The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy-Are They Biomarkers of Therapy-Related Toxicities?

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.

Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation.

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient's death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor's young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.

Vedolizumab in highly resistant acute gastrointestinal graft-versus-host disease after allogeneic stem cell transplantation: A single-center pediatric series.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving procedure in malignant and nonmalignant diseases. However, it is associated with a considerable risk of graft-versus-host disease (GvHD). Steroids are a first-line therapy for acute GvHD (aGvHD), but there is no standard treatment for steroid-resistant (SR) gastrointestinal (GI) aGvHD, which has a poor prognosis. The anti-integrin antibody, vedolizumab, could help in controlling SR GI aGvHD symptoms by blocking lymphocyte extravasation and infiltration of the intestinal wall. OBJECTIVES: To report the outcomes of 3 children with SR GI aGvHD after allo-HSCT, treated with vedolizumab as the last chance drug. MATERIAL AND METHODS: The study included 3 patients aged from 8 to 10 years who underwent HSCT in Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology at Wroclaw Medical University, Poland, and who developed severe SR GI aGvHD. All patients had grade IV SR aGvHD with GI stage 4 manifestation. Vedolizumab was given as salvage therapy after an ineffective treatment with etanercept, basiliximab, ruxolitinib, extracorporeal photopheresis, and mesenchymal stem cell infusions. Vedolizumab was administered intravenously at a dose of 300 mg. RESULTS: Only 1 patient achieved GvHD remission and was alive and well 9 months after the discontinuation of the therapy. One child developed a relapse of malignant disease and eventually died, and the third child died of severe aGvHD. CONCLUSION: Vedolizumab can be safely used in children with SR GI aGvHD, offering an additional chance for heavily pretreated patients. Prospective pediatric studies on both prophylactic and therapeutic use of the drug are warranted, according to the preliminary results.

Fludarabine-Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine-cyclophosphamide-ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication. Engraftment was achieved in 53/56 patients, and four patients died (two due to fungal infection, and two of neuroinfection). The median time to neutrophil engraftment was 14 days and to platelet engraftment was 16 days, and median donor chimerism was above 98%. The overall incidence of acute GVHD was 41.5%, and that of grade III-IV acute GVHD was 14.3%. Chronic GVHD was diagnosed in 14.2% of children. The probability of 2-year GVHD-free survival was 76.1%. In the univariate analysis, a higher dose of cyclophosphamide and previous IS therapy were significant risk factors for worse overall survival. Episodes of viral replication occurred in 33/56 (58.9%) patients, but did not influence OS. The main advantages of FluCyATG include early engraftment with a very high level of donor chimerism, high overall survival and a low risk of viral replication after HCT.

SARS-CoV-2 viral clearance during bone marrow aplasia after allogeneic hematopoietic stem cell transplantation-A case report.

Respiratory viral infections are known causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we report a unique case of a child with viral pneumonia caused by coinfection with human metapneumovirus (MPV), respiratory syncytial virus (RSV), and SARS-CoV-2 after HSCT. A 9-year-old girl with acute lymphoblastic leukemia underwent allogeneic HSCT from a matched, unrelated donor. During the post-transplant period, in profound leukopenia (below 10 leukocytes/µL), she was diagnosed with SARS-CoV-2, MPV, and RSV pneumonia and was treated with ribavirin and chloroquine. Before leukocyte recovery, the girl became asymptomatic, and SARS-CoV-2 and RSV clearance was achieved. The shedding of SARS-CoV-2 stopped before immune system recovery, and one may hypothesize that the lack of an inflammatory response might have been a contributing factor to the mild clinical course. Post-transplant care in HSCT recipients with COVID-19 infection is feasible in regular transplant units, provided the patient does not present with respiratory failure. Early and repeated testing for SARS-CoV-2 in post-transplant patients with concomitant infection mitigation strategies should be considered in children after HSCT who develop fever, respiratory symptoms, and perhaps gastrointestinal symptoms to control the spread of COVID-19 both in patients and in healthcare workers in hospital environments. Training of staff and the availability of personal protective equipment are crucial for containing SARS-CoV-2 infection.

Short Course of Eculizumab May Be Effective in Dialysis-Dependent Transplantation-Associated Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplantation: A Case Report.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) could induce several complications. The most frequent viral infections and graft-vs-host disease (GvHD) sometimes lead to thrombotic microangiopathy (TMA). It is associated with significant morbidity and mortality with the risk of death reaching 90%. Effective prevention and treatment are not available to date. Recent attempts at using antibody against C5 have been made. CASE REPORT: A 19-year-old girl with acute myeloid leukemia twice underwent alloHSCTs from her 10/10 HLA-matched sister. After the second HSCT severe acute steroid-resistant grade 4 GvHD occurred. Despite treatment with high doses of steroids, mycophenolate mofetil, biological therapy, and extracorporeal photopheresis, the patient developed TMA with acute kidney injury and the need for renal replacement therapy. The concentration of complement component 3 and activity of ADAMTS 13 were normal, and infection with Escherichia coli (E. coli) 0157H7 was excluded. Due to failure of all ordered therapies and severity of the condition, an attempt was taken to use eculizumab. Two 900-mg doses of eculizumab (Soliris) were administered at an interval of 2 weeks, which resulted in the improvement of renal function and amelioration of hemolysis and thrombocytopenia. Dialysis therapy was finished after 5 weeks, and then a third dose of the drug was administered. Eighteen months later, the patient is alive and well, with limited chronic GvHD. eGFR remains stable at 40 to 46 mL/min/1.73 m2, and mild hypertension requires treatment with angiotensin converting enzyme inhibitors and furosemide. CONCLUSION: Even a short course of eculizumab can be sufficient in controlling the TMA after HSCT, provided that the TMA-triggering factors are well controlled.

Successful Bone Marrow Recovery After an Immunoablative Regimen With Autologous Cord Blood Transplant in a Child With Idiopathic Severe Aplastic Anemia: A Case Report.

BACKGROUND: Aplastic anemia is a rare disease that manifests as bone marrow failure. The current treatment options include immunoablative therapy or allogeneic hematopoietic stem cell transplantation. We report a successful immunoablative regimen with autologous umbilical cord blood (auto-UCB) transplant in a 3-year-old boy with severe aplastic anemia. CASE REPORT: The immunoablation procedure consisted of 5 × 3.75 mg/kg antithymocyte globulin (Thymoglobulin) (total 18.75 mg/kg), methylprednisolone for 4 days, and cyclosporine A. The patient received auto-UCB containing 0.3 × 105 CD34+ cells per kilogram of body weight. Recovery of leukocyte count above 1000/µL was reached on post-transplant day +39, and recovery of granulocytes above 500/µL was reached on day +40. The final regular transfusions of packed red blood cells and platelet concentrate were performed on day +55. The complications that occurred in the post-transplant period were nausea, diarrhea, septic fever, and hepatic abscess formation. Post-transplant immunosuppression with cyclosporine A was discontinued 17.5 months after auto-UCB, and the patient remained in complete remission with normal blood counts and bone marrow morphology. SUMMARY: Auto-UCB transplantation without chemotherapy conditioning can be considered a therapeutic option for children with stored cord blood cells.

Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

Mutational analysis in podocin-associated hereditary nephrotic syndrome in Polish patients: founder effect in the Kashubian population.

Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

[Program of early detection of pulmonary neoplasms by the computed tomography - preliminary Szczecin experience]. / Program wczesnego wykrywania nowotworów pluc za pomoca tomografii komputerowej-- wstepne doswiadczenia Szczecina.

INTRODUCTION: Lung cancer (LC) remains one of the most serious epidemiological and clinical challenges both in the world and Poland. Results of LC therapy are far from satisfaction. One of the reasons of high LC mortality is its late detection. Currently, few centers in the world conduct LC screening programs based on low-dose spiral computed tomography (CT) of the chest. There have been no such programs in Poland up to date. MATERIAL AND METHODS: The program of LC early detection based on CT for citizens of Szczecin aged 55-65, who smoked at least 20 pack/years, was introduced on May 1st 2008 and was planned for 3 years. There were 3647 subjects examined till December 31st 2008. Algorithm of further action for detected lesions was based on the IELCAP and NELSON trial protocols. RESULTS: There were 25 malignancies detected, including 21 LC (17 females and 4 males) up to date (70% were in stage I TNM). In contrast - there was only 16.8% stage IA LC detected in the comparable group diagnosed on the symptoms basis. Fifty seven patients were treated surgically, of whom 16 underwent lobectomy or pneumonectomy coupled with radical mediastinal lymphadenectomy. There were 3 wedge resections and 2 segmentectomies performed, too. Perioperative mortality was 0%. There were 32 benign lesions of different clinical importance resected as well (tuberculoma, hamartoma, inflammatory, mycotic and sarcoidal lesions). In our group 1365 lesions were detected in 996 persons - they are followed up in accordance with the IELCAP algorithm. CONCLUSIONS: Early LC detection program initiated in Szczecin resulted in significant increase of stage IA TNM detected patients subsequently treated radically. There was also a large number of small non malignant lesions detected.

[Congenital and genetic related causes of end-stage renal disease--data from Polish Registry of Renal Rreplacement Therapy in Children 2000-2004]. / Genetycznie uwarunkowane i wrodzone choroby nerek prowadzace do schylkowej niewydolnosci nerek--dane z polskiego rejestru dzieci leczonych nerkozastepczo (2000-2004).

UNLABELLED: One of the objectives of Polish Registry of Renal Replacement Therapy in Children established on 31st Dec. 2000 was to collect complete data on etiology of end stage renal disease (ESRD) in polish children. MATERIAL AND METHODS: Data on 469 patients (251 boys, 218 girls) aged 0-22 years treated with renal replacement therapy (RRT) at 13 pediatric dialysis units in Poland from 2000 to 2004 were analyzed. The mean age at start of dialysis was 10 years and 3 months. Renal diseases were defined according to EDTA coding system. Data is presented for the whole group, in 5-year age groups and separately for both sexes. RESULTS: Congenital and genetic renal diseases were the cause of ESRF in 56% of the polish population of children and adolescents on RRT. 39% of causes were acquired diseases, 5% remained unidentified. Congenital and genetic causes dominated in children < 5 years of age (71%). They accounted for 49%, 61% and 45% of causes in the consecutive 5-year age groups. The most numerous group of congenital diseases leading to ESRF were uropathies 37% and 25% of causes in the consecutive age groups. In boys the most frequent uropathy was obstructive uropathy (25%), the majority caused by posterior urethral valves. In girls the most frequent uropathies were reflux nephropathy (10%) and nephropathy secondary to neurogenic bladder (9%). Uropathies were followed by renal hypo-dysplasia without urinary tract anomalies (11%) and cystic diseases (10%). CONCLUSIONS: Congenital kidney anomalies and genetic diseases are the leading cause of end-stage renal disease in children up to 15 years of age.

[A child with myelomeningocele as a dialytic patient]. / Dziecko z przepuklina oponowo-rdzeniowa jako pacjent dializacyjny.

The aim of the study was to present difficulties and problems of dialytic treatment in children with spina bifida (SB). Between 2000 and 2005 five girls with SB and neurogenic bladder were treated with renal replacement therapy (15% of all children with end stage kidney disease dialyzed at our centre). Four patients (pts) had hydrocephalus requiring ventriculoperitoneal shunt, they were wheelchair-bound due to lower limbs paralysis and mentally retarded. Only 1 girl had been supervised by nephrologist from the very beginning. Dialysis was started at the age of 3-17 yr and the first mode was automatic peritoneal dialysis (ADO) in 3 and hemodialysis (HD) in 2. During the treatment ADO was switched onto HD in 2 pts for sclerosing encapsulating peritonitis (1) and tunnel infection with spontaneous Tenckhoff catheter evacuation (1). Permanent central venous catheters served as vascular access in 3 cases, in 2 there were difficulties with creation of arteriovenous fistula. No neurological complications were noticed in pts with ventriculo-peritoneal shunt and ADO. Total period of renal replacement therapy was 9-99 mo. Only 2 pts were qualified to transplantation. Two pts died after 16 mo of dialysis, 2 were transplanted and 1 is still being treated with HD. All families were dysfunctional. In 4 cases insufficient parental support caused many disturbances during predialytic and dialytic period. We concluded that in Poland pediatric pts with SB create specific group with the number of problems and complications higher than in other children on dialysis.

[Polish nurses attitude toward organ transplatation]. / Postawy pielegniarek wobec przeszczepiania narzadów.

The aim of the study was to analyze basic knowledge and attitude toward organs transplantation (Tx) among nurses working in Polish hospitals. The original questionnaire was sent to 269 nurses and 246 answers were received: 122 from dialysis and/or transplantation units (group I) and 124 from other departments (group II). Knowledge, estimated with a ten-questions test, was higher in group I and also depended on sex, educational status, period of working and place of live. Nurses having in family a person waiting for Tx achieved better results in the test than others. 86.2% of responders agree to serve as a donor after death (group I--86.1%, group II--86.3%), 89.0% (86.1% vs 91.9%; p>0.05)--to be treated with cadaveric donor Tx and 80.9% (71.3% vs 90.3%; p<0.05)--with living related donor (LRD) kidney Tx. 98.0% (97.5% vs 98.4%) want to give the kidney for family Tx if they are asked to. 9.3% (4.1% vs 14.5%, p>0.05) claim that some form of financial support for living donors is justified. 74,4% (84.4% vs 64.5%, p>0.05) have talked with the family about Tx and 65,0% (77.0% vs 53.2%; p>0.05) transferred their opinion about organs donation. 40% of nurses who haven't agreed for organ donation after death want to be treated with Tx. The main sources of knowledge about Tx are medical publications (62.6%) and media (40.6%). Our study indicates, that nurses present positive attitude toward organ donation and reception independently of the place of work (dialysis/transplantation or other department). LRD kidney donation is the most accepted transplantational procedure.

Hypertension in dialysed children: the prevalence and therapeutic approach in Poland--a nationwide survey.

BACKGROUND: The aim of this nationwide analysis was to assess the incidence and current treatment profile of arterial hypertension in children undergoing chronic haemodialysis or peritoneal dialysis and attitudes of paediatric nephrologists towards the choice of antihypertensive drugs in their patients. METHODS: The study group consisted of 134 children (89 males, 45 females, mean age 10.7+/-5 years) from all 13 paediatric dialysis centres in Poland. The data were gathered through a questionnaire for each patient dialysed in November 2004. RESULTS: The overall incidence of hypertension in the study group was 55% (74 of 134 patients; 47 males, 27 females). The incidence rate was similar in boys and girls (53 vs 60%) and in those on haemodialysis and peritoneal dialysis (56 vs 54%). Chronic glomerulonephritis as an underlying renal disease was significantly more frequent in the hypertensive than in the normotensive subjects (37 vs 10%, P = 0.004). Residual urine output was higher in normotensives (41 vs 10 ml/kg body weight; P < 0.001). Among those treated with antihypertensives: 32% were treated by monotherapy, 36% received two drugs, 22% received three drugs, while 7% received > or = 4 drugs. The therapy was effective in only 57% of subjects. We observed no differences in biochemical and clinical parameters between those who responded to the therapy and those who failed to do so. Calcium channel blockers constituted the most frequently administered class of drugs [73% of children; in 43 out of 48 (90%) combined with other drugs, but in 11 out of 24 (46%) as a monotherapy]. In monotherapy, angiotensin-converting enzyme inhibitors and calcium channel blockers were administered most frequently. CONCLUSION: We conclude that the incidence of hypertension in dialysis children in Poland is high (55%). The effectiveness of antihypertensive treatment is rather low (58%) and the choice of drugs is limited.

Does a late referral to a nephrologist constitute a problem in children starting renal replacement therapy in Poland?--a nationwide study.

BACKGROUND: It is estimated that 20-50% of adult patients start chronic dialysis therapy without prior contact with a nephrologist. The aim of this nationwide study was to assess clinical and metabolic status of children at the start of chronic dialysis in Poland with regard to the timing of the referral to a nephrologist. METHODS: We studied data of 180 children (mean age 14+/-6 years) undergoing chronic dialysis in 13 (out of 14) dialysis pediatric centres in Poland. Patients were classified as early referrals (ERs) when they entered the dialysis programme at least 1 month after the first referral to a nephrologist or late referrals (LRs) when the dialysis was introduced within 1 month from the first visit. RESULTS: Seventy-nine percent of pediatric patients were referred early (ER) to the dialysis centre and 21% were referred late (LR) and had to start dialysis within a month. When starting dialysis, LR patients had significantly higher levels of urea and phosphate as well as lower calcium and haemoglobin in comparison with ERs. Hypertension, pulmonary oedema, fluid overload, treatment in the intensive care unit (ICU) and body mass index (BMI) below 10th percentile turned out to be more frequent in the LR group. Peritoneal dialysis (PD) was used as the first method of dialysis in 59% of ERs and 46% of LRs. The majority of ER patients was treated in the predialysis period with calcitriol, phosphate binders and low protein diet (84%, 89%, 92% of all children, respectively), and 20% of them received epoetin. In the up to 3 years observation of our initial cohort, we also found that the patients who were referred late were less likely to receive kidney transplant (P = 0.02). CONCLUSION: The results of the study indicate that the LR to a pediatric nephrologist was associated with poorer clinical and metabolic status of children entering chronic dialysis programmes.

[Regression of glomerulosclerosis in a girl with C3 nephropathy]. / Regresja stwardnienia kleibuszków nerkowych u chorej z nefropatia C3.

Regression of glomerular sclerosis was documented in experimental models as a result of RAA system blocking and/or cyclosporin A (CsA) treatment. Here we present a case of a girl suffering from nephrotic syndrome (NS) in whom unusual healing of glomerular changes appeared. First time the girl was admitted to our department at the age of 4 year with 2 years history of steroid-dependent NS. Kidney biopsy studied in light microscopy revealed 11 glomeruli among which 5 were totally sclerosed and the others showed mesangial proliferation and segmental mesangial matrix expansion. Diffuse interstitial mononuclear cells infiltration was also visible. In fluorescence microscopy only granular C3 and fibrinogen deposits were seen. C3 nephropathy was diagnosed and cyclophosphamide therapy started. As no effects appeared, CsA was introduced together with angiotensin converting enzyme inhibitor (ACEI) enalapril for two years without any relapse during treatment. Prednisone was gradually reduced and finally stopped after a year. On the second biopsy performed to assess CsA nephrotoxicity among 16 glomeruli evaluated in light microscopy only 1 was sclerosed, while the others presented just mild mesangial proliferation. No interstitial changes were found. Fluorescence showed IgA and IgM added to glomerular C3 deposits. CsA was then stopped and after 4 months relapses and steroid-dependency appeared again, so CsA was reintroduced. Actually the girl is 8-year-old, remission of NS has been observed for six months. As a conclusion we would like to suggest that treatment with CsA and ACEI may cause glomerular healing even in a case of advanced glomerulosclerosis.

Experience using presternal catheter for peritoneal dialysis in Poland: a multicenter pediatric survey.

OBJECTIVES: Permanent and adequate access to the peritoneal cavity is the key to successful chronic peritoneal dialysis (PD). A variety of catheter designs and implantation techniques have been developed to achieve optimal peritoneal access. One such new and modified PD catheter is the presternal catheter [swan neck presternal catheter (SNPC)], with the exit site located on the chest wall. DESIGN: A multicenter survey was undertaken to summarize 10 years of experience with the presternal catheter in children in Poland. SETTING: Four pediatric institutions using the SNPC in children: (1) Medical University of Warsaw, Warsaw; (2) Children's Memorial Health Institute, Warsaw; (3) District Children's Hospital, Szczecin; (4) University of Medical Sciences, Poznan. PATIENTS: During the past 10 years, 20 presternal catheters were implanted in 19 children, aged 0.2-17.7 years (mean 8 +/- 5.8 years), with end-stage renal failure.The main indications for the SNPC include urinary diversion (ureterocutaneostomy or vesicostomy), use of diapers, young age, obesity, abdominal wall weakness, and recurrent exit-site infections (ESI) with previous abdominal PD catheters. INTERVENTION: In all children the presternal catheter was implanted surgically under general anesthesia by one surgeon. Uniform operative technique and uniform perioperative management were used. RESULTS: The mean observation time for the 20 presternal catheters was 24.8 +/- 25 months (range 1-83 months). The ESI rate was 1/70.9 patient-months (0.17 episodes per year), tunnel infection rate was 1/248 patient-months (0.05 episodes per year), and the overall peritonitis rate was 1/26.6 patient-months (0.51 episodes per year). Non-infectious complications associated with the SNPC included disconnection of both sections (2 children) and trauma to the exit site located on the chest wall (4 children). Mean survival time of the presternal catheter, as calculated by the Kaplan-Meier method, was 57.5 +/- 8.5 months; 50% catheter survival reached 72 months. CONCLUSIONS: The good outcome in patients with a SNPC validates the rationale for the presternal catheter design and should encourage its more widespread use. The SNPC seems to be suitable for any patient on PD; however, this catheter is particularly useful in patients with specific indications (ie., higher tendency to ESI). The SNPC allows safe and long-term chronic PD in very young children using diapers and in patients with urinary diversion.