Skuteczność rituximabu w leczeniu nawrotu zespołu nerczycowego po transplantacji nerki o przebiegu klinicznym zależnym od plazmaferezy - opis przypadku

Leczenie nawrotu zespołu nerczycowego po transplantacji nerki jest trudne i w znacznej części przypadków nieskuteczne. Stosowane dotąd metody leczenia - nasilenie immunosupresji oraz powtarzana plazmafereza - nie są skuteczne u około połowy chorych. W przedstawianym przypadku 5,5-letniego pacjenta z natychmiastowym nawrotem zespołu nerczycowego po transplantacji po wykonaniu 18 zabiegów plazmaferezy stwierdzono "zależność" choroby od wymiany osocza - po zabiegu białkomocz zmniejszał się i ponownie zwiększał. Do leczenia włączono rituximab w dawce 4 × 375 mg/m2 i.v. pod kontrolą liczby komórek B CD19. Uzyskano długotrwałą (8-miesięczną) remisję, której towarzyszyła deplecja komórek B CD19 z krążenia. Nie odnotowano działań niepożądanych tego leczenia

Low Renal but High Extrarenal Phenotype Variability in Schimke Immuno-Osseous Dysplasia

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.PubMedWoSScopu

Phenotypic features of patients with Schimke immuno-osseous dysplasia (n = 34).

<p>Phenotypic features of patients with Schimke immuno-osseous dysplasia (n = 34).</p

Current Practices on Diagnosis, Prevention and Treatment of Post-Transplant Lymphoproliferative Disorder in Pediatric Patients after Solid Organ Transplantation: Results of ERN TransplantChild Healthcare Working Group Survey

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

Localization of <i>SMARCAL1</i> mutations detected in 34 subjects with Schimke immuno-osseous dysplasia.

<p>Legend: : recurrent mutations detected in at least three unrelated patients; Green font: novel mutations described for the first time in the current study. Reference sequence: ENST00000357276; NM_014140.</p