Stephen L Seliger

University of Maryland, Baltimore, Baltimore, Maryland, United States

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Publications (110)911.9 Total impact

  • Merrill F Elias, Stephen L Seliger, Rachael V Torres
    Nephrology Dialysis Transplantation 06/2015; DOI:10.1093/ndt/gfv263 · 3.49 Impact Factor
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    ABSTRACT: This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH). The natural history of LVH, an important risk factor for HF, is heterogeneous. NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression. Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers. The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    05/2015; 3(6). DOI:10.1016/j.jchf.2014.12.018
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    ABSTRACT: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated. N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors. In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50). Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association. Copyright © 2015 by the American Society of Nephrology.
    Clinical Journal of the American Society of Nephrology 01/2015; 10(2). DOI:10.2215/CJN.04910514 · 5.25 Impact Factor
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    ABSTRACT: Background and Aims: There is limited information on the risk of progression of chronic kidney disease (CKD) among individuals with CVD (cardiovascular disease). We studied the association between prevalent CVD and the risk of progression of CKD among persons enrolled in a long-term observational study. Methods: A prospective cohort study of 3,939 women and men with CKD enrolled in the chronic renal insufficiency cohort (CRIC) study between June 2003 and June 2008. Prevalent cardiovascular disease (myocardial infarction/revascularization, heart failure, stroke, and peripheral vascular disease) was determined by self-report at baseline. The primary outcome was a composite of either end-stage renal disease or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Results: One-third (1,316 of 3,939, 33.4%) of the study participants reported a history of any cardiovascular disease, and 9.6% (n = 382) a history of heart failure at baseline. After a median follow up of 6.63 years, 1,028 patients experienced the primary outcome. The composite of any CVD at baseline was not independently associated with the primary outcome (Hazard Ratio 1.04 95% CI (0.91, 1.19)). However, a history of heart failure was independently associated with a 29% higher risk of the primary outcome (Hazard Ratio 1.29 95% CI (1.06, 1.57)). The relationship between heart failure and risk of CKD progression was consistent in subgroups defined by age, race, gender, baseline eGFR, and diabetes. Neither the composite measure of any CVD or heart failure was associated with the rate of decline in eGFR. Conclusions: Self-reported heart failure was an independent risk factor for the development of the endpoint of ESRD or 50% decline in GFR in a cohort of patients with chronic kidney disease. © 2014 S. Karger AG, Basel.
    American Journal of Nephrology 11/2014; 40(5):399-407. DOI:10.1159/000368915 · 2.65 Impact Factor
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    Shabnam Salimi, Nawi Ng, Stephen L Seliger, Afshin Parsa
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    ABSTRACT: Background: Leukocytosis is a powerful predictor of incident chronic kidney disease (CKD) and related outcomes. However, the association between periodontitis measures and increased leukocytosis in the context of CKD has not been well described. We sought to identify which individual measures of periodontal disease may best associate with reduced estimated glomerular filtration rate (eGFR) and albuminuria, and to test if these measures were associated with increased leukocytosis in subjects with established CKD. Methods: We estimated, among 13,270 participants in the National Health and Nutrition Examination Survey III study, the associations between case-based definition of periodontitis, clinical attachment loss (CAL) and pocket depth (PD) as individual measures of periodontal disease, with renal function measures and leukocytosis. Results: In adjusted multivariate analyses, case-based definition of severe periodontitis was associated with albuminuria (β = 0.003, p = 0.01) but not with eGFR. However, CAL and PD were all individually associated with both albuminuria (β = 0.08, p < 0.001 and β = 0.06, p < 0.001, respectively) and eGFR (β = -0.05, p < 0.001 and β = -0.03, p < 0.001, respectively). We found significant associations between elevated CAL and PD with leukocytosis. Lastly, we found a marked association between the joint presence of CKD and elevated CAL or PD with leukocytosis (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4-7.5 and OR 3.2, 95% CI 1.1-9.7, respectively). Conclusion: Individual measures of periodontal disease are associated with renal function and heightened leukocytosis in CKD subjects. The significantly added inflammatory burden noted in CKD subjects with periodontal disease argue for targeting periodontitis treatment as part of our multifaceted approach to CKD patients. © 2014 S. Karger AG, Basel.
    Nephron Clinical Practice 11/2014; DOI:10.1159/000366445 · 1.65 Impact Factor
  • Shan Shan Chen, Stephen L Seliger, Linda F Fried
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    ABSTRACT: This review presents the role of combination therapy of rennin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease.
    Current Opinion in Nephrology and Hypertension 07/2014; DOI:10.1097/MNH.0000000000000043 · 4.24 Impact Factor
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    ABSTRACT: Background: Renal hemodynamic measurements are complicated to perform in patients with cirrhosis, yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics. Methods: In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic-sensitive and 2 diuretic-refractory ascites). Results: Patients with diuretic-refractory ascites had the lowest mean GFR (36.5 ml/min/1.73 m(2)) and RPF (133.6 ml/min/1.73 m(2)) when compared to those without ascites (GFR 82.9 ml/min/1.73 m(2), RPF 229.9 ml/min/1.73 m(2)) and with diuretic-sensitive ascites (GFR 82.3 ml/min/1.73 m(2), RPF 344.1 ml/min/1.73 m(2)). A higher mean filtration fraction (FF) (GFR/RPF 0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF ∼0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and β2-microglobulin performed better compared to Cr in estimating RPF, β-trace protein, β2-microglobulin, and SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index. Conclusion: The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention and reduce mortality from kidney failure in cirrhosis. © 2014 S. Karger AG, Basel.
    American Journal of Nephrology 06/2014; 39(6):543-552. DOI:10.1159/000363584 · 2.65 Impact Factor
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    ABSTRACT: Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by non-radiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the "bias", "precision" and "accuracy" of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG) and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores [differences between mGFR and estimated GFR (eGFR) or between mGFR and CrCl, or between mGFR and CG equation for each subject] (RMSE=23.56) was significantly better than that of CrCl (37.69, P=0.001), CG (RMSE=36.12, P=0.002) and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P=0.024), CG (P=0.0001), 4-variable MDRD (P=0.027) and CKD-EPI creatinine 2009 (P=0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%. CONCLUSIONS: The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than reported in non-cirrhotic subjects. (HEPATOLOGY 2013.).
    Hepatology 04/2014; 59(4). DOI:10.1002/hep.26556 · 11.19 Impact Factor
  • Journal of the American College of Cardiology 04/2014; 63(12):A768. DOI:10.1016/S0735-1097(14)60768-3 · 15.34 Impact Factor
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    ABSTRACT: Objectives To determine the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) in three large independent cohorts. Background The presently recommended 14 ng/L cutpoint for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods Data were included from three well characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease and kidney disease (subcohort 1) and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex and race. Results The 99th percentile values for the hs-cTnT assay in DHS, ARIC and CHS were 18, 22 and 36 ng/L respectively (subcohort 1) and 14, 21 and 28 ng/L respectively (subcohort 2). These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men aged 65-74 with no cardiovascular disease in our study had cTnT values above the current myocardial infarction threshold. Conclusions Use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.
    Journal of the American College of Cardiology 04/2014; 63(14). DOI:10.1016/j.jacc.2013.12.032 · 15.34 Impact Factor
  • Journal of the American College of Cardiology 04/2014; 63(12):A738. DOI:10.1016/S0735-1097(14)60738-5 · 15.34 Impact Factor
  • Journal of the American College of Cardiology 04/2014; 63(12):A771. DOI:10.1016/S0735-1097(14)60771-3 · 15.34 Impact Factor
  • Journal of the American College of Cardiology 04/2014; 63(12):A769. DOI:10.1016/S0735-1097(14)60769-5 · 15.34 Impact Factor
  • Daniel E Weiner, Stephen L Seliger
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    ABSTRACT: Both cognitive and physical function are commonly impaired in individuals with chronic kidney disease (CKD), resulting in important impacts on their quality of life and overall health. This review summarizes the burden of cognitive and physical impairment in CKD, focusing on recent research that highlights a possible unifying microvascular cause among these shared comorbid conditions. Multiple small studies have been published recently evaluating cognitive and physical functioning in people with CKD. These studies overall demonstrate a high burden of comorbid conditions in people with CKD, including microvascular disease, that may result in cognitive impairment. Additionally, studies demonstrate that physical function is substantially worse than expected in individuals with CKD, that decreased physical activity is associated with worse outcomes, that frailty is very common and associated with an increased risk of death, and that structured exercise programs have small but tangible short-term effects on markers of physical performance. Impaired cognitive function and physical performance are important factors impacting the lives of people with CKD. Further research is necessary to better treat these important comorbid conditions in people with CKD.
    Current Opinion in Nephrology and Hypertension 03/2014; DOI:10.1097/01.mnh.0000444821.87873.7b · 4.24 Impact Factor
  • Stephen L Seliger, Linda F Fried
    Clinical Journal of the American Society of Nephrology 01/2014; 9(2). DOI:10.2215/CJN.12411213 · 5.25 Impact Factor
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    ABSTRACT: Background Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥60 ml per minute per 1.73 m(2) or a decline of ≥50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217 .).
    New England Journal of Medicine 11/2013; 369(20). DOI:10.1056/NEJMoa1303154 · 54.42 Impact Factor
  • Stephen L Seliger, Christopher R Defilippi
    Coronary artery disease 10/2013; 24(8). DOI:10.1097/MCA.0000000000000045 · 1.30 Impact Factor
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    ABSTRACT: Cardiac troponin assays have become an indispensable tool in the diagnosis of acute myocardial infarction (MI). However, asymptomatic patients with chronic kidney disease often exhibit elevated levels of cardiac troponins with near ubiquitous detection using the new high-sensitive assays. This poses a challenge to physicians faced with differentiating between acute MI and a noncardiac etiology of chest pain or equivalent. Rather than rely on absolute cutoffs it is necessary to follow trends in levels at least over several hours. Even in the absence of an acute MI there is an association between chronic elevations of these biomarkers, underlying structural heart disease and poor prognosis. Although in the chronic setting the underlying cause of cardiac troponin elevation is likely a combination of factors, it should prompt further investigation for modifiable risk factors.
    Coronary artery disease 10/2013; DOI:10.1097/MCA.0000000000000046 · 1.30 Impact Factor
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    ABSTRACT: Objectives This study sought to determine whether the combined trajectories of cardiac biomarkers identify those older adults with initial low levels who have an increased risk for structural heart disease, incident heart failure (HF), and cardiovascular (CV) death. Background Initial low levels of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) identify older adults at lower risk for CV events. Methods We performed an observational study among older adults without prevalent HF in the CHS (Cardiovascular Health Study). NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years. In those with low baseline levels, a significant increase was defined as cardiac troponin T (cTnT) >50% and NT-proBNP >25% increase to >190 pg/ml. Left ventricular ejection fraction and left ventricular mass were measured by echocardiography at baseline and 5 years. Cox regression was used to estimate the association of change in biomarkers with HF and CV mortality. Results Among 2,008 participants with initially low biomarker concentrations, significant increases occurred in 14.8% for cTnT only, 13.2% for NT-proBNP only, and 6.1% for both. After 10 years, cumulative HF incidence was 50.4% versus 12.2% among those with both biomarkers versus neither biomarker increased. The adjusted relative risk comparing those with increases in both biomarkers versus neither biomarker was 3.56 for incident HF (95% confidence interval: 2.56 to 4.97) and 2.98 for CV mortality (95% confidence interval: 2.98 to 4.26). Among 1,340 participants with serial echocardiography, the frequency of new abnormal left ventricular ejection fraction was 11.8% versus 4% for those with increases in both biomarkers versus neither biomarker (p = 0.007). Conclusions Among older adults without HF with initially low cTnT and NT-proBNP, the long-term trajectory of both biomarkers predicts systolic dysfunction, incident HF, and CV death.
    08/2013; 1(4):353–360. DOI:10.1016/j.jchf.2013.04.007
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    ABSTRACT: The incidence of stroke is substantially higher among hemodialysis patients than among patients with earlier stages of CKD, but to what extent the initiation of dialysis accelerates the risk for stroke is not well understood. In this cohort study, we analyzed data from incident hemodialysis and peritoneal dialysis patients in 2009 who were at least 67 years old and had Medicare as primary payer. We noted whether each of the 20,979 hemodialysis patients initiated dialysis as an outpatient (47%) or inpatient (53%). One year before initiation, the baseline stroke rate was 0.15%-0.20% of patients per month (ppm) for both outpatient and inpatient initiators. Among outpatient initiators, stroke rates began rising approximately 90 days before initiation, reached 0.5% ppm during the 30 days before initiation, and peaked at 0.7% ppm (8.4% per patient-year) during the 30 days after initiation. The pattern was similar among inpatient initiators, but the stroke rate peaked at 1.5% ppm (18% per patient-year). For both hemodialysis groups, stroke rates rapidly declined by 1-2 months after initiation, fluctuated, and stabilized at approximately twice the baseline rate by 1 year. Among the 620 peritoneal dialysis patients, stroke rates were slightly lower and variable, but approximately doubled after initiation. In conclusion, these data suggest that the process of initiating dialysis may cause strokes. Further studies should evaluate methods to mitigate the risk for stroke during this high-risk period.
    Journal of the American Society of Nephrology 04/2013; DOI:10.1681/ASN.2012080841 · 9.47 Impact Factor

Publication Stats

4k Citations
911.90 Total Impact Points

Institutions

  • 2006–2015
    • University of Maryland, Baltimore
      • • Department of Medicine
      • • Division of Nephrology
      Baltimore, Maryland, United States
    • University of California, San Francisco
      • Veterans Affairs Medical Center
      San Francisco, CA, United States
  • 2008–2013
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 2001–2013
    • University of Washington Seattle
      • • Division of Nephrology
      • • Department of Medicine
      • • Department of Pathology
      Seattle, Washington, United States
  • 2005–2007
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2004
    • University of Chicago
      • Department of Health Studies
      Chicago, Illinois, United States