Publications by authors named "Isabella Guzzo"

41 Publications

Role of Hemoperfusion With CytoSorb Associated With Continuous Kidney Replacement Therapy on Renal Outcome in Critically III Children With Septic Shock.

Front Pediatr 2021 24;9:718049. Epub 2021 Aug 24.

Department of Pediatrics, Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Sepsis-associated acute kidney injury (SA-AKI) represents a relevant cause of mortality and morbidity in critically ill children. Since with the "inflammatory theory" the authors have been witnessed an important role of inflammatory mediators in the pathophysiology and in the prognosis of SA-AKI, making the need of adjunctive therapies in association with kidney replacement therapies mandatory. Hemoperfusion with CytoSorb is a safe and well-tolerated therapy in septic shock: the very high surface area of the absorber means it is able to efficiently remove cytokines and other medium size molecules involved in cytokine storm, thus playing a synergistic effect with Continuous Kidney Replacement Therapy (CKRT). We retrospectively analyzed data from a cohort of eight critically ill children treated from January 2018 to March 2020 describing the impact of CKRT plus hemoperfusion with CytoSorb on renal outcome in critically ill children with septic shock. We evidenced a significant reduction in interleukin (IL)-6 an IL-10 after hemoperfusion with CytoSorb in our pediatric population. Furthermore, we were able to show a significant improvement of creatinine and blood urea nitrogen (BUN) after blood purification and at pediatric intensive care units (PICU) discharge. We have observed a median of 2.5 CKRT days after stop of hemoperfusion (Q 0.25; Q 18.75). None of our patients required CKRT 30 days after PICU discharge (PICU-D). None of them developed CKD. Hemoperfusion with CytoSorb is a valuable therapeutic option in combination with CKRT in SA-AKI. More studies are warranted to confirm our results and in particular to define the role of this adjuvant therapy as a preemptive strategy to protect renal function in pediatric septic shock.
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http://dx.doi.org/10.3389/fped.2021.718049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423368PMC
August 2021

Hemoperfusion with CytoSorb to Manage Multiorgan Dysfunction in the Spectrum of Hemophagocytic Lymphohistiocytosis Syndrome in Critically Ill Children.

Blood Purif 2021 Aug 3:1-8. Epub 2021 Aug 3.

Pediatric Emergency Department Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluated the impact of hemoadsorption with CytoSorb combined with continuous kidney replacement therapy used as adjunctive therapy in 6 critically ill children with multiple organ dysfunction due to HLH. In our series, we found a reduction in inflammatory biomarkers in patients with HLH secondary to infection. Ferritin, one of the most important bedside biomarkers of HLH, showed a reduction in most of the treated patients. The same results were found measuring interleukin-6 and interleukin-10. The same patients showed hemodynamic stabilization measured by the Vasopressor-Inotropic-Score, and reduction in the organ disease score measured with the Pediatric Logistic Organ Dysfunction score. In our cohort, mortality was less than expected based on the Pediatric Index of Mortality 3 score at pediatric intensive care unit admission. Our study shows that hemoperfusion could be a valuable therapeutic option in HLH: stronger scientific evidence is needed to confirm our preliminary experience.
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http://dx.doi.org/10.1159/000517471DOI Listing
August 2021

Efficacy of CytoSorb in a Pediatric Case of Severe Multisystem Infammatory Syndrome (MIS-C): A Clinical Case Report.

Front Pediatr 2021 11;9:676298. Epub 2021 Jun 11.

Pediatric Emergency Department Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, Institute for Research and Health Care (IRCCS), Rome, Italy.

Multisystem inflammatory syndrome in children (MIS-C) has emerged during the COVID-19 pandemic as a new SARS-CoV-2-related entity, potentially responsible for a life-threatening clinical condition associated with myocardial dysfunction and refractory shock. We describe for the first time in a 14-year-old girl with severe MIS-C the potential benefit of an adjuvant therapy based on CytoSorb hemoperfusion and continuous renal replacement therapy with immunomodulatory drugs. We show in our case that, from the start of extracorporeal blood purification, there was a rapid and progressive restoration in cardiac function and hemodynamic parameters in association with a reduction in the most important inflammatory biomarkers (interleukin 6, interleukin 10, C-reactive protein, ferritin, and D-dimers). Additionally, for the first time, we were able to show with analysis of the sublingual microcirculation a delayed improvement in most of the important microcirculation parameters in this clinical case of MIS-C.
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http://dx.doi.org/10.3389/fped.2021.676298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232055PMC
June 2021

Prevalence of SARS-CoV-2-IgG Antibodies in Children with CKD or Immunosuppression.

Clin J Am Soc Nephrol 2021 Jun 7. Epub 2021 Jun 7.

G Montini, Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano, Italy

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http://dx.doi.org/10.2215/CJN.00330121DOI Listing
June 2021

Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe: data from the ESPN/ERA-EDTA Registry.

Pediatr Nephrol 2021 Aug 22;36(8):2337-2348. Epub 2021 Jan 22.

Department of Pediatrics, Bordeaux University Hospital, Bordeaux Population Health Research Center UMR 1219, University of Bordeaux, Bordeaux, France.

Background: For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival.

Methods: We included all children aged <15 years starting KRT 2007-2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression.

Results: Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007-2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007-2009 or 2010-2012 (adjusted HR: 0.98, 95% CI:0.71-1.35).

Conclusions: We found a stable incidence and increasing prevalence of European children on KRT 2007-2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.
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http://dx.doi.org/10.1007/s00467-021-04928-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260419PMC
August 2021

Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression.

Clin J Am Soc Nephrol 2021 03 14;16(3):449-451. Epub 2020 Dec 14.

Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy

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http://dx.doi.org/10.2215/CJN.13120820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011005PMC
March 2021

Resident foreign patients receive adequate dialysis but fewer preemptive transplantations: data from the Italian pediatric dialysis registry.

Pediatr Nephrol 2021 03 10;36(3):639-647. Epub 2020 Sep 10.

Department of Pediatrics, Paediatric Nephrology, Dialysis and Transplant Unit, IRCCS Istituto G Gaslini, Genoa, Italy.

Background: Sociocultural issues play a key role in children needing kidney replacement therapy (KRT).

Methods: Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2).

Results: We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups.

Conclusions: The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04730-0DOI Listing
March 2021

Unusual Presentation of Denys-Drash Syndrome in a Girl with Undisclosed Consumption of Biotin

J Clin Res Pediatr Endocrinol 2021 08 25;13(3):347-352. Epub 2020 Aug 25.

IRCCS Ospedale Pediatrico Bambino Gesù, Unit of Medical Laboratory, Rome, Italy

We describe a 46,XX girl with Denys-Drash syndrome, showing both kidney disease and genital abnormalities, in whom a misdiagnosis of hyperandrogenism was made. A 15 year-old girl was affected by neonatal nephrotic syndrome, progressing to end stage kidney failure. Hair loss and voice deepening were noted during puberty. Pelvic ultrasound and magnetic resonance imaging showed utero-tubaric agenesis, vaginal atresia and urogenital sinus, with inguinal gonads. Gonadotrophin and estradiol levels were normal, but testosterone was increased up to 285 ng/dL at Tanner stage 3. She underwent prophylactic gonadectomy. Histopathology reported fibrotic ovarian cortex containing numerous follicles in different maturation stages and rudimental remnants of Fallopian tubes. No features of gonadoblastoma were detected. Unexpectedly, testosterone levels were elevated four months after gonadectomy (157 ng/dL). Recent medical history revealed chronic daily comsumption of high dose biotin, as a therapeutic support for hair loss. Laboratory immunoassay instruments used streptavidin-biotin interaction to detect hormones and, in competitive immunoassays, high concentrations of biotin can result in false high results. Total testosterone, measured using liquid chromatography tandem mass spectrometry, was within reference intervals. Similar testosterone levels were detected on repeat immunoassay two weeks after biotin uptake interruption. Discordance between clinical presentation and biochemical results in patients taking biotin, should raise the suspicion of erroneous results. Improved communication among patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.
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http://dx.doi.org/10.4274/jcrpe.galenos.2020.2020.0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388055PMC
August 2021

Multimodal Therapeutic Approach of Cytokine Release Syndrome Developing in a Child Given Chimeric Antigen Receptor-Modified T Cell Infusion.

Crit Care Explor 2020 Jan 29;2(1):e0071. Epub 2020 Jan 29.

Department of Pediatric Hematology and Oncology, Bambino Gesù, Children's Hospital, IRCSS, Rome, Italy.

Objectives: To describe a pediatric case of cytokine release syndrome secondary to chimeric antigen receptor-modified T cells associated with acute respiratory distress syndrome.

Design: Case report.

Setting: PICU.

Patients: A 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia given chimeric antigen receptor cells developed severe cytokine release syndrome 7 days after the drug product infusion with progressive respiratory failure. He was admitted to PICU with a clinical picture of acute respiratory distress syndrome, requiring mechanical ventilation, and secondary hemophagocytic lymphohistiocytosis.

Interventions: Hemoadsorption with cartridge column (Cytosorb) in combination with continuous renal replacement therapy was associated to the anti-cytokine therapy (tocilizumab, a monoclonal antibody targeting interleukin-6 receptor).

Measurements And Main Results: Decrease of the inflammatory biomarkers (ferritin, interleukin-6, interleukin-10) in the first 96 hours associated with a progressive improvement of acute respiratory distress syndrome (Pao/Fio ratio) 7 day after the start of the multimodal treatment.

Conclusions: This case suggests that hemoadsorption with cartridge column in combination with continuous renal replacement therapy and tocilizumab is safe and potentially effective in pediatric patients with severe cytokine release syndrome.
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http://dx.doi.org/10.1097/CCE.0000000000000071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063902PMC
January 2020

Hemoperfusion with Cytosorb in pediatric patients with septic shock: A retrospective observational study.

Int J Artif Organs 2020 Sep 31;43(9):587-593. Epub 2020 Jan 31.

Pediatric Intensive Care Unit, Children's Hospital Bambino Gesù, Rome, Italy.

Objective: To determine the clinical effect of continuous hemoperfusion with Cytosorb associated with standard Continuous Renal Replacement Therapy on hemodynamics and on clinically relevant outcome parameters in children with septic shock.

Design: Retrospective analysis.

Setting: Pediatric intensive care unit.

Patients: Eight consecutive children with septic shock who received hemoperfusion with Cytosorb while on Continuous Renal Replacement Therapy.

Interventions: Continuous hemoperfusion with Cytosorb (adsorber was changed every 24 h).

Measurements And Main Results: Vasoactive-Inotropic Score was measured before and after the extracorporeal blood purification treatment. Bedside refractory septic shock score was calculated before the onset of the extracorporeal blood purification treatment. Time course of cytokines interleukin-6, interleukin-10, and tumor necrosis factor-alpha was measured at Time 0, then every 12 h until the end of blood purification treatment (72 or 96 h). Pediatric intensive care unit survival in our cohort was 90%. Median bedside refractory septic shock score was 2.1. Patients showed improved Vasoactive-Inotropic Score following blood purification (pre: 40.00 post: 8.89  = 0.0076). Measurement of cytokines level showed a significant reduction of interleukin-6 plasma levels (7977.27-210.18 pg/mL,  = 0.0077) and interleukin-10 plasma levels (from 687.19 to 36.95 pg/mL,  = 0.0180). In those patients with detectable tumor necrosis factor-alpha plasma level, its reduction was not significant ( = 0.138). The median removal ratio was 80% for interleukin-6, 90% for interleukin-10, and 29% for tumor necrosis factor-alpha.

Conclusion: The use of Cytosorb in combination with Continuous Renal Replacement Therapy as blood purification strategy in pediatric septic shock is associated with a rapid hemodynamic stabilization in the first 48 h of treatment and a significant reduction of interleukin-6 and interleukin-10.
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http://dx.doi.org/10.1177/0391398820902469DOI Listing
September 2020

Same Donor Laparoscopic Liver and Kidney Procurement for Sequential Living Donor Liver-Kidney Transplantation in Primary Hyperoxaluria Type I.

J Laparoendosc Adv Surg Tech A 2019 Dec 5;29(12):1616-1622. Epub 2019 Nov 5.

Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

Sequential liver-kidney transplantation (SeqLKT) from the same living donor has shown excellent results in children with primary hyperoxaluria type 1 (PH1), yet its experience is limited due to the invasiveness of two major procedures for liver-kidney procurement in a single donor. Despite laparoscopic nephrectomy and hepatic left lateral sectionectomy (LLS) being considered standard procedures in living donation, the sequential use of the two laparoscopic approaches in the same living donor has never been reported. Herein, we present the first two case series of laparoscopic liver-kidney procurement in the same living donor for SeqLKT in children with PH1 and review of the current literature on this topic. In the first case, a 15-month-old boy received a SeqLKT from his 32-year-old mother, who underwent a laparoscopic LLS and, after 8 months, a laparoscopic left nephrectomy. In the second case, a 34-month-old boy received a SeqLKT from his 40-year-old father who underwent laparoscopic LLS followed by hand-assisted right nephrectomy after 4 months. Both donors had uneventful postoperative courses and were discharged within 5 days from each surgery. The first recipient had no complication; the second child after liver transplantation developed a partial thrombosis of the inferior vena cava, which did not preclude the sequential kidney transplantation. After 12 months, donors and recipients displayed normal liver and renal functions. Sequential laparoscopic liver-kidney procurement in the same living donor is safe and feasible, and might be considered as a possible strategy to promote SeqLKT in children with PH1 from the same living donor.
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http://dx.doi.org/10.1089/lap.2019.0483DOI Listing
December 2019

Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience.

J Nephrol 2020 Aug 15;33(4):849-857. Epub 2019 Oct 15.

Pediatric Nephrology, Dialysis and Transplant Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, University of Milan, via della Commenda, 9, 20122, Milan, Italy.

Background: Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss.

Methods: We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival.

Results: 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft.

Conclusions: Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.
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http://dx.doi.org/10.1007/s40620-019-00660-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381476PMC
August 2020

Double extracorporeal blood purification in refractory pediatric septic shock.

Paediatr Anaesth 2019 09;29(9):966-967

Department of Emergency, Anaesthesia and Intensive Care, Pediatric Intensive Care Unit, Bambino Gesù Children's Hospital, Rome, Italy.

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http://dx.doi.org/10.1111/pan.13700DOI Listing
September 2019

Acute dialysis in children: results of a European survey.

J Nephrol 2019 Jun 4;32(3):445-451. Epub 2019 Apr 4.

Nephrology and Dialysis Unit, Pediatric Subspecialties Department, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.

The number of children with acute kidney injury (AKI) requiring dialysis is increasing. To date, systematic analysis has been largely limited to critically ill children treated with continuous renal replacement therapy (CRRT). We conducted a survey among 35 European Pediatric Nephrology Centers to investigate dialysis practices in European children with AKI. Altogether, the centers perform dialysis in more than 900 pediatric patients with AKI per year. PD and CRRT are the most frequently used dialysis modalities, accounting for 39.4% and 38.2% of treatments, followed by intermittent HD (22.4%). In units treating more than 25 cases per year and in those with cardiothoracic surgery programs, PD is the most commonly chosen dialysis modality. Also, nearly one quarter of centers, in countries with a gross domestic product below $35,000/year, do not utilize CRRT at all. Dialysis nurses are exclusively in charge of CRRT management in 45% of the cases and pediatric intensive care nurses in 25%, while shared management is practiced in 30%. In conclusion, this survey indicates that the choice of treatment modalities for dialysis in children with AKI in Europe is affected by the underlying ethiology of the disease, organization/set-up of centers and socioeconomic conditions. PD is utilized as often as CRRT, and also intermittent HD is a commonly applied treatment option. A prospective European AKI registry is planned to provide further insights on the epidemiology, management and outcomes of dialysis in pediatric AKI.
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http://dx.doi.org/10.1007/s40620-019-00606-1DOI Listing
June 2019

Dialysis modalities for the management of pediatric acute kidney injury.

Pediatr Nephrol 2020 05 18;35(5):753-765. Epub 2019 Mar 18.

Division of Nephrology and Dialysis, Department of Pediatrics, Bambino Gesù Children's Hospital and Research Institute, Piazza Sant'Onofrio 4, 00165, Rome, Italy.

Acute kidney injury (AKI) is an increasingly frequent complication among hospitalized children. It is associated with high morbidity and mortality, especially in neonates and children requiring dialysis. The different renal replacement therapy (RRT) options for AKI have expanded from peritoneal dialysis (PD) and intermittent hemodialysis (HD) to continuous RRT (CRRT) and hybrid modalities. Recent advances in the provision of RRT in children allow a higher standard of care for increasingly ill and young patients. In the absence of evidence indicating better survival with any dialysis method, the most appropriate dialysis choice for children with AKI is based on the patient's characteristics, on dialytic modality performance, and on the institutional resources and local practice. In this review, the available dialysis modalities for pediatric AKI will be discussed, focusing on indications, advantages, and limitations of each of them.
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http://dx.doi.org/10.1007/s00467-019-04213-xDOI Listing
May 2020

Haemodiafiltration use in children: data from the Italian Pediatric Dialysis Registry.

Pediatr Nephrol 2019 06 5;34(6):1057-1063. Epub 2019 Jan 5.

Dialysis Unit, Paediatric Nephrology and Dialysis Department, G Gaslini Children Hospital, Genoa, Italy.

Background: High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy.

Methods: We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry's database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors.

Results: One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres.

Conclusions: Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.
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http://dx.doi.org/10.1007/s00467-018-4184-zDOI Listing
June 2019

Renal Tubular Dysfunction Fully Accounts for Plasma Biochemical Abnormalities in Type 1A Pseudohypoparathyroidism.

J Clin Endocrinol Metab 2019 03;104(3):823-826

Nephrology Unit, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy.

Context: Type 1A pseudohypoparathyroidism (PHP-1A) is characterized by target organ resistance to PTH. Patients can present with various dysmorphic features; however, renal failure has not been classically described.

Case Description: A female patient came to our attention at the age of 7 years with characteristic signs of PTH resistance (i.e., hypocalcemia, hyperphosphatemia, and high serum PTH levels). She also presented with hypothyroidism, early-onset obesity, short metacarpal bones, and multiple subcutaneous ossifications, leading to a clinical diagnosis of pseudohypoparathyroidism. In addition to her genetic condition, she had bilateral renal hypodysplasia that was slowly progressing to end-stage kidney disease. She received a kidney transplant at the age of 16 years and, after transplantation, experienced rapidly normalized calcium, phosphate, and PTH levels, allowing f withdrawal of vitamin D supplementation.

Conclusions: To the best of our knowledge, ours is the first report of a patient with PHP-1A undergoing kidney transplantation. Normalization of biochemical parameters after the procedure demonstrated that renal tubular resistance to PTH is sufficient to explain the calcium/phosphate abnormalities observed in PHP-1A.
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http://dx.doi.org/10.1210/jc.2018-01193DOI Listing
March 2019

Protocol biopsies in pediatric renal transplantation: a precious tool for clinical management.

Pediatr Nephrol 2018 11 6;33(11):2167-2175. Epub 2018 Jul 6.

Renal Transplant Unit, Bambino Gesù Children's Research Hospital IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: Kidney transplantation is the best treatment for children with end-stage kidney disease. Early results have improved, but late graft loss is still a major problem. Non-invasive, fully reliable early biomarkers of acute rejection are currently missing.

Methods: Our aim was to evaluate the efficacy of protocol biopsies (PBXs) in a pediatric population. During 11 years, 209 renal transplantations were performed in 204 pediatric patients. Biopsies were performed 3-6 months, 1 year, and 5 years after transplantation. Procedure-related complications were systematically looked for by means of ultrasound scans.

Results: Unexpected findings (mainly subclinical rejections) requiring therapeutic intervention were found in 19.3% biopsies performed at 3-6 months, in 18.4% in 12-month biopsies and in none of those performed after 5 years. The 13.6% patients at 12-month biopsies and 23.6% at 5-year biopsies showed calcineurin inhibitor (CNI) toxicity. Interstitial fibrosis and tubular atrophy (IF/TA) was found in 17.6 and 83.6% of patients at 12-month and 5-year biopsies, respectively. Complications of the PBX were infrequent. Five-year estimated glomerular filtration rate (GFR) was not significantly different in patients who received treatment for any cause and patients with normal histology.

Conclusions: Although we do not have a control group, we may speculate that patients who received treatment returned to a "standard" condition possibly improving final outcome. Protocol biopsies are a powerful diagnostic tool for the management of pediatric renal transplant recipients. In view of the lack of evidence that biopsies taken 5 years after transplantation lead to any therapeutic change, their use should be reconsidered.
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http://dx.doi.org/10.1007/s00467-018-4007-2DOI Listing
November 2018

Viral load of EBV DNAemia is a predictor of EBV-related post-transplant lymphoproliferative disorders in pediatric renal transplant recipients.

Pediatr Nephrol 2017 08 9;32(8):1433-1442. Epub 2017 Mar 9.

Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children's Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation that can be classified into two major subtypes, namely, early lesions and non-early lesions, based on histopathological findings. In the vast majority of cases, proliferating cells are B lymphocytes and, most frequently, proliferation is induced by Epstein-Barr virus (EBV) infection.

Methods: The aim of our study was to evaluate the natural history of EBV infection and its possible evolution toward PTLD in a pediatric cohort of patients who received a renal transplant between January 2000 and December 2013. A total of 304 patients were evaluated for this study, of whom 103 tested seronegative for EBV at transplantation.

Results: Following transplantation, 50 of the 103 seronegative patients (48.5%) developed a first EBV infection, based on the results of PCR assays for EBV DNA, with 19 of these patients ultimately reverting to the negative state (<3000 copies/ml). Among the 201 seropositive patients only 40 (19.9%) presented a reactivation of EBV. Non-early lesions PTLD was diagnosed in ten patients, and early lesions PTLD was diagnosed in five patients. In all cases a positive EBV viral load had been detected at some stage of the follow-up. Having a maximum peak of EBV viral load above the median value observed in the whole cohort (59,909.5 copies/ml) was a significant and independent predictor of non-early lesions PTLD and all PTLD onset.

Conclusions: A high PCR EBV viral load is correlated with the probability of developing PTLD. The definition of a reliable marker is essential to identify patients more at risk of PTLD and to personalize the clinical approach to the single patient.
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http://dx.doi.org/10.1007/s00467-017-3627-2DOI Listing
August 2017

Acute kidney transplant rejection mediated by angiotensin II type 1 receptor antibodies in a pediatric hyperimmune patient.

Pediatr Nephrol 2017 01 17;32(1):185-188. Epub 2016 Oct 17.

Nephrology Unit, Department of Pediatrics, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: Several cases of severe antibody-mediated rejection (AMR) secondary to antibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been described with variable outcome.

Case-diagnosis/treatment: We report the case of a 13-year-old boy whose first kidney transplant failed due to steroid-resistant acute cellular rejection, with the subsequent development of sensitization. He received a second kidney transplant which was complicated by early humoral rejection, with weakly positive staining for the complement degradation product C4d. Test results were negative for donor-specific antibodies against human leukocyte antigens (HLA-DSA) and MHC class I-related chain A (MICA) but positive for AT1R-Ab. Retrospective testing of the sera collected during the first kidney transplant was also positive for AT1R-Ab. We therefore hypothesized that the failure of the first transplant was secondary to the same cause. Losartan was immediately introduced into the therapeutic regimen, and the patient showed an excellent clinical and histological recovery.

Conclusions: Testing for AT1R-Ab in any hypertensive patient with acute rejection who tests negative or weakly positive for C4d and negative for HLA-DSA and who is refractory to therapy is highly advisable. Pre-transplant AT1R-Ab may be indicative of the outcome in patients whose first transplant failed. Prompt initiation of treatment with losartan-immediately after transplantation in patients with pre-existing AT1R-Ab-should be encouraged.
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http://dx.doi.org/10.1007/s00467-016-3500-8DOI Listing
January 2017

Renal transplantation in sensitized children and young adults: a nationwide approach.

Nephrol Dial Transplant 2017 01;32(1):191-195

Italian National Transplant Centre, Italian National Institute of Health (ISS), Rome, Italy.

Background: High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes. Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list.

Methods: In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach.

Results: Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) ± 5.5)]. Mean time on the waiting list was 29.3 months (SD ± 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P < 0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m 2 respectively 1, 6, 12 and 24 months after transplant.

Conclusions: Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.
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http://dx.doi.org/10.1093/ndt/gfw369DOI Listing
January 2017

Waning of vaccine-induced immunity to measles in kidney transplanted children.

Medicine (Baltimore) 2016 Sep;95(37):e4738

Department of Public Health, University of Rome Tor Vergata Academic Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital-Research Institute (IRCCS) Virology Unit, Bambino Gesù Children's Hospital-Research Institute (IRCCS) Nephrology Unit, Bambino Gesù Children's Hospital-Research Institute (IRCCS) Research Unit in Congenital and Perinatal Infections, Bambino Gesù Children's Hospital-Research Institute (IRCCS), Rome, Italy.

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. Data on immune responses and long-term maintenance after vaccinations in such population are still limited.We cross-sectionally evaluated the maintenance of immune response to measles vaccine in kidney transplanted children on immunosuppressive therapy. Measles-specific enzyme-linked immunosorbent assay and B-cell enzyme-linked immunosorbent spot were performed in 74 kidney transplant patients (Tps) and in 23 healthy controls (HCs) previously vaccinated and tested for humoral protection against measles. The quality of measles antibody response was measured by avidity test. B-cell phenotype, investigated via flow cytometry, was further correlated to the ability of Tps to maintain protective humoral responses to measles over time.We observed the loss of vaccine-induced immunity against measles in 19% of Tps. Nonseroprotected children showed signs of impaired B-cell distribution as well as immune senescence and lower antibody avidity. We further reported as time elapsed between vaccination and transplantation, as well as the vaccine administration during dialysis are clinical factors affecting the maintenance of the immune memory response against measles.Tps present both quantitative and qualitative alterations in the maintenance of protective immunity to measles vaccine. Prospective studies are needed to optimize the vaccination schedules in kidney transplant recipients in order to increase the immunization coverage over time in this population.
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http://dx.doi.org/10.1097/MD.0000000000004738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402565PMC
September 2016

Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir.

Transplantation 2016 Apr;100(4):862-70

1 Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany. 2 Hanover Medical School, Hanover, Germany. 3 IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. 4 Faculty of Medicine, Department of Pediatric Nephrology, Hacettepe University, Ankara, Turkey. 5 University Children's Hospital, Department of General Pediatrics, Pediatric Nephrology, Münster, Germany. 6 Olga Children's Hospital, Clinic of Stuttgart, Stuttgart, Germany. 7 Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, United Kingdom. 8 Baskent University, Adana Teaching and Research Center, Department of Pediatric Nephrology, Adana, Turkey. 9 Great Ormond Street Hospital, Great Ormond Street, London, United Kingdom. 10 Ankara University Faculty of Medicine, Dikimevi, Ankara, Turkey. 11 University Children's Hospital, Hamburg, Germany. 12 University Children's Hospital, Tübingen, Germany. 13 University Children's Hospital, Freiburg, Germany. 14 Children's Hospital, Memmingen, Germany. 15 Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.

Background: Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection.

Methods: We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity.

Results: While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia.

Conclusion: Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.
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http://dx.doi.org/10.1097/TP.0000000000000888DOI Listing
April 2016

Cellular immune profile of kidney transplant patients developing anti-HLA antibodies during childhood.

Pediatr Nephrol 2016 Jun 21;31(6):1001-10. Epub 2015 Dec 21.

University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital and Research Institute (IRCCS), Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: In the field of kidney transplantation, identifying early signatures of humoral rejection is a key challenge.

Methods: We investigated the presence of anti-HLA antibodies and the distribution of lymphocyte subpopulations in 77 kidney-transplanted children and young adults compared to 23 healthy controls. Moreover, we tested whether the presence of anti-HLA antibodies could be related to modification in lymphocyte phenotype. Finally, we correlated the presence of anti-HLA antibodies and specific alteration of lymphocyte subsets with clinical outcomes.

Results: In kidney-transplanted children who developed anti-HLA antibodies, we observed an expansion of double-negative B cells (CD19 + CD27-IgD-), indicating premature aging of this compartment. Moreover, we reported signs of impaired B cell regulation, indicated by a higher IL-21R+ B cell frequency associated with an abnormal increase of follicular helper T cells. Finally, a considerable reduction in CD8+ effector T and invariant Natural killer T (NKT) cells was observed. The stability of graft function over time is significantly correlated with the frequency of peripheral effector CD4+ and CD8+ T cells and invariant NKT cells.

Conclusions: This study supports the usefulness of lymphocyte subset as one of a spectrum of early diagnostic tools required to identify patients at risk of developing donor alloimmune response.
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http://dx.doi.org/10.1007/s00467-015-3274-4DOI Listing
June 2016

Continuous renal replacement therapy in children: fluid overload does not always predict mortality.

Pediatr Nephrol 2016 Apr 12;31(4):651-9. Epub 2015 Nov 12.

Department of Nephrology and Urology, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.

Background: Mortality among critically ill children requiring continuous renal replacement therapy (CRRT) is high. Several factors have been identified as outcome predictors. Many studies have specifically reported a positive association between the fluid overload at CRRT initiation and the mortality of critically ill pediatric patients.

Methods: This study is a retrospective single-center analysis including all patients admitted to the pediatric intensive care unit (PICU) of our hospital who received CRRT between 2000 and 2012. One hundred thirty-one patients were identified and subsequently classified according to primary disease. Survival rates, severity of illness and fluid balance differed among subgroups. The primary outcome was patient survival to PICU discharge.

Results: Overall survival to PICU discharge was 45.8 %. Based on multiple regression analysis, mortality was independently associated with onco-hematological disease [odds ratio (OR) 11.7, 95 % confidence interval (CI) 1.3-104.7; p = 0.028], severe multiple organ dysfunction syndrome (MODS) (OR 5.1, 95 % CI 1.7-15; p = 0.003) and hypotension (OR 11.6, 95 % CI 1.4-93.2; p = 0.021). In the subgroup analysis, a fluid overload (FO) of more than 10 % (FO>10 %) at the beginning of CRRT seems to be a negative predictor of mortality (OR 10.9, 95 % CI 0.78-152.62; p = 0.07) only in children with milder disease (renal patients). Due to lack of statistical power, the independent effect of fluid overload on mortality could not be analyzed in all subgroups of patients.

Conclusions: In children treated with CRRT the underlying diagnosis and severity of illness are independent risk factors for mortality. The degree of FO is a negative predictor only in patients with milder disease.
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http://dx.doi.org/10.1007/s00467-015-3248-6DOI Listing
April 2016

Anterior ischemic optical neuropathy in children on chronic peritoneal dialysis: report of 7 cases.

Perit Dial Int 2015 Mar-Apr;35(2):135-9

Department of Nephrology and Urology, Bambino Gesù Children's Hospital, Rome, Italy.

Background: Anterior ischemic optic neuropathy (AION) is characterized by infarction of the optic nerve head due to hypoperfusion of the posterior ciliary arteries and causes sudden blindness in adults on chronic dialysis, but has rarely been described in children. Unlike adults, children do not have comorbidities related to aging.

Methods: We retrospectively analyzed data of 7 children on nocturnal continuous cycling peritoneal dialysis (CCPD) who developed AION identified within the Italian Registry of Pediatric Chronic Dialysis. We also summarized data from 10 cases reported in the literature.

Results: Our 7 patients suffered from acute onset bilateral blindness. Their mean age was 3.2 years and chronic hypotension had been observed prior the AION in 3 of the 7 children. Low systolic blood pressure (SBP) was associated with higher risk of developing AION according to statistical analysis. None recovered completely. In total, 11 out of 16 experienced a partial recovery and no clear evidence emerged favoring specific treatments.

Conclusions: Hypotensive children treated with CCPD are at increased risk of developing AION, which often results in irreversible blindness.
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http://dx.doi.org/10.3747/pdi.2013.00330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406308PMC
April 2016

Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells.

Stem Cells Dev 2015 Jan;24(1):93-103

1 Immunology Research Area, Ospedale Pediatrico Bambino Gesù, IRCSS , Roma, Italy .

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs+CpG. Inhibition is restored in CpG+MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4(+) and CD8(+) cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.
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http://dx.doi.org/10.1089/scd.2014.0155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273193PMC
January 2015

B-sides serologic markers of immunogenicity in kidney transplanted patients: report from 2012-2013 flu vaccination experience.

Transplantation 2014 Aug;98(3):259-66

1 Department of System Medicine, University of Rome, Tor Vergata, Rome, Italy. 2 University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Rome, Italy. 3 WHO National Influenza Centre, Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy. 4 National Council of Researches IFT Unit of Rome S. Camillo Hospital, Regional Transplant Center Lazio (CRTL), S. Camillo Hospital, Rome, Italy. 5 Pediatric Medicine and Infectious Disease, Pediatrics Medicine Department, Bambino Gesù Children's Hospital, Roma, Italy. 6 Department of Nephrology and Urology, Bambino Gesù Children's Hospital, Rome, Italy. 7 Address correspondence to: Paolo Palma, M.D., Ph.D., University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy and Luca Dello Strologo, M.D., Department of Nephrology and Urology, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy.

Background: Safety and immunogenicity data of seasonal influenza vaccination in transplanted patients (Tps) are controversial. Preexisting cross-reactive antibodies generated by repeated vaccination with drift variant strains could bias interpretation of immunogenicity data in Tp.

Methods: The unadjuvanted 2012-2013 seasonal influenza vaccine was administered to 81 kidney Tps being routinely vaccinated against influenza and 23 healthy controls (HCs). Immunogenicity was evaluated by both strain-specific antibody responses with standard hemagglutination inhibition assay and by memory B-cell enzyme-linked immunosorbent spot. Safety was also evaluated by measuring anti-human leukocyte antigen (HLA) antibodies.

Results: The majority of Tps were seroprotected before vaccination (81.5%, 81.5%, and 43.2% vs. 47.8%, 34.8%, and 30.4% in HC for H1N1, H3N2, and B strain, respectively) resulting into lower seroconversion rates (P≤0.01) as compared with HC (40.7%, 39.5%, and 54.3% vs. 73.9%, 82.6%, and 65.2% for H1N1, H3N2, and B strain, respectively). An inverse correlation was found between seroconversion rates and number of previous vaccinations in Tps. On the contrary, similar increase in the frequencies of strain-specific memory B cells were detected by B-cell enzyme-linked immunosorbent spot in both Tps and HCs after vaccination. No serious adverse events have been reported. Donor-specific HLA antibodies increased in two patients after vaccination, and de novo anti-HLA antibodies were identified in two additional patients (non-donor-specific HLA antibodies).

Conclusion: This report on safety and immunogenicity of the seasonal unadjuvanted 2012-2013 flu vaccination suggests that evaluating immunogenicity of influenza vaccination exclusively by hemagglutination inhibition assay may be misleading in individuals receiving yearly seasonal vaccines. Further investigations are required to understand the relation between vaccination and anti-HLA antibody development.
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http://dx.doi.org/10.1097/TP.0000000000000209DOI Listing
August 2014

Three-yr safety and efficacy of everolimus and low-dose cyclosporine in de novo pediatric kidney transplant patients.

Pediatr Transplant 2014 Jun;18(4):350-6

Department of Medical Science and Community Health, University of Milan, Milan, Italy; Division of General and Vascular Surgery, St. Joseph Hospital, Multimedica I.R.C.C.S., Milan, Italy.

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5-3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5-10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three-yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post-transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post-transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m(2), respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch-up growth. No malignancy or post-transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low-dose cyclosporine, and low-dose prednisone leads to good long-term efficacy in de novo pediatric KT recipients.
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http://dx.doi.org/10.1111/petr.12261DOI Listing
June 2014
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