Cynthia Delgado

Association between Body Composition and Frailty among Prevalent Hemodialysis Patients: A US Renal Data System Special Study

Studies of frailty among patients on hemodialysis have relied on definitions that substitute self-reported functioning for measures of physical performance and omit weight loss or substitute alternate criteria. We examined the association between body composition and a definition of frailty that includes measured physical performance and weight loss in a cross-sectional analysis of 638 adult patients receiving maintenance hemodialysis at 14 centers. Frailty was defined as having three of following characteristics: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. We performed logistic regression with body mass index (BMI) and bioelectrical impedance spectroscopy (BIS)-derived estimates of intracellular water (ICW), fat mass, and extracellular water (ECW) as the main predictors, and age, sex, race, and comorbidity as covariates. Overall, 30% of participants were frail. Older age (odds ratio [OR], 1.31 per 10 years; 95% confidence interval [95% CI], 1.14 to 1.50), diabetes (OR, 1.65; 95% CI, 1.13 to 2.40), higher fat mass (OR, 1.18; 95% CI, 1.02 to 1.37), and higher ECW (OR, 1.33; 95% CI, 1.20 to 1.47) associated with higher odds of frailty. Higher ICW associated with lower odds of frailty (OR, 0.80 per kg; 95% CI, 0.73 to 0.87). The addition of BMI data did not change the area under the receiver operating characteristics curve (AUC; AUC=0.66 versus 0.66; P=0.71), but the addition of BIS data did change the AUC (AUC=0.72; P<0.001). Thus, individual components of body composition but not BMI associate strongly with frailty in this cohort of patients receiving hemodialysis.

Comparison of Self-report−Based and Physical Performance−Based Frailty Definitions Among Patients Receiving Maintenance Hemodialysis

BACKGROUND A well-accepted definition of frailty includes measurements of physical performance, which may limit its clinical utility. STUDY DESIGN In a cross-sectional study, we compared prevalence and patient characteristics based on a frailty definition that uses self-reported function to the classic performance-based definition and developed a modified self-report-based definition. SETTING & PARTICIPANTS Prevalent adult patients receiving hemodialysis in 14 centers around San Francisco and Atlanta in 2009-2011. INDEX TESTS Self-report-based frailty definition in which a score lower than 75 on the Physical Function scale of the 36-Item Short Form Health Survey (SF-36) was substituted for gait speed and grip strength in the classic definition; modified self-report definition with optimized Physical Function score cutoff points derived in a development (one-half) cohort and validated in the other half. REFERENCE TEST Performance-based frailty defined as 3 of the following: weight loss, weakness, exhaustion, low physical activity, and slow gait speed. RESULTS 387 (53%) patients were frail based on self-reported function, of whom 209 (29% of the cohort) met the performance-based definition. Only 23 (3%) met the performance-based definition of frailty only. The self-report definition had 90% sensitivity, 64% specificity, 54% positive predictive value, 93% negative predictive value, and 72.5% overall accuracy. Intracellular water per kilogram of body weight and serum albumin, prealbumin, and creatinine levels were highest among nonfrail individuals, intermediate among those who were frail by self-report, and lowest among those who also were frail by performance. Age, percentage of body fat, and C-reactive protein level followed an opposite pattern. The modified self-report definition had better accuracy (84%; 95% CI, 79%-89%) and superior specificity (88%) and positive predictive value (67%). LIMITATIONS Our study did not address prediction of outcomes. CONCLUSIONS Patients who meet the self-report-based but not the performance-based definition of frailty may represent an intermediate phenotype. A modified self-report definition can improve the accuracy of a questionnaire-based method of defining frailty.

Deficient Counseling on Physical Activity among Nephrologists

Background: An evaluation of exercise counseling practices among nephrologists in 2001 demonstrated few clinicians assessing patients’ levels of physical activity (PA) and counseling to increase activity. Recent Kidney Disease Outcomes Quality Initiative (KDOQI) cardiovascular guidelines recommended that nephrologists counsel patients to increase PA. Our objective was to ascertain whether nephrologists’ counseling practices have changed. Methods: We administered a 30-item survey regarding exercise counseling to nephrologists attending the ASN meeting in 2007. Some questions were adapted from a prior survey administered in 2001 to assess differences in practice patterns compared to 6 years earlier. Results: Participants answered questions regarding opinions and practices relevant to PA (n = 198), KDOQI guidelines, self-reported PA, and demographic information (n = 173). Participants were 44 ± 11 years of age, 48% practicing in the USA, and 76% male. In multivariate analysis, older nephrologists (OR; 95% CI) (3.3; 1.2–9.0) and those more physically active (5.5; 2.0–14) were more likely to ask and counsel patients about PA. Opinions associated with less counseling behavior included lack of confidence in ability to discuss PA (0.2; 0.05–0.5). Multivariate comparison to previous respondents (n = 503) showed current nephrologists were not asking and counseling more (1.2; 0.81–1.8). Conclusion: Despite new guidelines, counseling behavior has not increased. Published guidelines are insufficient to reach younger nephrologists.

Association of self–reported frailty with falls and fractures among patients new to dialysis

Background: Although frailty has been linked to higher risk of falls and fracture in the general population, only few studies have examined the extent to which frailty is associated with these outcomes among patients with end-stage renal disease, who are at particularly high risk for these events. Methods: A total of 1,646 patients who were beginning maintenance hemodialysis in 297 dialysis units throughout the United States from September 2005 to June 2007 were enrolled in the Comprehensive Dialysis Study, and 1,053 Medicare beneficiaries were included in this study. Self-reported frailty was defined by the patients endorsing 2 or more of the following: poor physical functioning, exhaustion or low physical activity. Falls and fractures requiring medical attention were identified through Medicare claims data. We examined the association between frailty and the time to first fall or fracture using the Fine-Gray modification of Cox proportional hazards regression, adjusted for demographics, Quételets body mass index, diabetes mellitus, heart failure and atherosclerosis. Results: Seventy-seven percent of patients were frail by self-report. The median length of follow-up was 2.5 (1.0-3.9) years. Crude rates of first medically urgent falls or fractures were 66 and 126 per 1,000 person-years in non-frail and self-reported frail participants, respectively. After accounting for demographic factors, comorbidities and the competing risk of death, self-reported frailty was associated with a higher risk of falls or fractures requiring medical attention (hazards ratio 1.60, 95% CI 1.16-2.20). Conclusion: Participants reporting frailty experienced nearly twice the risk of medically urgent falls or fractures compared to those who did not report frailty.

Association of Performance-Based and Self–Reported Function–Based Definitions of Frailty with Mortality among Patients Receiving Hemodialysis

BACKGROUND AND OBJECTIVES Frailty is common among patients on dialysis and increases vulnerability to dependency and death. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the predictive ability of frailty on the basis of physical performance and self-reported function in participants of a US Renal Data System special study that enrolled a convenience sample of 771 prevalent patients on hemodialysis from 14 facilities in the Atlanta and northern California areas from 2009 to 2011. Performance-based frailty was assessed using direct measures of grip strength (weakness) and gait speed along with weight loss, exhaustion, and low physical activity; poor self-reported function was substituted for weakness and slow gait speed in the self-reported function-based definition. For both definitions, patients meeting three or more criteria were considered frail. RESULTS The mean age of 762 patients included in analyses was 57.1±14.2 years old; 240 patients (31%) met the physical performance-based definition of frailty, and 396 (52%) met the self-reported function-based definition. There were 106 deaths during 1.7 (interquartile range, 1.4-2.4) years of follow-up. After adjusting for demographic and clinical characteristics, the hazard ratio (HR) for mortality for the performance-based definition (2.16; 95% confidence interval [95% CI], 1.41 to 3.29) was slightly higher than that of the self-reported function-based definition (HR, 1.93; 95% CI, 1.24 to 3.00). Patients who met the self-report-based definition but not the physical performance definition of frailty (n=192) were not at statistically significantly higher risk of mortality than those who were not frail by either definition (n=330; HR, 1.41; 95% CI, 0.81 to 2.45), but those who met both definitions of frailty (n=204) were at significantly higher risk (HR, 2.46; 95% CI, 1.51 to 4.01). CONCLUSIONS Frailty, defined using either direct tests of physical performance or self-reported physical function, was associated with higher mortality among patients receiving hemodialysis. Future studies are needed to determine the utility of assessing frailty in clinical practice.

Outcomes of Infection-Related Hospitalization in Medicare Beneficiaries Receiving In-Center Hemodialysis

BACKGROUND Infection is a common cause of hospitalization in adults receiving hemodialysis. Limited data are available about downstream events resulting from or following these hospitalizations. STUDY DESIGN Retrospective cohort study using the US Renal Data System. SETTING & PARTICIPANTS Medicare beneficiaries initiating in-center hemodialysis therapy in 2005 to 2008. FACTORS Demographics, dual Medicare/Medicaid eligibility, body mass index, comorbid conditions, initial vascular access type, nephrology care prior to dialysis therapy initiation, residence in a care facility, tobacco use, biochemical measures, and type of infection. OUTCOMES 30-day hospital readmission or death following first infection-related hospitalization. RESULTS 60,270 Medicare beneficiaries had at least one hospitalization for infection. Of those who survived the initial hospitalization, 15,113 (27%) were readmitted and survived the 30 days following hospital discharge, 1,624 (3%) were readmitted to the hospital and then died within 30 days of discharge, and 2,425 (4%) died without hospital readmission. Complications related to dialysis access, sepsis, and heart failure accounted for 12%, 9%, and 7% of hospital readmissions, respectively. Factors associated with higher odds of 30-day readmission or death without readmission included non-Hispanic ethnicity, lower serum albumin level, inability to ambulate or transfer, limited nephrology care prior to dialysis therapy, and specific types of infection. In comparison, older age, select comorbid conditions, and institutionalization had stronger associations with death without readmission than with readmission. LIMITATIONS Findings limited to Medicare beneficiaries receiving in-center hemodialysis. CONCLUSIONS Hospitalizations for infection among patients receiving in-center hemodialysis are associated with exceptionally high rates of 30-day hospital readmission and death without readmission.

Sarcopenia among patients receiving hemodialysis: Weighing the evidence

There is no consensus on how best to define low muscle mass in patients with end‐stage renal disease. Use of muscle mass normalized to height‐squared has been suggested by geriatric societies but may underestimate sarcopenia, particularly in the setting of excess adiposity. We compared four definitions of low muscle mass in a prevalent hemodialysis cohort.

Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis

The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population has not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE-enrolled prevalent hemodialysis patients from San Francisco and Atlanta. Low muscle mass was defined as two standard deviations below sex-specific means for young adults from NHANES and indexed to height2, body weight, body surface area, or body mass index. We evaluated the association of sarcopenia (low muscle mass) by four indexing methods, weak hand grip strength, and slow gait speed with mortality. Seventy-eight deaths were observed during a mean follow-up of 1.9 years. Sarcopenia was not significantly associated with mortality after adjusting for covariates. No muscle mass criteria were associated with death, regardless of indexing metrics. In contrast, having weak grip strength or slow walking speed was associated with mortality in the adjusted model. Only gait slowness significantly improved the predictive accuracy for death with an increase in C-statistic from 0.63 to 0.68. However, both gait slowness and hand grip weakness significantly improved the net reclassification index compared to models without performance measures (50.5% for slowness and 33.7% for weakness), whereas models with muscle size did not. Neither sarcopenia nor low muscle mass by itself was a better predictor of mortality than functional limitation alone in patients receiving hemodialysis. Thus, physical performance measures, including slow gait speed and weak hand grip strength, were associated with mortality even after adjustment for muscle size and other confounders.

Two Distinct Isoforms of Matrix Metalloproteinase-2 Are Associated with Human Delayed Kidney Graft Function

Delayed graft function (DGF) is a frequent complication of renal transplantation, particularly in the setting of transplantation of kidneys derived from deceased donors and expanded-criteria donors. DGF results from tubular epithelial cell injury and has immediate and long term consequences. These include requirement for post-transplantation dialysis, increased incidence of acute rejection, and poorer long-term outcomes. DGF represents one of the clearest clinical examples of renal acute ischemia/reperfusion injury. Experimental studies have demonstrated that ischemia/reperfusion injury induces the synthesis of the full length secreted isoform of matrix metalloproteinase-2 (FL-MMP-2), as well as an intracellular N-terminal truncated MMP-2 isoform (NTT-MMP-2) that initiates an innate immune response. We hypothesized that the two MMP-2 isoforms mediate tubular epithelial cell injury in DGF. Archival renal biopsy sections from 10 protocol biopsy controls and 41 cases with a clinical diagnosis of DGF were analyzed for the extent of tubular injury, expression of the FL-MMP-2 and NTT-MMP-2 isoforms by immunohistochemistry (IHC), in situ hybridization, and qPCR to determine isoform abundance. Differences in transcript abundance were related to tubular injury score. Markers of MMP-2-mediated injury included TUNEL staining and assessment of peritubular capillary density. There was a clear relationship between tubular epithelial cell expression of both FL-MMP-2 and NTT-MMP-2 IHC with the extent of tubular injury. The MMP-2 isoforms were detected in the same tubular segments and were present at sites of tubular injury. qPCR demonstrated highly significant increases in both the FL-MMP-2 and NTT-MMP-2 transcripts. Statistical analysis revealed highly significant associations between FL-MMP-2 and NTT-MMP-2 transcript abundance and the extent of tubular injury, with NTT-MMP-2 having the strongest association. We conclude that two distinct MMP-2 isoforms are associated with tubular injury in DGF and offer novel therapeutic targets for the prevention of this disorder.

Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis

OBJECTIVE To test the performance of appetite assessment tools among patients receiving hemodialysis (HD). DESIGN Cross-sectional. SUBJECTS Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California. INTERVENTION We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]). MAIN OUTCOME MEASURES Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake. RESULTS Fifty-eight (26%) patients reported food intake ≤ 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake ≤ 50% (P < .001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤ 50% (C-statistic 0.80 and 0.76). Patients with food intake ≤ 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, P = .03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03). CONCLUSIONS Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well.