The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Post-Transplant Lymphoproliferative Disorders (Review for Seminars in Nephrology).

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of cases are associated with the Epstein-Barr virus and higher intensity of pharmacologic immunosuppression. The clinical presentations are numerous. The diagnosis is ideally by histology, except in cases where the tumor is inaccessible to biopsy. While some pre-emptive therapies and treatment strategies are available have reasonable success are available, they do not eliminate the high morbidity and significant mortality after PTLD.

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

Late effects in survivors of post-transplant lymphoproliferative disease.

BACKGROUND: Treatment of post-transplant lymphoproliferative disease (PTLD) varies, with only some patients receiving chemotherapy. Concern for chemotherapy toxicities may influence treatment decisions as little is known regarding the late effects (LE) in PTLD survivors. This report characterizes LE in PTLD survivors at our institution. PROCEDURE: Pediatric patients (0-18 years old) diagnosed with PTLD from 1990 to 2020 were examined. All patients included survived 6 months after completing chemotherapy or were 6 months from diagnosis if received no chemotherapy. Treatment with anti-CD20 antibody (rituximab) alone was not considered chemotherapy. Toxicities were classified per Common Terminology Criteria for Adverse Events Version 5.0. Chi-square tests assessed differences between categorical groups, or Fischer's exact test or the Fischer-Freeman-Halton exact test for limited sample sizes. RESULTS: Of the 44 patients included, 24 (55%) were treated with chemotherapy. Twenty-four (55%) were alive at last follow-up. Chemotherapy was not associated with differences in survival (odds ratio [OR] 1.40, confidence interval [CI]: 0.42-4.63; p = .31). All patients experienced LE. Grade 3 toxicity or higher was experienced by 82% of patients with no difference in incidence (OR 1.20, CI: 0.27-5.80; p > .99) or median toxicity grade (3.00 vs. 4.00, p = .21) between treatment groups. Patients who received chemotherapy were more likely to experience blood and lymphatic toxicity (58% vs. 25%, p = .03) and cardiac toxicity (46% vs. 15%, p = .03), but less likely to have infections (54% vs. 85%, p = .03). CONCLUSIONS: Survivors of PTLD experience LE including late mortality regardless of chemotherapy exposure. Further investigation to better understand LE could optimize upfront therapy for children with PTLD and improve outcomes.

Evaluating Kidney Function Decline in Children with Chronic Kidney Disease Using a Multi-Institutional Electronic Health Record Database.

BACKGROUND: The objectives of this study were to use electronic health record data from a US national multicenter pediatric network to identify a large cohort of children with CKD, evaluate CKD progression, and examine clinical risk factors for kidney function decline. METHODS: This retrospective cohort study identified children seen between January 1, 2009, to February 28, 2022. Data were from six pediatric health systems in PEDSnet. We identified children aged 18 months to 18 years who met criteria for CKD: two eGFR values <90 and ≥15 ml/min per 1.73 m2 separated by ≥90 days without an intervening value ≥90. CKD progression was defined as a composite outcome: eGFR <15 ml/min per 1.73 m2, ≥50% eGFR decline, long-term dialysis, or kidney transplant. Subcohorts were defined based on CKD etiology: glomerular, nonglomerular, or malignancy. We assessed the association of hypertension (≥2 visits with hypertension diagnosis code) and proteinuria (≥1 urinalysis with ≥1+ protein) within 2 years of cohort entrance on the composite outcome. RESULTS: Among 7,148,875 children, we identified 11,240 (15.7 per 10,000) with CKD (median age 11 years, 50% female). The median follow-up was 5.1 (interquartile range 2.8-8.3) years, the median initial eGFR was 75.3 (interquartile range 61-83) ml/min per 1.73 m2, 37% had proteinuria, and 35% had hypertension. The following were associated with CKD progression: lower eGFR category (adjusted hazard ratio [aHR] 1.44 [95% confidence interval (95% CI), 1.23 to 1.69], aHR 2.38 [95% CI, 2.02 to 2.79], aHR 5.75 [95% CI, 5.05 to 6.55] for eGFR 45-59 ml/min per 1.73 m2, 30-44 ml/min per 1.73 m2, 15-29 ml/min per 1.73 m2 at cohort entrance, respectively, when compared with eGFR 60-89 ml/min per 1.73 m2), glomerular disease (aHR 2.01 [95% CI, 1.78 to 2.28]), malignancy (aHR 1.79 [95% CI, 1.52 to 2.11]), proteinuria (aHR 2.23 [95% CI, 1.89 to 2.62]), hypertension (aHR 1.49 [95% CI, 1.22 to 1.82]), proteinuria and hypertension together (aHR 3.98 [95% CI, 3.40 to 4.68]), count of complex chronic comorbidities (aHR 1.07 [95% CI, 1.05 to 1.10] per additional comorbid body system), male sex (aHR 1.16 [95% CI, 1.05 to 1.28]), and younger age at cohort entrance (aHR 0.95 [95% CI, 0.94 to 0.96] per year older). CONCLUSIONS: In large-scale real-world data for children with CKD, disease etiology, albuminuria, hypertension, age, male sex, lower eGFR, and greater medical complexity at start of follow-up were associated with more rapid decline in kidney function.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: I-Methodology for the development of consensus practice guidelines.

The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities. The results of each working group (Definitions, Prevention, Management, and Epstein-Barr viral [EBV] load/Biomarker Monitoring) are presented in separate manuscripts within this volume of Pediatric Transplantation.

The IPTA Nashville consensus conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: II-consensus guidelines for prevention.

The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted.

Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Donor-derived cellfree DNA (cfDNA) is a less-invasive marker of allograft injury compared with kidney biopsy. However, donor-derived cfDNA has not yet been extensively tested in children, where the test may have different characteristics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assayed donor-derived cfDNA (AlloSure; CareDx) from 290 stored plasma samples from a prospective biobank at our center, collected from 57 children monthly in the first year postkidney transplant between January 2013 and December 2019. We assessed the kinetic changes in donor-derived cfDNA levels within the first year post-transplant. We analyzed donor-derived cfDNA levels for associations with biopsy-proven acute rejection using area under the receiver operating characteristic curve to longitudinal plasma and urine BK viral loads using linear mixed models. We analyzed the prognostic effect of an elevated donor-derived cfDNA level on the eGFR 30 days after the assay via Kolmogorov-Smirnov two-sample tests or on measured GFR or interstitial fibrosis at 12 months post-transplant. RESULTS: The donor-derived cfDNA levels in children remained persistently elevated for at least 4 months post-transplant, more so if there is greater disparity in size between the donor and the recipient, before reaching a steady low level. A donor-derived cfDNA level of >1% discriminated between biopsy-proven acute rejection with a receiver operating characteristic area under the curve of 0.82 (95% confidence interval, 0.71 to 0.93). During BK viruria or viremia, patients had a significantly higher median donor-derived cfDNA than before or after and a significant rise within the same patient. A donor-derived cfDNA of >0.5% predicted a wider spread in the eGFR over the next 30 days but not the 12-month outcomes. CONCLUSIONS: In children, donor-derived cfDNA is a valuable, less invasive biomarker for assessment of allograft rejection and injury. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_10_27_CJN03840322.mp3.

Simultaneous pediatric heart-kidney transplant outcomes in the US: A-25 year National Cohort Study.

BACKGROUND: Pediatric sHKTx remains uncommon in the US. We examined outcomes of pediatric sHKTx compared to PHTx alone. Our objective was to identify a threshold eGFR that justified pediatric sHKTx. METHODS: Data from the SRTR heart and kidney databases were used to identify 9245 PHTx, and 63 pediatric sHKTx performed between 1992 and 2017 (age ≤21 years). RESULTS: The median age for sHKTx was 16 years, and included 31 males (31/63 = 49%). Over half of sHKTx (36/63 = 57%) were performed in cases where pretransplant dialysis was initiated. Among patients who required pretransplant dialysis, the risk of death in sHKTx recipients was significantly lower than PHTx alone (sHKTx vs. PHTx: HR 0.4, 95% CI [0.2, 0.9], p = .01). In those without pretransplant dialysis, there was no improvement in survival between sHKTx and PHTx (p = .2). When stratified by eGFR, PHTx alone recipients had worse survival than sHKTx in the group with eGFR ≤35 ml/min/1.73 m2 (p = .04). The 1- and 5-year actuarial survival rates in pediatric sHKTx recipients were 87% and 81.5% respectively and was similar to isolated PHTx (p = .5). One-year rates of treated heart (11%) and kidney (7.9%) rejection were similar in sHKTx compared to PHTx alone (p = .7) and pediatric kidney transplant alone (p = .5) respectively. CONCLUSION: Pediatric sHKTx should be considered in HTx candidates with kidney failure requiring dialysis or eGFR ≤35 ml/min/1.73 m2 . The utility of sHKTx in cases of kidney failure not requiring dialysis warrants further study.

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes.

BACKGROUND AND OBJECTIVES: Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and noncases (n=350). RESULTS: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months. CONCLUSIONS: Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium.

INTRODUCTION: Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a "standard" higher dose. METHODS: We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An a priori cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival. RESULTS: Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) (P = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups (P = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%, P = 0.07). CONCLUSION: A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

Performance of the various serum creatinine-based GFR estimating equations in pediatric kidney transplant recipients, stratified by age and CKD staging.

BACKGROUND: Numerous equations are used to estimate glomerular filtration rate (eGFR), based on serum creatinine (SCr), demographic and anthropometric data, none established in pediatric kidney transplant recipients. This study aimed to validate the available SCr-based eGFR equations in comparison with a measured (mGFR), stratified by chronic kidney disease (CKD) stage and age at the time of testing. METHODS: One hundred twenty-seven pediatric kidney transplant recipients with 411 mGFR values (plasma clearance of iothalamate) were enrolled in this retrospective study. The bias, precision, and accuracy (percentage of estimates within 10% and 30% of mGFR) of five SCr eGFR equations (original Schwartz, CKiDSCr equation, Pottel, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) were assessed. RESULTS: Height-independent Pottel equation performed well across all the categories of age and CKD staging. CKiDSCr equation performed well in CKD stages II-V. The CKiDSCr equation had a lower bias in children < 15 years of age, while MDRD and CKD-EPI equations had less bias in children > 15 years. Overall, both the Pottel and CKiDSCr equations had high accuracy (80%) and low bias (< 5 ml/min/1.73 m2). In contrast, the original Schwartz, MDRD, and CKD-EPI equations displayed high bias and low precision/accuracy. CONCLUSIONS: Given their low bias and high accuracy across ages and CKD stages, the Pottel or the CKiDSCr equation is better to assess eGFR in pediatric kidney transplant recipients. The Pottel equation outperformed other eGFR equations in adolescents.

Cost burden of post-transplant lymphoproliferative disease following kidney transplants in Medicare-eligible patients by survival status.

AIMS AND OBJECTIVES: Patients diagnosed with post-transplant lymphoproliferative disease (PTLD) experience high mortality within the first 2 years of diagnosis; however, few data exist on the economic burden of PTLD in these patients. We determined the healthcare resource utilization (HRU) and cost burden of post-kidney transplant PTLD and evaluated how these differ by survival status. MATERIALS AND METHODS: Utilizing data from the United States Renal Data System and the Scientific Registry of Transplant Recipients, we identified 83,818 Medicare-covered kidney transplant recipients between 2007 and 2016, of which 347 had at least one Medicare claim during the first year after diagnosis of PTLD. We tabulated Medicare Part A and Part B and calculated per patient-year (PPY) costs. RESULTS: Patients diagnosed with PTLD in the first year post-transplant had Part A + B costs of $222,336 PPY, in contrast with $83,546 PPY in all kidney transplants. Post-transplant costs in the first year of PTLD diagnosis were similar regardless of the year of diagnosis. Cost burden for PTLD patients who died within 2 years of diagnosis was >3.3 times higher than PTLD patients still alive after 2 years. Of those who died within 2 years, the majority died within 6 months and costs were highest for these patients, with almost 7 times higher costs than PTLD patients who were still alive after 2 years. LIMITATIONS: Medicare costs were the only costs examined in this study and may not be representative of other costs incurred, nor be generalizable to other insured populations. Patients were only Medicare eligible for 3 years after transplant unless aged ≥62 years, therefore any costs after this cut-off were not included. CONCLUSIONS: PTLD represents a considerable HRU and cost burden following kidney transplant, and the burden is most pronounced in patients who die within 6 months.

Thrombotic Microangiopathy Following Onasemnogene Abeparvovec for Spinal Muscular Atrophy: A Case Series.

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity.

Post-transplant malignancies in pediatric organ transplant recipients.

The majority of cancer diagnoses in pediatric solid organ transplant recipients (SOTRs) are post-transplantation lymphoproliferative disorders (PTLD) or skin cancers. However, pediatric SOTRs are also at significantly elevated risk for multiple other solid and hematological cancers. The risks of specific cancers vary by transplanted organ, underlying disease, and immunosuppression factors. More than one-quarter of pediatric SOTRs develop cancer within 30 years of transplantation and their risk of solid cancer is 14 times greater than the general population. Pediatric SOTRs are at significantly higher risk of cancer-associated death. Improving patient survival among pediatric SOTRs puts them at risk of adult epithelial cancers associated with environmental carcinogenic exposures. Vaccination against oncogenic viruses and avoidance of excessive immunosuppression may reduce the risk of solid cancers following transplantation. Patient and family education regarding photoprotection is an essential component of skin cancer prevention. There is significant variability in cancer screening recommendations for SOTRs and general population approaches are typically not validated for transplant populations. An individualized approach to cancer screening should be developed based on estimated cancer risk, patient life expectancy, and screening test performance.

The progression of serum cystatin C concentrations within the first month of life after preterm birth-a worldwide systematic review.

Multiple single-center studies have examined the progression of kidney function biomarkers such as serum cystatin C (Cys C) in the first 30 days of life (DOL) after preterm birth, but from different ethnicities and in different gestational ages (GA), without a functional summary available. We performed a systematic literature review within PubMed, Google Scholar, and Scopus, with additional use of the snowballing method to find studies including data on serum Cys C concentrations in the first 30 DOL. We identified 15 papers that met criteria, published from 2000 to 2019, from 10 countries across 4 continents, in 1468 babies born preterm. Cys C was superior to creatinine in 11/13 studies, and equal in 2/13. For infants born at 24-28 weeks GA, the DOL1 Cys C concentrations ranged from 1.44 to 1.90 mg/L, from 1.20 to 1.77 on DOL3, and from 1.36 to 2.02 between DOL 4 and 30. For infants born at 29-33 weeks GA, the DOL1 Cys C values ranged from 1.41 to 1.96 mg/L, from 1.28 to 1.70 on DOL3, and 1.51 to 1.87 between DOL 4 and 30. For preterm infants born after 34 weeks GA, the DOL1 Cys C values ranged from 1.22 to 1.96 mg/L, from 1.24 to 1.85 on DOL3, and 1.22 to 1.82 between DOL 4 and 30. This systematic review provides generalizable worldwide reference data on Cys C that could be used to estimate progression or resolution of abnormal kidney function in the first months after preterm birth, stratified by GA.

Reassessing Rabbit Antithymocyte Globulin Induction in Kidney Transplantation (RETHINK): An Analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry.

BACKGROUND: There is no consensus on rabbit antithymocyte globulin (rATG) dose used for induction immunosuppression in pediatric kidney transplants. We aimed to identify whether a lower rATG dose provides safe and effective immunosuppression compared with a higher dose. METHODS: We retrospectively analyzed all first-time kidney transplant recipients (aged <21 y) in the North American Pediatric Renal Trials and Collaborative Studies registry since 1998 on mycophenolate mofetil- and tacrolimus-based immunosuppression with rATG induction. An a priori cutoff of 7.5 mg/kg cumulative rATG dose was used to identify low (<7.5 mg/kg) and high (≥7.5 mg/kg) exposure groups. Primary outcome was time to first-acute rejection episode. Secondary outcomes included graft function, patient survival, hospitalizations due to infections, and time to first-posttransplant lymphoproliferative disorder episode. RESULTS: Four hundred fifty-five patients met inclusion criteria (59% male, 49% whites, 26% blacks, 38% living donor source). Median cumulative rATG dose was 6.8 mg/kg with a median of 5 doses and a median 1.5 mg/kg/dose introduced at a median of postoperative 0 days. Sixty-four percent received <7.5 mg/kg total rATG. There was no difference in age at transplant, gender, race, end-stage renal disease causes, or HLA mismatch among groups. Time to first-acute rejection was similar (P = 0.07). There was no significant difference in graft or patient survival or time to posttransplant lymphoproliferative disorder. Hospitalization for infection rates was similar. CONCLUSIONS: These data demonstrate a wide variation in cumulative rATG induction dose. A smaller rATG dose <7.5 mg/kg may provide effective and safe immunosuppression compared with a higher dose.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

BACKGROUND: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. METHODS: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). RESULTS: The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. CONCLUSIONS: The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.

Kidney transplant practice patterns and outcome benchmarks over 30 years: The 2018 report of the NAPRTCS.

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.