Presence of tubuloreticular inclusions in ultrastructural studies of renal biopsies in children with lupus nephropathy - one-center preliminary study.

Introduction: Juvenile systemic lupus erythematosus (jSLE) is an autoimmune disease that develops as a result of multi-level immune dysregulation, including the interferon pathway. Nephropathy develops at an early stage and eventually affects 90% of patients. A renal biopsy allows one to classify lupus nephritis and determine the proper treatment. Biopsy assessment should be done not only in a light microscope but also in a transmission electron microscope (TEM). Its usage may reveal the presence of intracellular tubuloreticular inclusions (TRIs), considered as a morphological marker of interferon hyperactivity. Material and methods: Renal biopsies of 10 children with jSLE and nephropathy were analyzed in TEM. The location, structure, and size of TRIs were assessed. Demographic data, nephropathy manifestation, non-renal symptoms, and serological activity of lupus were analyzed. Results: All the patients were female with an average onset at 12.7 years of age and met SLE criteria. Nephropathy manifested with proteinuria (n = 10) and hematuria (n = 6). Glomerular filtration rate (GFR) was normal in all patients. In three children with early disease onset, it manifested with hematological disorders. TRIs were revealed in 7 biopsies, with the highest expression in the youngest children, with peripheral cytopenia, membranous glomerulonephritis, and lupus nephritis. Conclusions: Demonstration of TRIs in renal biopsies of children with juvenile systemic lupus may confirm the diagnosis of lupus nephritis and is a sign of involvement of the interferon pathway at the early stage of the disease.

The role of assessment of renal biopsy in electron microscopy in making a diagnosis of juvenile-onset systemic lupus erythematosus in a 16-year-old female patient with depression and proteinuria - a case report.

The course of juvenile-onset systemic lupus erythematosus may vary, from rapid multiorgan involvement to insidious development mimicking different medical conditions. Depressive disorder in adolescents poses considerable diagnostic difficulties due to the natural tendency to lowered mood in this age group. However, it may also be the manifestation of a systemic disease. We present a case of a 16-year-old female patient without any somatic symptoms in whom severe depression resistant to treatment was the preceding symptom of juvenile-onset systemic lupus erythematosus (jSLE). Because of isolated proteinuria and presence of antinuclear antibodies, renal biopsy was performed. Light microscopy showed only findings characteristic for membranous nephropathy. Examination on electron microscopy showed characteristic tubuloreticular inclusions (TRIs) which were crucial for making the diagnosis of systemic lupus erythematosus. The evaluation of renal biopsy specimens by electron microscopy could be a useful diagnostic step to confirm the diagnosis, especially in difficult cases where the criteria for SLE are not fully met. The association of mental symptoms with systemic lupus erythematosus and other autoimmune disorders is well documented. However, the increasing prevalence of depression in children and adolescents poses a risk of delaying the diagnosis of a systemic disease.

Multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab in children with steroid-resistant nephrotic syndrome.

The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants.

[Variety of thrombotic thrombocytopenic purpura clinical course in Polish family members with ADAMTS 13 gene mutation]. / Róznorodnosc przebiegu klinicznego maloplytkowej plamicy zakrzepowej u czlonków polskiej rodziny z mutacja genu ADAMTS 13.

The congenital form of thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrom) is a result of genetically conditioned dysfunction of protease ADAMTS 13 enzyme which is responsible for von Wiellebrand factor multimer disintegration. The disease is inherited autosomally and recessively. The decrease of ADAMTS 13 activity results in intravascular clotting process activation with rapid lowering of platelet count, haemolytic anaemia, and occurence of schistocytes. Clinically, the disease is characterized by a range of symptoms such as severe jaundice in neonatal period, embolicthrombotic incidents of nervous system and progressive dysfunction of kidneys and other organs. Delaying diagnosis and hence administering of freshly frozen plasma leads to death. Molecular diagnosis allows for identification of genetical profile of the patient, and showing lowered enzyme activity is a basis for regular prophylactic plasma administration which is the protease donor. In our study we present members of a Polish family identified with ADAMTS 13 mutation. 52 old male with heterozygotic mutation of exon 29 (4143_4144insA) and in exon 19 (c2281G>A; Gly761Ser), experienced a few episodes of ischaemic stroke with ongoing neurological deficiency and developed chronic kidney disease. His 16-year old daughter with double homozygotic mutation in exon 29 (4143_4144insA) after severe episode of TTP at the age of 4 has been receiving plasma every 2 weeks for 12 years, which prevented her from other disorders. Target treatment introduced to clinical practice by means of ADAMTS 13 obtained by genetic recombination technology raises hopes.

[The role of some selected risk factors in the development of the nephrotoxicity of immunosuppressive medications used after the heart transplantation in children and young adults]. / Rola wybranych czynników ryzyka w rozwoju nefrotoksycznosci leków immunosupresyjnych stosowanych po przeszczepie serca u dzieci i mlodych doroslych.

The goal of this research was the assessment of non-genetic and genetic risk factors of renal lesions in children after heart transplants. The research was carried out in 22 pediatric heart transplant recipients who have had a long-term treatment with calcineurin inhibitors. Renal function was assessed directly after the transplantation and then in 3 months intervals with the monitoring of calcineurin inhibitors concentration in the plasma. A significant renal lesion has been confirmed, which was a time-function in all examined patients, although its severity varied. Acute renal insufficiency, transplant rejection and ATG usage in the peri-transplant and the post-transplant periods have not proven to influence the complications mentioned above. The relationship between "high TGFbeta production genotype" and the intensity of nephrotoxicity of calcineurin inhibitors has been confirmed.

[Necrotizing glomerulonephritis in decursu vasculitis after vaccination against influenza]. / Zmartwiajace zapalenie klebuszków nerkowych w przebiegu ukladowego zapalenia naczyn po szczepieniu przeciw grypie.

Vaccinations against influenza are common, acceptable way of prevention of influenza, which develops as epidemic on huge areas of Europe. We described 17 years old girl, who has developed vasculitis after vaccination against influenza vaccine Vaxigrip produced by Aventis Pasteur. Aggressive immunosuppressive treatments caused regression majority of clinical symptoms and normalization of renal function tests.

[Genetic conditions of synthesis of selected cytokines in children with nephrotic syndrome]. / Genetyczne uwarunkowania syntezy wybranych cytokin u dzieci z zespolem nerczycowym.

In this study a genetic determination of some cytokines synthesis is presented in group of 23 children with various kinds of nephrotic syndrome (NS). The gene polymorphisms of TNF-alpha, TGF-beta, IL-6, IL-10, INF-gamma were identified using PCR-SSP method combined with the measurement of levels of TNF-alpha, TGF-beta, IL-6, IL-10, INF-gamma synthesis. The differences in occurring frequency of high, middle and low genotypes TNF-alpha, TGF-beta and IL-6 synthesis between children with NS and control group were revealed. Significantly more frequently high TGF-beta and high IL-6 synthesis genotype in NS group were found. Because of high variability of cytokine level in blood in duration of NS and methodic difficulties of their measurement, identification of cytokines genes polymorphisms seems to be a method that can objectively describe the cytokine participation in NS pathophysiology.