Expanding the Spectrum of Extracorporeal Strategies in Small Infants with Hyperammonemia.

Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be required. Continuous treatments are preferred, and a high-dose continuous renal replacement therapy (CRRT) must be prescribed to ensure a fast ammonia depletion. Many of the children with hyperammonemia are newborns, with lower blood volume than older children. The majority of the CRRT systems are adult-based, with large extracorporeal priming volumes and inadequate UF control. Recent strides have been made in the development of CRRT systems more suitable for young children with smaller sets to use in adult machines and dedicated monitors for neonates and infants. The main advantage of the machines for adults is the higher dialysis fluid flows, however with greater hemodynamic risks. Pediatric monitors have been designed to reduce the extracorporeal volume and to increase the precision of the treatment. However, they have substantial limitation in clearance performances. In this review, we discuss on current strategies to provide CRRT in newborns and small infants with hyperammonemia. We also presented our experience with the use of CARPEDIEM™ implemented in a CVVHDF modality, boosting the diffusive clearance with a post-replacement convective mechanism.

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.

Clinical and genetic characteristics of Dent's disease type 1 in Europe.

BACKGROUND: Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis-nephrocalcinosis, progressive chronic kidney disease (CKD) and kidney failure (KF). Current management is symptomatic and does not prevent disease progression. Here we describe the contemporary DD1 picture across Europe to highlight its unmet needs. METHODS: A physician-based anonymous international e-survey supported by several European nephrology networks/societies was conducted. Questions focused on DD1 clinical features, diagnostic procedure and mutation spectra. RESULTS: A total of 207 DD1 male patients were reported; clinical data were available for 163 with confirmed CLCN5 mutations. Proteinuria was the most common manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithiasis. After 5.5 years, ≈50% of patients presented with renal dysfunction, 20.7% developed CKD stage ≥3 and 11.1% developed KF. At the last visit, hypercalciuria was more frequent in paediatric patients than in adults (73.4% versus 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation, decreased glomerular filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared with those with early-stop mutations. CONCLUSIONS: Results from this large DD1 cohort confirm previous findings and provide new insights regarding age and genotype impact on CKD progression. Our data strongly support that DD1 should be considered in male patients with CKD, nephrocalcinosis/hypercalciuria and non-nephrotic proteinuria and provide additional support for new research opportunities.

How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak.

BACKGROUND: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. METHODS: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0-18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. RESULTS: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). CONCLUSIONS: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.

Can real-time near-infrared spectroscopy monitoring detect graft venous thrombosis after pediatric kidney transplantation?

BACKGROUND: A prompt detection of graft venous thrombosis might preserve the transplanted organ. A real-time near-infrared spectroscopy (NIRS) monitoring of the allograft perfusion could fulfill this goal. The aim of this work was to report the trend of allograft perfusion (rSO2) after pediatric kidney transplantation (KT) complicated by graft venous thrombosis. CASE PRESENTATION: An infant, affected by end-stage kidney disease due to posterior urethral valves, underwent non-living donor KT. The allograft presented both arterial and venous variants and required a complex bench surgery reconstruction. The perfusion of the allograft was monitored by real-time transcutaneous NIRS. The early post-operative was conditioned by worsening clinical conditions, and a graft venous thrombosis was detected after four hours since the transplantation. NIRS monitoring lasted for 348 minutes. Median lower pole rSO2-value was 65% (IQR 62-66%), while the median upper pole rSO2-value was 70% (IQR 70-71%). These data reflected the congestion of the lower pole, observed at the end of the transplantation. The lower pole showed inferior rSO2 values (p<0.0001). At the end of the monitoring, the decrease in peripheral rSO2, measured in left lower limb as a benchmark, was consistent with the ongoing hypovolemic shock and severe acute anemia. CONCLUSION: Transcutaneous NIRS might be a reliable device for monitoring allograft and peripheric perfusion after pediatric KT. The modifications of rSO2 values helped the clinicians manage the patients in the post-operative and early detect acute complications.

Extraperitoneal kidney transplantation: a comparison between children weighting ≤15 kg and >15 kg. Experience of a single institution.

Extraperitoneal approach is sometimes recommended for kidney transplantation (KT) in children weighting <15 kg. We hypothesized that this approach might be as successful as in patients with normal weight. Data of all consecutive KTs performed between 2013 and 2019 were retrospectively reviewed. Early outcomes and surgical complications were compared between children weighing ≤15 kg (low-weight (LW) group) and those weighing >15 kg (Normal-weight (NW) group). All the 108 KTs were performed through an extraperitoneal approach. The LW group included 31 patients (mean age 3.5 ± 1.4 years), whose mean weight was 11.1 ± 2.0 kg. In the LW group,-a primary graft nonfunction (PNGF) occurred in one patient (3.2%), surgical complications occurred in nine (29%), with four venous thrombosis. In the NW group, PNGF occurred in one case (1.3%), delayed graft function (DGF) in eight (10%), surgical complications in 11 (14%) with only one case of venous thrombosis. In both groups, no need for patch during wound closure and no wound dehiscence were reported. The extraperitoneal approach can be effectively used in LW children. No differences were observed in the overall complication rate (P = 0.10), except for the occurrence of venous thrombosis (P = 0.02). This might be related to patients' characteristics of the LW group.

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.

Bench thrombolysis and "autotransplantation" as a rescue treatment for venous thrombosis after living-donor kidney transplantation.

BACKGROUND: Allograft venous thrombosis is a severe complication after kidney transplantation (KT). Early diagnosis and prompt treatment are crucial in preserving the survival of the allograft. In this study, we aimed to describe an emergent strategy for the management of acute allograft venous thrombosis. CASE PRESENTATION: A 4-year-old girl, weighing 13.5 kg, was diagnosed with bilateral congenital renal hypodysplasia, urogenital sinus and anorectal malformation. The patient was referred to our department for living-donor KT. Her mother was eligible as a donor, presenting a body weight ratio of 1:4.5. Thrombosis of the inferior vena cava (ICV) was also identified, without any predisposing factor for thrombophilia. KT was performed by an extraperitoneal approach without complications. Venous anastomosis required a human vascular graft sutured to the ICV, and renal artery was anastomosed to the aorta. On postoperative day (POD) 8, acute abdominal pain and hematuria led to the diagnosis of an allograft venous thrombosis. An emergent laparotomy was required to explant the allograft, followed by bench surgery. The allograft was irrigated with thrombolytic agents and lactated Ringer's solution and then after removing the venous vascular graft, it was reimplanted through vascular anastomosis with the ICV and aorta. The recovery of perfusion and function was good with diuresis since day 4 after re-surgery. At 2-year follow-up, the child presented normal allograft function with an estimated GFR of 65 ml/min/1.73 m2 . CONCLUSION: According to our experience, explantation of the kidney allograft, followed by irrigation with thrombolytics in bench surgery, and reimplantation resulted in unexpected optimal outcomes in the case of allograft venous thrombosis.

Returning to dialysis after kidney allograft failure: the experience of the Italian Registry of Paediatric Chronic Dialysis.

BACKGROUND: The need for dialysis after kidney allograft failure (DAGF) is among the top five reasons for dialysis initiation, making this an important topic in clinical nephrology. However, data are scarce on dialysis choice after transplantation and clinical outcomes for DAGF in children. METHODS: Patients receiving chronic dialysis < 18 years were recorded from January 1991 to January 2019 by the Italian Registry of Pediatric Chronic Dialysis (IRPCD). We investigated factors influencing choice of dialysis modality, patient outcome in terms of mortality, switching dialysis modality, and kidney transplantation. RESULTS: Among 118 patients receiving DAGF, 41 (35%) were treated with peritoneal dialysis (PD), and 77 (65%) with haemodialysis (HD). Significant predictors for treatment with PD were younger age at dialysis start (OR 0.85 per year increase [95%CI 0.72-1.00]) and PD use before kidney transplantation (OR 8.20 [95%CI 1.82-37.01]). Patients entering DAGF in more recent eras (OR 0.87 per year increase [95%CI 0.80-0.94]) and with more than one dialysis modality before kidney transplantation (OR 0.56 for being treated with PD [0.12-2.59]) were more likely to be initiated on HD. As compared to patients on HD, those treated with PD exhibited increased but non-significant mortality risk (HR 2.15 [95%CI 0.54-8.6]; p = 0.28) and higher prevalence of dialysis-related complications during DAGF (p = 0.002) CONCLUSIONS: Patients entering DAGF in more recent years are more likely to be initiated on HD. In this specific population of children, use of PD seems associated with a more complicated course. A higher resolution version of the Graphical abstract is available as Supplementary information.

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

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.

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.

Complications of therapeutic apheresis in pediatric kidney transplantation.

In the setting of kidney transplantation, therapeutic apheresis (TA) is employed both for pre-intervention procedures and during the post-transplant period. In pediatric nephrology units, TA is usually performed as a therapeutic plasma exchange (TPE) with dialysis equipment, and using non-plasma replacement fluids. In children undergoing kidney transplantation, complications of TPE are mainly related to its depletive properties combined with the iatrogenic immunodeficiency status of the patient. Moreover, the use of small central venous catheters and the equipment standardized for adults can increase the risk of adverse events. Focusing on these preconditions, TA in kidney-transplanted children should be performed in specialized centers with specific protocols and a trained staff.

Therapeutic Plasma Exchange in Neonates and Infants: Successful Use of a Miniaturized Machine.

Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications. Still, technical issues due to extracorporeal circulation in neonates have burdened TPE so far, since machines developed for adults require a relatively large blood volume to operate. We in this study, describe our preliminary experience of TPE for treating 2 potentially life-threatening conditions in neonatal age. To overcome the aforementioned limitations, plasmapheresis was performed in both cases using a machine specifically designed for patients weighing less than 10 kg.

Comamonas testosteroni-associated peritonitis in a pediatric peritoneal dialysis patient.

Comamonas testosteroni (C. testosteroni) has been rarely observed as an infectious agent in clinical practice. Few reports described its potential pathogenicity in bloodstream and abdominal infections. Here, we report our experience in the treatment of a C. testosteroni-associated peritonitis in a four-year-old girl receiving chronic peritoneal dialysis (PD). The organism was shown to be highly susceptible to appropriate antibiotic therapy. Infection responded promptly and the patient was managed conservatively without withdrawal from PD.

Joint hypermobility, growing pain and obesity are mutually exclusive as causes of musculoskeletal pain in schoolchildren.

OBJECTIVES: Chronic musculoskeletal pain (MSP) is common in children and can be due to several non-inflammatory conditions such as the benign joint hypermobility syndrome (BJHS), and growing pains (GP). We evaluated frequency, risk factors and causes of MSP in a large cohort of healthy schoolchildren. METHODS: We conducted a cross sectional study in a cohort of healthy schoolchildren, aged 8-13 years, by collecting information and performing a physical examination. The anamnesis was focused on family history for MSP, presence and sites of MSP interfering with the regular daily activities during the previous 6 months and presence of GP. Physical examination included body mass index, pubertal stage and musculoskeletal examination focused on the presence of hypermobility according to the Beighton criteria. RESULTS: Two hundred and eighty-nine schoolchildren, 143 females and 146 males, participated in the study. Chronic MSP occurred in 30.4% of subjects, BJHS occurred in 13.2%. GJH was more frequent in symptomatic subjects than in asymptomatic ones (p=0.054). Symptomatic subjects were more frequently pre-pubertal than pubertal (p=0.006). In general, GP, BJHS and obesity (OB) were mutually exclusive as causes of MSP as, among 88 symptomatic subjects, 52.3% had GP, 40.9% presented BJHS, 4.5% were OB and only two (2.3%) presented both BJHS and OB. After puberty, GP persisted in 66.7%, BJHS in 26.7% and in association with OB in 6.7%. CONCLUSIONS: Approximately one third of schoolchildren suffer from MSP. BJHS, GP and OB are mutually exclusive as causes of MSP in schoolchildren. Pubertal stage plays an important role in the physiopathology of this condition.