Doctor of Medicine, Upstate Medical University (2012)
Master of Science, Stanford University, EPIDM-MS (2018)
Glenn Chertow, Postdoctoral Faculty Sponsor
BACKGROUND: Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co-morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.METHODS: Dual energy X-ray absorptiometry-derived appendicular lean mass index (ALMI, kg/m2 ) and fat mass index (FMI, kg/m2 ) were assessed in 14850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow-up through 2011. Sarcopenia was defined using sex-specific and race/ethnicity-specific standard deviation scores compared with young adults (T-scores) as an ALMI T-score<-2 and relative sarcopenia as fat-adjusted ALMI (ALMIFMI ) T-score<-2. Glomerular filtration rate (GFR) was estimated using creatinine-based (eGFRCr ) and cystatin C-based (eGFRCys ) regression equations.RESULTS: Three (3.0) per cent of National Health and Nutrition Examination Survey participants met criteria for sarcopenia and 8.7% met criteria for relative sarcopenia. Sarcopenia and relative sarcopenia were independently associated with mortality (HR sarcopenia 2.20, 95% CI 1.69 to 2.86; HR relative sarcopenia 1.60, 95% CI 1.31 to 1.96). The corresponding population attributable risks were 5.2% (95% CI 3.4% to 6.4%) and 8.4% (95% CI 4.8% to 11.2%), respectively. Relative sarcopenia remained significantly associated with mortality (HR 1.32, 95% CI 1.08 to 1.61) when limited to the subset who did not meet the criteria for sarcopenia. The risk of mortality associated with relative sarcopenia was attenuated among persons with higher FMI (P for interaction <0.01) and was not affected by CKD status for either sarcopenia or relative sarcopenia.CONCLUSIONS: Sarcopenia and relative sarcopenia are significantly associated with mortality regardless of CKD status. Relative sarcopenia is nearly three-fold more prevalent amplifying its associated mortality risk at the population level. The association between relative sarcopenia and mortality is attenuated in persons with higher FMI.
View details for PubMedID 30784237
OBJECTIVE: Obesity, defined by body mass index (BMI), is associated with lower mortality risk in patients with chronic kidney disease (CKD). BMI and % body fat (%BF) are confounded by muscle mass, while DXA derived fat mass index (FMI) overcomes this limitation. We compared the associations between obesity and mortality in persons with CKD using multiple estimates of adiposity, and determined whether muscle mass, inflammation and weight loss modify these associations.METHODS: Obesity was defined using BMI and DXA-derived FMI and %BF cut-offs in 2,852 NHANES participants with CKD from 1999-2006 and linked to the National Death Index with follow up through 2011. Cox proportional hazards models assessed associations between mortality and measures of obesity.RESULTS: Obesity based on FMI and continuous variables, FMI, BMI and %BF were associated with lower mortality. The protective association of obesity was less pronounced among participants with higher muscle mass and was no longer significant after adjustment for prior weight loss. Inflammation did not modify these associations.CONCLUSIONS: We observed lower mortality associated with higher fat mass, particularly among persons with lower muscle mass. The prevalence of >10% weight loss was half as common among obese compared to non-obese participants and confounded these associations.
View details for PubMedID 30709713
It is controversial whether an altered relationship between adiposity and mortality occurs with aging. We evaluated associations between adiposity and mortality in younger and older participants before and after considering historical weight loss.This study utilized whole-body Dual Energy Absorptiometry (DXA) data from the National Health and Nutrition Examination Survey (NHANES) in adults ≥20 years of age. Fat Mass Index (FMI), determined by DXA, was converted to age-, sex-, and race-specific Z-Scores. Percent change in weight from the maximum reported weight was determined and categorized. Cox proportional hazards models assessed associations between quintile of FMI Z-Score and mortality. Sequential models adjusted for percent weight change since the maximum weight.Participants with lower FMI were more likely to have lost weight from their maximum, particularly among older participants with lower FMI. Substantially greater risk of mortality was observed for the highest quintile of FMI Z-Score compared to the second quintile among younger individuals [HR 2.50 (1.69,3.72) p<0.001]. In contrast, a more modest association was observed among older individuals in the highest quintile [HR 1.23 (0.99,1.52) p=0.06] (p for interaction <0.001). In both the younger and older participants, the risks of greater FMI Z-Score were magnified when adjusting for percent weight change since maximum reported weight.Older people with low fat mass report greater historical weight loss, potentially explaining substantially altered relationships between fat mass and mortality in older individuals. As a result, epidemiologic studies performed in older populations will likely underestimate the causal risks of excess adiposity.
View details for DOI 10.1093/gerona/glz144
View details for PubMedID 31168573
End stage renal disease (ESRD) is associated with sarcopenia and skeletal fragility. The objectives of this cross-sectional study were to (1) characterize body composition, bone mineral density (BMD) and bone structure in hemodialysis patients compared with controls, (2) assess whether DXA areal BMD (aBMD) correlates with peripheral quantitative CT (pQCT) measures of volumetric BMD (vBMD), cortical dimensions and MRI measures of trabecular microarchitecture, and (3) determine the magnitude of bone deficits in ESRD after adjustment for muscle mass. Thirty ESRD participants, ages 25 to 64 years, were compared with 403 controls for DXA and pQCT outcomes and 104 controls for MRI outcomes; results were expressed as race- and sex- specific Z-scores relative to age. DXA appendicular lean mass index (ALMI kg/m2) and total hip, femoral neck, ultradistal and 1/3rd radius aBMD were significantly lower in ESRD, vs. controls (all p < 0.01). pQCT trabecular vBMD (p < 0.01), cortical vBMD (p < 0.001) and cortical thickness (due to a greater endosteal circumference, p < 0.02) and MRI measures of trabecular number, trabecular thickness, and whole bone stiffness were lower (all p < 0.01) in ESRD, vs. controls. ALMI was positively associated with total hip, femoral neck, ultradistal radius and 1/3rd radius aBMD and with tibia cortical thickness (R = 0.46 to 0.64). Adjustment for ALMI significantly attenuated bone deficits at these sites: e.g. mean femoral neck aBMD was 0.79 SD lower in ESRD, compared with controls and this was attenuated to 0.33 with adjustment for ALMI. In multivariate models within the dialysis participants, pQCT trabecular vBMD and cortical area Z-scores were significant and independently (all p < 0.02) associated with DXA femoral neck, total hip, and ultradistal radius aBMD Z-scores. Cortical vBMD (p = 0.01) and cortical area (p < 0.001) Z-scores were significantly and independently associated with 1/3rd radius areal aBMD Z-scores (R2 = 0.62). These data demonstrate that DXA aBMD captures deficits in trabecular and cortical vBMD and cortical area. The strong associations with ALMI, as an index of skeletal muscle, highlight the importance of considering the role of sarcopenia in skeletal fragility in patients with ESRD.
View details for DOI 10.1016/j.bone.2019.05.022
View details for PubMedID 31158505
Patients on dialysis are physically inactive, with most reporting activity levels below the fifth percentile of healthy age-matched groups. Several small studies have reported efficacy of diverse exercise interventions among persons with CKD and those on dialysis. However, no single intervention has been widely adopted in real-world practice, despite a clear need in this vulnerable population with high rates of mortality, frailty, and skilled nursing hospitalizations.We describe a pragmatic clinical trial for an exercise intervention among patients transitioning to dialysis. We will use an existing framework - Exercise is Medicine (EIM) - developed by the American College of Sports Medicine. After undertaking formative qualitative research to tailor the EIM framework to the advanced CKD population (eGFR < 30 ml/min/1.73m2), we will randomize 96 patients from two regions-Atlanta and Bay Area-in two intervention arms with incremental levels of clinical-community integration: physical activity assessment during Nephrology clinical visit, brief counseling at pre-dialysis education, and physical activity wearable (group 1) versus group 1 intervention components plus a referral to a free, EIM practitioner-led group exercise program over 16 weeks (group 2; 8 week core intervention; 8-week follow up). We will assess efficacy by comparing between group differences in minutes/week of objectively measured moderate intensity physical activity. To evaluate implementation, we will use questionnaires for assessing barriers to referral, participation and retention along the path of the intervention. Further we will have a plan for dissemination of the intervention by partnering with relevant stakeholders.The overall goal is to inform the development of a practical, cost-conscious intervention "package" that addresses barriers and challenges to physical activity commonly faced by patients with advanced CKD and can be disseminated amongst interested practices.ClinicalTrials.gov identifier (Dated:10/17/2017): NCT03311763 .
View details for PubMedID 30208854
At our institution, we have noted that end-stage renal disease patients choosing a home dialysis modality after education often initiate renal replacement therapy with in-center hemodialysis (HD) instead. We interviewed 24 such patients (23 choosing peritoneal dialysis [PD], one choosing home HD) to determine reasons for this mismatch. The most common reasons cited for not starting home dialysis were: lack of confidence/concerns about complications, lack of space or home-related issues, a feeling of insufficient education, and perceived medical or social contraindications. We propose several potential strategies to help patients start with their preferred modality.
View details for DOI 10.3747/pdi.2015.00047
View details for PubMedID 27385810
Acute interstitial nephritis (AIN) is a common cause of acute kidney injury and has been associated with a variety of medications. This is the case of 30-year-old man with Hodgkin's lymphoma who on routine labs before chemotherapy was found to have acute nonoliguric renal failure. A kidney biopsy was performed and confirmed the diagnosis of acute interstitial nephritis. The patient had taken several medications including a higher dose of Carnivora, a Venus flytrap extract, composed of numerous amino acids. The medication was discontinued and kidney function improved towards the patient's baseline indicating that this may be the possible cause of his AIN. Proximal tubular cell uptake of amino acids increasing transcription of nuclear factor-kappaB is a proposed mechanism of AIN from this compound.
View details for DOI 10.1155/2014/486173
View details for PubMedID 24839571