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  1. Article ; Online: Response to: Focal segmental glomerulosclerosis recurrence in a young adult with kidney transplant after mRNA COVID-19 vaccination.

    Crane, Clarkson / Ingulli, Elizabeth

    Pediatric nephrology (Berlin, Germany)

    2022  Volume 37, Issue 9, Page(s) 2219

    MeSH term(s) COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Glomerulosclerosis, Focal Segmental/therapy ; Humans ; Kidney Transplantation/adverse effects ; RNA, Messenger ; Recurrence ; Vaccination ; Young Adult
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger
    Language English
    Publishing date 2022-05-13
    Publishing country Germany
    Document type Letter ; Comment
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05601-6
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  2. Article: Prevention, diagnosis, and management of donor derived infections in pediatric kidney transplant recipients.

    Epperson, Katrina / Crane, Clarkson / Ingulli, Elizabeth

    Frontiers in pediatrics

    2023  Volume 11, Page(s) 1167069

    Abstract: Donor derived infections (DDIs) in pediatric kidney transplant recipients remain challenging to diagnose and can result in serious morbidity and mortality. This review summarizes the current guidelines and recommendations for prevention, diagnosis, and ... ...

    Abstract Donor derived infections (DDIs) in pediatric kidney transplant recipients remain challenging to diagnose and can result in serious morbidity and mortality. This review summarizes the current guidelines and recommendations for prevention, diagnosis, and treatment of unexpected DDIs in pediatric kidney transplant recipients. We provide a contemporary overview of DDI terminology, surveillance, epidemiology, and recommended approaches for assessing these rare events with an emphasis on the pediatric recipient. To address prevention and risk mitigation, important aspects of donor and pediatric candidate evaluations are reviewed, including current Organ Procurement and Transplantation Network (OPTN) and American Society of Transplantation (AST) recommendations. Common unexpected DDI encountered by pediatric transplant teams including multi-drug resistant organisms, tuberculosis, syphilis, West Nile Virus, toxoplasmosis, Chagas disease, strongyloidiasis, candidiasis, histoplasmosis, coccidioidomycosis, and emerging infections such as COVID-19 are discussed in detail. Finally, we consider the general challenges with management of DDIs and share our experience with a novel application of next generation sequencing (NGS) of microbial cell-free DNA that will likely define a future direction in this field.
    Language English
    Publishing date 2023-04-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2023.1167069
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  3. Article ; Online: Rates of idiopathic childhood nephrotic syndrome relapse are lower during the COVID-19 pandemic.

    Crane, Clarkson / Bakhoum, Christine / Ingulli, Elizabeth

    Pediatric nephrology (Berlin, Germany)

    2022  Volume 37, Issue 11, Page(s) 2679–2685

    Abstract: Background: Infections are thought to be primarily responsible for triggering relapse in children with steroid-sensitive nephrotic syndrome (NS). The COVID-19 pandemic promoted physical distancing, facial mask wearing, and greater attention to infection- ...

    Abstract Background: Infections are thought to be primarily responsible for triggering relapse in children with steroid-sensitive nephrotic syndrome (NS). The COVID-19 pandemic promoted physical distancing, facial mask wearing, and greater attention to infection-prevention measures resulting in decreased transmission of infections. We hypothesized there would also be a decreased rate of NS relapse during this period.
    Methods: We conducted a single-center retrospective chart review of children with steroid-sensitive NS. Demographics, rate of relapses, and rate of hospitalizations were collected for a baseline pre-pandemic period (BPP) and for the social distancing period during the pandemic (SDP).
    Results: One hundred twenty-two children with primary steroid-sensitive NS were identified and 109 were followed for the duration of the study period. The paired rate of relapse per subject per year was significantly lower during the SDP (0.6 relapses per subject per year ± 1 SD) compared to the BPP (1.0 relapses per subject per year ± 0.9 SD), P < 0.01. A subgroup of 32 subjects who were newly diagnosed with NS during the BPP similarly had significantly fewer relapses during the SDP (0.8 ± 1 SD) than during the BPP (1.4 ± 1 SD), P = 0.01.
    Conclusions: Our results support the hypothesis of lower rates of NS relapse and hospitalizations during social distancing for all subjects in our cohort and a subgroup of those newly diagnosed. Lower relapse rates were likely attributable to decreased transmission of infections and greater attention to infection prevention. A higher resolution version of the Graphical abstract is available as Supplementary information.
    MeSH term(s) COVID-19/epidemiology ; Child ; Chronic Disease ; Humans ; Nephrosis, Lipoid ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/epidemiology ; Pandemics/prevention & control ; Recurrence ; Retrospective Studies ; Steroids
    Chemical Substances Steroids
    Language English
    Publishing date 2022-02-24
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05483-8
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  4. Article ; Online: Revision ureteroneocystostomy in pediatric renal transplant patients for symptomatic vesicoureteral reflux and its effect on recurrent hospitalizations.

    Campbell, Paul / Ingulli, Elizabeth / Christman, Matthew / Marietti, Sarah

    Journal of pediatric urology

    2022  Volume 18, Issue 5, Page(s) 675.e1–675.e7

    Abstract: Background: Nearly 13,000 pediatric renal transplantations have been performed since 1987 with improving overall mortality and morbidity; however, graft infection remains a significant post-transplant concern. Recurrent urinary tract infections in ... ...

    Abstract Background: Nearly 13,000 pediatric renal transplantations have been performed since 1987 with improving overall mortality and morbidity; however, graft infection remains a significant post-transplant concern. Recurrent urinary tract infections in pediatric patients with vesicoureteral reflux into their renal transplant can result in graft dysfunction, increased hospital cost, and impaired social and cognitive development due to time spent hospitalized.
    Objective: To evaluate the effect of revision ureteroneocystostomy on pediatric renal transplant patients with symptomatic vesicoureteral reflux in reducing hospitalizations and recurrent urinary tract infections.
    Methods: We retrospectively reviewed pediatric patients from 2002 through 2021 who underwent renal transplantation and required revision ureteroneocystostomy due to symptomatic vesicoureteral reflux. We analyzed the differences in days hospitalized, days hospitalized due to urinary tract infection, and treated urinary tract infections prior to and after revision ureteroneocystostomy.
    Results: Ten patients requiring revision ureteroneocystostomy secondary to symptomatic vesicoureteral reflux were identified. There was no difference in the observation time between transplant to revision, and revision to last follow up (2.3 years (IQR 1.3-6.5) vs 1.7 years (IQR 1-6.7), p = 0.4446). Overall, there was a significant decrease in the total number of hospitalization days (21.5 days (IQR 3-43) vs 5.5 days (IQR 0-9), p = 0.006), total number of hospitalization days related to urinary tract infection (14.5 days (IQR 3-28) vs 0 days (IQR 0-3), p = 0.008) and treated urinary tract infections (3.5 (IQR 3-6) vs 1 (IQR 0-2), p = 0.019) following revision ureteroneocystostomy. The rate of hospitalization days for urinary tract infection was also significantly decreased following revision ureteroneocystostomy (7.15 per/year (IQR 0.4-11.75) vs 0 per/year (IQR 0-0.8), p = 0.008).
    Discussion: Symptomatic vesicoureteral reflux in pediatric transplant patients is difficult to manage and some patients will ultimately require surgery. There have been previous studies on the success of revision ureteroneocystostomy in treating reflux but no data on the reduction in hospitalizations associated with recurrent infections following the procedure. Limitations of this study are the small cohort size, retrospective nature, multi-surgeon study, and inherent selection bias due to evaluation of only surgical patients.
    Conclusion: Revision ureteroneocystostomy can limit the negative consequences of recurrent graft infections with reduction in hospitalization days and improved hospitalization rates due to urinary tract infections. The reduction in hospitalizations can greatly improve the cost of care along with quality of life for transplant patients and should be strongly considered in children with symptomatic vesicoureteral reflux who have failed conservative therapy.
    Language English
    Publishing date 2022-09-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2237683-5
    ISSN 1873-4898 ; 1477-5131
    ISSN (online) 1873-4898
    ISSN 1477-5131
    DOI 10.1016/j.jpurol.2022.09.006
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  5. Article ; Online: Antibody response to 2- and 3-dose SARS-CoV-2 mRNA vaccination in pediatric and adolescent kidney transplant recipients.

    Crane, Clarkson / Phebus, Erin / Ingulli, Elizabeth

    Pediatric nephrology (Berlin, Germany)

    2022  Volume 38, Issue 2, Page(s) 611–614

    Abstract: Background: Additional "booster" doses of mRNA SARS-CoV-2 vaccines have become standard of care for immunosuppressed patients, including kidney transplant recipients (KTR). While these additional doses have been shown to be efficacious in the adult KTR ... ...

    Abstract Background: Additional "booster" doses of mRNA SARS-CoV-2 vaccines have become standard of care for immunosuppressed patients, including kidney transplant recipients (KTR). While these additional doses have been shown to be efficacious in the adult KTR population, there is paucity of data for pediatric and adolescent KTR.
    Methods: We conducted a retrospective single-center observational study to determine the proportion of pediatric and adolescent KTR who seroconverted following two- and three-dose regimens of an mRNA SARS-CoV-2 vaccine series.
    Results: Forty-three pediatric and adolescent KTR at our center received at least two doses of an mRNA SARS-CoV-2 vaccine. Seroconversion was noted in 56% of those who received a 2-dose series and increased to 85% in those who received a third dose. In the 16 patients who did not seroconvert after a two-dose series, 12 (75%) seroconverted following the third dose. No serious adverse effects of immunization were noted.
    Conclusions: Our results demonstrate that additional SARS-CoV-2 vaccine doses are not only safe and efficacious in pediatric and adolescent KTR, but may be necessary to optimize antibody response. A higher resolution version of the Graphical abstract is available as Supplementary information.
    MeSH term(s) Adult ; Humans ; Adolescent ; Child ; Antibody Formation ; COVID-19 Vaccines ; SARS-CoV-2 ; Kidney Transplantation ; Retrospective Studies ; COVID-19 ; Vaccination ; RNA, Messenger ; Transplant Recipients ; Antibodies, Viral
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger ; Antibodies, Viral
    Language English
    Publishing date 2022-06-27
    Publishing country Germany
    Document type Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05661-8
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  6. Article ; Online: Balancing B cell responses to the allograft: implications for vaccination.

    Crane, Clarkson / Loop, Lauren / Anterasian, Christine / Geng, Bob / Ingulli, Elizabeth

    Frontiers in immunology

    2022  Volume 13, Page(s) 948379

    Abstract: Balancing enough immunosuppression to prevent allograft rejection and yet maintaining an intact immune system to respond to vaccinations, eliminate invading pathogens or cancer cells is an ongoing challenge to transplant physicians. Antibody mediated ... ...

    Abstract Balancing enough immunosuppression to prevent allograft rejection and yet maintaining an intact immune system to respond to vaccinations, eliminate invading pathogens or cancer cells is an ongoing challenge to transplant physicians. Antibody mediated allograft rejection remains problematic in kidney transplantation and is the most common cause of graft loss despite current immunosuppressive therapies. The goal of immunosuppressive therapies is to prevent graft rejection; however, they prevent optimal vaccine responses as well. At the center of acute and chronic antibody mediated rejection and vaccine responses is the B lymphocyte. This review will highlight the role of B cells in alloimmune responses including the dependency on T cells for antibody production. We will discuss the need to improve vaccination rates in transplant recipients and present data on B cell populations and SARS-CoV-2 vaccine response rates in pediatric kidney transplant recipients.
    MeSH term(s) Allografts ; Antibodies ; B-Lymphocytes ; COVID-19/prevention & control ; COVID-19 Vaccines ; Child ; Humans ; SARS-CoV-2 ; T-Lymphocytes ; Vaccination
    Chemical Substances Antibodies ; COVID-19 Vaccines
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.948379
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  7. Article ; Online: An Unexpected Kidney Biopsy Finding in a Patient with Newly Diagnosed SLE.

    Crane, Clarkson R / Shayan, Katayoon / Ingulli, Elizabeth

    Kidney360

    2021  Volume 2, Issue 9, Page(s) 1544–1545

    MeSH term(s) Biopsy ; Humans ; Kidney/diagnostic imaging ; Lupus Erythematosus, Systemic/complications ; Nephritis, Interstitial/diagnosis
    Language English
    Publishing date 2021-09-30
    Publishing country United States
    Document type Journal Article
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0003192021
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  8. Article ; Online: Immunologic response of mRNA SARS-CoV-2 vaccination in adolescent kidney transplant recipients.

    Crane, Clarkson / Phebus, Erin / Ingulli, Elizabeth

    Pediatric nephrology (Berlin, Germany)

    2021  Volume 37, Issue 2, Page(s) 449–453

    Abstract: Background: In the general population, mRNA SARS-CoV-2 vaccines are highly efficacious. Early reports suggest a diminished antibody response in immunosuppressed adult solid organ transplant (SOT) patients, but this has not been reported in pediatrics.!## ...

    Abstract Background: In the general population, mRNA SARS-CoV-2 vaccines are highly efficacious. Early reports suggest a diminished antibody response in immunosuppressed adult solid organ transplant (SOT) patients, but this has not been reported in pediatrics.
    Methods: Adolescent kidney transplant recipients (KTR) at our center who received both doses of an mRNA SARS-CoV-2 vaccine had SARS-CoV-2 spike (S) protein antibody presence evaluated 4-8 weeks after their second dose of the vaccine as part of routine clinical care.
    Results: Thirteen of 25 fully vaccinated patients (52%) had a positive spike antibody. Median age of participants was 19 years old (IQR 18-20) and the median time from transplant was 5 years (IQR 4-9 years). KTR were treated with an immunosuppression regimen including a calcineurin inhibitor, corticosteroid, and antimetabolite (9 with mycophenolate, 3 with azathioprine, and 1 without an antimetabolite due to viremia). Of those who had an antibody response, fewer had a mycophenolate-containing immunosuppressant regimen than non-responders. There was a trend toward better vaccine response and higher anti-S antibody titers at lower doses of mycophenolate. Three patients with prior COVID-19 infection all had a positive antibody response.
    Conclusion: Our results suggest vaccine response in adolescent KRT is lower than that of the general population, but similar to that previously described in adult SOT patients and slightly better than that seen in adult KTR. This data demonstrates vaccination is safe and supports immunizing KTR who remain hesitant. Future studies should focus on better understanding of the cellular immune response to vaccination and strategies to enhance vaccine immunogenicity in pediatric SOT patients.
    MeSH term(s) Adolescent ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/complications ; COVID-19/immunology ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/pharmacology ; Child ; Female ; Humans ; Immunogenicity, Vaccine ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation ; Male ; RNA, Messenger ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/immunology ; Transplant Recipients
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; Immunosuppressive Agents ; RNA, Messenger ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2021-09-15
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-021-05256-9
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  9. Article ; Online: Nephrectomy improves both antihypertensive requirement and left ventricular mass for pediatric renal hypertension.

    Cornwell, Laura B / Rojas, Andres Moreno / Ogundipe, Eniola / Golding, Ian / Marietti, Sarah / Ingulli, Elizabeth G

    Pediatric nephrology (Berlin, Germany)

    2023  Volume 38, Issue 7, Page(s) 2147–2153

    Abstract: Background: Renal hypertension causes left ventricular (LV) hypertrophy leading to cardiomyopathy. Nephrectomy has been utilized to improve blood pressure and prepare for kidney transplantation in the pediatric population. We sought to investigate ... ...

    Abstract Background: Renal hypertension causes left ventricular (LV) hypertrophy leading to cardiomyopathy. Nephrectomy has been utilized to improve blood pressure and prepare for kidney transplantation in the pediatric population. We sought to investigate antihypertensive medication (AHM) requirement and LV mass in patients undergoing nephrectomy with renal hypertension.
    Methods: We performed a single institution retrospective review from 2009 to 2021 of children who have undergone nephrectomy for hypertension. Primary outcome was decrease in number of AHM. Secondary outcomes included change in LV mass and elimination of AHM. LV mass was measured using echocardiogram area-length and linear measurements. Non-parametric analyses were utilized to assess significance.
    Results: Thirty-one patients underwent nephrectomy. Median age was 12.5 years (0.8-19 years). Median of 3 AHM (range 1-5 medications) were used pre-operatively and patients had been managed for median 2.5 years. Twenty-nine had preoperative echocardiogram. Forty-eight percent of patients had LVH at nephrectomy. Median AHM after surgery was 1 (range 0-4 medications) at 30 days and 12 months, (p < 0.001). By 12 months after nephrectomy, 79.2% of patients had decreased the number of AHM. Eight (26%) patients were on no AHM 30 days after surgery, and 13 (43%) at 12 months. Systemic vascular disease and multicystic dysplastic kidney were the only factors associated with lack of improvement in AHM (p = 0.040). Fourteen patients had pre- and post-operative echocardiogram and 11 (79%) had improvement in LV mass (p = 0.016, 0.035).
    Conclusions: Nephrectomy is effective in improving LV mass and reducing AHM for children with renal hypertension. Improvement is less likely in patients with systemic vascular disease and multicystic dysplastic kidneys. A higher resolution version of the Graphical abstract is available as Supplementary information.
    MeSH term(s) Humans ; Child ; Antihypertensive Agents/therapeutic use ; Hypertension, Renal/drug therapy ; Nephrectomy/adverse effects ; Hypertension/complications ; Hypertension/drug therapy ; Blood Pressure ; Multicystic Dysplastic Kidney/complications ; Hypertrophy, Left Ventricular/etiology
    Chemical Substances Antihypertensive Agents
    Language English
    Publishing date 2023-01-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05854-1
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  10. Article ; Online: Mechanism of cellular rejection in transplantation.

    Ingulli, Elizabeth

    Pediatric nephrology (Berlin, Germany)

    2011  Volume 25, Issue 1, Page(s) 61–74

    Abstract: The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the ... ...

    Abstract The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance.
    MeSH term(s) Adolescent ; Animals ; Child ; Disease Models, Animal ; Graft Rejection/immunology ; Graft Survival/immunology ; Humans ; Organ Transplantation ; T-Lymphocytes, Regulatory/immunology ; Transplantation, Homologous
    Language English
    Publishing date 2011-06-01
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-008-1020-x
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