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(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.

Pierson syndrome (PIERSS) is a rare autosomal recessive disorder characterized by the combination of congenital nephrotic syndrome (CNS) and extrarenal symptoms including ocular malformations and neurodevelopmental deficits. PIERSS is caused by biallelic pathogenic variants in the LAMB2 gene leading to the defects of β2-laminin, the protein mainly expressed in the glomerular basement membrane, ocular structures, and neuromuscular junctions. Severe complications of PIERSS lead to the fatal outcome in early childhood in majority of the cases. We report a case of 5-year-old girl with severe phenotype of PIERSS caused by biallelic functional null variants of the LAMB2 gene. Due to consequences of CNS, the patient required bilateral nephrectomy and peritoneal dialysis since early infancy. The course was additionally complicated by tubulopathy, life-threatening infections, severe hypertension, erythropoietin-resistant anemia, generalized muscular hypotonia, neurogenic bladder, profound neurodevelopmental delay, epilepsy, gastrointestinal problems, secondary hypothyroidism, and necessity of repeated ocular surgery due to microcoria, cataract, and nystagmus. Due to multidisciplinary efforts, at the age of 4 years, the kidney transplantation was possible. Currently, the renal graft has an excellent function; however, the girl presents severe neurodevelopmental delay. The report presents a unique long-term follow-up of severe PIERSS with a few new phenotypical findings. It highlights the clinical problems and challenges in management of this rare condition.

Background and Aims Growth retardation is one of considerable problems in children with chronic kidney disease (CKD) with a great impact on life activity and quality of life. Recombinant human growth hormone (rhGH) treatment has been used for more than 30 years to improve growth velocity and final growth in children with CKD. In Poland rhGH therapy in children with CKD is available since 1994. The aim of the study was to assess growth velocity in all children with CKD treated with rhGH in Poland since 1994. Method We retrospectively analyzed 321 polish children with CKD (mean age: 10.2±7.60, 210 ♂ (65%) qualified to the rhGH therapy between 1994 and 2019. Among 321 children, 180 (56.1%) were on conservative treatment (CT), 118 (36.7%) on chronic dialysis (RRT) and 23 (7.2%) after kidney transplantation (KTx). In 240 (75%) patients who were treated continuously for at least 12 months we have evaluated: growth velocity and mean annual values of selected biochemical parameters. Results Mean height SDS at the beginning of the treatment was -2.73±1.04 SD, among children on CT -2.22±1.20, on RRT -2.9±1.11, after KTx -3.07±1.30. Mean time of rhGH treatment was 23±10.7 months. During one-year rhGH treatment mean growth velocity in 240 children was: 8.5 ± 2.7 cm (ΔSDS 0.78±1.02) and mean height SDS increased significantly (-2,73±1.04 vs. -1.92±1.11, p Conclusion 1. Growth hormone treatment is highly effective in children with CKD especially those who are treated consevatively. 2. Early initiation of rhGH therapy is the crucial factor determining response to the treatment in children with CKD.

Background Post-transplantation lymphoproliferative disorder (PTLD) is a complication of organ transplantation and a life-threatening condition. Children who underwent organ transplantation are at risk of developing lymphoproliferative disorders and, among them, non-Hodgkin lymphoma (NHL) is the most serious. Objectives The objective of this study was to describe the clinical course of NHL after liver and kidney transplantation. Material and methods Retrospective analysis of medical records of children who underwent liver/kidney transplantation and developed NHL. Results Nine children were identified, all girls, 6 after liver and 3 after kidney transplantations. Age at transplantation ranged from 1 year to 13 years (median: 4 years), while age at lymphoma diagnosis from 4 to 17 years (median: 12 years). Time from transplantation to lymphoma diagnosis ranged from 7 months to 12 years (median: 9 years). All but 1 patient developed mature B-cell lymphoma, 4 children - diffuse large B-cell lymphoma (DLBCL), 2 children - Burkitt's lymphoma, 1 child - mature B-cell leukemia, 1 child - Burkitt-like lymphoma, while 1 patient was diagnosed with T-cell lymphoblastic lymphoma. High levels of Epstein-Barr virus (EBV) DNA were found in blood of 3 patients, and EBV in tissue samples was detected in 4 patients. Six patients presented with stage III and 2 with stage IV disease. Two patients had graft involvement. Three children received chemotherapy according to R-CHOP, 3 LMB protocol (2 with addition of rituximab), while 1 received CHOP and 5 courses of COP. T-cell lymphoma patient was treated with Euro-LB protocol. Six out of 8 treated patients are alive with a median follow-up of 6 years. Two children died from disease progression during treatment and 1 from cerebral herniation before starting therapy. All patients experienced at least 1 toxic episode of grade 3 and 4 according to Common Toxicity Criteria Adverse Event (CTCAE). Complications of chemotherapy were manageable and there were no transplanted organ failures. Conclusions Our study provides further data on the treatment and outcome of monomorphic PTLD and indicates that it is feasible to treat solid organ recipients with multiagent chemotherapy.

SIOD is rare disorder related to SMARCAL1 or SMARCAL2 gene mutation, including (among other comorbidities) T-cell immunodeficiency, nephrotic syndrome, and renal failure. Up to 22% of primary patients may develop various autoimmune disorders. We report the case of 11-year-old male with SIOD, who presented ITP at 2 years after renal transplantation with decrease in platelet count (from normal) to 56 000/μL and then (gradually) to 2000/μL. There was no effect of iv. methylprednisolone/dexamethasone. As the presence of antibodies against GPIIb/IIIa, GPIb, and GPIaIIa platelet glycoproteins was confirmed, patient was given 50 g of IVIG and then was put on plasmapheresis; however, both showed poor direct effect. As we were afraid to give rituximab (due to expected overimmunosuppression), we prescribed the oral TPO-receptor agonist (eltrombopag). Patient responded after 17 days of therapy, to the final dose of 50 mg/d (approx. 2 mg/kg). The antiplatelet antibodies disappeared after four plasmapheresis. Overall, the therapy was continued for 7 weeks and was stopped at platelet count of 433 000/μL. Platelet count remained stable in 8-month follow-up. Combination of plasmapheresis and TPO-receptor agonist was effective in post-renal transplant acute ITP in patient with SIOD.

Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently—rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1–2 days) post-transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2–4 weekly doses of 375 mg/m2 of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury. Conclusion: The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol. What is Known: • nephrotic syndrome may recur immediately after renal transplantation • plasmapheresis combined with pharmacotherapy is used as rescue management • rituximab was reported as effective drug both in primary and post-transplant nephrotic syndrome What is New: • rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug • there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action

Concentration of soluble urokinase receptor (suPAR) was regarded as viable marker to differentiate the focal segmental glomerulosclerosis (FSGS) from other glomerulopathies and also as predictive parameter for progression of renal disease.The aim of this study was to evaluate serum and urine (s)(u)suPAR concentration in steroid-sensitive and steroid-resistant nephrotic children treated with different (double and triple-drug) regimens.Overall 43 children were evaluated including 14 patients with steroid-resistant nephrotic syndrome (SRNS) aged 9±6 years and 29 with steroid-sensitive nephrotic syndrome (SSNS) aged 9±5 years, as well as control group (n=59). The concentration of suPAR was measured with ELISA kit (R∧D Systems Inc.).There was no difference in serum suPAR level between SRNS (6404, range: 4613-9575 pg/mL) and SSNS (5745, range: 4666-8246 pg/mL) patients, and also in urinary suPAR: SRNS (2877, range: 847- 19121 pg/mL) and SSNS (2854, range: 328-7434 pg/mL), respectively. There was no statistically significant difference in serum biomarker concentrations between patients with severe course of the disease, in combination therapy, with three drugs: CsA + MMF + Pred (5968, range: 4613-9575 pg/mL) in comparison with patients receiving double therapy: CsA + Pred or MMF + Pred (5449, range: 4666-6623 pg/mL, 5905, range: 5102-6730 pg/mL, respectively). SuPAR concentration in the urine of patients treated with Pred + MMF was lower (1493, range: 328-4444 pg/mL) than in patients receiving Pred + CsA (3193, range: 629-7434 pg/mL), as well as lower than in patients with triple combination of drugs (3318, range: 448-5570 pg/mL), however the difference was not statistically significant.Serum and urine concentration of suPAR did not different between different clinical patterns of nephrotic syndrome in children, regardless the immunosuppressive treatment used.

UNLABELLED Rituximab (anti-B CD20 ab.) in recently widely used in renal transplantation. CASE HISTORY A 10-yr-old patient with end-stage renal failure due to multidrug-resistant NS was transplanted with renal graft from deceased donor and presented immediate recurrence of NS. PF was started on day 3 and patient received MP pulses, however with no effect. Rituximab (4 × 375 mg/m(2)) was administered. Chest radiographs taken at that time were normal. Partial remission was achieved and the patient was discharged in good condition. Sequential recurrence appeared two wk afterward. Twelve sessions of PF were performed and six pulses of MP were given, effecting a partial remission. Three months after the last dose of rituximab, patient was admitted with increasing respiratory failure, requiring mechanical ventilation. Infectious background, including CMV, BKV, mycoplasma, and pneumocystis, was not confirmed. The patient was treated with MP pulses, IVIG, and a variety of antibiotics. Ground-glass opacity was confirmed on lung CT images. Respiratory failure worsened, despite aggressive ventilation and patient passed away after three wk at ICU. A destruction of alveolar epithelium and extended pulmonary fibrosis was confirmed in the autopsy report. The case represents a fatal RALI.

SIOD is an autosomal recessive disorder caused by mutations in SMARCAL 1 gene. It is characterized by spondyloepiphyseal dysplasia with disproportionate short stature, facial dysmorphism, nephrotic syndrome with focal glomerulosclerosis and progressive renal failure, recurrent lymphopenia, T-cell immunodeficiency and pigment naevi. The prevalence of SOID is estimated at 1 in 1-3 mln live births. Aim: To present clinical observations in pts with SIOD. Material: A retrospective review of 4 case reports of SIOD pts. Results: Molecular analysis confirmed different mutations in SMARCAL 1 gene in pts and their parents. Pts 2 and 4 were related. The pts were born with intrauterine growth restriction but no SIOD features were observed. They appeared with time. Because of terminal renal failure all pts underwent RT. Primary immunodeficiency was also observed. There were respiratory symptoms present. They ranged from staphylococcal (SA) pneumonia (pt 1) to mild upper respiratory tract infections (pt 4). Chest X-rays were normal. | No of pt | age*/ sex | onset of NS [yrs] | age of RT [yrs] | age of SMARCAL 1 identification [yrs] | weight/height* [kg/cm] | respiratory disease | || | 1 | 10.10 / M | 3.9 | 7.7 | 10.7 | 19.5/107 | SA pneumonia, recurrent upper and lower respiratory tract infections | | 2 | 10.8 / M | 1.6 | 9.3 | 8 | 21.5/115 | pneumonia, bronchitis | | 3 | 8.9 / F | 2.9 | 5.5 | 7.2 | 13.8/87 | congenital pneumonia, several respiratory infections, sinusitis | | 4 | 5.9 / M | 1.4 | 5.0 | 4.4 | 14.2/91 | several mild upper respiratory tract infections | * * date: Dec 2014, NS-nephrotic syndrome, RT-renal transplantation The pts characteristic Conclusions: It may be possible that differences in frequency and severity of respiratory infections in SIOD pts are due to different mutations in SMARCAL 1 gene.

BACKGROUND Despite prospective crossmatching and modern immunosuppression, early acute rejection is still present in cadaveric renal transplantation. The purpose of this study was to evaluate the incidence of preformed anti-donor antibodies, detected by 2 solid-phase techniques, and to analyze their impact on early renal allograft outcome. MATERIAL/METHODS Flow crossmatch detecting the presence of anti-donor IgG and IgM antibodies was performed in pre-transplant sera of 279 patients with negative cytotoxic crossmatch. Screening for IgG antibodies detected by bead-based multiplex technique was performed in sera of 69 patients from the FCXM group. The incidence of early biopsy-proven rejection and graft failure within 3 months after transplantation was analyzed. RESULTS Anti-donor IgG antibodies were detected in 33 patients (11.8%) by flow crossmatch and in 10 patients by multiplex (14.5%). IgM antibodies were detected in 23 patients (8.2%). All multiplex-positive sera were also positive for IgG by flow crossmatch, but in 18 cases no antibodies were found by multiplex technique. Biopsy-proven acute rejection within 3 months after transplantation was observed in 16 patients, and 5 allografts were lost due to immunological reasons. Presence of IgG antibodies was found to have no effect on early outcome, while the presence of IgM antibodies was associated with significantly higher rejection rate and immune-related graft failure. CONCLUSIONS Anti-donor IgG antibodies detected by bead-based and cell-based technique have no impact on biopsy-proven rejection rate or graft failure. Anti-donor IgM detected by flow crossmatch have significant impact on early transplantation outcome.

Early recurrence of nephrotic syndrome after renal transplantation is a common serious adverse event in children with severe primary FSGS, affecting long-term outcome. There is no consensus in terms of uniform management in these cases. We describe the long-term effect of four unadjusted doses of 375 mg/m(2) i.v. rituximab, given to a five and a half-yr-old, nephrectomized child with immediate recurrence of nephrotic syndrome post-transplantation and dependency from repeated PF. Rituximab was introduced at three months post-transplantation after performing 18 sessions of PF and development of established dependency of the disease from plasma exchange. Complete remission of proteinuria was achieved with four doses, and it was maintained during next eight months of follow-up. Complete B CD(19) cell depletion was observed during four months after final dose, followed by severe depletion after eight months. No side effects of therapy were noted. Patient was free from PF, which was stopped while introducing rituximab, remaining non-proteinuric on triple immunosuppression (CsA, MMF, Pred).

Grenda R, Jarmuzek W, Piątosa B, Rubik J. Long-term effect of rituximab in maintaining remission of recurrent and plasmapheresis-dependent nephrotic syndrome post-renal transplantation – Case report. Pediatr Transplantation 2011: 15: E121–E125. © 2010 John Wiley & Sons A/S. Abstract: Early recurrence of nephrotic syndrome after renal transplantation is a common serious adverse event in children with severe primary FSGS, affecting long-term outcome. There is no consensus in terms of uniform management in these cases. We describe the long-term effect of four unadjusted doses of 375 mg/m2 i.v. rituximab, given to a five and a half-yr-old, nephrectomized child with immediate recurrence of nephrotic syndrome post-transplantation and dependency from repeated PF. Rituximab was introduced at three months post-transplantation after performing 18 sessions of PF and development of established dependency of the disease from plasma exchange. Complete remission of proteinuria was achieved with four doses, and it was maintained during next eight months of follow-up. Complete B CD19 cell depletion was observed during four months after final dose, followed by severe depletion after eight months. No side effects of therapy were noted. Patient was free from PF, which was stopped while introducing rituximab, remaining non-proteinuric on triple immunosuppression (CsA, MMF, Pred).