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Background: Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR.From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed.Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1–11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009).pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.A higher resolution version of the Graphical abstract is available asSupplementary informationA higher resolution version of the Graphical abstract is available asSupplementary informationMethods: Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR.From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed.Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1–11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009).pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.A higher resolution version of the Graphical abstract is available asSupplementary informationA higher resolution version of the Graphical abstract is available asSupplementary informationResults: Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR.From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed.Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1–11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009).pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.A higher resolution version of the Graphical abstract is available asSupplementary informationA higher resolution version of the Graphical abstract is available asSupplementary informationConclusions: Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR.From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed.Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1–11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009).pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.A higher resolution version of the Graphical abstract is available asSupplementary informationA higher resolution version of the Graphical abstract is available asSupplementary informationGraphical Abstract: Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR.From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed.Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1–11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009).pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.A higher resolution version of the Graphical abstract is available asSupplementary informationA higher resolution version of the Graphical abstract is available asSupplementary information [ABSTRACT FROM AUTHOR]

Background: The prognosis of Henoch-Schönlein purpura (HSP), IgA vasculitis, depends on kidney involvement. There is no consensus on the initiation of treatment for HSP nephritis (HSPN). Some centres start treatment before performing a kidney biopsy (KB) while in others, treatment is dictated by the importance of the clinical, biological and histological signs. The aim of this study was to evaluate which of these two approaches is associated with a better kidney outcome at 5-year follow-up. Methods: This multicentre, retrospective, nonrandomised study included children treated for HSPN between 2006 and 2010 in a French paediatric nephrology unit. One group had an early KB at diagnosis (before starting treatment or in the 15 following days). In the second group, initial treatment was decided without performing a KB. Results: Among the 107 children included, 63.5% had an early KB at diagnosis. Follow-up at 5 years was completed in 44 children (28 KB at diagnosis, 16 no KB at diagnosis). Median urine protein/creatinine at 5 years was 2.5 mg/mmol in the early biopsy diagnosis group and 12.5 mg/mmol in the non-biopsy group. An antiproteinuric treatment was given, at 5 years, to 35.7% of the early biopsy at diagnosis children and in 62.5% of the non-biopsied children. Conclusions: Children with early KB at diagnosis seem to have a better renal outcome at 5 years compared to those without an early biopsy at diagnosis or biopsied later. However, this is a small patient cohort and data are missing. Further work is needed to build consensual guidelines on the management of HSPN in children. [ABSTRACT FROM AUTHOR]

Gain-of-function mutations in with no lysine (K) 1 (WNK1) and WNK4 genes are responsible for familial hyperkalemic hypertension (FHHt), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. More recently, FHHt-causing mutations in the Kelch-like 3-Cullin 3 (KLHL3-CUL3) E3 ubiquitin ligase complex have shed light on the importance of WNK's cellular degradation on renal ion transport. Using full exome sequencing for a 4-generation family and then targeted sequencing in other suspected cases, we have identified new missense variants in the WNK1 gene clustering in the short conserved acidic motif known to interact with the KLHL3-CUL3 ubiquitin complex. Affected subjects had an early onset of a hyperkalemic hyperchloremic phenotype, but normal blood pressure values"Functional experiments in Xenopus laevis oocytes and HEK293T cells demonstrated that these mutations strongly decrease the ubiquitination of the kidney-specific isoform KS-WNK1 by the KLHL3-CUL3 complex rather than the long ubiquitous catalytically active L-WNK1 isoform. A corresponding CRISPR/Cas9 engineered mouse model recapitulated both the clinical and biological phenotypes. Renal investigations showed increased activation of the Ste20 proline alanine-rich kinase-Na+-Cl- cotransporter (SPAK-NCC) phosphorylation cascade, associated with impaired ROMK apical expression in the distal part of the renal tubule. Together, these new WNK1 genetic variants highlight the importance of the KS-WNK1 isoform abundance on potassium homeostasis. [ABSTRACT FROM AUTHOR]

Background: Relapsing nephrotic syndrome (NS) after transplantation can be a challenge to treat. The result of the consequent long-lasting proteinuria is the loss of the graft. Disease recurrence after renal transplantation occurs in around half of cases, and the efficacy of therapeutic strategies is often limited. Recently, ofatumumab, a second-generation and fully human anti-CD20 monoclonal antibody, has been shown to be effective in severe situations. Methods: We retrospectively collected data from the medical records of children with recurrence of NS after renal transplantation treated with ofatumumab in France, after failure of previous treatments. Results: Six patients were included in this study in five centers with a median duration of follow-up of 10.5 months. Two different ofatumumab regimens were administered. The primary outcome was proteinuria at 6 months after the last dose of ofatumumab. No patient achieved a complete remission, 3/6 had a partial remission, and 3/6 had no response to ofatumumab. Four patients exhibited a minor allergic reaction with the first infusion. One patient died of infection, as a consequence of multiple factors. No malignancies were observed; however, the time of follow-up was not sufficient to see such disease. Conclusions: Altogether, these results suggest ofatumumab has a poor efficacy in treating recurrence of NS after renal transplantation. However, it could be discussed in multidrug-resistant refractory NS, but infectious complications and overimmunosuppression have to be balanced. There is a need for further studies to confirm these findings and safety and to determine a standardized protocol in this indication. [ABSTRACT FROM AUTHOR]

Background. Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation (KTx) in children. This can lead to delayed graft loss. As themanagement of children with recurrent FSGS is not well established, apheresis strategies could be a cornerstone to control the disease. Immunoadsorption (IA) is a recent apheresis therapy. There have been few studies examining IA in this setting.We report the results of IA for management of recurrent FSGS after KTx in children in France. Methods. We included all children treated with IA for early FSGS recurrence after KTx between January 2011 and June 2014 in France. We excluded genetic forms of FSGS. Patients' characteristics and technical data on IA were retrospectively collected. Recurrence was defined as nephrotic proteinuria during the post-transplantation period. Partial and complete remissions were defined when urine protein:creatinine ratios were less than 0.2 and 0.05 g/mmol, respectively. Results. Twelve patients, from six paediatric KTx units, presenting with FSGS recurrence between 0 and 21 days after KTx were treated with IA. Ten of 12 children were responders: 2 achieved partial remission and 8 complete remission. The decrease of proteinuria rapidly occurred within the first 10 sessions after initiating IA. After 3months of IA, two patients maintained remission without IA and eight became IA dependent. No severe side effects were reported. Conclusions. Our study reports on the efficacy of IA in the recurrence of FSGS after KTx in children. Further prospective controlled studies are required to confirm these results and to optimize themanagement of FSGS recurrence after paediatric KTx. [ABSTRACT FROM AUTHOR]