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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: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. Methods: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post‐transplant. Results: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p =.02), increased number of hospitalizations (82% vs. 67%, p =.01), and viral replications (79% vs. 47%, p <.0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow‐up (−7 vs. −1 mL/min/1.73 m2, p =.05). Conclusions: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post‐transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post‐transplant outcomes. [ABSTRACT FROM AUTHOR]

This article discusses the challenges and considerations in choosing the best kidney for pediatric kidney transplant recipients. The longevity of the graft is often threatened by the development of donor-specific antibodies and rejection, leading to graft loss. Factors such as HLA matching, age of the donor, and the choice between living and deceased donors are explored. The article also discusses the potential benefits of utilizing kidney exchange programs. While more research is needed, this symposium has provided valuable insights into selecting the best kidney for pediatric transplant recipients. [Extracted from the article]

Introduction: There are no guidelines regarding management of failed pediatric renal transplants. Materials & Methods: We performed a first of its kind multicenter study assessing prevalence of transplant nephrectomy, patient characteristics, and outcomes in pediatric renal transplant recipients with graft failure from January 1, 2006, to December 31, 2016. Results: Fourteen centers contributed data on 186 pediatric recipients with failed transplants. The 76 recipients that underwent transplant nephrectomy were not significantly different from the 110 without nephrectomy in donor or recipient demographics. Fifty‐three percent of graft nephrectomies were within a year of transplant. Graft tenderness prompted transplant nephrectomy in 91% (P <.001). Patients that underwent nephrectomy were more likely to have a prior diagnosis of rejection within 3 months (43% vs 29%; P =.04). Nephrectomy of allografts did not affect time to re‐listing, donor source at re‐transplant but significantly decreased time to (P =.009) and incidence (P =.0002) of complete cessation of immunosuppression post‐graft failure. Following transplant nephrectomy, recipients were significantly more likely to have rejection after re‐transplant (18% vs 7%; P =.03) and multiple rejections in first year after re‐transplant (7% vs 1%; P =.03). Conclusions: Practices pertaining to failed renal allografts are inconsistent—40% of failed pediatric renal allografts underwent nephrectomy. Graft tenderness frequently prompted transplant nephrectomy. There is no apparent benefit to graft nephrectomy related to sensitization; but timing / frequency of immunosuppression withdrawal is significantly different with slightly increased risk for rejection following re‐transplant. [ABSTRACT FROM AUTHOR]

Graft survival was also significantly higher in the second transplant ( I p i = 0.009) with 70% having functioning grafts for a median follow-up of 25.2 months. Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease (ESKD) in children and is quite challenging to manage both before and after kidney transplantation. The authors make a concluding statement that "Knowing that re-transplants are not destined to fail and that severe recurrence is less likely in a second transplant may encourage more frequent and more timely re-transplantation in this unique population and improve patient overall survival and quality of life". The hypothesis behind pre-transplant plasmapheresis is that it may prevent or decrease the severity of recurrence and improve proteinuria and graft survival by removing circulating permeability factors associated with recurrence. [Extracted from the article]

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. The TAC dose was tapered after two doses of BELA and discontinued after the 4th dose of BELA. Belatacept (BELA) has been used successfully in adult kidney transplant (KTx) recipients for immunosuppression. [Extracted from the article]

Abstract: Early signs of subclinical CV dysfunction can be detected by ultrasound for CIMT. Although A‐A are at high risk for CV disease, CIMT of A‐A kidney transplant recipients has not been previously investigated. The aim of this prospective, controlled, longitudinal study was to investigate determinants of CIMT in a multiracial pediatric kidney transplant population, with a focus on A‐A. Transplant recipients (n = 42) had BMI, waist‐to‐height ratio, fasting glucose, lipid panel, HbA1c%, and CIMT measured at 1, 18, and 30 months post‐transplant. Twenty‐four healthy children (14 A‐A) served as controls. CIMT of A‐A transplant (0.49, 0.49, and 0.48 mm) was higher than non‐AA transplant (0.43, 0.44, and 0.44 mm) at 1, 18, and 30 months and higher than A‐A controls (0.47 mm). Hyperparathyroidism prior to transplant predicted high CIMT‐for‐race. A‐A race was associated with 10% higher CIMT vs non‐A‐A transplant. Metabolic syndrome was associated with 0.03 ± 0.01 mm increase in CIMT among A‐A transplant recipients only. In conclusion, A‐A kidney transplant recipients have increased CIMT. Metabolic syndrome disproportionately affects CIMT of A‐A children post‐transplant. Identification of subclinical CV damage, detected by CIMT, may provide an opportunity for early detection of CV risk in this vulnerable population. [ABSTRACT FROM AUTHOR]

Abstract: The development of dnDSA anti‐HLA antibodies has been shown to be a significant risk factor for graft failure. In 2008, we instituted a routine protocol of standardized monitoring and treatment of dnDSA in pediatric kidney transplant recipients. Of 67 first‐time pediatric kidney transplant recipients, 26 (38%) developed dnDSA after 1.36 (IQ 1‐2.14) years. Coefficient of variance of tacrolimus, a surrogate marker of non‐adherence, was found to be the single most important risk factor for dnDSA development. Overall, there was a significant reduction in dnDSA with treatment in 19 (76%) children. No difference in graft survival and estimated glomerular filtration rate was noted between dnDSA negative and those treated for dnDSA. There was an increased risk of hospitalization in those treated for dnDSA. This study suggests that early detection and treatment of dnDSA can help to prevent graft failure and preserve graft function in the short term. Future studies and longer follow‐up are needed to fully elucidate the effect of early detection and treatment of dnDSA in pediatric kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Carnitine deficiency is known to occur in chronic hemodialysis; however, the effect of continuous renal replacement therapy ( CRRT) on carnitine homeostasis has not been studied. We hypothesized that children receiving CRRT are at risk for deficiency because of continuous removal, absent intake, decreased production, and comorbidities related to critical illness. Records of patients with acute kidney injury receiving CRRT at Children's National Health System between 2011 and 2014 were reviewed for total carnitine ( TC), free carnitine ( FC), feeding modality, severity of illness, and survival outcome. The proportion of carnitine-deficient patients at baseline, 1, 2, and ≥3 weeks on CRRT were compared by chi-square, and relationships with other variables assessed by Pearson's correlation and logistic regression. The study group included 42 CRRT patients, age 7.9 + 1.1 years. At baseline, 30.7% and 35.7% of patients were TC and FC deficient. Within 1 week, 64.5% (P = 0.03) and 70% (P = 0.03) were TC and FC deficient, and prevalence of deficiency increased to 80% (P = 0.01) and 90% (P = 0.008) by 2 weeks; 100% of patients were TC and FC deficient after being on CRRT for ≥3 weeks (P = 0.005 and P = 0.01, respectively, vs. baseline). TC and FC levels negatively correlated with days on CRRT (r = −0.39, P = 0.001 and r = −0.35, P = 0.005). Patients with TC and FC deficiency had 5.9 and 4.9 greater odds of death than those with normal levels (P = 0.02 and P = 0.03). Carnitine is significantly and rapidly depleted with longer time on CRRT, and carnitine deficiency is associated with increased mortality. Consequences of deficiency and benefits of supplementation in the pediatric CRRT population should be investigated. [ABSTRACT FROM AUTHOR]

Long-term graft survival and function has not kept pace with short-term success in kidney transplant (Tx) recipients. LAR ≥6 months post-Tx may contribute to lack of improvement; risk factors for LAR are not well known. Of 64 Tx recipients followed over six yr, 23 (35.9%) had LAR ( LAR group) and 41 had no LAR (no LAR group). Of all variables, significant risk factors for LAR included DGF, (43.4% LAR vs. 14.6% in no LAR group, p = 0.0096); de novo DSA (65.2% vs. 26.8%, p = 0.003); mean COV% of TAC (41.8% vs. 34.6%, p = 0.03); and non-adherence (34.8% vs. 7.3%, p = 0.0043). DGF and DSA remained statistically significant (p = 0.002 and 0.003, respectively); COV% TAC had borderline significance (p = 0.057), and non-adherence was not significant on multivariate regression analysis. Patients with LAR had inferior graft survival and function, whereas graft function was stable in the no LAR group over a mean follow-up of 31.2 months. Patients with de novo DSA and DGF should be considered at risk of LAR; an early diagnosis and treatment of LAR may improve graft survival and function. [ABSTRACT FROM AUTHOR]

Transplantation has become the treatment of choice for children with end-stage organ failure. It is widely acknowledged by those practicing in the field of transplant medicine that taking care of pediatric transplant recipients is a complex endeavor for all parties involved, including patients, families, and providers. [Extracted from the article]

Upadhyay K, Midgley L, Moudgil A. Safety and efficacy of alemtuzumab in the treatment of late acute renal allograft rejection. Abstract: Safety and efficacy of alemtuzumab in the treatment of AR in children after renal transplantation is unknown. Five episodes of refractory late AR in three children (three episodes in patient 1 and a single episode in patients 2 and 3 occurring after 7-23 months of transplantation) were treated with one dose of alemtuzumab as a rescue therapy. Four episodes (Banff IA-IB) in patients 1 and 2 reversed fully or partially with alemtuzumab, whereas patient 3 with Banff IB-IIA AR failed to respond. Patient 1 had recurrent AR 5, 13, and 15 months later; first two episodes responded to retreatment with alemtuzumab, and the last episode was not treated causing allograft failure. Patient 2 had steroid-responsive AR after two months and had a functioning allograft 25 months later. A transient reduction in all lymphocyte subsets except natural killer cells occurred in all patients. Patient 3 (treated with steroids, ThymoglobulinR, intravenous immunoglobulin, and rituximab prior to alemtuzumab) suffered many bacterial infections during one-yr period after therapy. However, symptomatic viral infections were not observed in any of the children. Treatment with alemtuzumab may prolong allograft survival in multidrug-resistant AR but may not prevent recurrent AR in non-adherent children. [ABSTRACT FROM AUTHOR]

Sgambat K, Tuchman S, Ryan L, Wood R, Moudgil A. Low bone mineral density and nutritional vitamin D deficiency in pediatric renal transplant recipients: Assessment of risk factors and response to oral vitamin D therapy. Pediatr Transplantation 2011: 15: 790-797. © 2011 John Wiley & Sons A/S. Abstract: VitD deficiency and bone disease are common after Tx. Prevalence and risk factors for low VitD and BMD and response to VitD therapy were investigated in pediatric renal Tx recipients. 25-hydroxy VitD levels of 71 Tx were compared to 54 healthy AA children. DXA of 44 Tx were compared to 47 AA controls. Of Tx, 59% were AA. Majority (59.1%) of Tx were VitD deficient (23.9%) or insufficient (35.2%). Prevalence of low VitD levels was double in AA (73.9%) vs. non-AA Tx (37.7%), (p = 0.003). Low VitD among Tx was associated with AA ethnicity (p < 0.01), winter (p < 0.05), older age (p < 0.05), males (p < 0.05) and time <6 months post Tx (p < 0.05). Tx with low VitD were treated with oral ergocalciferol or cholecalciferol (23 each); 13% treated with ergocalciferol vs. 82.6% treated with cholecalciferol achieved repletion (p < 0.0001). Of 36 Tx with whole body DXA, 19.5% had BMD ( z < −1) after height adjustment. AA Tx had 3.4-fold higher risk of low BMD vs. controls (p < 0.05). Low VitD and BMD are prevalent in children after renal Tx. Better repletion of VitD is achieved with cholecalciferol. [ABSTRACT FROM AUTHOR]

Moudgil A, Martz K, Stablein DM, Puliyanda DP. Good outcome of kidney transplants in recipients of young donors: a NAPRTCS data analysis. Pediatr Transplantation 2011: 15:167-171. © 2010 John Wiley & Sons A/S. NAPRTCS data were analyzed to assess outcome of TX recipients from YDs (<5 yr) in comparison with IDs (6-35 yr) and ODs (36-55 yr). Of 9854 TX in NAPRTCS (1987-2003), 469 were YD. Patient survival (PS) and graft survival (GS) were compared between DD TX after 1995; 81YD, 1324 ID, and 429 OD and eGFR were compared among functioning grafts (YD 31, ID 439, OD 174) at three yr. PS was comparable in all groups; GS at one, two, and three yr in TX of YD (91.1%, 83.8%, 79.7%), ID (93.5%, 89.7%, 83.6%), and OD (92.2%, 87.2%, 82.4%) was comparable. The eGFR in YD was comparable to ID but better than OD (86.5 vs. 79.7 vs. 67.2 mL/min/1.73 m, p 0.139 and <0.0003). Primary graft non-function was more frequent in TX from YD than ID and OD (3.7% vs. 0.3 and 0.7%, p = 0.004); the incidence of vascular thrombosis was similar. The aforementioned data show that pediatric recipients of YD had equivalent patient and graft survival. Although primary graft non-function was higher, eGFR of functioning grafts was comparable to ID. With further improvements in care, kidneys from YD may present a viable option for transplantation. [ABSTRACT FROM AUTHOR]

PTLD is a complication of EBV infection. We examined the efficacy of EBV-PCR monitoring to detect early replication in an attempt to prevent EBV-associated PTLD. Blood EBV levels in 156 renal transplant recipients (58 children) from three institutions over nine yr were retrospectively analyzed. Patients who were asymptomatic and at high risk for PTLD were monitored for EBV infection by PCR or serology followed by PCR at the time of EBV seropositivity. More children than adults had positive EBV-PCR (12/58 vs. 2/98, p < 0.001). Adults remained asymptomatic and viremia resolved post-therapy. 3/12 EBV-PCR positive children developed PTLD (3/12 children vs. 0/2 adults, p = NS). Two out of three with PTLD were initially monitored by serology, and later by PCR. PTLD resolved post-therapy in all three patients. The remaining 9/12 EBV-PCR positive children stayed asymptomatic. None of the children and adults with negative EBV-PCR developed PTLD. EBV-PCR monitoring in high-risk renal transplant recipients, especially in children, may allow early diagnosis and intervention, and therefore may help in preventing EBV-associated PTLD. [ABSTRACT FROM AUTHOR]

There are little data on prevalence of dyslipidemia in pediatric kidney TX recipients in the modern IS era. LP profiles of 38 TX recipients receiving triple IS with MMF, prednisone, and tacrolimus were compared with those of 11 children on HD using mixed model multiple linear regression analysis of repeated measures after adjusting for age, sex, ethnicity, duration of ESRD, and BMI. TC and LDL levels were significantly higher in TX compared with HD, whereas there was no difference in the HDL, VLDL, and TG levels. TC and LDL in TX children had no association with age, sex, ethnicity, and duration of ESRD, stage of chronic kidney disease, DM, BMI percentile, and gain in percentage IBW. Five children treated with atrovastatin had a significant reduction in TC, LDL, VLDL, and TG at 3–6 months post-treatment compared with pretreatment levels, whereas there was no difference in HDL or tacrolimus levels after treatment. No side effects of therapy were observed. Although dyslipidemia remains a significant problem in pediatric renal TX recipients in the modern era, the prevalence may have decreased with use of newer IS drugs. [ABSTRACT FROM AUTHOR]

Management of BKV infection is not well defined. Eighteen pediatric renal transplant patients with BKV-PCR (+) were divided into three groups; Group 1: Viruria only (6), Group 2: Viremia with stable GFR (4), Group 3: Viremia with >25% decline in GFR and BKVAN on biopsy (8). With initial BKV-PCR(+), Group 1 received no treatment; Group 2 had MMF reduced 30%; Group 3: 6/8 had CNI discontinuation, 2/8 had reduced MMF and cidofovir. BKV, GFR and histology were compared pre- and post-treatment. In Group 1 viruria decreased in all patients; GFR remained stable. Group 2 showed reduced viremia with no GFR change. Group 3 showed reduced viremia in 8/8 patients. Patients with >50% decline in GFR from baseline (6/8) showed worse histology: 2/6 lost grafts despite no BKV on follow-up biopsy. Our results show that with viruria alone no treatment is necessary; with viremia and stable GFR, reduced immunosuppression decreases viremia and maintains GFR. With viremia and reduced GFR, immunosuppression reduction with or without cidofovir decreases viremia and stabilizes GFR in most patients. Greater than 50% reduction in GFR at BKVAN diagnosis correlates with risk for graft loss. Serial monitoring of BKV viremia with early intervention may prevent BKVAN graft loss in children. [ABSTRACT FROM AUTHOR]

Adenovirus infection has been associated with the development of hemorrhagic cystitis in bone marrow transplant recipients. However, limited information exists regarding adenovirus-associated hemorrhagic cystitis in solid organ transplantation, especially in renal transplant recipients. In most cases, the disease is self-limited. However, some patients may have a protracted course. Although no particular antiviral agent has been identified as the gold standard of therapy, cidofovir has been found to be effective in a number of bone marrow transplant recipients. In this study, we report a five-yr-old boy who presented with adenovirus-associated hemorrhagic cystitis 68 days after renal transplant and was successfully treated with reduction of immunosuppression and an intermediate dose of intravenous cidofovir. [ABSTRACT FROM AUTHOR]

Central venous catheter is commonly utilized as a hemodialysis access in the pediatric population. Long-standing central venous catheters can be complicated by superior vena cava (SVC) stenosis and thrombosis that can rarely present as pleural effusions. We report a case of a 5-year-old boy on chronic hemodialysis who presented with combined pleural and pericardial effusions, which was secondary to catheter induced SVC stenosis. Both the pleural effusion and the pericardial effusion in this patient subsequently improved with the relief of SVC stenosis. This case report highlights the serious complications of SVC stenosis associated with long-standing central venous catheters which is an under-recognized problem in the pediatric population. [ABSTRACT FROM AUTHOR]

The NAPRTCS has collected clinical information on children undergoing renal transplantation since 1987 and now includes information on 12 920 renal transplants in 11 870 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in patient and allograft outcomes after pediatric renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation and also provides historical perspective. This report highlights current practices in an era of major changes in DD kidney allocation and continuing steroid minimization. This report presents outcomes of the patients in the NAPRTCS transplant registry up to end of 2017. In particular, an increase in the cumulative incidence of late first AR has occurred in the most recent cohort, while all prior cohorts had a lower cumulative incidence of late first AR. [ABSTRACT FROM AUTHOR]

Background: Prior to transplantation, effects of advanced CKD contribute to malnutrition and impaired growth. After transplant, children are expected to thrive, however, in a subset of transplant recipients this does not occur. Factors associated with post‐transplant FTT are poorly understood. Objective: A retrospective cohort study was conducted to determine factors associated with FTT and association of FTT with infections and hospitalizations. Methods: Records of 119 children transplanted between 2005 and 2016 were reviewed. FTT was defined by ≥2 of the following post‐transplant criteria: (a) low BMI or deceleration in BMI z‐score, (b) poor growth velocity, and (c) chronic hypoalbuminemia at 1 or 3 years post‐transplant. Association of FTT with deceased donor transplant, de novo DSA, intolerance to MMF, anemia, vitamin D deficiency, and CIC was investigated by logistic regression. Poisson regression was used to identify outcomes associated with FTT. Results: Low pre‐transplant BMI and post‐transplant CIC dependence were independently associated with FTT after transplant. Odds of FTT at 1 year post‐transplant decreased by 0.5 for each 1 unit increase in pre‐transplant BMI z‐score. Requirement for CIC conferred 3.8 and 7.8 higher odds of FTT at 1 and 3 years. Patients with FTT had 2.7 and 2.6 times infections and hospitalizations during the first year, and 4.2 and 4.3 times infections and hospitalizations over 3 years post‐transplant. Conclusions: Children with low BMI prior to transplant and those requiring CIC after transplant are at increased risk for post‐transplant FTT. FTT is associated with adverse outcomes, evidenced by increased infections and hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients are at high risk for CV morbidity. However, the measure of obesity that best predicts CV risk has not been established. Objective: A prospective, controlled study was conducted to compare the ability of BMI, WC, and WHr to identify CV risk in pediatric kidney transplant recipients. Methods: Transplant recipients, aged 3‐20 years, had echocardiogram, CIMT, BMI, WC, WHr, blood pressure, lipids, and leptin measured. Receiver operating characteristic analysis was used to compare the ability of BMI, WC, and WHr to detect a composite adverse CV outcome. Presence of the composite outcome was defined by ≥3 of the following five criteria: (a) LVH, (b) high CIMT, (c) impaired myocardial strain, (d) dyslipidemia, and/or (e) hypertension. Multivariate analysis was conducted by generalized estimating equation regression. Results: We analyzed 108 visits of 42 transplant recipients. Prevalence of obesity by WHr (43.5%) was higher than BMI (24.1%) and WC (12.0%). Proportion of WHr‐obese who met criteria for the adverse CV outcome was higher (62.2%) than BMI (34.6%) and WC‐obese (33.3%). Leptin levels were higher in children with obesity. Area under the ROC curve for WHr‐obese (0.77) was higher compared to BMI (0.47) and WC (0.48) to detect the CV outcome, P = 0.0006. WHr‐obesity was associated with 5.72 increased odds of having the adverse CV outcome, P = 0.0001, while BMI and WC were not significant. Conclusion: WHr is more sensitive than BMI or WC to detect subclinical CV risk and should be included in screening of pediatric kidney transplant recipients. [ABSTRACT FROM AUTHOR]