Vikas R Dharnidharka

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (134)714.87 Total impact


  • No preview · Article · Jan 2016
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    ABSTRACT: Comparisons of perceived barriers to adherence in pediatric and adolescent SOT have not been systematically conducted despite association between medication non-adherence and poor outcome. Fifteen centers in CTOT-C enrolled patients in a cross-sectional study. Subjects' guardians completed the PMBS and subjects over eight completed the Adolescent Scale (AMBS). Association of three identified PMBS factors and subject age was assessed. Secondary analyses assessed associations between PMBS, AMBS, and patient demographics. Three hundred sixty-eight subjects or their guardians completed PMBS or AMBS. A total of 107 subjects were 6-11 yr; 261 were ≥12. Unadjusted and propensity-adjusted analyses indicated higher perceived barriers in guardians of adolescents as compared to guardians of pre-adolescents medication scheduling and frustration domains regardless of organ (p < 0.05). PMBS and AMBS comparisons revealed that guardians reported fewer ingestion issues than patients (p = 0.018), and differences appeared more pronounced within younger responders for scheduling (p = 0.025) and frustration (p = 0.019). Screening revealed guardians of older patients report increased perceived barriers to adherence independent of socioeconomic status. Guardians of adolescents reported fewer perceived barriers to ingestion/side effects than patients themselves, particularly in pre-adolescents (8-11 yr). Brief screening measures to assess perceived barriers should be further studied in adherence improvement programs.
    No preview · Article · Dec 2015 · Pediatric Transplantation
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    ABSTRACT: We examined United States Renal Data System registry records for Medicare-insured kidney transplant recipients in 2000-2011 to study the clinical and cost impacts of urinary tract infections (UTI), pneumonia, and sepsis in the first year post-transplant among a contemporary, national cohort. Infections were identified by billing diagnostic codes. Among 60,702 recipients, 45% experienced at least one study infection in the first year post-transplant, including UTI in 32%, pneumonia in 13%, and sepsis in 12%. Older recipient age, female sex, diabetic kidney failure, non-standard criteria organs, sirolimus-based immunosuppression and steroids at discharge were associated with increased risk of first-year infections. By time-varying, multivariate Cox regression, all study infections predicted increased first-year mortality, ranging from 41% (aHR 1.41, 95%CI 1.25-1.56) for UTI alone, 6-to-12-fold risk for pneumonia or sepsis alone, to 34-fold risk (aHR 34.38, 95%CI 30.35-38.95) for those with all three infections. Infections also significantly increased first-year costs, from $17,691 (standard error (SE) $591) marginal cost increase for UTI alone, to approximately $40,000-$50,000 (SE $1054-1238) for pneumonia or sepsis alone, to $134,773 (SE $1876) for those with UTI, pneumonia and sepsis. Clinical and economic impacts persisted in years 2-3 post-transplant. Early infections reflect important targets for management protocols to improve post-transplant outcomes and reduce costs of care. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · Transplant International

  • No preview · Article · Nov 2015
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    ABSTRACT: Background: Graft failure risk is highest during emerging adulthood (17-24 years) in kidney and heart transplant. It is unknown whether a similar association exists in liver transplant recipients. Methods: We sought to estimate the relative hazards of graft failure at different current ages, compared with those aged 21 to 24 years. We evaluated 17 181 patients recorded in the Scientific Registry of Transplant Recipients who received a first isolated liver transplant at 40 years or younger (1988-2013) and had 6 months or longer of graft function. We used time-dependent Cox models to estimate the association between current age and failure risk, defined as retransplant or death after graft failure; observation was censored at death with graft function. Results: There were 2540 failures. Absolute graft failure rates were highest in ages 25 to 29 years (3.0/100 person-years). Compared with individuals with the same time since transplantation, those aged 21 to 24 years had significantly higher failure rates than those younger than 17 years and older than 34 years; hazards did not differ for those aged 25 to 29 years (1.03 [0.86, 1.24]) and were lower, but not significantly, for those aged 17 to 20 years (hazards ratio, 0.83; 95% confidence interval, 0.68-1.01) and ages 30 to 34 years (hazards ratio, 0.84; 95% confidence interval, 0.70-1.01). Conclusions: Among young first isolated liver transplant recipients, graft failure risks are highest in the period from 21 to 29 years of age.
    No preview · Article · Nov 2015 · Transplantation
  • Isa F Ashoor · Vikas R Dharnidharka
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    ABSTRACT: We wanted to identify practice patterns and perceived barriers among pediatric nephrologists regarding STI screening and reproductive health counseling in adolescent renal transplant recipients. We created an online Likert-scaled survey. Response rate was 54%. The majority (83%) believed STI risk in their patients was similar to or higher than healthy teens. Interestingly, while 67% felt moderately or very confident in asking about sexual activity and counseling about safer sex, only 43% routinely or always inquired about sexual activity, and only 42% routinely or always counseled about safer sex. Fifty-four percent routinely or always discussed contraceptive options and implications of unintentional pregnancy. Fifty-one percent routinely or always referred patients to a gynecologist or adolescent provider for contraception prescription. The most common counseling mechanism was informal discussions in clinic (87%). Ten percent had no mechanism in place. Major barriers included time limitations, adolescents' fear regarding confidentiality, and lack of professional training. This is the first report of perceptions and practice patterns of pediatric nephrologists regarding STI screening and reproductive health counseling. Providers seem to recognize the importance of counseling; however, translation into practice remains low. Professional training in this area and increased encounter time could improve counseling delivery and thereby reduce risk in this population. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Aug 2015 · Pediatric Transplantation
  • B J Foster · M Dahhou · X Zhang · V Dharnidharka · V Ng · J Conway
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    ABSTRACT: Emerging adulthood (17-24 years) is a period of high risk for graft failure in kidney transplant. Whether a similar association exists in heart transplant recipients is unknown. We sought to estimate the relative hazards of graft failure at different current ages, compared with patients between 20 and 24 years old. We evaluated 11 473 patients recorded in the Scientific Registry of Transplant Recipients who received a first transplant at <40 years old (1988-2013) and had at least 6 months of graft function. Time-dependent Cox models were used to estimate the association between current age (time-dependent) and failure risk, adjusted for time since transplant and other potential confounders. Failure was defined as death following graft failure or retransplant; observation was censored at death with graft function. There were 2567 failures. Crude age-specific graft failure rates were highest in 21-24 year olds (4.2 per 100 person-years). Compared to individuals with the same time since transplant, 21-24 year olds had significantly higher failure rates than all other age periods except 17-20 years (HR 0.92 [95%CI 0.77, 1.09]) and 25-29 years (0.86 [0.73, 1.03]). Among young first heart transplant recipients, graft failure risks are highest in the period from 17 to 29 years of age. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    No preview · Article · Jul 2015 · American Journal of Transplantation
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    ABSTRACT: Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation-a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Jun 2015 · Pediatric Transplantation
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    ABSTRACT: Introduction: Previous studies from our group have shown that activity of the biomarker enzyme IDO elevates prior to acute rejection in kidney transplant recipients, as commonly inferred by ratio of enzyme product kynurenines (kyn) to enzyme substrate tryptophan (trp). Acute rejection episodes increase the risk for chronic rejection, a leading cause of allograft loss. The relationship between serum IDO activity and chronic rejection has not been previously studied. We investigated the possible association of kyn/trp ratio elevation to biopsy-proven transplant glomerulopathy (TG), a phenotype of chronic rejection and to presence of serum antibodies to the kidney-associated self-antigens fibronectin (FN) and collagen IV (Col IV), shown by some in our group to be strongly associated with TG. Methods: Kyn and trp were quantitated using mass spectrometry m/z transitions of 209>94 and 205>146, respectively, using D5-tryptophan and D6-kynurenine as internal standards, from serum samples extracted from our Kidney Translational Research Core. Samples were chosen which had been obtained within 2 weeks of a biopsy which showed chronic rejection. Antibodies to FN and Col IV were measured by ELISA developed by our group using techniques previously described. Results: In 56 patients with predominantly chronic rejection on allograft kidney biopsy, the kyn/trp ratio (median 6.9, IQR 5.32, 10.3) was not significantly higher compared to the level in 46 with other features but no chronic rejection (median 6.65, IQR 4.67, 9.62, p = 0.37 by non-parametric two-tailed Mann-Whitney test). Similarly, the kyn/trp ratio in TG patients (n=38) was not significantly higher compared to non-TG (n=64; median 6.95, IQR 5.23, 10.43 in TG versus median 6.65, IQR 5.12, 9.67 in non-TG, p = 0.55).The kyn/trp ratios did not show a significant correlation with either FN (two-tailed Spearman r = 0.10, p = 0.29) or Col IV (Spearman r = 0.14, p = 0.15). Conclusions: In this cross-sectional analysis, serum kyn/trp ratio was not elevated at time of biopsy-proven chronic rejection, nor did it associate with high levels of antibodies to kidney-specific self-antigens. Further studies should assess the longitudinal associations of these serum biomarkers prior to, rather than concomitant to, the development of established chronic rejection.
    No preview · Conference Paper · May 2015
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    ABSTRACT: Univariate analyses suggest that adolescents have worse long-term allograft survival versus younger children across different SOT. This study's objective was to determine whether multivariate analyses of a large national database recording all deceased SOT (KI; LI; HR; LU) also show worse adolescent allograft survival in the different organs. Using data from the national Scientific Registry for Transplant Recipients in the USA for pediatric primary SOT from 1989 to 2010, we calculated median half-lives and constructed K-M graft survival curves. Recipient age at transplant (<12 or adolescent 12-17 yr) was fitted with other identical covariates into multivariate Cox proportional hazards models. In all SOT recipients, unadjusted graft survival curves demonstrated better graft survival for adolescents initially, followed by crossing of the lines, such that adolescent SOT recipients had worse survival after one yr (KI), 4.6 yr (LI), 4.4 yr (HR), and 1.6 yr (LU). Multivariate models of the post-cross period showed a significantly higher AHR for worse graft survival in adolescent age across all four SOTs: AHR 1.400 (KI), 1.958 (LI), 1.414 (HR), and 1.576 (LU). Improving adolescent long-term outcomes across all four organs will be a defining issue in the future. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Apr 2015 · Pediatric Transplantation
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    ABSTRACT: Improvements across many facets of transplantation have led to better 1-yr outcomes of transplanted organs. In this study, we assessed whether longer-term attrition rates improved in pediatric kidney (KI), liver (LI), heart (HR) and lung (LU) transplant (TX) survival. We analyzed data between 1989 and 2008 from 5747 KI, 7348 LI, 5103 HR, and 715 LU TXs (under 18 yr of age at transplant, first solitary transplant only), from the National Scientific Registry of Transplant Recipients database in the USA. Kaplan-Meier (K-M) or ordinary least square (OLS) estimates were used to calculate median and projected survival half-lives. Attrition rates, defined as percent failing within a given time period, were stratified by year of TX. Median half-lives from 1989 TX year to 2005 TX year have shown a major improvement only in LI TX, remaining unchanged in HR and KI TX, or remaining very low in LU TX. All four organ TX types have shown a dramatic drop in first-year attrition rates from 1989 to 2008. However, longer-term attrition rates (1-3, 3-5, 5-10 yr) have remained largely unchanged for all four organ TX types. Further progress in long-term survival will need targeting end-points beyond first-year rejection and survival rates. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Apr 2015 · Pediatric Transplantation
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    ABSTRACT: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described. We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ≥23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension. Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation. © 2015 S. Karger AG, Basel.
    No preview · Article · Mar 2015 · American Journal of Nephrology
  • Source
    Vikas R Dharnidharka · Michael E Seifert
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    ABSTRACT: Early kidney transplant results in children lagged behind corresponding results in adults. Multiple advances over the last three decades have eliminated that gap. Most children now have equal or superior long-term allograft and patient survival compared to adult recipients. However, black children in the USA continue to have comparatively inferior allograft survival results to non-black children, even after extensive adjustments for socioeconomic status and access to transplantation.
    Preview · Article · Mar 2015 · Kidney International
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    Vikas R Dharnidharka · Thallachallour Mohanakumar

    Preview · Article · Feb 2015 · New England Journal of Medicine
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    ABSTRACT: Background: Limited data are available on the outcome implications of prescription narcotic use before kidney transplantation. Methods: We examined a novel database wherein national transplant registry identifiers for kidney transplant recipients were linked to records from a large U.S. pharmaceutical claims clearinghouse (2005-2010). We selected recipients with 1 year of captured pretransplant pharmaceutical fill records (N=31,197). Opioid analgesic fills in the year before transplantation were normalized to morphine equivalents (ME) and expressed as mg/kg exposures. Adjusted associations of ME level with posttransplant graft and patient survival (adjusted hazards ratio, aHR) were quantified by multivariate Cox regression. Results: Among the 29% of the sample who filled opioid prescriptions in the year before transplantation, the 25th, 50th, and 75th percentiles of annual ME were 1.8, 5.5, and 23.7 mg/kg, respectively. Three-year graft survival was 88.0% and 84.4% in live donor recipients with upper quartiles of ME use, compared with 92.0% among those who did not receive prescription narcotics (P<0.0001). Adjusted risks of posttransplant death and all-cause graft loss in live donor recipients with the highest quartile of narcotic use were 2.3 times (aHR, 2.27; 95% confidence interval, 1.66-3.10) and 1.8 times (aHR, 1.75; 95% confidence interval, 1.37-2.26), respectively, that of narcotic nonusers. Graded associations of pretransplant opioid exposure level with death and graft loss after deceased donor transplantation were also observed. Conclusions: Although associations may in part reflect underlying conditions or behaviors, high levels of prescription opioid use before kidney transplantation predict increased risk of posttransplant death and graft loss.
    No preview · Article · Dec 2014 · Transplantation
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    Jodi M. Smith · Vikas R. Dharnidharka
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    ABSTRACT: Significant progress has been made in pediatric kidney transplantation. Advances in immunosuppression have dramatically decreased rates of acute rejection leading to improved short term graft survival but similar improvements in long term graft survival remain elusive. Changes in allocation policy provide the pediatric population with timely access to transplant but there remains concern about the impact of less HLA matching and a decrease in living donors. This report presents data from North America on these successes and the ongoing challenges that face the pediatric transplant community.
    Preview · Article · Dec 2014 · The Open Urology & Nephrology Journal
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    Faris Hashim · Jon A. Gregg · Vikas R Dharnidharka
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    ABSTRACT: Cytomegalovirus (CMV) is one of the most frequent opportunistic infection in renal transplant (RTx) recipients. Valganciclovir (VGC) has been showed to be safe and highly effective in prophylaxis of CMV infection in RTx recipients. Recently, an increase in delayed onset CMV disease has been noted with some arguing that longer prophylaxis may decrease the late-onset disease. We retrospectively tested the hypothesis that extended term prophylaxis (ETP) of VGC for 12 months is more effective than short term prophylaxis (STP) of 6 months in preventing CMV infection and disease in pediatric RTx performed at the University of Florida from July 2003 to December 2010. In this period, all recipients underwent prospective CMV PCR (Polymerase Chain Reaction) monitoring and were maintained on similar immunosuppression. Eighty six patients received RTx during that period. All eligible subjects had to have at least 12 months of graft survival and 18 months of follow up, leaving 73 eligible subjects in final study group. CMV infection or disease occurred in 6/29 (20%) in the STP group vs 6/44 (14%) in the ETP group with no statistical significant difference (P= 0.42). Donor positive/recipients negative CMV serology status (D+/R-) were associated with a higher risk of CMV infection in both univariate and multivariate analysis (P=0.01). Anemia and Leucopenia directly associated with VGC were similar in both groups (P=0.58 and P=0.2 respectively). Biopsy-proven acute rejection was also non-significant in both groups (P=0.39). Although ETP for CMV from 6 months to 12 months is safe and has minimal adverse effect, it did not reduce CMV infection or disease. Further controlled studies in pediatrics age group are considered to compare longer versus shorter periods of prophylaxis and their impact on prevention of CMV infection, resistance, cost, and toxicity.
    Preview · Article · Dec 2014 · The Open Urology & Nephrology Journal
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    Asha Moudgil · Karen Martz · Therese Moore · William E. Harmon · Vikas R. Dharnidharka
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    ABSTRACT: Background: Many pediatric transplant (TX) centers routinely monitor Epstein-Barr (EB) viral load (VL) by real time quantitative PCR and intervene to prevent post-transplant lymphoproliferative disorder (PTLD). Some children develop asymptomatic persistent VL (PVL). Outcome of different interventions in preventing PTLD and other undesired effects on acute rejection (AR), graft failure (GF) and function amongst children with asymptomatic PVL is not known. Methods: NAPRTCS centers invited to enter data on children with asymptomatic PVL (≥ 6 months) into the EB VL registry. Comparison group included children into the NAPRTCS TX arm during the same period without PVL or VL monitoring. EB VL were arbitrarily divided into low (1-10), medium (>10-100) and high (>100times detection limit for the center) ratio. Results: Of 645 children (18 centers), 85 (13.2%) developed onset of PVL at a mean of 6.4 ± 6.3 months post-TX. PVL children were more likely to be younger (< 5 years) at TX and less likely to be African-American and majority (75.3%) was mismatched for EBV (donor EBV IgG positive and recipient negative). Thymoglobulin induction was used in 29.4% children with PVL versus 37% in controls (p=ns). PTLD developed in 7/85 (8.2%) children with PVL versus 5/560 (0.9%) controls (p < 0.0001). EB VL ratios were not different in those with and without PTLD. EB PVL as time varying covariate did not affect patient survival, GF and AR (HR, 0.85, 0.53 and 0.99). The change in GFR overtime in children with PVL was comparable to controls. Conclusion: Children with PVL (actual load not predictive) are at increased risk for PTLD, but not for AR, death, GF or loss of graft function.
    Preview · Article · Dec 2014 · The Open Urology & Nephrology Journal
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    Vikas R. Dharnidharka

    Preview · Article · Dec 2014 · The Open Urology & Nephrology Journal
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    Faris Hashim · Shehzad Rehman · Jon A Gregg · Vikas R Dharnidharka
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    ABSTRACT: The placement of ureteral stent (UrSt) at kidney transplantation reduces major urological complications but increases the risk for developing nephropathy from the BK virus. It is unclear whether UrSt placement increases nephropathy risk by increasing risk of precursor viral replication or by other mechanisms. We retrospectively investigated whether UrSt placement increased the risk for developing BK Viremia (BKVM) in adult and pediatric kidney transplants performed at the University of Florida between July 1, 2007, and December 31, 2010. In this period all recipients underwent prospective BKV PCR monitoring and were maintained on similar immunosuppression. Stent placement or not was based on surgeon preference. In 621 transplants, UrSt were placed in 295 (47.5%). BKVM was seen in 22% versus 16% without UrSt ( P = 0.05 ). In multivariate analyses, adjusting for multiple transplant covariates, only UrSt placement remained significantly associated with BKVM ( P = 0.04 ). UrSt placement significantly increased the risk for BKVM. Routine UrSt placement needs to be revaluated, since benefits may be negated by the need for more BK PCR testing and potential for graft survival-affecting nephritis.
    Preview · Article · Sep 2014 · Journal of Transplantation

Publication Stats

4k Citations
714.87 Total Impact Points

Institutions

  • 2013-2015
    • Washington University in St. Louis
      • Department of Pediatrics
      San Luis, Missouri, United States
  • 2000-2014
    • University of Florida
      • • Department of Pediatrics
      • • College of Medicine
      Gainesville, Florida, United States
  • 2002-2012
    • Florida Hospital for Children
      Orlando, Florida, United States
  • 2011
    • George Washington University
      • Department of Medicine
      Washington, Washington, D.C., United States
  • 2003
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 2001
    • Harvard University
      Cambridge, Massachusetts, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1997-1999
    • Boston Children's Hospital
      • Division of Nephrology
      Boston, MA, United States