Corrigendum: The new Italian registry of infantile thrombosis (RITI): a reflection on its journey, challenges and pitfalls.

[This corrects the article DOI: 10.3389/fped.2023.1094246.].

Renal Involvement in Multisystem Inflammatory Syndrome in Children: Not Only Acute Kidney Injury.

Kidney involvement has been poorly investigated in SARS-CoV-2 Multisystem Inflammatory Syndrome in Children (MIS-C). To analyze the spectrum of renal involvement in MIS-C, we performed a single-center retrospective observational study including all MIS-C patients diagnosed at our Pediatric Department between April 2020 and May 2022. Demographic, clinical, pediatric intensive care unit (PICU) admission's need and laboratory data were collected at onset and after 6 months. Among 55 MIS-C patients enrolled in the study, kidney involvement was present in 20 (36.4%): 13 with acute kidney injury (AKI) and 7 with isolated tubular dysfunction (TD). In eight patients, concomitant AKI and TD was present (AKI-TD). AKI patients needed higher levels of intensive care (PICU: 61.5%, p < 0.001; inotropes: 46.2%, p = 0.002; second-line immuno-therapy: 53.8%, p < 0.001) and showed lower levels of HCO3- (p = 0.012), higher inflammatory markers [neutrophils (p = 0.092), PCT (p = 0.04), IL-6 (p = 0.007)] as compared to no-AKI. TD markers showed that isolated TD presented higher levels of HCO3- and lower inflammatory markers than AKI-TD. Our results indicate a combination of both pre-renal and inflammatory damage in the pathogenesis of kidney injury in MIS-C syndrome. We highlight, for the first time, the presence of tubular involvement in MIS-C, providing new insights in the evaluation of kidney involvement and its management in this condition.

The AngioVac System in Childhood and Adolescence: A New Venovenous Extracorporeal Membrane Oxygenation-Like Configuration.

Intravascular and intracardiac clots, thrombi, and vegetative material can be safely and effectively treated with the AngioVac System (AngioDynamics, Latham, NY) as an alternative to open surgery. However, this technology is still not performed in children or adolescents as a rule. We aimed to present our experience with two cases (a 10 year old girl and a 17 year old male adolescent) with concurrent hypoxemia in whom this device was successfully used in combination with venovenous extracorporeal membrane oxygenation to remove caval thrombi and cavoatrial septic material, respectively. This extracorporeal circuit configuration allowed adequate respiratory support during the procedure. No endovascular recurrence of the pathologic material was found at 2 and 1 year of follow-up, respectively.

The new Italian registry of infantile thrombosis (RITI): A reflection on its journey, challenges and pitfalls.

Introduction: Thrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management. Methods: We present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management. Results: The RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0-18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled. Discussion: The RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

Nadir creatinine as a predictor of renal outcomes in PUVs: A systematic review and meta-analysis.

Background: Posterior urethral valves (PUVs) represent the most severe pediatric obstructive uropathy, responsible for chronic renal failure in up to 65% of cases and progression to end-stage kidney disease (ESKD) in about 8%-21% of patients. Unfortunately, renal outcomes have poorly improved over time. The key point is to identify patients at risk; thus, several prenatal and postnatal prognostic factors have been analyzed to improve clinical outcomes. Postnatal nadir creatinine seems to accurately predict long-term renal prognosis, but there is no definitive evidence to support this finding. Objective: We performed a systematic review with meta-analysis to analyze the predictive value of nadir creatinine on long-term renal function in infants with PUVs. Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Cochrane Library were systematically searched for studies published from January 2008 to June 2022. All the articles were checked independently by two reviewers in two steps. Results: A total of 24 articles were screened, and 13 were included for data extraction. Data from 1,731 patients with PUVs were analyzed, with a mean follow-up of 5.5 years; of these, on average, 37.9% developed chronic kidney disease (CKD) and 13.6% developed ESKD. All the articles evaluated nadir creatinine as a predictor of CKD, most using a level of 1 mg/dL, with statistical significance at the 5% level. The relative risk of developing CKD in patients with creatinine values higher than the nadir cutoff considered was 7.69 (95% CI: 2.35-25.17, I 2 = 92.20%, p < 0.001). Conclusions: Nadir creatinine is the best prognostic factor for long-term renal function in patients affected by PUV. A value above the cutoff of 1 mg/dL should be considered a significant predictor for the risk of CKD and ESKD. Further studies are needed to define different nadir creatinine cutoffs for better stratification of the different CKD stages and for the development of reliable scores, which include the association of several variables.

Complex Bench Surgery Does Not Increase the Risk of Vascular Complications after Pediatric Kidney Transplantation.

INTRODUCTION: Vascular complications are severe complications of pediatric kidney transplantation (KT). We aimed to investigate whether a complex bench surgery (BS) affects the outcomes. METHODS: All pediatric KT performed at the University Hospital of Padua from 2015 to 2019 were analyzed, comparing those in which a standard BS was possible to those that necessitated a complex BS. The rates of vascular complications, patients' outcome, and graft survival were compared in the two groups. RESULTS: Eighty KTs were performed in 78 patients with a median age of 11 years (interquartile range [IQR] 4.3-14) and a median body weight of 24 kg (IQR 13-37). Thirty-nine donor kidneys (49%) needed a complex BS due to anomalies of renal veins in 12 (31%) and renal arteries in 16 (41%). The remaining 11 grafts (28%) underwent an elongation of the vein. There was no difference in the rate of primary graft non function (p = 0.97), delayed graft function (p = 0.72), and overall survival (p = 0.27). The rates of vascular complications, bleedings, and venous graft thrombosis were similar (p = 0.51, p = 0.59, p = 0.78, respectively). No arterial thrombosis or stenosis was reported. CONCLUSION: Complex BS did not compromise survival of the graft and did not put the allograft at risk of vascular complications, such as bleedings or thrombosis.

Risk factors for end stage renal disease in children with anorectal malformation and outcome comparison to children with isolated urological anomalies.

BACKGROUND: End stage renal disease (ESRD) requiring kidney transplant (KT) remains an important cause of morbidity in anorectal malformations (ARM) patients. Current literature is scarce on defining the risk factors for ESRD and the outcomes of KT in ARM patients. OBJECTIVE: This study aimed to identify predisposing factors to ESRD in ARM patients and verify if the long term outcome of KT in these patients differs from pure urological anomalies (UA). STUDY DESIGN: Databases of ARM and KT patients treated at our center between 2000 and 2016 were used for comparing characteristics of ARM cases which developed ESRD and those who did not, and the outcome features of MAR-KT vs UA-KT. RESULTS: Out of 117 ARM patients, 9 developed ESRD. All of them had a complex ARM. Association with UA were significantly higher in ARM-KT compared to other ARM patients (100% vs. 52%, p = 0.001). The most common UA associated to KT in ARM patients was renal dysplasia. During the same period 23 patients underwent KT as a sequelae of pure urological anomalies (UA-KT group). The most represented UA were primary vesico-ureteral reflux (65.2%) and posterior urethral valves (14%) in UA-KT (table 2). ARM-KT patients required more often hemodialysis before KT (50% vs. 8.7%, p = 0.05) and an aorto-caval anastomosis at the transplant (75% vs. 30%, p = 0.04) compared to UA-KT. Moreover ARM-KT patients experienced more often graft failure and and the need for a second KT (50% vs. 8.6%, p = 0.02). DISCUSSION: To our knowledge, this is the first study describing the differences in terms of risk factors and outcomes of KT in ARM patients. We observed a need for KT in 7% of ARM, which is at the higher end of the range reported in the literature. Bilateral dysplasia and cloaca malformation seem the leading cause to ESRD for ARM patients compared to vesico-ureteral reflux and posterior urethral valve in UA-KT. Our experience showed that KT has worst outcome in ARM vs pure UA patients. CONCLUSION: Patients with complex ARM are more frequently associated to renal dysplasia which lead to KT. Graft in ARM patients seems to be the more vulnerable and prone to failure.

Management of the congenital solitary kidney: consensus recommendations of the Italian Society of Pediatric Nephrology.

BACKGROUND: In recent years, several studies have been published on the prognosis of children with congenital solitary kidney (CSK), with controversial results, and a worldwide consensus on management and follow-up is lacking. In this consensus statement, the Italian Society of Pediatric Nephrology summarizes the current knowledge on CSK and presents recommendations for its management, including diagnostic approach, nutritional and lifestyle habits, and follow-up. We recommend that any antenatal suspicion/diagnosis of CSK be confirmed by neonatal ultrasound (US), avoiding the routine use of further imaging if no other anomalies of kidney/urinary tract are detected. A CSK without additional abnormalities is expected to undergo compensatory enlargement, which should be assessed by US. We recommend that urinalysis, but not blood tests or genetic analysis, be routinely performed at diagnosis in infants and children showing compensatory enlargement of the CSK. Extrarenal malformations should be searched for, particularly genital tract malformations in females. An excessive protein and salt intake should be avoided, while sport participation should not be restricted. We recommend a lifelong follow-up, which should be tailored on risk stratification, as follows: low risk: CSK with compensatory enlargement, medium risk: CSK without compensatory enlargement and/or additional CAKUT, and high risk: decreased GFR and/or proteinuria, and/or hypertension. We recommend that in children at low-risk periodic US, urinalysis and BP measurement be performed; in those at medium risk, we recommend that serum creatinine also be measured; in high-risk children, the schedule has to be tailored according to kidney function and clinical data.

Management of Hypertensive Crises in Children: A Review of the Recent Literature.

Hypertensive emergency is a life-threatening condition associated with severe hypertension and organ damage, such as neurological, renal or cardiac dysfunction. The most recent guidelines on pediatric hypertension, the 2016 European guidelines and the 2017 American guidelines, provide recommendations on the management of hypertensive emergencies, however in pediatric age robust literature is lacking and the available evidence often derives from studies conducted in adults. We reviewed PubMed and Cochrane Library from January 2017 to July 2021, using the following search terms: "hypertension" AND "treatment" AND ("emergency" OR "urgency") to identify the studies. Five studies were analyzed, according to our including criteria. According to the articles reviewed in this work, beta-blockers seem to be safe and effective in hypertensive crises, more than sodium nitroprusside, although limited data are available. Indeed, calcium-channel blockers seem to be effective and safe, in particular the use of clevidipine during the neonatal age, although limited studies are available. However, further studies should be warranted to define a univocal approach to pediatric hypertensive emergencies.

SARS-CoV2 Related Multi System Inflammatory Syndrome in a Child with Chronic Kidney Disease: Case Report.

Since April 2020, several paediatric cases were reported with a multisystemic inflammatory syndrome related with SARS-CoV2, called MIS-C. In this case report, we describe a 2-year-old male with end-stage renal disease (ESRD) in renal replacement therapy (RRT) with peritoneal dialysis and severe hypertension affected by a severe SARS-CoV2 related illness characterised by multiorgan failure and need for intensive care, with clinical and instrumental features compatible with MIS-C. Most paediatric patients with kidney disease experience mild SARS-CoV2 disease and to our knowledge, this is the first case of a child with chronic kidney disease suffering from MIS-C. We believe that chronic kidney disease together with dialysis status and severe hypertension play a crucial role on developing severe forms of SARS-CoV2 related disease.

Usefulness of 99mTc-dimercaptosuccinic acid renal scan in the diagnosis and follow-up of acute tubulointerstitial nephritis in children.

BACKGROUND: Symptoms and signs of acute tubulointerstitial nephritis (ATIN) are nonspecific; therefore, renal biopsy is often necessary to clarify the diagnosis. The aim of this study was to evaluate the use of 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis and follow-up of ATIN. METHODS: We retrospectively reviewed the charts of five patients (nine renal units) with a median age of 14 years who underwent DMSA scan after a clinical and/or biopsy-proven diagnosis of ATIN. The exam was performed within 1 month after disease onset and repeated at a median time of 12 months after the acute phase. RESULTS: DMSA renal scans performed during the acute phase allowed the discovery of suggestive findings, including diffuse reduction of the renal uptake of radionuclide and presence of multiple 'cold' focal lesions in a corticomedullary distribution. The follow-up scintigraphy resulted normal in two patients who were treated with steroids and in one patient who presented a mild renal dysfunction in the acute phase. By contrast, the control scan showed persistent renal damage in one patient who was further readmitted because of hypertension and in one renal transplanted patient who presented a Stage 3 acute kidney injury in the acute phase. CONCLUSIONS: DMSA renal scan might be a reliable tool for an early non-invasive diagnosis of ATIN in children and might be particularly useful in those patients who are not candidates for a kidney biopsy. Moreover, DMSA scan gives accurate follow-up evaluation, as it allows monitoring of the evolution of acute renal parenchymal inflammation with potential risk of renal scar formation. Due to the small sample size, our findings warrant further validation in a larger study.

Clinico-pathological correlation in duplex system ectopic ureters and ureteroceles: can preoperative work-up predict renal histology?

PURPOSE: Upper pole histology has been poorly investigated in duplex system ectopic ureters and ureteroceles. We aimed to determine the differences in histology between the conditions, and to identify clinical markers of renal damage. METHODS: Twenty-two patients undergoing partial nephrectomy between 2001 and 2007 for poorly functioning upper poles associated with ectopic ureters (n = 11) or ureteroceles (n = 11) were considered. Histology was classified into three groups: normal, chronic interstitial nephritis (CIN), and dysplasia. Clinical and radiological variables were compared between the two conditions and between cases with normal and abnormal histology. RESULTS: Of the 22 upper pole specimens, 9 had normal histology, 8 dysplasia, and 5 CIN. Statistical analysis failed to show any significant difference in preoperative variables or histology between ectopic ureters and ureteroceles, and in preoperative variables between cases with normal and abnormal histology. CONCLUSIONS: We did not find significant differences in the histology of upper poles associated with ectopic ureters and ureteroceles. Histology was normal in more than one-third of patients, although the poles were poorly functioning. We hypothesize that these poles were hypoplasic rather than dysplasic. We failed to identify predictors of histological damage. Hence, the latter cannot be considered a factor guiding our decision-making.