Vikas R Dharnidharka

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

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Publications (115)602.89 Total impact

  • [Show abstract] [Hide abstract]
    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 · 1.63 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 · 1.63 Impact Factor
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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 · 1.63 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 · 2.65 Impact Factor
  • 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 · 8.52 Impact Factor
  • Faris Hashim, Jon A. Gregg, Vikas R. Dharnidharka
    The Open Urology & Nephrology Journal 12/2014; 7(1):152-157. DOI:10.2174/1874303X01407010152
  • The Open Urology & Nephrology Journal 12/2014; 7(1):123-128. DOI:10.2174/1874303X01407010123
  • Jodi M. Smith, Vikas R. Dharnidharka
    The Open Urology & Nephrology Journal 12/2014; 7(1):115-122. DOI:10.2174/1874303X01407010115
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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
  • 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 · 2.88 Impact Factor
  • Vikas R Dharnidharka, Paolo Fiorina, William E Harmon
    New England Journal of Medicine 08/2014; 371(6):549-58. DOI:10.1056/NEJMra1314376 · 54.42 Impact Factor
  • Vikas R. Dharnidharka, Laura E. Hesemann
    Pediatric Transplantation 08/2014; 18(5). DOI:10.1111/petr.12291 · 1.63 Impact Factor
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    ABSTRACT: Descriptions of the sequelae of ABO-incompatible (ABOi) kidney transplantation are limited to single-center reports, which may lack power to detect important effects.
    Transplantation 07/2014; 98(1):54-65. DOI:10.1097/TP.0000000000000029 · 3.78 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 · 1.63 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 · 2.20 Impact Factor
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    ABSTRACT: Immune cells utilize the IDO enzymatic conversion of trp to kyn to determine T-cell activation vs. anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here, we analyzed the difference between urine IDO levels in stable post-transplant vs. healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one-time urine samples, from 34 well children at general pediatric clinics, to the first-month post-transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first-month post-kidney transplant (median 16.6, range 3.9-44.0) vs. healthy children (median 9.2, range 3.51-17.0; p = 0.0057 by nonparametric Mann-Whitney test). Higher urine IDO levels even with stable transplant suggest a continuous ongoing low-grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies.
    Pediatric Transplantation 02/2014; 18(3). DOI:10.1111/petr.12232 · 1.63 Impact Factor
  • Elizabeth I. Anyaegbu, Vikas R. Dharnidharka
    Pediatric Clinics of North America 01/2014; 61(1):131–151. · 2.20 Impact Factor
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    ABSTRACT: Background: Limited data are available on the outcome implications of prescription narcotics 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 01/2014; 99(1):1. DOI:10.1097/TP.0000000000000248 · 3.78 Impact Factor
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    ABSTRACT: Background: Limited data exist on medication use aside from immunosuppression among large samples of kidney transplant recipients. Methods: We examined a novel database wherein Organ Procurement and Transplantation Network (OPTN) registry data were linked to records from a US pharmaceutical claims clearinghouse (2005-2010 claims) to examine pharmaceutical care at the first transplant anniversary (n = 16,157). We quantified the use of the following medication types within ±60 days of the first-year OPTN report according to estimated glomerular filtration rate (eGFR): antihypertensives, lipid-lowering, bone and mineral, and anemia treatments. Adjusted associations of medication use with eGFR and other clinical factors were quantified by multivariate logistic regression. Results: Requirements for multiple antihypertensive agents rose with lower eGFR, with β-blockers comprising the most commonly used antihypertensive agent. The adjusted likelihood of vitamin D (adjusted odds ratio (aOR) 2.07, 95% CI 1.19-3.59) and especially erythrocyte-stimulating agents (aOR 19.94, 95% CI 7.01-56.00) rose in a graded manner to peak with eGFR <15 versus >90, whereas statin use was most common with eGFR 30-59 ml/min/1.73 m(2). Black race was independently associated with increased use of all classes of antihypertensives and vitamin D, but lower adjusted statin use. Rapamycin-based immunosuppression was associated with increased use of statins and erythrocyte-stimulating agents. Conclusions: Integrated registry and pharmacy fill data provide a novel tool for pharmacoepidemiologic investigations of delivered post-transplant care. Transplant recipients with reduced renal function have increased requirements for pharmaceutical care of comorbidities. Causes of racial variation in medication fills warrant further investigation. © 2013 S. Karger AG, Basel.
    American Journal of Nephrology 11/2013; 38(5):420-429. DOI:10.1159/000356092 · 2.65 Impact Factor
  • Vikas R Dharnidharka, Gregory A Storch, Daniel C Brennan
    New England Journal of Medicine 11/2013; 369(19):1858-9. DOI:10.1056/NEJMc1310006#SA2 · 54.42 Impact Factor

Publication Stats

3k Citations
602.89 Total Impact Points

Institutions

  • 2013–2015
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2001–2014
    • University of Florida
      • • Department of Pediatrics
      • • College of Medicine
      • • Department of Anesthesiology
      Gainesville, Florida, United States
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2002–2012
    • Florida Hospital for Children
      Orlando, Florida, United States
  • 2011
    • George Washington University
      Washington, Washington, D.C., United States
  • 2008–2011
    • Walter Reed National Military Medical Center
      • Department of Surgery
      Washington, Washington, D.C., United States
  • 2006
    • Yale University
      New Haven, Connecticut, United States
  • 1999–2004
    • Boston Children's Hospital
      • Division of Nephrology
      Boston, MA, United States
  • 2003
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 1998–2001
    • Harvard University
      Cambridge, Massachusetts, United States