Unusual presentation of Rosai-Dorfman disease (RDD) in the bone in adolescents

Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare idiopathic histiocytic disorder. The usual presentation of RDD is painless bilateral cervical lymphadenopathy. Extranodal RDD with lymphadenopathy occurs in almost 50% of patients but extranodal RDD, without lymphadenopathy, is very rare. Isolated RDD in the bone occurs in only 2% of patients but it is histologically similar to its nodal counterpart. There are only 14 previously reported cases of RDD in the bone without lymph node involvement in children. Here we describe two new patients--one with rib and lung involvement and the other with multi-osseous involvement.     

Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch‐and‐wait strategy after complete resection

Data on management of pediatric marginal zone lymphoma (MZL) are scarce. This retrospective study assessed characteristics and outcome in 66 patients who were <18 years old. Forty‐four (67%) had an extranodal MZL (EMZL), 21 (32%) a nodal MZL (NMZL), and one patient a splenic MZL. Thirty‐three patients (50%) received a variable combination of adjuvant chemotherapy/immunotherapy/radiotherapy, while the remainder, including 20 of 21 with NMZL, entered an active observation period. Overall survival was excellent (98 ± 2%), although 11 patients relapsed (17%; NMZL, n = 1; EMZL, n = 10), seven after any therapy and four after complete resection only. In conclusion, outcome of NZML, in particular, seems to be excellent after (in)complete resection and observation only.     

Three‐yr safety and efficacy of everolimus and low‐dose cyclosporine in de novo pediatric kidney transplant patients

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty‐seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5–3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5–10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three‐yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post‐transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post‐transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m², respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch‐up growth. No malignancy or post‐transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low‐dose cyclosporine, and low‐dose prednisone leads to good long‐term efficacy in de novo pediatric KT recipients.     

Preformed and de novo DSA are associated with T‐cell–mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy

Despite growing interest about the impact of donor‐specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single‐center chart review of children (0‐16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient‐ and donor‐characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex^® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow‐up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty‐eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6‐7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.     

Clinical and histopathologic features of antibody‐mediated rejection among pediatric renal transplant recipients with preformed vs de novo donor‐specific antibodies

Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy‐proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow‐up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA. Patients with pDSA developed ABMR earlier (median = 63 vs 1344 days, P = .017), while patients with dnDSA were more likely to have strong Class II iDSA (100% vs 28%, P = .009). Viral infection or non‐adherence was more common in patients developing dnDSA (88.8% vs 28.6%, P < .01). Pathology in those with pDSAs demonstrated worse transplant glomerulitis (g score 1.57 ± 0.98 vs 0.56 ± 0.73, P = .031); however, those with dnDSAs exhibited higher C4d+ ABMR (P = .013). Patients developing dnDSAs showed ABMR later post‐transplant with predominance of HLA‐Class II iDSAs. Inadequate immunosuppression likely contributes to dnDSA formation. Patients with no DSA who have unprotocolized decreases in immunosuppression should be screened for dnDSA as it could lead to early intervention and potentially better outcomes.     

Pretransplant six‐minute walk test predicts peri‐ and post‐operative outcomes after pediatric lung transplantation

The purpose of the pretransplant assessment in lung transplantation is to determine a patient's need for transplant as well as their potential survival post‐procedure. In 2005, the UNOS introduced the LAS, a calculation based on multiple physiologic measures to determine need and likelihood for survival. Measures include NYHA class and the 6‐MWT. Some adult studies indicate a positive correlation with 6‐MWT and waiting list survival. In pediatric/adolescent patients, there are minimal data regarding the predictive value of physiologic markers in either wait list survival or post‐transplant outcome. A retrospective cohort study of 60 consecutive lung transplantations from 1990 to 2008 was performed at a pediatric tertiary care facility. Functional pretransplant assessments were abstracted from the medical record and compared with outcomes after transplantation. Results: a 6‐MWT of >1000 ft (305 m) prior to transplantation correlated with a shorter ICU stay (7 vs. 11 days, p = 0.046) and fewer days of mechanical ventilation (2 vs. 4, p = 0.04). A pretransplant 6‐MWT greater than 750 ft (229 m) correlated with shorter overall hospitalization (37 vs. 20 days, p = 0.03). Measuring pretransplant 6‐MWT tests for pediatric patients is valuable in predicting peri‐operative outcomes after lung transplantation.     

Outcome of duct‐to‐duct vs. Roux‐en‐Y hepaticojejunostomy biliary anastomoses in below 15‐kg pediatric liver transplant recipients

The best type of biliary anastomosis to use in lower weight pediatric liver transplant recipients is debatable. In this study, we share a single center's experience comparing the rate of anastomotic biliary complications based on the type of biliary anastomosis performed in this population of patients. A retrospective review of pediatric liver transplants for recipients weighing <15 kg from 11/2003 till 12/2011 was performed. Patients were grouped based on the type of biliary anastomosis into two groups: duct‐to‐duct (d‐d) and Roux‐en‐Y hepaticojejunostomy (h‐j) anastomoses. A total of 24 patients (12 males, 12 females) with a mean age of 26 ± 20 months and a mean weight of 9.27 ± 2.63 kg (range = 5.3–13.9 kg) were studied. All anastomotic complications occurred in patients who received left lateral segments. No statistical differences were found in the post‐operative biliary (p = 0.86) or vascular (p = 0.99) complications between the two groups. Acknowledging the limited sample size, our data suggest that duct‐to‐duct anastomosis can be performed safely in pediatric liver transplantation recipients weighing below 15 kg.     

Mortality after pediatric kidney transplantation in England – a population‐based cohort study

The aim of this study was to explore mortality after pediatric kidney transplantation in England over the last decade. We used data from HES to select all kidney transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed with the ONS to identify all deaths occurring among this study cohort. Data for 1189 pediatric recipients were compared to 17 914 adult recipients (number of deaths, 33 vs. 2052, respectively, p < 0.001), with median follow‐up 4.4 yr (interquartile range 2.2–7.3 yr). There was no difference in mortality within the pediatric cohort; age 0–1 (n = 25, patient survival 100.0%), age 2–5 (n = 198, patient survival 96.0%), age 6–12 (n = 359, patient survival 97.5%), and age 13–18 (n = 607, patient survival 97.4%), respectively (p = 0.567). The most common causes of death were renal (n = 8, 24.2%), infection (n = 6, 18.2%), and malignancy (n = 5, 15.2%). All deaths from malignancy were secondary to PTLD. In a fully adjusted Cox regression model, only white ethnicity was significantly associated with risk of pediatric mortality post‐kidney transplantation (hazard ratio 2.7, 95% confidence interval [1.0–7.3], p = 0.047). To conclude, this population‐based cohort study confirms low mortality after pediatric kidney transplantation with short follow‐up.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a clinicoradiological profile of three cases including two with skeletal disease

Originally described as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. A rare entity, RDD is often under-diagnosed because of a low index of suspicion by both radiologist and pathologist. Through this article, we wish to apprise radiologists of the spectrum of disease that can be encountered in this disorder. RDD can mimic other common childhood skeletal diseases including benign Langerhans cell histiocytosis and lymphoma. The clinical and radiological manifestations of RDD vary depending upon organ involvement, and its imaging features are often confused with those of other disorders. RDD should be considered in the differential diagnosis of unifocal and multifocal skeletal involvement caused by granulomatous diseases, infections, pseudogranulomatous lesions and malignancy. As long-term outcome is usually good, a conservative approach is justified in most cases. Contrasted with its typical appearance, presenting with bilateral symmetrical cervical adenopathy (as shown in one patient), we also report extranodal involvement of bone in two patients. Extranodal disease occurs along with concomitant nodal disease in about 43% of patients. In 23% of patients, isolated extranodal RDD can be seen, most commonly in the head and neck. In two of our patients, we observed extranodal involvement with skeletal involvement away from the head and neck not associated with lymphadenopathy. Skeletal involvement in RDD without lymphadenopathy is rare, occurring only in 2% of all the patients reported to date.     

Effects of Remifentanil Anesthesia on Cardiac Electrophysiologic Properties in Children Undergoing Catheter Ablation of Supraventricular Tachycardia

Remifentanil is commonly used during anesthesia in pediatric electrophysiologic studies (EPS). The purpose of this study is to determine the effects of remifentanil on the cardiac electrophysiologic properties of children undergoing ablation of supraventricular tachycardia (SVT). A prospective study was performed in patients undergoing EPS before ablation of SVT. Each patient received two different anesthetic protocols: protocol 1 = propofol (200 mcg/kg/min) and protocol 2 = propofol (120 mcg/kg/min) plus remifentanil (0.3 mcg/kg/min). EPS data were measured during the steady state of each protocol. Paired Student t test was performed for analysis of continuous data. All p values <0.05 were considered statistically significant. Fifteen patients were enrolled between April 2005 and January 2006. The mean age was 13.3 ± 2.9 years (range 6.7 to 17.7). Seven patients had atrioventricular (AV) nodal re-entry tachycardia; 5 patients had Wolff-Parkinson-White syndrome; 2 patients had a concealed accessory pathway; and 1 patient was not inducible. Of the 14 patients who underwent ablation, 13 (93%) achieved successful. The baseline sinus cycle length extended from 884 ± 141 ms during protocol 1 to 980 ± 165 ms during protocol 2 (p = 0.01), and the Wenckebach cycle length lengthened from 377 ± 96 ms to 406 ± 109 ms (p = 0.01). No other variables measured (atrial-His (AH) and His-ventricular (HV) interval, atrioventricular node (AVN), and atrial, ventricular, and accessory pathway effective refractory periods) changed significantly between the two different protocols. In pediatric patients undergoing EPS before ablation of SVT, remifentanil appears to slow both sinus and AV nodal function. These effects should be taken into consideration when performing EPS.     

Vasoactive–inotropic score after pediatric heart transplant: A marker of adverse outcome

VIS, a quantitative index of pressor support, has been shown to be a predictor of morbidity and mortality in infants younger than six months who underwent CPB. Data on its prognostic utility following pediatric OHT are lacking. This study compared clinical outcomes in children with differential VIS after pediatric OHT. A retrospective cohort study of 51 consecutive heart transplants from 2004 to 2011 was performed at a pediatric tertiary care facility. Peak VIS was computed within initial 24 and 48 h after OHT and was weighted for peak dose and administration of any or all of six pressors. Patients with peak VIS ≥ 15 constituted high VIS group. Children who persistently required a higher magnitude of pressor support for the first 48 h after OHT, as reflected by high peak VIS, had significantly longer ICU stay (30.2 vs. 15.9 days, p = 0.01), pressor (11.4 vs. 6.8 days, p = 0.02) and ventilatory durations (12.4 vs. 5.9 days, p = 0.05), and higher rates of short‐term morbidities. Patients with longer CPB (213 vs. 153 min, p = 0.005) time have higher peak VIS. High peak VIS at 48 h is an effective, yet simple clinical marker for adverse outcomes in pediatric OHT recipients.     

Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living‐donor–dominant program

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.     

The successful use of alemtuzumab for treatment of steroid‐refractory acute graft‐versus‐host disease in pediatric patients

SR‐aGVHD remains a significant cause of morbidity and mortality in allogeneic HCT recipients. Alemtuzumab has been used with success in adult patients but has not been studied in the pediatric setting. To estimate the effectiveness of alemtuzumab for the treatment of SR‐aGVHD in pediatric patients, we retrospectively reviewed the charts of 19 patients (median age 4 yr, range 0.5–28 years) with grades II (n = 3), III (n = 10), or IV (n = 6) SR‐aGVHD who received alemtuzumab treatment. Patients received a median dose of 0.9 mg/kg alemtuzumab (range 0.3–2 mg/kg) divided over 2–6 days. Eighty‐nine percent of patients received additional courses. A complete response, defined as GVHD of grade 0 at four wk following the first alemtuzumab course, was observed in nine patients (47%). A partial response, defined as an improvement in grade after four wk, was observed in five patients (26%). There was no response in five patients (26%). The overall response rate at four wk was 73%. Infectious complications included bacteremia (47%), presumed or documented fungal infections (21%), adenovirus viremia (52%), EBV viremia (36%), and CMV viremia (36%). We conclude that alemtuzumab is effective for SR‐aGVHD in pediatric patients with a tolerable spectrum of complications.     

Epstein‐Barr viral load monitoring for diagnosing post‐transplant lymphoproliferative disorder in pediatric liver transplant recipients

This study aimed to investigate the incidence of PTLD in pediatric liver transplant recipients and the risk factors for the development of PTLD. We also determined clinically useful quantitative EBV PCR parameters for aiding in the diagnosis of EBV‐associated PTLD in the pediatric liver transplant recipients at our institute. We reviewed children < 18 years old who had undergone liver transplantations and quantitative analysis of whole blood EBV load at our institute from January 2006 to March 2015. A total of 142 liver transplant recipients were included, and their median age was 1.5 years. Clinically significant high‐level EBV DNAemia ≥ 10 000 copies/mL at least twice was observed in 53.5% and PTLD occurred in 9.9%. Among PTLD group, graft failure and mortality rate were as high as 21.4% and 14.3%, respectively. Deceased donor, presence of high‐level EBV DNAemia, and primary CMV infection following transplant were associated with an increased risk for PTLD in the multivariate analysis. The peak titer at 10 875 copies/mL could be used as a cutoff value with a sensitivity of 92.9% and a specificity of 37.9%; the rate of increase in EBV load suggested a sensitivity of 64.3% and a specificity of 70.9% at the cutoff value of 44 000 copies/mL/week. In conclusion, the incidence of PTLD following liver transplant in children was as high as 10%. PTLD is associated with significant morbidity and mortality. Close monitoring of EBV DNAemia is crucial for the early diagnosis and proper treatment of PTLD in pediatric liver transplant recipients.     

Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: A seven‐yr experience

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven‐yr experience using alemtuzumab induction and steroid‐free protocol in the pediatric population as safe and effective. Twenty‐one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single‐dose alemtuzumab and were maintained on a steroid‐free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow‐up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m², respectively. Three patients developed acute T‐cell‐mediated rejection due to non‐adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single‐dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low‐dose MMF maintenance therapy.     

Transplantation of adult‐size kidneys in small pediatric recipients: A single‐center experience

RTx of adult‐size kidneys presents a size mismatch in small pediatric recipients, and there are potential surgical complications. This study reveals the outcomes of intra‐ and extraperitoneal RTx in low‐weight (less than 15 kg) pediatric recipients. We studied 51 pediatric patients weighing less than 15 kg who received a living‐related donor renal transplant between 2009 and 2017. The intraperitoneal (group A, n = 24) and extraperitoneal (group B, n = 27) approaches were compared. In group A, the mean age, Ht, and weight were 3.8 ± 1.6 years, 83.7 ± 6.5 cm, 10.5 ± 1.8 kg; in group B, 5.0 ± 1.9 years, 95.3 ± 7.3 cm, and 13.0 ± 1.4 kg. Single renal artery grafts (21 in group A and 16 in group B) and double renal artery grafts (three in group A and 11 in group B) were performed. Of the patients with double renal artery transplants, one in group A and six in group B underwent ex vivo arterial reconstruction. The eGFR (mL/min/1.73 m²) at 1‐week post‐transplant in group A was significantly higher than that in group B; the eGFRs at 4 weeks post‐transplant did not differ. One graft was lost in group B because of vascular thrombosis. Post‐transplant complications included ileus and transplant ureteral stenosis. There was no significant difference in 5‐year graft survival rate (group A 100%, group B 91.7%). Both transplant approaches are feasible to adapt to a size mismatch between the adult‐size donor kidney and low‐weight pediatric recipients.     

Long‐term outcomes of living donor kidney transplants in pediatric recipients following laparoscopic vs. open donor nephrectomy

We compared long‐term outcomes of LDKT in pediatric recipients following either laparoscopic (LDN) or ODN. In our retrospective single‐center study, we compared 38 pediatric LDKT recipients of a laparoscopically procured kidney with a historic ODN group comprising 17 pediatric recipients. In our center, the first pure laparoscopic non‐hand‐assisted LDN for a pediatric LDKT recipient was performed in June 2001. Demographic data of donors and recipients were comparable between groups. Mean follow‐up was 64 months in the LDN group and 137 months in the ODN group. Patient survival was comparable between groups. Graft survival at one and five yr was 97% (LDN) vs. 94% (ODN) and 91% (LDN) vs. 88% (ODN; p = n.s.), respectively. Serum creatinine at one and five yr was 1.16 ± 0.47 mg/dL (LDN) vs. 1.02 ± 0.38 mg/dL (ODN) and 1.38 ± 0.5 mg/dL (LDN) vs. 1.20 ± 0.41 mg/dL (ODN), respectively. The type and frequency of surgical complications did not differ between groups. DGF and acute rejection rates were similar between groups. In the ODN group, a higher proportion of right donor kidneys was used. In the ODN group, all kidneys had singular arteries, whereas in the LDN group five kidneys had multiple arteries. Arterial multiplicity was associated with a higher incidence of DGF. In our experience, LDN does not compromise long‐term graft outcomes in pediatric LDKT recipients. Arterial multiplicity of the donor kidney may be a risk factor for impaired early graft function in the pediatric population.     

The use of hepatitis B immunoglobulin with or without hepatitis B vaccine to prevent de novo hepatitis B in pediatric recipients of anti‐HBc–positive livers

Prophylactic measures are used to reduce DNHB after HBsAg‐negative patients receive anti‐HBc–positive liver grafts. This study investigated the incidence of DNHB and clinical outcomes in pediatric LT recipients under HBIG prophylaxis, with or without hepatitis B vaccination. Between 1995 and 2013, 51 HBsAg‐negative pediatric recipients underwent living‐donor LT from anti‐HBc–positive donors. The median (range) age was 4 (0.1‐17) years, 23 (45%) were male, and 71% were negative for both anti‐HBc and anti‐HBc. During a median follow‐up of 12.1 (0.06‐19.9) years, 13 (25.4%) developed DNHB; 7 of the 13 achieved HBsAg seroconversion after administration of LAM or ETV. Among studied patients, 20 (39%) received hepatitis B vaccination, and 2 of them (10%) developed DNHB. At last follow‐up, 41% (21/51) discontinued HBIG either after successful HBV vaccination (n = 17) or retransplantation with anti‐HBc–negative grafts (n = 4). In conclusion, pediatric LT recipients of anti‐HBc–positive grafts, most of them were naïve to HBV infection, were at high risk of DNHB, and consistent monitoring for the early detection of DNHB was necessary. A combination use of post‐LT vaccination is promising prophylactic strategy against DNHB.     

Non‐invasive differentiation of non‐rejection kidney injury from acute rejection in pediatric renal transplant recipients

Acute kidney injury (AKI) is a major concern in pediatric kidney transplant recipients, where non‐alloimmune causes must be distinguished from rejection. We sought to identify a urinary metabolite signature associated with non‐rejection kidney injury (NRKI) in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant participants were obtained at time of kidney biopsy and quantitatively assayed for 133 metabolites by mass spectrometry. Metabolite profiles were analyzed via projection on latent structures discriminant analysis. Mixed‐effects regression identified laboratory and clinical predictors of NRKI and distinguished NRKI from T cell–mediated rejection (CMR), antibody‐mediated rejection (AMR), and mixed CMR/AMR. Urine samples (n = 199) without rejection were split into NRKI (n = 26; ΔSCr ≥25%), pre‐NRKI (n = 35; ΔSCr ≥10% and <25%), and no NRKI (n = 138; ΔSCr <10%) groups. The NRKI discriminant score (dscore) distinguished between NRKI and no NRKI (AUC = 0.86; 95% CI = 0.79‐0.94), confirmed by leave‐one‐out cross‐validation (AUC = 0.79; 95% CI = 0.68‐0.89). The NRKI dscore also distinguished between NRKI and pre‐NRKI (AUC = 0.82; 95% CI = 0.71‐0.93). In a linear mixed‐effects regression model to account for repeated measures, the NRKI dscore was independent of concurrent rejection, but there was a non‐statistical trend for higher dscores with rejection severity. A second exploratory classifier developed to distinguish NRKI from clinical rejection had similar test characteristics (AUC = 0.81, 95% CI = 0.70‐0.92, confirmed by LOOCV). This study demonstrates the potential of a urine metabolite classifier to detect NRKI in pediatric kidney transplant patients and non‐invasively discriminate NRKI from rejection.