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Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients. However, pediatric data remain scarce, and many of the treatments are extrapolated from the adult literature. Controversies exist about the type and duration of prophylactic therapies and the optimal dosing of antiviral agents. This review provides an up-to-date overview of treatment modalities used to prevent and treat CMV disease in solid organ transplant (SOT) recipients.

Background Understanding disparities in pediatric kidney transplants is important to provide equitable care. We compared transplant outcomes between English-speaking (ES) and interpreter-needing (IN) pediatric kidney transplant recipients. Methods Through retrospective review, primary kidney transplant recipients, 0-21 years transplanted between 2005 and 2019, were divided into ES and IN cohorts. Continuous and categorical variables were compared using Wilcoxon rank-sum, Welch two-sample t-test, and chi-squared analyses. Patient survival, graft survival, and rejection-free survival were evaluated using Kaplan-Meier methods and Cox regression. Days hospitalized were evaluated using negative binomial regression. Results Our sample included 211 ES and 37 IN transplant recipients. Compared with the ES, the IN cohort was older at transplant (14.56 vs. 11.03 years; p < 0.01), had more time between kidney failure and transplant (0.9 vs. 0.3 years; p < 0.01), and more often received deceased over living donor transplants (78.4% vs. 30.4%; p < 0.01). Multivariate Cox proportional-hazard models evaluating adjusted 5-year patient survival demonstrated decreased 5-year post-transplant survival in the IN cohort (aHR = 10.10, 95% CI: 1.5, 66.8; p = 0.02). We did not identify differences in 5-year death-censored graft survival (aHR = 0.57; 95% CI: 0.14, 2.4; p = 0.4) nor rejection-free survival (aHR = 0.8; 95% CI: 0.4, 1.5; p = 0.5). We found significantly fewer hospitalization events in the IN cohort during the first year post-transplant (aRR: 0.62; 95% CI: 0.4, 0.9; p = 0.01) but no difference 5-year post-transplant. The IN cohort had more missed outpatient appointments (10.4% vs. 2.8%; p = 0.03) and undetectable serum immunosuppressant levels (mean: 3.8% vs. 1.3%; p = 0.02) 5 years post-transplant. Conclusions Pediatric kidney transplant recipients requiring interpreter services for healthcare delivery demonstrate fewer post-transplant interactions with their healthcare team (fewer hospitalizations and more no-show visits) and lower 5-year patient survival compared with recipients not requiring interpreters. Graphical abstract, Author(s): Stephanie P. Kerkvliet [sup.1] , Carlos J. Perez Kerkvliet [sup.2] , Ziou Jiang [sup.3] , Michael Evans [sup.3] , Sarah J. Kizilbash [sup.4] Author Affiliations: (1) grid.17635.36, 0000000419368657, Department [...]

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used off-label in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Background: Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Methods: Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Results: Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2–11.2 years), and median time post‐transplant was 1.9 years (IQR 0.8–3.8 years). Median diarrheal duration was 16 days (IQR 6.0–41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty‐one (53%) patients developed acute kidney injury. Thirty‐five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: −17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Conclusion: Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment. [ABSTRACT FROM AUTHOR]

Background: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post‐transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. Methods: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. Results: Twenty‐six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1–10.3). EBV DNA load monitoring by qPCR was performed at 1–3 month intervals. EBV DNAemia onset occurred at a median of 73 days post‐transplant (IQR 52–307), followed by DNAemia peak at a median of 268 days (IQR 112–536). Rituximab was administered at a median of 9 days post peak (IQR 0–118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375–439) weekly for 1–4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow‐up (median 2094 days post‐transplant [IQR 1538–3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. Conclusions: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short‐term reduction in DNA load; however, recurrent DNAemia is common. [ABSTRACT FROM AUTHOR]

Background: The optimal age of kidney transplantation for infants and toddlers with kidney failure is unclear. We aimed to evaluate the patient survival associated with kidney transplantation before 2 years of age versus remaining on the waitlist until ≥2 years. Method: We used the Scientific Registry of Transplant Recipients to identify all children added to the deceased‐donor waitlist before 2 years of age between 1/1/2000 and 4/30/2020. For each case aged <2 years at transplant, we created a control group comprising all candidates on the waitlist on the case's transplant date. Patient survival was evaluated using sequential Cox regression. Dialysis‐free time was defined as graft survival time for cases and the sum of dialysis‐free time on the waitlist and graft survival time for controls. Results: We observed similar patient survival for posttransplant periods 0–3 and 4–12 months but higher survival for period >12 months for <2‐year decreased‐donor recipients (aHR: 0.32; 95% CI: 0.13–0.78; p =.01) compared with controls. Similarly, patient survival was higher for <2‐year living‐donor recipients for posttransplant period >12 months (aHR: 0.21; 95% CI: 0.06–0.73; p =.01). The 5‐year dialysis‐free survival was higher for <2‐year deceased‐ (difference: 0.59 years; 95% CI: 0.23–0.93) and living‐donor (difference: 1.84 years; 95% CI: 1.31–2.25) recipients. Conclusion: Kidney transplantation in children <2 years of age is associated with improved patient survival and reduced dialysis exposure compared with remaining on the waitlist until ≥2 years. [ABSTRACT FROM AUTHOR]

Background: Pediatric data on risk factors and the clinical course of BK DNAemia are limited. We aimed to determine the effects of BK DNAemia on transplant outcomes and delineate the safety and efficacy of various treatment approaches. Methods: This retrospective‐cohort study included 161 transplants (age ≤ 21 years) performed at a single center between 1/1/2012 and 1/1/2020. We used Cox proportional models to evaluate the effects of BK DNAemia on patient survival (PS), graft survival (GS), and acute rejection (AR), using BK as a time‐dependent covariate. We also assessed the effects of pharmacological intervention on BK DNAemia duration using intervention as a time‐dependent covariate. Results: BK‐free survival was 69.1% at 1‐year and 54.6% at 3‐year posttransplant. After multivariate adjustment, BK DNAemia was associated with young age at transplant (aHR, age 5–<12 vs. ≥12 (years): 2.5 (1.4–4.5); p =.001) and steroid‐based immunosuppression (IS) (aHR: 2.2 [1.1–4.5]; p =.03). We found no effect of DNAemia on AR (aHR: 1.25; p =.5), PS (aHR: 2.85; p =.22), and GS (aHR: 0.56; p =.41). Of 70 patients with DNAemia, 22 (31.4%) received no treatment, 20 (28.6%) received IS reduction alone, and 28 patients (40%) received treatment with at least one pharmacological agent (leflunomide, IVIG, ciprofloxacin, cidofovir). Sixty‐three patients (90%) cleared DNAemia with median time to resolution of 2.4 months (IQR:1.4–5.6). We found no significant effect of BK‐directed pharmacological treatment on time to resolution (aHR: 0.64;p =.13). BK‐directed agents were well tolerated. Conclusions: BK DNAemia is associated with a young age at transplant and steroid‐based maintenance IS. We found no effect of BK DNAemia on AR, GS, and PS. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids have been an integral part of maintenance immunosuppression for pediatric kidney transplantation. However, prolonged steroid therapy is associated with significant toxicities resulting in several SW/avoidance strategies in recent years. Method/Objective: This comprehensive review aims to discuss steroid‐related toxicities and the safety, efficacy, and benefit of steroid avoidance/withdrawal immunosuppression in pediatric kidney transplant recipients. Results: Initial studies of SW/avoidance conducted in the setting of CSA and AZA showed an increased incidence of AR but no increase in graft loss or mortality with SW/avoidance maintenance immunosuppression. Studies performed under modern immunosuppression (induction therapy, Tac, and MMF) show no significant increase in AR or graft loss with SW/avoidance immunosuppression. Furthermore, SW/avoidance immunosuppression is associated with significant improvement in growth, BMI, BP control, and lipid profile in pediatric kidney transplant recipients. Despite these data, SW/avoidance remains controversial, and only 40% of pediatric kidney transplant recipients in the United States are currently on SW/avoidance maintenance immunosuppression. Conclusion: SW/avoidance maintenance immunosuppression is safe and associated with fewer side effects compared with steroid‐inclusive maintenance immunosuppression in pediatric kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking. Method: We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank‐sum test, Fisher's exact test, and Kaplan‐Meier methods to compare outcomes. Results: Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P =.049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P =.06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P =.02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P =.05). We observed no difference in 5‐year graft survival between the groups (95.0% vs 91.7%, P =.73). Patient survival was 100% in both groups over a median follow‐up of 44.2 months. Surgical complications were similar between the groups. Conclusion: Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes. [ABSTRACT FROM AUTHOR]