Therapeutic Plasma Exchange in Pediatric Renal Transplantation Experience of One Decade and 389 Sessions.

OBJECTIVE: There are no specific recommendations for therapeutic plasma exchange (TPE) in children after renal transplantation. The purpose of this study was to report the experience with TPE in a pediatric transplant setting. MATERIALS AND METHODS: 59 patients (mean age 12.5 ± 4.5 years) undergoing renal transplantation. Indications for TPE included the recurrence of nephrotic syndrome (NS; n = 30) and atypical hemolytic uremic syndrome (n = 6), chronic antibody-mediated rejection (cAMR; n = 20), sensitization (n = 2), and immune thrombocytopenia (n = 1). The single-filtration TPE was performed in all cases. In 74.7% of patients, fresh frozen plasma was used as a replacement fluid. In 25.3% of patients, 4% albumin solution was used as a replacement fluid. Criteria for TPE efficacy included a decrease of proteinuria and normalization of renal function in NS; a normalization of platelet count, C3, and hemoglobin concentration in aHUS; improvement in renal function; and reduction of donor-specific antibodies in cAMR; and removal of antiplatelet antibodies in immune thrombocytopenia. RESULTS: Efficacy results for patients with NS: 59.3% achieved remission, 25.9% achieved partial remission, and 14.8% achieved no remission, respectively. For patients with atypical hemolytic uremic syndrome there was remission in 66.6% and no remission in 33.4%. For patients with cAMR there was remission in 75% and no remission in 25%. Antiplatelet antibodies disappeared after TPE in 1 patient. In 9% of TPE procedures, minor complications were noted. All patients were on posttransplant maintenance immunosuppression and several children received additional treatment (intravenous immunoglobulin therapy or rituximab) during TPE therapy. CONCLUSION: TPE therapy (combined with immunosuppression) was an effective tool in most pediatric cases after renal transplantation with low incidence of minor adverse events.

Combined Liver-Kidney Transplantation in Children: Single-Center Experiences and Long-Term Results.

Combined liver-kidney transplantation (CLKT) is a rare procedure in pediatric patients in which liver and kidney from 1 donor are transplanted to a recipient during a single operation. The aim of our study was to analyze indications and results of CLKT in children. MATERIALS AND METHODS: Between 1990 and 2017 we performed 722 liver transplantations in children; we performed 920 kidney transplantations in children since 1984. Among them, 25 received CLKT. Primary diagnosis was fibro-polycystic liver and kidney disease in 17 patients, primary hyperoxaluria type 1 in 6 patients, and atypical hemolytic uremic syndrome-related renal failure in 2 children. Age of patients at CLKT was 3 to 23 years (median 16 years) and body mass was 11 to 55 kg (median 35.5kg). All patients received whole liver graft. Kidney graft was transplanted after liver reperfusion before biliary anastomosis. Cold ischemia time was 5.5 to 13.3 hours (median 9.4 hours) for liver transplants and 7.3 to 15 hours (median 10.4 hours) for kidney transplants. In 8 patients X-match was positive. We analyzed posttransplant (Tx) course and late results in our group of pediatric recipients of combined grafts. RESULTS: Tx follow-up ranged from 1.5 to 17 years (median 4.5 years). Two patients died: 1 patient with oxalosis lost renal graft and died 2.6 years after Tx due to complications of long-term dialysis, and 1 died due to massive bleeding in early postoperative period. Twelve patients were transferred under the care of adult transplantation centers. Six patients were dialyzed after CLKT due to acute tubular necrosis, and time of kidney function recovery was 10 to 27 days in these patients. In 1 patient with aHUS, renal function did not recover. In children with oxalosis, hemodialysis was performed for 1 month after Tx as a standard, with the aim to remove accumulated oxalate. Primary immunosuppression consisted of daclizumab or basiliximab, tacrolimus, mycophenolate mofetil, and steroids. Acute rejection occurred in 4 liver and 3 kidney grafts. One patient required liver retransplantation due to hepatitis C virus recurrence and 2 patients required kidney retransplantation. Two patients required dialysis. CONCLUSIONS: CLKT in children results in low rate of rejection and high rate of patient and graft survival.

Disparities in policies, practices and rates of pediatric kidney transplantation in Europe.

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

Effect of hosts on competition among clones and evidence of differential selection between pathogenic and saprophytic phases in experimental populations of the wheat pathogen Phaeosphaeria nodorum.

BACKGROUND: Monoculture, multi-cropping and wider use of highly resistant cultivars have been proposed as mechanisms to explain the elevated rate of evolution of plant pathogens in agricultural ecosystems. We used a mark-release-recapture experiment with the wheat pathogen Phaeosphaeria nodorum to evaluate the impact of two of these mechanisms on the evolution of a pathogen population. Nine P. nodorum isolates marked with ten microsatellite markers and one minisatellite were released onto five replicated host populations to initiate epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out over two consecutive host growing seasons and two pathogen collections were made during each season. RESULTS: A total of 637 pathogen isolates matching the marked inoculants were recovered from inoculated plots over two years. Genetic diversity in the host populations affected the evolution of the corresponding P. nodorum populations. In the cultivar mixture the relative frequencies of inoculants did not change over the course of the experiment and the pathogen exhibited a low variation in selection coefficients. CONCLUSIONS: Our results support the hypothesis that increasing genetic heterogeneity in host populations may retard the rate of evolution in associated pathogen populations. Our experiment also provides indirect evidence of fitness costs associated with host specialization in P. nodorum as indicated by differential selection during the pathogenic and saprophytic phases.

Sexual recombinants make a significant contribution to epidemics caused by the wheat pathogen Phaeosphaeria nodorum.

We conducted a 2-year mark-release-recapture field experiment to quantify the relative contributions of immigration and sexual and asexual reproduction to epidemics of Stagonospora nodorum blotch caused by Phaeosphaeria nodorum. The epidemic was initiated using nine genetically distinct P. nodorum isolates. Infected plants were sampled four times across two growing seasons. In total, 1,286 isolates were recovered and assayed with 10 microsatellite markers and 1 minisatellite marker. The proportion of isolates having multilocus haplotypes (MLHTs) identical to the inoculated isolates decreased steadily from 86% in the first collection to 25% in the fourth collection. The novel isolates that had different MLHTs compared with the marked inoculants originated through immigration and sexual recombination. By the end of the experiment, nearly three-quarters of the novel isolates originated from sexual recombination. Our results indicate that recombinant offspring and airborne immigrant ascospores can make significant contributions to epidemics of Stagonospora nodorum blotch during a growing season.

Kidney transplantation in children with bladder augmentation or ileal conduit diversion.

INTRODUCTION: Various congenital and acquired diseases of the lower urinary tract can lead to chronic renal failure requiring renal replacement therapy. AIM: The aim of the study was to assess problems and results of kidney transplantation in children with significant lower urinary tract dysfunction. MATERIALS AND METHODS: Between 1984 and 2007, there were 33 kidney transplantations in children with end-stage renal disease and severe lower tract dysfunction out of 539 kidney transplantations performed in our department. The patients were 23 males and 10 females. Thirty patients received a kidney from a deceased donor, the remaining 3 from a living related donor. The age at transplantation ranged from 2.25 years to 19 years. In 26 patients an ileal conduit modo Bricker was created (in 21 patients at transplant operation). Bladder augmentation was performed in 6 patients and a continent urinary reservoir was created in 1. RESULTS: Post-transplant follow-up ranged from 7 to 88 months (mean 32 months). Overall patient survival is 100% and graft survival is 97%. Creatinine concentrations ranged from 0.3 to 3.4 mg% (mean 0.92 mg%). Surgical complications were diagnosed in 16 patients. All surgical complications were treated successfully and none of them caused graft loss. Urinary tract infections (UTI) were the most commonly observed complication, occurring in 26/33 (78%) patients, but the majority of these UTI were asymptomatic and had no influence on graft function. CONCLUSIONS: Kidney transplantation in children with lower urinary tract dysfunction and end-stage renal failure offers excellent medium term results in our experience, despite the creation of non-standard urinary drainage. Recurrent urinary tract infections are the most common complications in these patients, but in the majority of cases this does not lead to impairment of graft function.

Concordant evolution of mitochondrial and nuclear genomes in the wheat pathogen Phaeosphaeria nodorum.

We compared patterns of mitochondrial restriction fragment length polymorphism (RFLP) diversity with patterns of nuclear RFLP diversity to investigate the effects of selection, gene flow, and sexual reproduction on the population genetic structure and evolutionary history of the wheat pathogen Phaeosphaeria nodorum. A total of 315 fungal isolates from Texas, Oregon, and Switzerland were analyzed using seven nuclear RFLP probes that hybridized to discrete loci and purified mitochondrial DNA that hybridized to the entire mtDNA genome. Forty-two different mitochondrial haplotypes and 298 different nuclear haplotypes were detected. The two most frequent mtDNA haplotypes were present in every population and represented 32% of all isolates. High levels of gene flow, low levels of population subdivision, no evidence for either host specificity or cyto-nuclear disequilibrium were inferred from the analysis of both genomes. The concordance in estimates of these population genetic parameters from both genomes suggests that the two genomes experienced similar degrees of migration, genetic drift and selection.

Is positive flow cytometric cross-match a risk factor for early cadaveric kidney graft dysfunction?

INTRODUCTION: The final decision about transplantation is based primarily on a negative result of a complement-dependent cytotoxicity cross-match. The significance of a positive flow cytometric cross-match (FCXM) is unclear. MATERIALS AND METHODS: From July 2002 to October 2004, FCXM was performed prior to cadaveric kidney transplantation in 63 patients aged 1.5 to 26 years (mean 13 +/- 5). Immunosuppression (not adjusted to results of FCXM) was considered standard (prednisone + mycophenolate mofetil or azathioprine + cyclosporine or rapamycin) in 57%, or "enhanced" (+ monoclonal antibodies and/or tacrolimus) in 43% of patients. RESULTS: Immunoglobulin IgG and/or IgM antibodies against T and/or B cells were found in 14/63 patients (22.2%). The distribution of immunosuppressive regimens was similar for FCXM(+) and FCXM(-) patients. Deteriorated graft function (creatinine > or =1.5 mg/dL) or demand for dialysis was observed in 6/14 (42.9%) FCXM(+) group versus 6/49 (12.2%) in the FCXM(-) group. During the first month after kidney transplantation biopsy-proven rejection episodes occurred more frequently among the FCXM(+) than the FCXM(-) group: 21.4% versus 4.1%, respectively. During the first 3 months after transplantation two of four kidneys in the FCXM(+) group (14.3%) demonstrated histological evidence of rejection plus one case of immunological cause of graft failure later found to be associated with an extremely high panel-reactive antibodies that were absent before transplantation (altogether 21.4%). Only one kidney (2.0%) was lost due to rejection among the FCXM(-) group. CONCLUSION: A positive flow cytometric cross-match should be considered an important risk factor for early kidney graft dysfunction.

The Frequencies and Spatial Distribution of Mating Types in Stagonospora nodorum Are Consistent with Recurring Sexual Reproduction.

ABSTRACT To test the hypothesis that Stagonospora nodorum undergoes regular cycles of sexual recombination, a total of 1,207 isolates sampled from 18 fields in 12 geographical regions in six countries on five continents were analyzed for mating type frequency and distribution using polymerase chain reaction amplification of the mating type locus. Restriction fragment length polymorphism and random amplified polymorphic DNA fingerprints were used to clone-correct the data sets. Both mating types were often found on the smallest spatial scales tested, including within the same lesion, the same leaf, and the same 1-m(2) plot. In only one case out of the 18 fields tested was there a significant departure from the expected 1:1 ratio. Combining this result with previous data on the population structure of S. nodorum, we conclude that this pathogen undergoes regular cycles of sexual recombination in all regions we examined.

[Results of treatment with recombinant human growth hormone in children with growth retardation in end-stage renal disease]. / Wyniki leczenia rekombinowanym ludzkim hormonem wzrostu niskoroslosci dzieci ze schylkowa niewydolnoscia nerek.

The aim of the study was to estimate the results of recombinant human growth hormone (rhGH) treatment in children with end-stage renal disease (ESRD). 60 growth retarded children with ESRD (mean age 11.2 +/- 7.2 years) were treated with rhGH at a dose of 1-1.1 IU/kg/week. The time of observation was 24 months. Thirty children completed first year, 18--second year of treatment. The mean growth velocity prior to the treatment was 3.03 +/- 1.9, during first year of the study--7.52 +/- 2.42, during second year 6.68 +/- 2.87 cm/year. The negative correlation between growth velocity and patient's age (r = -0.39; p < 0.05) suggest the better growth results in younger children during rhGH treatment. The rhGH therapy is effective method of treatment in growth retarded children with ESRD. Side effects are rare.

[Quality of life in children and adolescent with end-stage renal disease treated with dialysis and kidney transplantation]. / Ocena jakosci zycia dzieci i mlodziezy ze schylkowa niewydolnoscia nerek leczonych dializami i przeszczepieniem nerki.

This study investigates the quality of life of 139 patients remaining on alternative therapies for end-stage renal disease. Data from self-report questionnaires concerning physical activity, physical and social well-being, signs of depression and general assessment of situation, and "hope for future" were compared. Results indicate that self-assessment of quality of life (physical activity, physical and social well-being) among transplant patients is the best compared to both dialysis groups. These differences sustained in spite of deterioration of general health state with time. There were no differences between dialysis groups in terms of evaluated parameters. Overall results of quality of life assessment expressed by patients treated with hemodialysis seem to slightly improve during treatment.

[Evaluation of the efficacy, tolerance and safety of Biotrakson use in patients with kidney failure]. / Ocena skutecznosci, tolerancji i bezpieczenstwa stosowania Biotraksonu u chorych z niewydolnoscia nerek.

Increased susceptibility to infection is observed in patients with chronic renal failure (CRF). Therefore, when antibiotic therapy is indicated, it is reasonable to use a drug which is usually reserved as a second-choice antibiotic in other patients. Antibiotic prevention before surgical procedures with a high risk of infection, especially before renal transplantation is also often necessary. Evaluation of Biotrakson (ceftriakson) (produced in Poland) efficacy in patients with CRF was the aim of this study. The antibiotic was administered in a single, complete prophylactic dose or once daily when given therapeutically in 25 patients: 13 with end-stage renal disease treated with hemodialysis, 5 with end-stage renal disease treated with peritoneal dialysis, 4 with chronic renal failure, 1 with acute renal failure treated with peritoneal dialysis, 2 after renal transplantation. The antibiotic was given for local and generalised bacterial infections in 10 patients; in 15 the drug was administered prophylactically before serious surgical procedures (including 10 patients before renal transplantation). Resolution of infection was observed in 9 out of 10 treated patients (90%). When the antibiotic was given prophylactically, its efficacy was assessed as good in 8 of 10 patients (80%) after renal transplantation and in 4 of 5 patients (80%) after other surgical procedures. There were no significant adverse side effects in any patient. Biotrakson is, therefore, an effective drug for therapeutic and preventive use in patients with renal failure.