Pediatric Kidney Transplant Patients Research Articles

Navigating normalcy: designing personal health visualizations for pediatric kidney transplant recipients and caregivers.

Patients with chronic illnesses, including kidney disease, consider their sense of normalcy when evaluating their health. Although this concept is a key indicator of their self-determined well-being, they struggle to understand if their experience is typical. To address this challenge, we set out to explore how to design personal health visualizations that aid participants in better understanding their experiences post-transplant, identifying barriers to normalcy, and achieving their desired medical outcomes. Pediatric kidney transplant patients and their caregivers participated in three asynchronous design sessions involving sharing experiences, presenting symbolic objects, and providing feedback on visualizations to understand their perceptions of normalcy post-transplant. Data analysis of design session 1 and 2 comprised deductive and inductive analysis. We used affinity diagramming to identify thematic areas about participants' transplant experiences. Comprehension of design session three normalcy visualizations was also evaluated. Participants effectively engaged in the design sessions, revealing diverse perspectives on their experiences. We found there is a significant need for visualizations that depict normalcy to better inform patients and caregivers about their health. Normalcy Visualizations should incorporate three key design principles: personal values, facilitating peer and self-comparison, and seamlessly communicating abstract concepts to help youth kidney transplant recipients comprehend and contextualize if their transplant experience is normal and what normalcy means to them. By incorporating holistic aspects of patients' and caregivers' lives into personal health visualizations, they can be cognizant of their progress to normalcy and empowered to make decisions that help them feel normal.

The association of Torque Teno viral load with CMV and BKV infection in pediatric and adolescent kidney transplant patients.

Background: Long-term allograft and patient survival after kidney transplantation (KTX) depends on the balance between over- and under-immunosuppression (IS). High levels of IS predispose to opportunistic infections. Plasma load of Torque Teno Virus (TTV), a non-pathogenic highly prevalent Annellovirus, is associated with its hosts immune status, especially after solid organ transplantation. Objectives: To investigate the association of plasma TTV load and opportunistic viral infections after pediatric KTX. Study design: This retrospective study includes all pediatric KTX patients followed at the Medical University of Vienna 2014–2020. PCR for Cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), and TTV was performed every 4–8 weeks at routine follow-up visits. Results: 71 pediatric KTX patients were followed with TTV measurements for a median of 2.7 years. TTV plasma load was associated with CMV DNAemia at the next visit with an OR of 2.37 (95 % CI 1.15–4.87; p = 0.03) after adjustment for time after KTX and recipient age. For a cut-off of 7.68 log10 c/mL TTV a sensitivity of 100 %, a specificity of 61 %, a NPV 100 %, and a PPV of 46 % to detect CMV DNAemia at the next visit was calculated. TTV plasma loads were also associated with BKV DNAuria and BKV DNAemia at the next visit, but not with EBV DNAemia. Conclusions: This is the first study to analyse associations between TTV plasma loads and opportunistic viral infections in pediatric KTX. We were able to present a TTV cut-off for the prediction of clinically relevant CMV DNAemia that might be useful in clinical care.

Kidney transplant to vesicostomy: A safe strategy for children with end stage renal disease and lower urinary tract anomalies

Resolution of underlying urinary tract anomalies prior to kidney transplantation in patients with end stage renal disease (ESRD) secondary to uropathy, has been historically supported under the argument that this would help prevent infectious complications and graft loss. We propose to perform earlier kidney transplantation with a transient vesicostomy, deferring resolution of the uropathy to the post-transplantation period. The aim of this study was to evaluate the outcomes of kidney transplantation in children with a vesicostomy. A retrospective, multicenter study was performed including all patients under 18 years of age who underwent kidney transplantation with a vesicostomy, between January 2005 and December 2020 and had at least one year of follow up. Data related with the indication and timing of vesicostomy, time until transplantation, post-transplantation complications, urinary tract infections (UTI) and graft survival rate were collected. Of the 758 transplantations performed in the study period, 16 patients met the inclusion criteria. Mean age at transplantation was 58 months (range 20-151), and mean weight was 13.5Kg (range 8.4-20). Mean time from vesicostomy to kidney transplantation was 30 months (range 0-70). There were 2 (12.5%) ureteral complications that required reoperation. Eighteen episodes of UTI were identified in 8 patients (50%), accounting for 0.4 UTIs per patient-year of follow-up. UTIs did not lead to graft loss in any of the cases. Urinary tract reconstruction was performed in 5 patients (31.3%) at an interval of 1-91 months post-transplantation. After a mean follow-up of 44.8 months (range 13-200) from transplantation, patients with vesicostomy had a mean creatinine clearance of 86.6ml/min/1.73m2, with a mean serum creatinine level of 0.6mg/dl. Graft survival rate was 100%. Early kidney transplantation into a vesicostomy permits a resolution of the ESRD, avoiding deleterious effects related to dialysis. With a low rate of UTIs, we found no graft loss due to infectious complications. This strategy permits careful planning and better timing for the urinary tract reconstruction without delaying kidney transplantation. Kidney transplantation in pediatric patients with vesicostomy seems to be a safe and effective strategy. UTI rate was similar to that reported in the literature of patients with corrected urinary anomalies undergoing kidney transplantation without urinary diversion.

Follow-up biopsies identify high rates of persistent rejection inpediatric kidney transplant recipients after treatment of T cell-mediated rejection.

Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients. Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available. Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (≥i1t1 and <i2t2) in 59% and Banff ≥1A (≥i2t2) in 41%. Acute rejection was persistent in 32 (55%) of FUB. Borderline rejection had higher rates of complete resolution of rejection compared to grade ≥1A (53% vs. 33%, p = .033). Incomplete resolution of rejection on FUB was re-treated in 25 (78%) of cases. Change in eGFR from index to FUB did not differ between those with complete and incomplete resolution (5.7 ± 32.2 vs. 13.1 ± 51.3, p = .28) and was not a sensitive marker of identifying persistent rejection. FUB were effective at detecting persistent rejection, which was common among pediatric transplant patients after standard TCMR treatment. Until more effective rejection treatments or sensitive biomarkers are available, FUB may be effectively utilized to identify patients with ongoing rejection who would benefit from further treatment.

Utilization of donor-derived Cell-Free DNA in pediatric kidney transplant recipients: A single center study.

Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p = .0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34-3.12] vs. 0.24% [0.08-0.78], p < .0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27-1.8] vs. 0.26% [0.08-2], p = .0437). Median change in dd-cfDNA after rejection treatment was -0.57% (-1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0-19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p = .2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.

Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.

Mycophenolic acid (MPA) is an immunosuppressant commonly prescribed in pediatric kidney transplantation to prevent graft rejection. Large variabilities in MPA plasma exposures have been observed in this population, which could result in severe adverse effects. The majority of the MPA pharmacokinetic data have been reported in adult populations, whereas information in pediatric patients is still very limited. The objective of this study was to establish a novel, nonlinear mixed-effects model for MPA and investigate the clinical variables affecting MPA population pharmacokinetics in pediatric kidney transplant recipients. Data were collected retrospectively from pediatric kidney transplant patients (≤ 18 years when MPA concentrations were initially collected; on oral administration of mycophenolate mofetil) in Calgary, Alberta, Canada. Nonlinear mixed-effect modeling was conducted using stochastic approximation expectation-maximization in Monolix 2021R2 (Lixoft SAS, France) to determine population pharmacokinetic estimates, interindividual variabilities, and interoccasional variabilities. Covariate models were constructed using the Model Proposal function in Monolix in conjunction with a systematic stepwise inclusion/elimination protocol. The best model was selected based on objective function values, relative standard errors, goodness-of-fit plots, prediction-corrected visual predictive checks, and numerical predictive checks. A total of 50 pediatric kidney transplant patients (25 female) with 219 MPA plasma concentration-time profiles were included. The average age (± standard deviation) and posttransplant time for the sample population were 12.8 ± 4.8 years and 762 ± 1160 days, respectively. The majority of study subjects (i.e., > 85% based on all occasions) were co-administered tacrolimus. A two-compartment, first-order absorption with lag time and linear elimination structural model with lognormal distributed proportional residual errors best described the MPA concentration-time data. The absorption rate constant (2.52 h-1 or 0.042 min-1), lag time (0.166 h or 9.96 min), volumes of distributions of the central (22.8 L) and peripheral (216 L) compartments, and intercompartment clearance (17.6 Lh-1 or 0.293 Lmin-1) were consistent with literature values; whereas total MPA clearance (0.72 Lh-1 or 0.012 Lmin-1) was relatively reduced, likely due to the general lack of cyclosporine interactions and the stabilized graft functions from significantly longer posttransplant time in our sample population. Of the clinical variables tested, only estimated glomerular filtration rate (eGFR) was identified a significant covariate affecting total MPA clearance with a positive, exponential relationship. The final population pharmacokinetic model was successfully evaluated/validated using a variety of complementary methods. We have successfully constructed and validated a novel population pharmacokinetic model of MPA in pediatric kidney transplant patients. A positive, nonlinear relationship between eGFR and total MPA clearance identified in our model is likely attributed to multiple concurrent mechanisms, which warrant further systematic investigations.

Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients.

Tacrolimus, the most common immunosuppressant for organ transplant, has a narrow therapeutic range and is metabolized by CYP3A4/5. Trough concentration monitoring and dosing adjustments are used to reach a therapeutic range. CYP3A5 intermediate and normal metabolizers (*1 allele carriers; IM/NM) demonstrate faster tacrolimus metabolism than poor metabolizers (PM). We analyzed the electronic health records of 93 patients aged <21 years for the first 8 weeks after a kidney transplant between January 2010 and December 2021. The target tacrolimus trough was 10-15 ng/mL in the first 4 weeks and 7-10 ng/mL in the next 4 weeks. Banked DNA was collected and genotyped for CYP3A5*3, *6, *7, and *8 alleles. We found that CYP3A5 IM/NM (n = 21) took longer than PM (n = 72) to reach the therapeutic range (7 vs. 4 days, p = 0.048). IM/NM had more dose adjustments (8 vs. 6, p = 0.025) and needed >150% of the required daily dose compared with PM. The concentration/dose ratio was influenced by age and concomitant fluconazole (p = 0.0003, p = 0.034, respectively) and the average daily dose decreases with age in CYP3A5 PM (p = 0.001). Tremors were more common in patients who ever had a trough concentration >15 ng/mL compared with those who never had a trough concentration >15 ng/mL (OR 3.31, 95% CI 1.03-8.98, p = 0.038). Using standard dosing, CYP3A5 IM/NM took longer to reach the goal range and require more dose adjustments and higher doses than PM. Preemptive genotyping could decrease the number of dose changes necessary to reach a therapeutic dose. We have implemented pre-transplant CYP3A5 testing at our institution.

Pre-Existing Intrarenal Parvovirus B19 Infection May Relate to Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients.

Viral infections can lead to transplant dysfunction, and their possible role in rejection is described. In total, 218 protocol biopsies performed in 106 children at 6, 12 and 24 months after transplantation were analyzed according to Banff '15. RT-PCR for cytomegalovirus, Epstein-Barr virus, BK virus and Parvovirus B19 was performed on blood and bioptic samples at the time of transplant and each protocol biopsy. The prevalence of intrarenal viral infection increases between 6 and 12 months after transplantation (24% vs. 44%, p = 0.007). Intrarenal Parvovirus B19 infection is also associated with antibody-mediated rejection (ABMR) (50% ABMR vs. 19% T-cell-mediated rejection, p = 0.04). Moreover, Parvovirus infection is higher at 12 months of follow-up and it decreases at 48 months (40.4% vs. 14%, p = 0.02), while in 24% of grafts, Parvovirus is already detectable at the moment of transplantation. Intrarenal Parvovirus B19 infection seems to be related to ABMR in pediatric kidney recipients. The graft itself may be the way of transmission for Parvovirus, so performance of a PCR test for Parvovirus B19 should be considered to identify high-risk patients. Intrarenal Parvovirus infection presents mainly during the first-year post-transplantation; thus, we recommend an active surveillance of donor-specific antibodies (DSA) in patients with intrarenal Parvovirus B19 infection during this period. Indeed, it should be considered a treatment with intravenous immunoglobulins in patients with intrarenal Parvovirus B19 infection and DSA positivity, even in the absence of ABMR criteria for kidney biopsy.

Neurocognitive deficits may not resolve following pediatric kidney transplantation.

Pediatric chronic kidney disease (CKD) patients are at risk for cognitive deficits with worsening disease progression. Limited, existing cross-sectional studies suggest that cognitive deficits may improve following kidney transplantation. We sought to assess cognitive performance in relationship to kidney transplantation and kidney-specific medical variables in a sample of pediatric kidney transplant patients who provided cross-sectional and longitudinal observations. A retrospective chart review was conducted in patients who completed pre- and/or post-transplant neurocognitive testing at the University of Iowa from 2015-2021. Cognitive outcomes were investigated with developmentally appropriate, standardized measures. Mixed linear models estimated the impact of transplant status on cognitive function (z-scores). Subsequent post-hoc t-tests on change scores were limited to patients who had provided pre- and post-transplant assessments. Thirty eight patients underwent cognitive assessments: 10 had both pre- and post-transplant cognitive assessments, 11 had pre-transplant assessments only, and 17 had post-transplant data only. Post-transplant status was associated with significantly lower full-scale IQ and slower processing speed compared to pre-transplant status (estimate=-0.32, 95% confidence interval [CI]=-0.52: -0.12; estimate=-0.86, CI=-1.17: -0.55, respectively). Post-hoc analyses confirmed results from the mixed models (FSIQ change score=-0.34, 95% CI=-0.56: -0.12; processing speed change score=-0.98, CI=-1.28: -0.68). Finally, being ≥80months old at transplant was associated with substantially lower FSIQ compared to being <80 months (estimate=-1.25, 95% CI=-1.94: -0.56). Our results highlight the importance of monitoring cognitive function following pediatric kidney transplant and identify older transplant age as a risk factor for cognitive deficits.

IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients

BK virus-associated nephropathy (BKPyVAN) induces kidney allograft dysfunction. Although decreasing immunosuppression is the standard for managing BK virus (BKPyV) infection, this strategy is not always effective. The use of polyvalent immunoglobulins (IVIg) may be of interest in this setting.We performed a retrospective single-center evaluation of the management of BKPyV infection in pediatric kidney transplant patients. Among the 171 patients who underwent transplantation between January 2010 and December 2019, 54 patients were excluded (combined transplant n = 15, follow-up in another center n = 35, early postoperative graft loss n= 4). Thus, 117 patients (120 transplants) were included.Overall, 34 (28%) and 15 (13%) transplant recipients displayed positive BKPyV viruria and viremia, respectively. Three had biopsy-confirmed BKPyVAN. The pre-transplant prevalence of CAKUT and HLA antibodies was higher among BKPyV-positive patients compared to non-infected patients. After the detection of BKPyV replication and/or BKPyVAN, the immunosuppressive regimen was modified in 13 (87%) patients: either by decreasing or changing the calcineurin inhibitors (n = 13) and/or switching from mycophenolate mofetil to mTor inhibitors (n = 10). Starting IVIg therapy was based on graft dysfunction or an increase in the viral load despite reduced immunosuppressive regimen. Seven of 15(46%) patients received IVIg. These patients had a higher viral load (5.4 [5.0–6.8]log vs. 3.5 [3.3–3.8]log). In total, 13 of 15 (86%) achieved viral load reduction, five of seven after IVIg therapy.As long as specific antivirals are not available for the management of BKPyV infections in pediatric kidney transplant patients, polyvalent IVIg may be discussed for the management of severe BKPyV viremia, in combination with decreased immunosuppression.

Peritoneal transformation shortly after kidney transplantation in pediatric patients with preceding chronic peritoneal dialysis.

The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry. While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD. Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.

Effects of Body Mass Index Changes In Pediatric Kidney Transplant Patients

The negative effects of pretransplant obesity and post-transplant body mass index (BMI) increase on graft survival have been reported in recent years. The aim of this study is to evaluate the effects of BMI changes on post-transplant graft function, lipid profile, and blood pressure. The study included 133 pediatric patients transplanted between 1994 and 2019 in Ege University. BMI Z-scores (BMIZs) were calculated according to age and sex before and after transplantation using the World Health Organization criteria. Patients with BMIZs >+1 standard deviation (SD) were defined as overweight, and those with BMIZs >+2 SD were defined as obese: Group 1: Obese or overweight before transplantation; Group 2: Thin or normal weight before and 2 years after transplantation; and Group 3: Thin or normal weight before transplantation and obese or overweight 2 years after transplantation. At the time of transplantation 8% of the patients were overweight, and 1% were obese. Overweight and obesity statistically significantly increased (31.6%) 2 years after renal transplantation (P=.001). Obese and overweight patients have lower high-density lipoprotein levels and were younger at the time of transplantation. Graft functions, lipid levels, and blood glucose levels of the groups were similar (P > .05). The only significant difference between the groups was that Group 1 patients were younger than Group 2. Obesity develops at a significant rate in pediatric patients after renal transplantation. In this study, we could not demonstrate negative effects of obesity and being overweight in terms of post-transplant graft function, lipid profile, blood glucose, and blood pressure.

Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study.

The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8]years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. FGF23 level was 440.8 [63.4-5916.3]pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5]pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292]pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9]mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.

Can we identify "at-risk" children and adolescents for poor transplant outcomes in the psychosocial evaluation before solid organ transplantation? The reliability and validity study of Pediatric Transplant Rating Instrument (P-TRI) in Turkish pediatric renal transplant patients.

This study aims to translate the Pediatric Transplant Rating Instrument (P-TRI) to conduct a validity and reliability study on Turkish children and define a cutoff value of this scale. A total of 151 pediatric kidney transplant patients were included in the study. The files of the patients were reviewed by two clinicians, and the scale was filled for inter-rater reliability. One of the clinicians filled the scale again after one month for intra-rater reliability. Glomerular filtration rate (GFR) and creatinine values were used for predictive validity. A GFR below <60 ml/min/1.73m2 and creatinine up to 3.0mg/dl was defined as risk factors. Correlation of P-TRI with GFR (r=.252, p=.003) and creatinine (r=-.249, p=.002) was performed, and the internal consistency of the scale items as measured by Cronbach's alpha coefficient was found to be 0.825. When the test was performed again, the intra-class correlation coefficient was found as .922 for intra-rater reliability and as .798 for inter-rater reliability. For both creatinine and GFR, the best cutoff point for the total score was found to be 66.5. Patients who received P-TRI above 66.5 could be at risk in the post-transplant period. Identification of these patients before transplantation and following these young people more closely will aid in the prevention of serious consequences. The reliability and validity scores are satisfactory for use in transplantation clinics for psychosocial evaluation and compliance in Turkish pediatric renal transplantation patients.

Contrast-enhanced voiding urosonography (CEVUS) as a safe alternate means of assessing vesicoureteral reflux in pediatric kidney transplant patients.

Although voiding cystourethrogram (VCUG) is currently the gold standard in VUR evaluation, there is ionizing radiation exposure. Contrast-enhanced voiding urosonography (CEVUS) uses ultrasound contrast agents to visualize the urinary tract and has been reported to be safe and effective in VUR evaluation in children. CEVUS application has yet to be specifically described in VUR evaluation in the pediatric kidney transplant population. The purpose of this study was to report the use of CEVUS and VCUG in evaluating and managing VUR in pediatric renal transplant patients. Retrospective review was conducted for pediatric kidney transplant patients (18 years and younger) who underwent VCUG or CEVUS to assess for transplant VUR from July 2019 through June 2021. Demographic information, reason for VUR evaluation, fluoroscopy time, and postimaging complications were evaluated. Costs of imaging modalities were also considered. Eight patients were evaluated for transplant VUR during the study period. Of the 3 patients who underwent VCUG, all 3 had VUR (median grade 3). Median fluoroscopy time was 18s and dose-area product was 18.7 uGy*m2 . Of the 5 patients who underwent CEVUS, 4 had VUR (median grade 4). There were no complications for either modality. Based on clinical and radiographic findings, patients were recommended no intervention, behavioral modification, or ureteral reimplantation. The total cost of CEVUS was $800 less than that of VCUG. CEVUS can provide an alternate means of safely evaluating VUR in kidney transplant patients with similar outcomes, potentially lower costs, and no exposure to ionizing radiation.

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry

BackgroundRandomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far.MethodsIn this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554).ResultsMost baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable.ConclusionsIn conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Management of pediatric dialysis and kidney transplant patients after natural or man-made disasters.

Pediatric patients on kidney replacement therapy (KRT) are among the most vulnerable during large-scale disasters, either natural or man-made. Hemodialysis (HD) treatments may be impossible because of structural damage and/or shortage of medical supplies, clean water, electricity, and healthcare professionals. Lack of peritoneal dialysis (PD) solutions and increased risk of infectious/non-infectious complications may make PD therapy challenging. Non-availability of immunosuppressants and increased risk of infections may result in graft loss and deaths of kidney transplant recipients. Measures to mitigate these risks must be considered before, during, and after the disaster including training of staff and patients/caregivers to cope with medical and logistic problems. Soon after a disaster, if the possibility of performing HD or PD is uncertain, patients should be directed to other centers, or the duration and/or number of HD sessions or the PD prescription adapted. In kidney transplant recipients, switching among immunosuppressants should be considered in case of non-availability of the medications. Post-disaster interventions target treating neglected physical and mental problems and also improving social challenges. All problems experienced by pediatric KRT patients living in the affected area are applicable to displaced patients who may also face extra risks during their travel and also at their destination. The need for additional local, national, and international help and support of non-governmental organizations must be anticipated and sought in a timely manner.

417.12: Eculizumab Therapy for Late Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients

417.12: Eculizumab Therapy for Late Antibody-Mediated Rejection in Pediatric Kidney Transplant Patients

Relationship Between Angiotensin II Type 1 Receptor Antibody Positivity and Cytokine Gene Polymorphism in Renal Transplant Patients When Organ Rejection Occurs.

Kidney transplant remains the gold standard for the treatment of end-stage renal disease. Relationships between the presence of non-HLA antibodies, antibodies to AT1R, and cytokine gene polymorphisms with rejection have recently been shown. We sought to determine whether the presence of antibodies to AT1R and cytokine gene polymorphisms affected the development of rejection in pediatric and adult patients, whether a relationship is present between cytokine polymorphism and level of antibodies to AT1R, and whether their presence can be a biomarker pretransplant. Our study included 100 pediatric and adult kidney transplant patients plus 50 healthy controls. Levels of AT1R antibodies (by enzyme-linked immunosorbent assay) and gene polymorphisms of the cytokines transforming growth factor β, tumor necrosis factor α, interleukins 6 and 10, and interferon gamma cytokines (by sequence- specific primer-polymerase chain reaction) were studied retrospectively and evaluated with the SPSS statistical program. We found no statistically significant relationship between levels of antibodies to AT1R and gene polymorphisms among the studied cytokines in patients with rejection compared with the healthy controls and patients with uneventful courses posttransplant. However, higher levels of antibodies to AT1R were observed in pediatric compared with adult transplant recipients (P < .001). A statistically significant relationship was also observed between transforming growth factor β1 C/C G/C low-release and interleukin 6 G/C high-release gene polymorphism and levels of antibodies to AT1R (P < .001). Because we observed that some gene polymorphisms among the studied cytokines may affect AT1R antibody levels, future studies are needed to understand the mechanism of the relationship. In addition, studies with larger groups are required to sufficiently confirm that higher antibody levels are present in pediatric versus adult patients.

Cardiovascular disease risk factors and lifestyle modification strategies after pediatric kidney transplantation: what are we dealing with, and what can we target?

Kidney transplantation in pediatric patients can lead to partial improvement of some of the cardiometabolic parameters that increase the risk for cardiovascular disease (CVD) in patients with chronic kidney disease. However, even after restoration of kidney function, transplant recipients remain at risk for CVD due to the continual presence of traditional and non-traditional risk factors, including the side effects of immunosuppression and chronic inflammation. This educational review describes the prevalence of CVD risk factors in pediatric kidney transplant recipients and presents available evidence for therapeutic lifestyle changes and other non-pharmacologic strategies that can be used to improve traditional and modifiable CVD risk factors. Although trial-grade evidence for interventions that improve CVD in pediatric kidney transplant recipients is limited, potential strategies include lowering dietary sodium and saturated fat intake and increasing physical activity levels. Intensive follow-up may help patients achieve guideline-recommended goals for reducing their overall CVD risk.