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Allograft outcome; Hyperparathyroidism; Kidney transplantation Resultado del aloinjerto; Hiperparatiroidismo; Trasplante de riñón Resultat de l'aloempelt; Hiperparatiroïdisme; Trasplantament de ronyó Introduction Little is known about the consequences of deranged chronic kidney disease–mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. Methods This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. Results We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82–4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28–2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71–4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87–2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. Conclusion Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children. This study was supported by a research grant from the European Society for Paediatric Nephrology to AP. The authors gratefully acknowledge the funding of the Cooperative European Paediatric Renal Transplant Initiative Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology, and the German Society for Paediatric Nephrology and by grants from the pharmaceutical companies Astellas and Novartis.

Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear.In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mutsup0/sup-type MMAemia, one patient had a mutsup-/sup-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0-15.1 years).Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; Plt; 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; Plt; 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 msup2/sup, in LTx 99.8 ± 29.9 mL/min/1.73 msup2/sup, and in LKTx 31.5 ± 21.2 mL/min/1.73 msup2/sup. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 msup2/sup) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 msup2/sup; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 msup2/sup; P = 0.0403).In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

We describe a 46,XX girl with Denys-Drash syndrome (DDS), showing both kidney disease and genital abnormalities, in whom a misdiagnosis of hyperandrogenism was made. A 15 year-old girl was affected by neonatal nephrotic syndrome, progressing to end stage kidney failure. Hair loss and voice deepening were noted during puberty. Pelvic ultrasound and MRI showed utero-tubaric agenesis, vaginal atresia and urogenital sinus, with inguinal gonads. Gonadotrophin and estradiol levels were normal, but testosterone levels increased up to 285 ng/dL at Tanner stage 3. She underwent prophylactic gonadectomy and histopathology reported fibrotic ovarian cortex containing numerous follicles in different maturation stages and rudimental remnants of Fallopian tubes. No features of gonadoblastoma were detected. Unexpectedly, testosterone levels were found elevated 4 months after gonadectomy (157 ng/dL). Recent medical history revealed a chronic assumption of a high daily dose of biotin, as a therapeutic support for hair loss. Laboratory immunoassay instruments used streptavidin-biotin interaction to detect hormones and, in competitive immunoassays, high concentrations of biotin can result in false high results. Total testosterone, measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), was found within reference intervals. Similar testosterone levels were detected repeating the immunoassay two weeks after biotin uptake interruption. Discordance between clinical presentation and biochemical results in patients taking biotin, should rise the suspicion of erroneous results. Improved communication among patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.

Background Randomized 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. Methods In 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). Results Most 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. Conclusions In 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 abstract

Although a disease is defined as rare when it has a prevalence of less than 1:2000, the overall prevalence of rare diseases in the population is greater than 1%. Among potential organ donors, a similar frequency is observed. To date, guidelines have not been established, and operational decisions have been made empirically, case- by-case, based on the experience and expertise of clinicians. For this reason, the Italian Superior Health Council (CSS) has appointed a working Group to address "patients with a rare disease as potential organ donors," with the aim of devising recommendations for the management of transplant cases in which the donors have a rare disease. This group evaluated 493 diseases (10% of all rare diseases, including over 95% of patients with a rare disease) to deliver a technical report dealing with the suitability of organ donation and transplantation, with a focus on the organs most frequently used, including kidney, liver, heart, lung, and pancreas. This work has made it clear that a rare disease "per se" does not contraindicate organ donation at all. Indeed, in donors affected by a rare disease, almost 80% of the organs are suitable for transplantation, approximately 7% are unsuitable, and approximately 14% are suitable as non-standard with an acceptable risk.

Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26.One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented.This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

CRADLE was a 36-month multicenter study in pediatric (≥1 to

BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) is rare among children but leads to kidney failure (KF) in almost 30% of cases with renal involvement [1]. Kidney transplantation (KT) is the treatment of choice in adults with AAV and KF, while data among children are limited to small case series [2, 3]. We report the outcomes of KT in a multicentre cohort of patients with childhood-onset AAV. METHOD Patients with AAV diagnosed before the age of 18 years who had undergone KT were identified at one Canadian and 20 European centres. We analysed patient and graft survival and the rates of rejection, AAV relapse and infections. Eighteen patients from this cohort had already been reported in previous articles [1, 2]; their follow-up was extended and further relevant data were retrieved. RESULTS We included 55 patients, of whom 38 (69%) had microscopic polyangiitis (MPA) and 17 (31%) granulomatosis with polyangiitis (GPA). Their median age at diagnosis and transplantation was, respectively, 12 (interquartile range, IQR 9–14) and 14 (IQR 12–16) years (Table 1). Living donor transplantation was performed in 20 cases (36%) and deceased donor transplantation in 35 (64%). At the time of transplantation, all patients were in clinical remission and ANCA was positive in 14/54 (26%). As immunosuppressive therapy, 46 patients (84%) received glucocorticoids, tacrolimus and either mycophenolate mofetil or azathioprine. The median follow-up after transplantation was 54 months (IQR 21–91). Acute rejection was reported in 22 patients (40%), 12 of whom experienced it during the first post-transplant year, while chronic rejection was established in two (4%). AAV relapsed in five cases (9%) and involved the graft in 4/5. Positive ANCA at transplantation was significantly associated with relapse (29% versus 2%; P = 0.02). Infections occurred in 34 patients (62%), and were mainly bacterial infections of the urinary tract or viral infections due to CMV (8/34), EBV (5/34) and BK virus (4/34). No patient developed malignancy. At last visit, all patients were alive and 48 (87%) had a functioning graft. Graft function impairment (eGFR CONCLUSION KT in childhood-onset AAV has a relatively good graft and patient survival, while the rate of complications and the risk of vasculitis relapse appear low. Positive ANCA at the time of transplantation may be a risk factor for both AAV relapse and graft function impairment.

Background: Preexistent LUTD are considered a hostile environment, which might negatively impact KTx survival. In such cases, surgical reconstruction of the bladder is required. However, there is still disagreement on the optimal timing of the reconstruction procedure. Methods: This is a multicenter analysis of data from the CERTAIN Registry. Included were 62 children aged 8.18 ± 4.90 years, with LUTD. Study endpoints were the duration of initial posttransplant hospitalization, febrile UTIs, and a composite failure endpoint comprising decline of eGFR, graft loss, or death up to 5 years posttransplant. Outcome was compared to matched controls without bladder dysfunction. Results: Forty-one patients (66.1%) underwent pretransplant and 14 patients (22.6%) posttransplant reconstruction. Bladder augmentation was performed more frequently in the pretransplant (61%) than in the posttransplant group (21%, p =.013). Outcome in the pre- and posttransplant groups and in the subgroups of patients on pretransplant PD with major bladder surgery either pre- (n = 14) or posttransplant (n = 7) was comparable. Outcomes of the main study cohort and the matched control cohort (n = 119) were comparable during the first 4 years posttransplant; at year 5, there were more events of transplant dysfunction in the study cohort with LUTD than in controls (p =.03). Conclusions: This multicenter analysis of the current practice of LUTD reconstruction in pediatric KTx recipients shows that pre- or posttransplant surgical reconstruction of the lower urinary tract is associated with a comparable 5-year outcome. in press

There are several databases across the world that collect pediatric KT data. We compare the hospitalization outcomes for pediatric KT recipients from a large Canadian transplant center (SickKids database; The Hospital for Sick Children Kidney Transplantation Institutional Database), United States (NAPRTCS), and Europe (CERTAIN registry).An institutional retrospective review of KT was performed between 2000 and 2015. Baseline characteristics, duration of initial hospitalization/readmission at 1-5 and 6- to 11-month posttransplant, and 1-year graft survival data were collected. Corresponding data from the NAPRTCS 2014 Annual Transplant Report and CERTAIN registry were compared.Posttransplant, patients from NAPRTCS had the shortest duration of hospitalization within the first month (10.4 days, SE 0.2), followed by SickKids (20.3 days, SE 0.7) and CERTAIN (25.5 days, SE 0.7). For both living and deceased donor populations, patients from SickKids were most likely to be hospitalized at 1- to 5-month posttransplant (82.4% [89/108]; 72.1% [98/136]), followed by Europe (52.1% [198/380]; 61.6% [501/813]) and United States (45.4% [2379/5241]; 51.4% [2517/4896]). Patients from Europe were most likely to be hospitalized at 6- to 12-month posttransplant (42.1% [160/380]; 51.7% [420/813]), followed by SickKids (35.2% [38/108]; 37.5% [51/136]) and United States (28.3% [1387/4901]; 31.6% [1411/4465]). Across all databases, the most commonly addressed issues during readmissions were infectious complications.The differences observed in this investigation may reflect the local reimbursement models, resources for outpatient management, and practice variations across a large Canadian transplant center, United States, and European countries.

Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second-tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long-term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and the C3/C2, C3/C16 ratios. The disease burden showed a direct correlation with MCA and FGF21, for both diseases. All transplanted patients showed a significant reduction of MCA in comparison to baseline values, with some differences dependent on the type of transplantation. Our study provided new insights in understanding the disease pathophysiology, showing similarities between MCA and FGF21 in predicting disease burden, long-term complications and in evaluating the impact of organ transplantation.

WOS: 000530171600001 PubMed: 32367310 Background Secondary hyperparathyroidism (SHPT) may persist after renal transplantation (RTx), inducing hypophosphatemia and hypercalcemia that precludes the use of vitamin D analogs. The calcimimetic cinacalcet improved plasma calcium and parathyroid hormone (PTH) levels in randomized controlled trials in adults after RTx, but pediatric data are scarce. Methods In this retrospective study, we analyzed 20 pediatric patients from the Cooperative European Paediatric Renal TransplAnt Initiative (CERTAIN) Registry who received cinacalcet after RTx. The results are presented as median and interquartile range (25th-75th percentile). Results At 13.7 (11.0-16.5) years of age, 20 pediatric patients received a renal allograft. Cinacalcet was introduced at 0.4 (0.3-2.7) years post-transplant at an estimated glomerular filtration rate (eGFR) of 50 (34-66) mL/min/1.73 m(2), plasma calcium of 2.58 (2.39-2.71) mmol/L, age-standardized (z score) phosphate of - 1.7 (- 2.7-- 0.4), and PTH of 136 (95-236) ng/L. The starting dose of cinacalcet was 0.5 (0.3-0.8) mg/kg per day, with a maximum dose of 1.1 (0.5-1.3) mg/kg per day. With a follow-up of 3.0 (1.5-3.6) years on cinacalcet therapy, eGFR remained stable; PTH levels decreased to 66 (56-124) ng/L at the last follow-up (p = 0.015). One patient displayed hypocalcemia (1.8 mmol/L). Cinacalcet was withdrawn in three patients (hypocalcemia, parathyroidectomy, incompliance). Nephrocalcinosis of the graft was not reported. Conclusions This pilot study suggests that cinacalcet as off-label therapy for SHPT after pediatric RTx is efficacious in controlling post-transplant SHPT with acceptable tolerability. Continuing cinacalcet even with normal PTH can lead to dangerous life-threatening hypocalcemia. Therefore, at each subsequent visit, the need to continue cinacalcet must be assessed. Dietmar Hopp Stiftung; European Society for Paediatric Nephrology (ESPN); German Society for Paediatric Nephrology (GPN); AstellasAstellas Pharmaceuticals; NovartisNovartis The authors received financial support from the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), and the German Society for Paediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

BACKGROUND Brain death secondary to traumatic brain injury is one of the main sources of organs for transplantation but it can be associated with disseminated intravascular coagulation, which has been considered a relative contraindication for kidney donation. METHODS We describe two successful pediatric cases of kidney transplantation from a single donor with disseminated intravascular coagulation. RESULTS A 17-year-old male donor died from head injury and both kidneys were offered to our center. Within 24 h, donor's Hb and platelets dropped to 8.3 g/dl and 32 000/mcl, respectively, serum creatinine reached 2.01 mg/dl, and urinalysis showed proteinuria (300 mg/dl). Pre-implant biopsy showed massive occlusion of glomerular capillaries by fibrin thrombi containing fragmented red blood cells and inflammatory cells, and acute tubular damage. Arterioles and small arteries were spared. A diagnosis of DIC was made. The kidneys were transplanted in a 16-year-old girl and a 13-year-old boy. Slow recovery of graft function was observed in both recipients. On post-operative day 3, platelets dropped to a minimum value of 66 000 and 86 000/mcl, respectively. Diuresis was always present. On day 4, platelets started to rise. Six months later, both recipients attained normal renal function. A six-month protocol biopsy showed no microthrombi or other signs of disseminated intravascular coagulation. CONCLUSIONS Despite the limited data available in literature, the outcome of these two cases is positive. Thus, pre-implant kidney biopsy, even if it reveals massive thrombotic occlusion of glomerular capillaries compatible with diagnosis of disseminated intravascular coagulation, should not be considered an absolute contraindication to transplantation.

Treatment of post-transplant focal segmental glomerulosclerosis (FSGS) recurrence is still debated. The use of the fully human anti-CD20 monoclonal antibody ofatumumab has been suggested. Two boys with FSGS received a kidney transplantation at the age of 15 years from a deceased and a living donor. Maintenance therapy consisted of calcineurin inhibitors, antiproliferative agents, and prednisone. Early post-transplant FSGS recurrence was observed after 2 and 3 days. Rituximab infusion and plasmapheresis sessions were performed with transient clinical improvement in the first patient, and no apparent response in the second patient. Both patients were treated with two ofatumumab infusions, which induced in patient #1 a complete and stable remission for more than 12 months and in patient #2 a partial remission with a progressive reduction of proteinuria and normalization of serum protein levels. Ofatumumab may be a therapeutic option for post-transplant FSGS recurrence in patients who respond poorly to rituximab.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

Background and Aims Kidney transplantation (KTx) in pediatric ages is successful, leading to optimal patients and graft survival with indication, in adolescent age, to transition toward an adult transplant facility. To date, the transition process of adolescents and young adults with KTx is not well defined. Transfer to a different medical facility marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Some studies report unexpected loss rates in kidney grafts as high as 24%–42% within 3 years after transfer. In addition, some studies show that the age ranging from 18 to 26 years is the age in which graft losses are most concentrated, an age that coincides with the transition. Several makers have been shown to influence non-adherence rate in kidney transplanted patients during transition: a bad doctor-patient relationship, the absence of specialized centers capable to face these particular needs and care requests, the lack of psychological support, and a low availability of specialized nurses. Moreover, many patients are lost to follow-up as the result of breakdowns in the transition and transfer to adult medical care. Method In this study we enrolled patients transited from the pediatric transplant Centre to the adult transplant nephrological facility between 2017 and 2020. Data of KTx, baseline renal disease, post-transplant medications and post-transplant complications were recorded. Follow-up of renal function were performed and analyzed during the transition process and forward during the adult follow-up. Results Data of 19 patients (pts) were analysed. Six were male (31.6%) and 13 female (68.4%). The cause of renal dysfunction was malformations in 10 patients (52.6%), glomerulonephritis (GN) in 5 pts (26.3%) and genetic syndromes in 4 pts (21.1%). They received the kidney transplantation at a median age of 12 years [IQR 10-18]. Median age at transition resulted 31 years [interquartile range (IQR) 30-33]. Seven pts (36.8%) had a history of post-transplant lymphoproliferative disease (PTLD). All patients were receiving steroids, 11 pts (57.9%) cyclosporine A and 8 pts (42.2%) tacrolimus; only 9 pts (47.4%) were receiving mycophenolate or azathioprine. The median follow-up at the adult Transplant Centre was 1 year [IQR 1-2]. After transition, five patients experienced complications: 2 pts developed PTLD de novo, 2 pts had a recurrence of native GN after reduction of immunosuppression for PTLD and pregnancies (one pt underwent re-tx), 1 pt experienced an acute cellular rejection after transition to another Centre and is developing ESRD. The median eGFR slightly decreased from baseline at transition to the last follow-up (80 ml/min/1.73 m2 at baseline [55-112]; 74 ml/min/1.73m2 at last follow-up [35-98]) but this was not significant (p=0.127). Conclusion Our results confirm that the transition from pediatric to adult transplant Centre is not a simple process. Several factors linked to the patient and to the kidney have to be considered in the development of post-transplant complications: the age of transplantation with long term immunosuppression; infections typical of pediatric ages that may develop in adulthood, such as EBV, that force to modulate immunosuppression exposing the patient to increased risk of rejection or recurrence of native disease; the exposure to different immunological stimuli and physiological events such as pregnancies in female patients. These patients may develop complications linked to non-adherence and low compliance to immunosuppressive medications, but also complications typical of adult age, like arterial hypertension, obesity, diabetes, and dyslipidemias. Therefore, defining effective practices for recipient transition and transfer from pediatric to adult medical care are essential to optimize the KTx patients follow-up and outcome.

(1) Background: Post-transplant lymphoproliferative disease (PTLD) is a significant complication of solid organ transplantation (SOT). However, there is lack of consensus in PTLD management. Our aim was to establish a present benchmark for comparison between international centers and between various organ transplant systems and modalities, (2) Methods: A cross-sectional questionnaire of relevant PTLD practices in pediatric transplantation was sent to multidisciplinary teams from 17 European center members of ERN TransplantChild to evaluate the centers’ approach strategies for diagnosis and treatment and how current practices impact a cross-sectional series of PTLD cases, (3) Results: A total of 34 SOT programs from 13 European centers participated. The decision to start preemptive treatment and its guidance was based on both EBV viremia monitoring plus additional laboratory methods and clinical assessment (61%). Among treatment modalities the most common initial practice at diagnosis was to reduce the immunosuppression (61%). A total of 126 PTLD cases were reported during the period 2012–2016. According to their histopathological classification, monomorphic lesions were the most frequent (46%). Graft rejection after PTLD remission was 33%. Of the total cases diagnosed with PTLD, 88% survived, (4) Conclusions: There is still no consensus on prevention and treatment of PTLD, which implies the need to generate evidence. This might successively allow the development of clinical guidelines.

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

After 2 decades as a low-cost transplant centre in India, our rates of kidney transplantation are low compared to the burden of end-stage kidney disease (ESKD). We performed this study to identify possible barriers inhibiting paediatric kidney transplant and to assess the outcomes of paediatric ESKD. A retrospective chart review of ESKD patients (2013 - 2018) at a tertiary paediatric nephrology centre was conducted. Medical/non-medical barriers to transplant were noted. Patient outcomes were classified as "continued treatment," "lost to follow-up (LTFU)" or "died." Of 155 ESKD patients (monthly income 218 USD [146, 365], 94% self-pay), only 30 (19%) were transplanted (28 living donor). Sixty-five (42%) were LTFU, 19 (12%) died, and 71 (46%) continued treatment. LTFU/death was associated with greater travel distance (300 km [60, 400] vs 110 km [20, 250] km, P

HTN after renal transplantation is associated with cardiovascular morbidity. ABPM allows diagnosis of masked HTN and isolated nocturnal HTN. Longitudinal ABPM data in children post-transplant are limited. ABPM was performed in children post-transplant and repeated in 6-12 months. BP indices were used to determine the prevalence of masked HTN, masked uncontrolled HTN (masked HTN in patients on antihypertensive medications), and isolated nocturnal HTN. Linear regression determined the association between LVMI and ABPM indices. Thirty children underwent a baseline ABPM. Ambulatory HTN was present in 25 (83%). Masked HTN was present in 18 (60%) and isolated nocturnal HTN in 13 (43%). Nocturnal ambulatory BP was higher than corresponding daytime BPs (P

Kidney transplantation is the best treatment for children with end-stage kidney disease. Early results have improved, but late graft loss is still a major problem. Non-invasive, fully reliable early biomarkers of acute rejection are currently missing. Our aim was to evaluate the efficacy of protocol biopsies (PBXs) in a pediatric population. During 11 years, 209 renal transplantations were performed in 204 pediatric patients. Biopsies were performed 3–6 months, 1 year, and 5 years after transplantation. Procedure-related complications were systematically looked for by means of ultrasound scans. Unexpected findings (mainly subclinical rejections) requiring therapeutic intervention were found in 19.3% biopsies performed at 3–6 months, in 18.4% in 12-month biopsies and in none of those performed after 5 years. The 13.6% patients at 12-month biopsies and 23.6% at 5-year biopsies showed calcineurin inhibitor (CNI) toxicity. Interstitial fibrosis and tubular atrophy (IF/TA) was found in 17.6 and 83.6% of patients at 12-month and 5-year biopsies, respectively. Complications of the PBX were infrequent. Five-year estimated glomerular filtration rate (GFR) was not significantly different in patients who received treatment for any cause and patients with normal histology. Although we do not have a control group, we may speculate that patients who received treatment returned to a “standard” condition possibly improving final outcome. Protocol biopsies are a powerful diagnostic tool for the management of pediatric renal transplant recipients. In view of the lack of evidence that biopsies taken 5 years after transplantation lead to any therapeutic change, their use should be reconsidered.

Background Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.

Ozcakar, Zeynep/0000-0002-6376-9189; Memaran, Nima/0000-0002-9510-3154; DUZOVA, ALI/0000-0002-4365-2995; Sugianto, Rizky Indrameikha/0000-0002-7929-507X WOS: 000511956000006 PubMed: 31811541 Background High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. Methods This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. Results At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. Conclusions BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).

Exhaustion of vascular accesses is a major complication in patients undergoing hemodialysis, especially in pediatric setting. We report the case of a boy treated for loss of hemodialysis access after a combined liver-kidney transplantation and transient renal dysfunction. An interventional dilatation of calcific superior vena cava allowed to insert a stable central venous line for dialysis until full graft recovery. Careful management of central lines allows to spare the main vessels and reduces the need for unusual accesses.

Background: Sequential liver-kidney transplantation (SeqLKT) from the same living donor has shown excellent results in children with primary hyperoxaluria type 1 (PH1), yet its experience is limited due to the invasiveness of two major procedures for liver-kidney procurement in a single donor. Despite laparoscopic nephrectomy and hepatic left lateral sectionectomy (LLS) being considered standard procedures in living donation, the sequential use of the two laparoscopic approaches in the same living donor has never been reported. Methods: Herein, we present the first two case series of laparoscopic liver-kidney procurement in the same living donor for SeqLKT in children with PH1 and review of the current literature on this topic. Results: In the first case, a 15-month-old boy received a SeqLKT from his 32-year-old mother, who underwent a laparoscopic LLS and, after 8 months, a laparoscopic left nephrectomy. In the second case, a 34-month-old boy received a SeqLKT from his 40-year-old father who underwent laparoscopic LLS followed by hand-assisted right nephrectomy after 4 months. Both donors had uneventful postoperative courses and were discharged within 5 days from each surgery. The first recipient had no complication; the second child after liver transplantation developed a partial thrombosis of the inferior vena cava, which did not preclude the sequential kidney transplantation. After 12 months, donors and recipients displayed normal liver and renal functions. Conclusions: Sequential laparoscopic liver-kidney procurement in the same living donor is safe and feasible, and might be considered as a possible strategy to promote SeqLKT in children with PH1 from the same living donor.

Background: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome. Case-Diagnosis/Treatment: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d. Test results were negative for donor-specific antibodies against human leukocyte antigens (HLA-DSA) and MHC class I-related chain A (MICA) but positive for AT1R-Ab. Retrospective testing of the sera collected during the first kidney transplant was also positive for AT1R-Ab. We therefore hypothesized that the failure of the first transplant was secondary to the same cause. Losartan was immediately introduced into the therapeutic regimen, and the patient showed an excellent clinical and histological recovery. Conclusions: Testing for AT1R-Ab in any hypertensive patient with acute rejection who tests negative or weakly positive for C4d and negative for HLA-DSA and who is refractory to therapy is highly advisable. Pre-transplant AT1R-Ab may be indicative of the outcome in patients whose first transplant failed. Prompt initiation of treatment with losartan--immediately after transplantation in patients with pre-existing AT1R-Ab--should be encouraged.

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.Presumptive BKPyVAN (defined as sustained [3 wk] high-level BK viremia10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P0.01) but also with younger recipient age (OR, 1.1 per y younger; P0.001) and obstructive uropathy (OR, 12.4; P0.01) as primary renal disease.Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Context Type 1A pseudohypoparathyroidism (PHP-1A) is characterized by target organ resistance to PTH. Patients can present with various dysmorphic features; however, renal failure has not been classically described. Case Description A female patient came to our attention at the age of 7 years with characteristic signs of PTH resistance (i.e., hypocalcemia, hyperphosphatemia, and high serum PTH levels). She also presented with hypothyroidism, early-onset obesity, short metacarpal bones, and multiple subcutaneous ossifications, leading to a clinical diagnosis of pseudohypoparathyroidism. In addition to her genetic condition, she had bilateral renal hypodysplasia that was slowly progressing to end-stage kidney disease. She received a kidney transplant at the age of 16 years and, after transplantation, experienced rapidly normalized calcium, phosphate, and PTH levels, allowing f withdrawal of vitamin D supplementation. Conclusions To the best of our knowledge, ours is the first report of a patient with PHP-1A undergoing kidney transplantation. Normalization of biochemical parameters after the procedure demonstrated that renal tubular resistance to PTH is sufficient to explain the calcium/phosphate abnormalities observed in PHP-1A.

Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx. We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10–15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry. Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m2; control 74.8 ± 29.1 mL/min/1.73 m2; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57). These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise.

WOS: 000422685400019 PubMed: 28983694 Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are scarce. Within the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national, retrospective study investigating the vaccination coverage before transplantation of 254 European children with end-stage renal disease (mean age 10.0 +/- 5.6 years). Only 22 out of 254 patients (8.7%) presented complete vaccination coverage. In particular, the respective vaccination coverage against human papillomavirus (27.3%), pneumococci (42.0%), and meningococci (47.9%) was low. Patients with complete pneumococcal vaccination coverage had numerically less lower respiratory tract infections during the first 3 years post-transplant than children without vaccination or with an incomplete status (16.4% vs 27.7%, p = 0.081). Vaccine-preventable diseases post-transplant were 4.0 times more frequently in unvaccinated than in vaccinated patients. Factors associated with an incomplete vaccination coverage were non-Caucasian ethnicity (OR 9.21, p = 0.004), chronic dialysis treatment before transplantation (OR 6.18, p = 0.001), and older age at transplantation (OR 1.33, p < 0.001). The vaccination coverage in paediatric kidney transplant candidates is incomplete. Paediatric nephrologists, together with primary-care staff and patients' families, should therefore make every effort to improve vaccination rates before kidney transplantation. German Center for Infection Research (DZIF) We cordially thank our study nurse Annette Mechler for her continuous excellent contribution to the CERTAIN Registry. We thank Prof. Dr. Annette Mankertz, Robert Koch-Institute Berlin, Germany, for her helpful advice. BH is an awardee of the "DZIF Clinical Leave Stipend" by the German Center for Infection Research (DZIF).

WOS: 000427973600018 PubMed: 29322328 Background Avoidance of vaccine-preventable infections in paediatric renal allograft recipients is of utmost importance. However, the development and maintenance of protective vaccination titres may be impaired in this patient population owing to their need for immunosuppressive medication. Methods In the framework of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN), we therefore performed a multi-centre, multi-national study and analysed vaccination titres pre-and post-transplant in 155 patients with serial titre measurements in comparison with published data in healthy children. Results The percentage of patients with positive vaccination titres before renal transplantation (RTx) was low, especially for diphtheria (38.5%, control 75%) and pertussis (21.3%, control 96.3%). As few as 58.1% of patients had a hepatitis B antibody (HBsAb) titre > 100 IU/L before RTx. 38.1% of patients showed a vaccination titre loss post-transplant. Patients with an HBsAb titre between 10 and 100 IU/L before RTx experienced a significantly (p < 0.05) more frequent hepatitis B vaccination titre loss post-transplant than patients with an HBsAb titre > 100 IU/L. The revaccination rate post-transplant was low and revaccination failed to induce positive titres in a considerable number of patients (27.3 to 83.3%). Treatment with rituximab was associated with a significantly increased risk of a vaccination titre loss post-transplant (odds ratio 4.26, p = 0.033). Conclusions These data show a low percentage of patients with positive vaccination titres pre-transplant, a low revaccination rate post-transplant with limited antibody response, and a high rate of vaccination titre losses. CERTAIN Registry; Dietmar Hopp Stiftung; pharmaceutical company Astellas; pharmaceutical company Novartis We gratefully acknowledge the support of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung and by grants from the pharmaceutical companies Astellas and Novartis.

Dyslipidemia contributes to cardiovascular morbidity and mortality in pediatric transplant recipients. Data on prevalence and risk factors in pediatric cohorts are, however, scarce. We therefore determined the prevalence of dyslipidemia in 386 pediatric renal transplant recipients enrolled in the CERTAIN registry. Data were obtained before and during the first year after RTx to analyze possible non-modifiable and modifiable risk factors. The prevalence of dyslipidemia was 95% before engraftment and 88% at 1 year post-transplant. Low estimated glomerular filtration rate at 1 year post-transplant was associated with elevated serum triglyceride levels. The use of TAC and of MPA was associated with significantly lower concentrations of all lipid parameters compared to regimens containing CsA and mTORi. Immunosuppressive regimens consisting of CsA, MPA, and steroids as well as of CsA, mTORi, and steroids were associated with a three- and 25-fold (P

Cystinuria is an autosomal recessive disease that causes l-cystine precipitation in urine and nephrolithiasis. Disease severity is highly variable; it is known, however, that cystinuria has a more severe course in males. The aim of this study was to compare l-cystine metastability in first-morning urine collected from 24 normal female and 24 normal male subjects. Samples were buffered at pH 5 and loaded with l-cystine (0.4 and 4 mM final concentration) to calculate the amount remaining in solution after overnight incubation at 4 °C; results were expressed as Z scores reflecting the l-cystine solubility in each sample. In addition, metabolomic analyses were performed to identify candidate compounds that influence l-cystine solubility. l-cystine solubility Z score was +0.44 ± 1.1 and −0.44 ± 0.70 in female and male samples, respectively (p

HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. While "typical" HUS is usually associated with Shiga toxin-producing Escherichia coli infections and recovers in the majority of cases, aHUS is caused by mutations of complement components or antibodies against CFH leading to uncontrolled activation of alternative complement pathway and often to ESRD. Recently, THBD gene mutations have been reported in aHUS. Theoretically, the risk of disease recurrence after renal transplantation should be low because THBD is primarily a membrane-bound protein expressed by endothelial cells; however, a small proportion of THBD is present as a soluble form in plasma. We report the case of a 19-yr-old man with aHUS secondary to a THBD mutation that relapsed twice after two renal transplantations performed 12 yr apart. Despite successful control of HUS with plasma exchange and eculizumab after the second transplantation, the graft was ultimately lost due to severe steroid-resistant cellular rejection. The present report suggests that THBD mutations may favor-relapse of aHUS after renal transplantation.

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. Data on immune responses and long-term maintenance after vaccinations in such population are still limited. We cross-sectionally evaluated the maintenance of immune response to measles vaccine in kidney transplanted children on immunosuppressive therapy. Measles-specific enzyme-linked immunosorbent assay and B-cell enzyme-linked immunosorbent spot were performed in 74 kidney transplant patients (Tps) and in 23 healthy controls (HCs) previously vaccinated and tested for humoral protection against measles. The quality of measles antibody response was measured by avidity test. B-cell phenotype, investigated via flow cytometry, was further correlated to the ability of Tps to maintain protective humoral responses to measles over time. We observed the loss of vaccine-induced immunity against measles in 19% of Tps. Nonseroprotected children showed signs of impaired B-cell distribution as well as immune senescence and lower antibody avidity. We further reported as time elapsed between vaccination and transplantation, as well as the vaccine administration during dialysis are clinical factors affecting the maintenance of the immune memory response against measles. Tps present both quantitative and qualitative alterations in the maintenance of protective immunity to measles vaccine. Prospective studies are needed to optimize the vaccination schedules in kidney transplant recipients in order to increase the immunization coverage over time in this population.

Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P < 0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein–Barr virus (EBV) infection. The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation. Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (

Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge. We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes. In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells. This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.