Work Group. We extracted data from systematic reviews and observational studies with sample size over 100 and mean follow-up time of at least 5 years. Studies had to have an adequate comparison group that excludes subjects with contraindications to kidney donation. RESULTS: For the long-term donor outcomes, we extracted 5 systematic reviews and 40 observational studies. Moderate grade evidence reveals an association between living kidney donation and greater risk of end-stage renal disease. This association is true for donors of all races with African American donors sustaining the greatest increase in absolute risk. We found very low grade evidence that kidney donation is associated with lower kidney function, proteinuria, hypertension, and psychosocial outcomes. Consistent evidence from 3 studies reveals that donors are at higher risk for preeclampsia and gestational hypertension with postdonation pregnancies and compared with healthy matched nondonors. CONCLUSIONS: Living kidney donation appears to be associated with a small absolute increase in risk of end-stage renal disease, hypertension, and pregnancy complications, such as preeclampsia and gestational hypertension.

Timing of dialysis initiation, duration and frequency of hemodialysis sessions, and membrane flux: a systematic review for a KDOQI clinical practice guideline.

BACKGROUND: In 2006, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) published clinical practice guidelines for hemodialysis adequacy. Recent studies evaluating hemodialysis adequacy as determined by initiation timing, frequency, duration, and membrane type and prompted an update to the guideline. STUDY DESIGN: Systematic review and evidence synthesis. SETTING & POPULATION: Patients with advanced chronic kidney disease receiving hemodialysis. SELECTION CRITERIA FOR STUDIES: We screened publications from 2000 to March 2014, systematic reviews, and references and consulted the NKF-KDOQI Hemodialysis Adequacy Work Group members. We included randomized or controlled clinical trials in patients undergoing long-term hemodialysis if they reported outcomes of interest. INTERVENTIONS: Early versus late dialysis therapy initiation; more frequent (>3 times a week) or longer duration (>4.5 hours) compared to conventional hemodialysis; low- versus high-flux dialyzer membranes. OUTCOMES: All-cause and cardiovascular mortality, myocardial infarction, stroke, hospitalizations, quality of life, depression or cognitive function scores, blood pressure, number of antihypertensive medications, left ventricular mass, interdialytic weight gain, and harms or complications related to vascular access or the process of dialysis. RESULTS: We included 32 articles reporting on 19 trials. Moderate-quality evidence indicated that earlier dialysis therapy initiation (at estimated creatinine clearance [eClcr] of 10-14mL/min) did not reduce mortality compared to later initiation (eClcr of 5-7mL/min). More than thrice-weekly hemodialysis and extended-length hemodialysis during a short follow-up did not improve clinical outcomes compared to conventional hemodialysis and resulted in a greater number of vascular access procedures (very low-quality evidence). Hemodialysis using high-flux membranes did not reduce all-cause mortality, but reduced cardiovascular mortality compared to hemodialysis using low-flux membranes (moderate-quality evidence). LIMITATIONS: Few studies were adequately powered to evaluate mortality. Heterogeneity of study designs and interventions precluded pooling data for most outcomes. CONCLUSIONS: Limited data indicate that earlier dialysis therapy initiation and more frequent and longer hemodialysis did not improve clinical outcomes compared to conventional hemodialysis.

Cystatin C and cognitive impairment 10 years later in older women.

BACKGROUND: Results of prospective studies examining the association between cystatin C and incident cognitive impairment have been inconsistent. We tested the hypothesis that there is a U-shaped association in older women between cystatin C and risk of incident cognitive impairment 10 years later. METHODS: We conducted a longitudinal analysis of a prospective cohort of 1,332 community-dwelling elderly women without dementia at baseline who had baseline cystatin C and serum creatinine measurements and completed an extended cognitive battery of neuropsychological tests with determination of cognitive status 10 years later. Incident cognitive impairment was defined as either new onset of adjudicated diagnosis of mild cognitive impairment or dementia. RESULTS: Incident mild cognitive impairment or dementia was identified among 140 (26.0%) women in quartile 1 (Q1), 122 (22.6%) in Q2, 121 (22.5%) in Q3, and 156 (28.9%) in Q4 of cystatin C. In the fully adjusted model, compared to women in Q2-Q3 of cystatin C, adjusted odds ratios (95% CI) for incident cognitive impairment were 1.31 (0.98-1.75) for Q1, and 1.25 (0.94-1.66) for Q4 Compared to women in Q2-Q3 of estimated glomerular filtration rate (eGFRCysC), adjusted odds ratios (95% CI) for incident cognitive impairment after 10 years of follow-up were 1.18 (0.88-1.58) for Q4 (eGFRCysC 76.1-109.4mL/min/1.73 m(2)) and 1.26 (0.94-1.67) for Q1 (eGFRCysC 21.8-55.5mL/min/1.73 m(2)). CONCLUSIONS: These results support a U-shaped association between cystatin C concentration and risk of cognitive impairment or dementia 10 years later, but the association is not independent of potential confounding factors.

Hemodialysis patient outcomes: provider characteristics.

BACKGROUND/AIMS: Physician characteristics are associated with differential performance on quality measures and patient outcomes in several medical fields. We aimed to determine whether characteristics of physicians who provide care to dialysis patients were associated with patient outcomes. METHODS: This cohort study used United States Renal Data System data for patients who initiated in-center hemodialysis between October 1, 2003, and September 30, 2006 (n = 91,276). Patient characteristics were defined and physicians identified from Part B Medicare claims for outpatient dialysis services submitted during months 4-6 of hemodialysis. Physician characteristics were obtained from the American Medical Association Physician Master File. Associations of physician characteristics with 1-year patient mortality and first hospitalization were determined using Cox proportional hazards analysis; associations with quality of care (defined by influenza vaccination and waitlisting for kidney transplant) were determined using logistic regression. RESULTS: Physician characteristics were not associated with patient mortality. After adjustment for patient and other provider characteristics, patients whose physicians had practiced longer or were in administrative, research, or teaching practices were more likely to be hospitalized; patients whose providers practiced in smaller metropolitan statistical areas (MSAs) were less likely. More years since training was associated with greater chance of waitlisting, and practicing in smaller MSAs with less chance. Graduation from a foreign medical school, practicing in smaller MSAs, and travelling farther from office to dialysis unit were associated with greater odds of influenza vaccination. CONCLUSIONS: Several characteristics of physicians seeing incident outpatient hemodialysis patients were associated with hospitalization and quality of care, but none with mortality.

Provider and care characteristics associated with timing of dialysis initiation.

BACKGROUND AND OBJECTIVES: There is a trend in the United States to maintenance dialysis initiation at higher levels of estimated GFR. This study aimed to determine whether provider characteristics and pre-ESRD nephrology care and vascular access are independently associated with higher estimated GFR at initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used US Renal Data System data for patients who initiated dialysis in 2006 (n=83,621) and American Medical Association Physician Master File data for provider characteristics. Patient characteristics and estimated GFR were defined, and providers at dialysis initiation were identified. Earlier dialysis initiation was defined as initiation at estimated GFR>10 ml/min per 1.73 m(2). Nephrologist density per 100 ESRD patients was calculated by Health Service Area in 2006. Associations between provider characteristics and estimated GFR were determined using logistic regression and linear regression models, accounting for provider clustering. RESULTS: Of the cohort, 47.8% of patients initiated dialysis at estimated GFR>10 ml/min per 1.73 m(2), and 16.2% of patients initiated dialysis at estimated GFR≥15 ml/min per 1.73 m(2). Predialysis nephrologist care for 0-12 months was associated with greater odds of earlier initiation compared with no care. Patients initiating with an arteriovenous fistula or graft were more likely to initiate earlier than patients initiating with a catheter. Provider sex was not associated with timing of dialysis initiation as measured by estimated GFR. Care by providers who graduated from nondomestic medical schools was associated with greater odds of earlier initiation. Greater provider experience was associated with lower likelihood of earlier initiation. CONCLUSION: This study supports the hypothesis that provider factors are associated with timing of dialysis initiation in the United States.

Predictors of provider-patient visit frequency during hemodialysis.

BACKGROUND/AIMS: In 2004, the Centers for Medicare and Medicaid Services tied reimbursement for outpatient hemodialysis services to the number of times per month providers see their dialysis patients, resulting in increased provider-patient visit frequency. Greater provider-patient visit frequency is associated with lower hospitalization risk for hemodialysis patients, and determinants of visit frequency are uncertain. We aimed to identify patient, provider, and dialysis facility characteristics associated with provider visit frequency. METHODS: This retrospective cohort study used United States Renal Data System (USRDS) data for point-prevalent patients receiving in-center hemodialysis on January 1, 2006 (n = 144,860). Patient characteristics were defined from January 1 to June 30, 2006, and provider-patient visit frequency (<4 vs. ≥4 visits/month) from July 1 to December 31, 2006. Patient characteristics were obtained from the USRDS. Provider data were obtained from the American Medical Association Physician Master File. We determined longitudinal associations between patient, provider, and facility characteristics and provider-patient visit frequency using logistic regression. RESULTS: Patient characteristics independently associated with greater provider-patient visit frequency included older age, African-American race, longer dialysis duration, higher comorbidity score, Medicaid eligibility, urban residence, better compliance with dialysis, and more hospital days during run-in. Provider characteristics associated with greater provider-patient visit frequency included more years in practice, graduation from a foreign medical school, shorter distance between provider office and dialysis unit, and caring for more dialysis patients; facility characteristics included free-standing, independent status. CONCLUSION: After the Medicare reimbursement policy change, several patient, provider, and facility characteristics were independently associated with greater dialysis provider-patient visit frequency.

Cystatin C and risk of hip fractures in older women.

To test the hypothesis that older women with higher cystatin C are at increased risk of hip fracture independent of traditional risk factors including hip bone mineral density (BMD), we performed a case-cohort analysis nested in a cohort of 4709 white women attending a Year 10 (1997-1998) examination of the Study of Osteoporotic Fractures that included a random sample of 1170 women and the first 300 women with incident hip fracture occurring after Year 10 examination. Serum cystatin C and creatinine were measured in Year 10 sera. In a model adjusted for age, clinical site, body mass index, and total hip BMD, higher cystatin C was associated with an increased risk of hip fracture (p for linear trend 0.008) with women in quartile 4 having a 1.9-fold higher risk (hazard ratio [HR] 1.91; 95% confidence interval [CI], 1.24-2.95) compared with those in quartile 1 (referent group). Further adjustment for additional risk factors only slightly attenuated the association; the risk for hip fracture was 1.7-fold higher (HR 1.74; 95% CI, 1.11-2.72) in women in quartile 4 compared with those in quartile 1. In contrast, neither serum creatinine nor creatinine-based estimated glomerular filtration rate (eGFRCr ) were associated with risk of hip fracture. Older women with higher cystatin C, but not higher serum creatinine or lower eGFRCr , have an increased risk of hip fracture independent of traditional risk factors. These findings suggest that cystatin C may be a promising biomarker for identification of older adults at high risk of hip fracture.

Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline.

BACKGROUND: In 2007, the National Kidney Foundation (NKF) published clinical practice guidelines and recommendations for treating patients with diabetes and kidney diseases. Given recent studies that may enhance our understanding of the benefits and harms of glycemic, lipid, and albuminuria management in patients with diabetes and chronic kidney disease (CKD), the NKF commissioned a systematic review to evaluate data on the management of these patients. STUDY DESIGN: Systematic review and evidence synthesis. SETTING & POPULATION: Patients with type 1 or 2 diabetes with or without CKD. SELECTION CRITERIA FOR STUDIES: English-language publications indexed in the MEDLINE database from January 2003 to October 2010, as well as cited references in these publications and publications identified after consultation with the NKF Diabetes Work Group were screened. Randomized controlled trials providing evidence for the management of hyperglycemia, dyslipidemia, and albuminuria in individuals with diabetes were included. INTERVENTIONS: (1) Intensive glycemic control; (2) lipid management; (3) interventions aimed at prevention of incident albuminuria and/or progression of albuminuria in normotensive patients. OUTCOMES: For all interventions, all-cause mortality was the primary outcome and secondary clinical outcomes included death from cardiovascular causes, incident kidney failure, and nonfatal cardiovascular events. Intermediate outcomes included changes in albuminuria and measures of kidney function. For intensive glycemic control only, severe and mild hypoglycemia were secondary and intermediate outcomes, respectively. RESULTS: 5 studies (n=27,159) assessed the impact of intensive versus conventional glycemic control strategies on clinical outcomes in type 2 diabetes. Intensive glycemic control reduced the development of micro- and macroalbuminuria, but did not reduce the incidence of primary or secondary clinical outcomes and was associated with a 2.5-fold increase in severe hypoglycemia. 11 studies (n=7,539) assessed lipid management. Statins did not reduce all-cause mortality or stroke compared to placebo in adults with diabetes and CKD. Fenofibrate increased regression of microalbuminuria to normoalbuminuria compared to placebo. 3 studies reported inconsistent effects of different angiotensin II receptor blockers on the incidence of microalbuminuria, and one study reported that telmisartan reduced macroalbuminuria in normotensive participants. No study demonstrated a benefit on primary or secondary clinical outcomes. LIMITATIONS: Patients with CKD constituted a subgroup in most studies. Substantial heterogeneity with respect to population, interventions, outcome measures, and duration of follow-up. CONCLUSIONS: Intensive glycemic control and lipid interventions did not improve clinical outcomes in patients with type 2 diabetes. Although interventions typically improved albuminuria, evidence was insufficient to determine whether treatment of albuminuria in normotensive patients provides beneficial effects on clinical outcomes. More intensive clinical management of patients with diabetes and CKD has inherent risks, including severe hypoglycemia, which should be considered when formulating treatment strategies.