Vikas R Dharnidharka

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

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Publications (123)671.21 Total impact

  • 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.
    Pediatric Transplantation 08/2015; DOI:10.1111/petr.12579 · 1.44 Impact Factor
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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.
    Pediatric Transplantation 06/2015; 19(5). DOI:10.1111/petr.12531 · 1.44 Impact Factor
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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.
    2015 American Transplant Congress,; 05/2015
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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.
    Pediatric Transplantation 04/2015; 19(5). DOI:10.1111/petr.12464 · 1.44 Impact Factor
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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.
    Pediatric Transplantation 04/2015; 19(5). DOI:10.1111/petr.12465 · 1.44 Impact Factor
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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.
    American Journal of Nephrology 03/2015; 41(2):165-76. DOI:10.1159/000377685 · 2.67 Impact Factor
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    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 past three decades have eliminated that gap. Most children now have equal or superior long-term allograft and patient survival compared with adult recipients. However, black children in the United States continue to have allograft survival results inferior to those of non-black children, even after extensive adjustments for socioeconomic status and access to transplantation.
    Kidney International 03/2015; 87(3):492-494. DOI:10.1038/ki.2014.366 · 8.56 Impact Factor
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    Vikas R Dharnidharka · Thallachallour Mohanakumar
    New England Journal of Medicine 02/2015; 372(6):569-71. DOI:10.1056/NEJMcibr1415117 · 55.87 Impact Factor
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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.
    Transplantation 12/2014; 99(1):1. DOI:10.1097/TP.0000000000000248 · 3.83 Impact Factor
  • Vikas R. Dharnidharka
    The Open Urology & Nephrology Journal 12/2014; 7(1):113-114. DOI:10.2174/1874303X01407010113
  • 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.
    The Open Urology & Nephrology Journal 12/2014; 7(1):115-122. DOI:10.2174/1874303X01407010115
  • 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.
    The Open Urology & Nephrology Journal 12/2014; 7(1):152-157. DOI:10.2174/1874303X01407010152
  • 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.
    The Open Urology & Nephrology Journal 12/2014; 7(1):123-128. DOI:10.2174/1874303X01407010123
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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.
    Journal of Transplantation 09/2014; 2014:459747. DOI:10.1155/2014/459747
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    Jodi M Smith · Vikas R Dharnidharka
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    ABSTRACT: The more potent immunosuppressive therapy that has successfully reduced the incidence of acute rejection and improved graft outcomes has also resulted in a higher incidence of viral complications. Sensitive molecular methods now allow for the detection of subclinical viral infection, which is increasingly recognized due to the adoption of routine post-transplant viral surveillance protocols. The goal of viral surveillance is the detection of subclinical viral infection that triggers an intervention; one that either prevents progression to viral disease or leads to early diagnosis of viral disease, which is associated with improved outcomes. Knowledge of the epidemiology and natural history of subclinical viral infection and viral disease, as well as patient-specific risk factors, is required to establish the optimal surveillance schedule which achieves the goal of early diagnosis. Evidence that detection of subclinical viral infection can impact viral disease is variable depending on the virus. This review will summarize the current data on the role of viral surveillance for BK virus (BKV), cytomegalovirus (CMV), and the Epstein-Barr virus (EBV) in the pediatric kidney transplant population.
    Pediatric Nephrology 08/2014; 30(5). DOI:10.1007/s00467-014-2866-8 · 2.86 Impact Factor
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    Vikas R Dharnidharka · Paolo Fiorina · William E Harmon
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    ABSTRACT: Transplantation in children with kidney failure once presented many technical, immunologic, and logistic problems that led to worse patient and allograft survival, as compared with adults. Advances in all these areas and the development of pediatric-trial groups have resulted in dramatic improvements, such that young children now have the best long-term graft survival among all age groups, including adults.
    New England Journal of Medicine 08/2014; 371(6):549-58. DOI:10.1056/NEJMra1314376 · 55.87 Impact Factor
  • Vikas R. Dharnidharka · Laura E. Hesemann
    Pediatric Transplantation 08/2014; 18(5). DOI:10.1111/petr.12291 · 1.44 Impact Factor
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    ABSTRACT: Background: Descriptions of the sequelae of ABO-incompatible (ABOi) kidney transplantation are limited to single-center reports, which may lack power to detect important effects. Methods: We examined U.S. Renal Data System registry data to study associations of ABOi live-donor kidney transplantation with clinical complications in a national cohort. Among 14,041 Medicare-insured transplants in 2000 to 2007, 119 non-donor-A2 ABOi transplants were identified. A2-incompatible (n=35) transplants were categorized separately. Infection and hemorrhage events were identified by diagnosis codes on billing claims. Associations of ABO incompatibility with complications were assessed by multivariate Cox regression. Results: Recipients of ABOi transplants experienced significantly (P<0.05) higher incidence of wound infections (12.7% vs. 7.3%), pneumonia (7.6% vs. 3.8%), and urinary tract infections (UTIs) or pyelonephritis (24.5% vs. 15.3%) in the first 90 days compared with ABO-compatible recipients. In adjusted models, ABO incompatibility was associated with twice the risk of pneumonia (adjusted hazard ratio [aHR], 2.22; 95% confidence interval [CI], 1.14-4.33) and 56% higher risk of UTIs or pyelonephritis (aHR, 1.56; 95% CI, 1.05-2.30) in the first 90 posttransplantation days, and 3.5 times the relative risk of wound infections in days 91 to 365 (aHR, 3.55; 95% CI, 1.92-6.57). ABOi recipients, 19% of whom underwent pre- or peritransplant splenectomy, experienced twice the adjusted risk of early hemorrhage (aHR, 1.96; 95% CI, 1.19-3.24). A2-incompatible transplantation was associated only with early risk of UTIs or pyelonephritis. Conclusion: ABOi transplantation offers patients with potential live donors an additional transplant option but with higher risks of infectious and hemorrhagic complications. Awareness of these complications may help improve protocols for the management of ABOi transplantation.
    Transplantation 07/2014; 98(1):54-65. DOI:10.1097/TP.0000000000000029 · 3.83 Impact Factor
  • Atul Poudel · Judy Lew · William Slayton · Vikas R Dharnidharka
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    ABSTRACT: Bartonella henselae (Bh) is the cause of cat-scratch fever. When infection is symptomatic, it typically presents with singular lymphadenitis and fever. Less commonly, the infection can become disseminated and cause endocarditis, osteomyelitis, and micro-abscesses in multiple sites including liver, spleen, eyes, and brain, especially in immunocompromised patients. Hemophagocytic lymphohistiocytosis (Hlh) is a rare and severe multisystem disorder that may be triggered by infections. In one prior case, Bh, like other infections, has induced Hlh, an immune-mediated disease that can be characterized by septic-like presentation with persistent fevers, hepatosplenomegaly, and pancytopenia. In an immunocompromised transplant recipient, the onset of Hlh can be difficult to discern from a severe presentation of Bh. We report a case of criteria-proven secondary Hlh occurring after Bh infection in an 11-yr-old girl who was 13 months post-renal transplant. The patient developed multi-organ failure, and her severe clinical presentation required a thorough evaluation for infectious and non-infectious possibilities including post-transplant lymphoproliferative disorder and rejection. Early recognition of Hlh allowed for better directed therapies, leading to recovery of the patient and resolution of both Bh and Hlh.
    Pediatric Transplantation 05/2014; 18(3):E83-7. DOI:10.1111/petr.12235 · 1.44 Impact Factor
  • Elizabeth I Anyaegbu · Vikas R Dharnidharka
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    ABSTRACT: Over the last two decades, essential hypertension has become common in adolescents, yet remains under-diagnosed in absence of symptoms. Diagnosis is based on normative percentiles that factor in age, sex and height. Evaluation is more similar to adult essential hypertension than childhood secondary hypertension. Modifiable risk factors such as obesity, sodium consumption and low exercise should be addressed first. Many anti-hypertensive medications now have specific regulatory approval for children. Sports participation need not be limited in mild or well-controlled cases. Primary care physicians play an important role in reduction of cardiovascular mortality by early detection and referral when needed.
    Pediatric Clinics of North America 02/2014; 61(1):131-151. DOI:10.1016/j.pcl.2013.09.011 · 2.12 Impact Factor

Publication Stats

3k Citations
671.21 Total Impact Points


  • 2013–2015
    • Washington University in St. Louis
      • Department of Pediatrics
      San Luis, Missouri, United States
  • 2002–2014
    • University of Florida
      • • Department of Pediatrics
      • • College of Medicine
      Gainesville, Florida, United States
  • 2002–2012
    • Florida Hospital for Children
      Orlando, Florida, United States
  • 2008
    • Walter Reed National Military Medical Center
      • Department of Surgery
      Washington, Washington, D.C., United States
  • 2006
    • Yale University
      New Haven, Connecticut, United States
  • 2003
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 2001
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 1998–2001
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1999
    • Boston Children's Hospital
      • Division of Nephrology
      Boston, MA, United States