Vikas R Dharnidharka

Driscoll Children's Hospital, Corpus Christi, Texas, United States

Are you Vikas R Dharnidharka?

Claim your profile

Publications (97)489.17 Total impact

  • Jodi M Smith, Vikas R Dharnidharka
    [Show abstract] [Hide abstract]
    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 (Berlin, Germany). 08/2014;
  • Vikas R Dharnidharka, Paolo Fiorina, William E Harmon
    New England Journal of Medicine 08/2014; 371(6):549-58. · 54.42 Impact Factor
  • Vikas R. Dharnidharka, Laura E. Hesemann
    Pediatric Transplantation 08/2014; 18(5). · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    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. · 3.78 Impact Factor
  • Atul Poudel, Judy Lew, William Slayton, Vikas R Dharnidharka
    [Show abstract] [Hide abstract]
    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. · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 1.50 Impact Factor
  • Elizabeth I Anyaegbu, Vikas R Dharnidharka
    [Show abstract] [Hide abstract]
    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. · 1.78 Impact Factor
  • Elizabeth I. Anyaegbu, Vikas R. Dharnidharka
    Pediatric Clinics of North America 01/2014; 61(1):131–151. · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    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. · 2.62 Impact Factor
  • Vikas R Dharnidharka, Gregory A Storch, Daniel C Brennan
    New England Journal of Medicine 11/2013; 369(19):1858-9. · 54.42 Impact Factor
  • Vikas R Dharnidharka, Nazia Kulsum-Mecci
    Pediatric Transplantation 09/2013; · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.
    Pediatric Radiology 09/2013; · 1.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively. We prospectively tested 217 blood and 167 urine serial samples, collected monthly for 12 months after transplantation from 29 consecutive children receiving a kidney transplant. The indoleamine 2,3-dioxygenase activity was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with AR, MIE, or stable group (no events) in the next 30 days. Using absolute cutoffs and allocating to samples to AR, MIE, or stable group, mean serum kyn/trp ratios were significantly elevated in the group that experienced AR (P=0.0007). Similarly, peripheral blood CD4-ATP levels were significantly lower in the group experiencing MIE (P=0.0351). Urine kyn/trp ratios and blood tacrolimus levels were not different between AR and stable groups. Within-subject analyses, accounting for repeated measures in subjects, also showed that, over time, serum kyn/trp ratios were higher before AR (P=0.031) and blood CD4-ATP levels were lower before MIE (P=0.008). These results from our pilot discovery group suggest that a panel of biomarkers together can predict overimmunosuppression or underimmunosuppression. Further independent validation in a multicenter cohort is suggested.
    Transplantation 07/2013; · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.
    Journal of the American Society of Nephrology 02/2013; · 8.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: On October 2005, the Organ Procurement and Transplant Network implemented a new allocation policy for kidney transplants (KTX) from deceased donors (DD) ages <35 years to increase an access to transplantation from young donors for pediatric (ages <18 years) recipients, which is known as Share-35 (S35). However, many of these kidneys were allocated to adult recipients. The intent of this study was to analyze the graft outcomes from S35 kidneys in pediatric and adult recipients, stratified further by recipient age, to assess if recipient age affects the outcome from these presumably ideal kidneys. METHODS: The Organ Procurement and Transplant Network database from October 2005 to November 2010 involving 18,461 S35-KTX was used to calculate cumulative graft survival (CGS), death-censored graft survival, and patient survival using Kaplan-Meier estimates. The differences between survival curves were tested for significance by log-rank method after adjusting for various donor, recipient, and transplant-associated variables. RESULTS: With S35 implementation, children received a higher proportion of DD ages <35 years. Within the pediatric age group, adolescents (ages 13-17 years) had the worst CGS. Among adults, the highest CGS was obtained in middle-aged adults, whereas young adults (ages 18-25 years) showed worse CGS. CGS in young children (ages <12 years) was comparable with those in middle-aged adults. In older adults (ages >55 years), CGS was lowered by higher patient death rates. CONCLUSIONS: Recipient age affects allograft survival from high-quality young DD kidneys, such as S35 kidneys. Best survival occurs in middle-aged adults and in children ages <12 years, whereas adolescents and young adults do not derive an optimal benefit.
    Transplantation 11/2012; · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.
    American Journal of Transplantation 10/2012; 12(10):2710-2718. · 6.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: : Posttransplant lymphoproliferative disorders (PTLDs) are associated with significant morbidity and mortality among solid-organ transplant patients, but approaches to diagnosis and management vary considerably. An international multidisciplinary panel evaluated current understanding of risk factors and classification systems and developed recommendations to aid in PTLD prevention. We considered evidence on PTLD risk factors including Epstein-Barr virus serostatus and immunosuppression and identified knowledge gaps for future research. Recommendations address prophylactic and preemptive strategies to minimize PTLD development, including modulation of immunosuppression and antiviral drug regimens. Finally, new classification criteria were outlined that may help facilitate standardized reporting and improve our understanding of PTLD.
    Transplantation 09/2012; 94(8):784-793. · 3.78 Impact Factor
  • Eihab Al Khasawneh, Carlos E Araya, Vikas R Dharnidharka
    [Show abstract] [Hide abstract]
    ABSTRACT: Al Khasawneh E, Araya CE, Dharnidharka VR. Missed viral surveillance testing visits associate with full blown viral diseases in children receiving kidney transplants. Abstract:  Surveillance testing for major viral infections such as CMV, EBV, and BKV early in their natural history course may allow for early intervention and prevention of FBVD, but the testing is expensive and optimal interval/frequency are uncertain. At our center we initiated routine monthly viral surveillance for CMV, EBV, and BKV in July 2008 for the first 12 months post-transplant. Here, we retrospectively analyzed for outcome of the patients who missed three or more surveillance tests in the first 12 months post-transplant vs. those who did not. Of 21 patients, five missed three or more surveillance tests. Two of those five developed FBVD (one BKV nephropathy and one EBV-PTLD). None of the 16 patients with more regular surveillance testing developed FBVD. The incidence of viral replication was similar in both groups. The odds ratio for FBVD if viral surveillance tests were missed was 23.57 (p-value of 0.047). In this small group of contemporaneous patients on identical immunosuppression, those patients who missed regular viral surveillance were more likely to develop FBVD. Prospective randomized trials to confirm the benefit of regular viral testing are recommended.
    Pediatric Transplantation 08/2012; · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.
    American Journal of Transplantation 06/2012; 12(10):2719-2729. · 6.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.
    American Journal of Transplantation 06/2012; 12(10):2730-2743. · 6.19 Impact Factor

Publication Stats

2k Citations
489.17 Total Impact Points

Institutions

  • 2014
    • Driscoll Children's Hospital
      Corpus Christi, Texas, United States
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2001–2014
    • University of Florida
      • • College of Medicine
      • • Department of Pediatrics
      Gainesville, Florida, United States
  • 2002–2012
    • Florida Hospital for Children
      Orlando, Florida, United States
  • 2011
    • Swedish Medical Center Seattle
      Seattle, Washington, United States
  • 2008–2011
    • Walter Reed National Military Medical Center
      Washington, Washington, D.C., United States
  • 2007
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Angeles, CA, United States
  • 2006
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 1998–2001
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States