Functional immune monitoring of BK Virus and donor-specific T-cell effector immune responses to guide treatment decision-making after kidney transplantation; an illustrative case report and literature review.

Differential diagnosis between Polyoma virus associated-nephropathy (PVAN) and T-cell mediated rejection (TCMR) might be challenging, as respective treatment approaches are totally opposite. Here we report the illustrative case of a kidney transplant recipient with PVAN who developed a persistent acute TCMR after full abrogation of viral infection through immunosuppression modulation. By simultaneous functional immune monitoring of BKV and donor-specific T-cell responses using IFN-γELISPOT assay, we retrospectively demonstrated the predominant effector mechanisms responsible of allograft injury and thus, potential guidance for treatment decision-making. Furthermore, the evidence of an efficient T-cell alloimmunity abrogation accompanied by a sustained anti-viral response after sirolimus addition, promotes the potential benefit of converting patients to an mTOR-based immunosuppression in case of PVAN.

Social and economic determinants of pediatric health inequalities: the model of chronic kidney disease.

Purpose of this review is to deal with priorities and strategies to significantly tackle inequalities in the management of pediatric diseases in low-middle-income countries. This issue has become a focal point of epidemiological and public health, with special reference to chronic nontransmissible diseases. We will provide our readership with an essential overview of the cultural, institutional, and political events, which have occurred over the last 20 y and which have produced the current general framework for epidemiology and public health. Then the most recent epidemiological data will be evaluated, in order to quantify the interaction between the medical components of the disease profiles and their socioeconomic determinants. Finally, a focus will be added on models of pediatric chronic kidney diseases, which are in our opinion amongst the most sensitive markers of the interplay between health and society. Collaborative, pediatrician-initiated, multicentre projects in these fields should be given priority in calls for grants supported by public agencies. The involvement of a critical mass of those working in the "fringes" of pediatric care is a final, essential mean by which significant results can be produced under the sole responsibility and research interest of centers of excellence.

Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality.

BACKGROUND: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol METHODS: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study. RESULTS: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units. CONCLUSIONS: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.

Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

The Italian Society for Pediatric Nephrology (SINePe) consensus document on the management of nephrotic syndrome in children: Part I - Diagnosis and treatment of the first episode and the first relapse.

This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at first presentation. It is the first consensus document of its kind to be produced by all the pediatric nephrology centres in Italy, in line with what is already present in other countries such as France, Germany and the USA. It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses. NS is one of the most common pediatric glomerular diseases, with an incidence of around 2-7 cases per 100000 children per year. Corticosteroids are the mainstay of treatment, but the optimal therapeutic regimen for managing childhood idiopathic NS is still under debate. In Italy, shared treatment guidelines were lacking and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. On the basis of the 2015 Cochrane systematic review, KDIGO Guidelines and more recent data from the literature, this working group, with the contribution of all the pediatric nephrology centres in Italy and on the behalf of the Italian Society of Pediatric Nephrology, has produced a shared steroid protocol that will be useful for National Health System hospitals and pediatricians. Investigations at initial presentation and the principal causes of NS to be screened are suggested. In the early phase of the disease, symptomatic treatment is also important as many severe complications can occur which are either directly related to the pathophysiology of the underlying NS or to the steroid treatment itself. To date, very few studies have been published on the prophylaxis and treatment of these early complications, while recommendations are either lacking or conflicting. This consensus provides indications for the prevention, early recognition and treatment of these complications (management of edema and hypovolemia, therapy and prophylaxis of infections and thromboembolic events). Finally, recommendations about the clinical definition of steroid resistance and its initial diagnostic management, as well as indications for renal biopsy are provided.

SXR rs3842689: a prognostic factor for steroid sensitivity or resistance in pediatric idiopathic nephrotic syndrome.

AIM: of the study was to analyse the impact of SXR rs3842689 polymorphism on the response to corticosteroids in pediatric idiopathic nephrotic syndrome. PATIENTS & METHODS: 66 children (56 steroid-sensitive, ten steroid-resistant) were studied for SXR gene polymorphism distribution. RESULTS: Steroid sensitive patients accounted for 96% of cases with In/In polymorphism, but only for 53% of cases with Del/Del polymorphism At odds ratio analysis, Del/Del represented a clear risk factor of steroid resistance (OR: 20.57; p = 0.009), while In/In was a favourable prognostic factor of steroid sensitivity. CONCLUSION: The analysis of SXR polymorphism is a promising tool to predict both the favourable response to corticosteroids and the risk of developing steroid resistance.

Neurophysiological correlates of eye movement desensitization and reprocessing sessions: preliminary evidence for traumatic memories integration.

We have investigated the potential role of eye movement desensitization and reprocessing (EMDR) in enhancing the integration of traumatic memories by measuring EEG coherence, power spectra and autonomic variables before (pre-EMDR) and after (post-EMDR) EMDR sessions during the recall of patient's traumatic memory. Thirteen EMDR sessions of six patients with post-traumatic stress disorder were recorded. EEG analyses were conducted by means of the standardized Low Resolution Electric Tomography (sLORETA) software. Power spectra, EEG coherence and heart rate variability (HRV) were compared between pre- and post-EMDR sessions. After EMDR, we observed a significant increase of alpha power in the left inferior temporal gyrus (T = 3.879; P = 0.041) and an increased EEG coherence in beta band between C3 and T5 electrodes (T = 6.358; P < 0.001). Furthermore, a significant increase of HRV in the post-EMDR sessions was also observed (pre-EMDR: 6.38 ± 6.83; post-EMDR: 2.46 ± 2.95; U-Test = 45, P = 0.043). Finally, the values of lagged coherence were negatively associated with subjective units of disturbance (r(24) = -0.44, P < 0.05) and positively associated with parasympathetic activity (r(24) = 0.40, P < 0.05). Our results suggest that EMDR leads to an integration of dissociated aspects of traumatic memories and, consequently, a decrease of hyperarousal symptoms [Correction made here after initial publication].

Aberrant EEG functional connectivity and EEG power spectra in resting state post-traumatic stress disorder: a sLORETA study.

The aim of the present study was to explore the modifications of EEG power spectra and EEG connectivity of resting state (RS) condition in patients with post-traumatic stress disorder (PTSD). Seventeen patients and seventeen healthy subjects matched for age and gender were enrolled. EEG was recorded during 5min of RS. EEG analysis was conducted by means of the standardized Low Resolution Electric Tomography software (sLORETA). In power spectra analysis PTSD patients showed a widespread increase of theta activity (4.5-7.5Hz) in parietal lobes (Brodmann Area, BA 7, 4, 5, 40) and in frontal lobes (BA 6). In the connectivity analysis PTSD patients also showed increase of alpha connectivity (8-12.5Hz) between the cortical areas explored by Pz-P4 electrode. Our results could reflect the alteration of memory systems and emotional processing consistently altered in PTSD patients.

Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine in pediatric kidney transplant patients.

AIM: Cyclosporine is characterized by a wide interindividual variability in its pharmacokinetics. The objective of this study was to evaluate the effects of ABCB1 and SXR SNPs on cyclosporine exposure in a group of kidney transplant patients followed up from childhood to adulthood. PATIENTS & METHODS: Recipients were genotyped for ABCB1 C1236T, G2677T/A and C3435T, and for SXR RS3842689 and A7635G. Dose-adjusted trough levels and weight-adjusted daily doses were compared among patients according to allelic status by a generalized estimation equation approach that allows longitudinal data analyses. RESULTS: A genotype-dependent effect was found in all ABCB1 genotypes and in one of the SXR SNPs. This effect was particularly evident for the TT genotype of the ABCB1 G2677T/A SNP, the TT genotype of the ABCB1 C3435T SNP and for heterozygotes of the deletion of 6 bp in the promoter region of SXR. CONCLUSION: The presence of specific ABCB1 and SXR SNPs could significantly affect cyclosporine exposure during a kidney transplant patient's development from childhood to adulthood in a time-dependent fashion.