The development of donor‐specific HLA antibodies (DSA) is associated with worse renal allograft survival in adult patients. This study assessed the natural history of de novo DSA, and its impact on renal function in pediatric renal transplant recipients (RTR). HLA antibodies were measured prospectively using single‐antigen‐bead assays at 1, 3, 6 and 12 months posttransplant followed by 12‐monthly intervals and during episodes of allograft dysfunction. Of 215 patients with HLA antibody monitoring, 75 (35%) developed DSA at median of 0.25 years posttransplant with a high prevalence of Class II (70%) and HLA‐DQ (45%) DSA. DSA resolved in 35 (47%) patients and was associated with earlier detection (median, inter‐quartile range 0.14, 0.09–0.33 vs. 0.84, 0.15–2.37 years) and lower mean fluorescence intensity (MFI) (2658, 1573–3819 vs. 7820, 5166–11 990). Overall, DSA positive patients had more rapid GFR decline with a 50% reduction in GFR at mean 5.3 (CI: 4.7–5.8) years versus 6.1 (5.7–6.4) years in DSA negative patients (p = 0.02). GFR decreased by a magnitude of 1 mL/min/1.73 m2 per log10 increase in Class II DSA MFI (p < 0.01). Using Cox regression, independent factors predicting poorer renal allograft outcome were older age at transplant (hazard ratio 1.1, CI: 1.0–1.2 per year), tubulitis (1.5, 1.3–1.8) and microvasculature injury (2.9, 1.4–5.7). In conclusion, pediatric RTR with de novo DSA and microvasculature injury were at risk of allograft failure.
Post-infectious glomerulonephritis (PIGN) is one of the most common causes of acute glomerulonephritis in children. Although post-streptococcal glomerulonephritis (PSGN) is still common, there is a wide spectrum of causative agents of PIGN. Non-streptococcal organisms are emerging as the main aetiological agents in high-income countries. Nephritis-associated plasmin receptor (NAPlr) and streptococcal pyrogenic exotoxin B (SPeB) are the two common antigens implicated in the pathogenesis of PSGN. Both NAPlr and SPeB activate the alternative complement pathway, resulting in low serum complement levels, and have an affinity to plasmin and glomerular proteins. The clinical presentation of PIGN varies from a benign asymptomatic condition to rapidly progressive glomerulonephritis requiring dialysis. In most cases, PIGN is self-limiting and the evidence base for the treatments used is quite weak. Renal biopsy is indicated when there are atypical features, rapid progression or inadequate recovery, or where an alternative diagnosis has to be considered. IgA-dominant nephritis, endocarditis-associated nephritis and shunt nephritis are special sub-subtypes of PIGN. The prognosis is generally excellent, although long-term follow-up may be needed.
AimsTo investigate access to paediatric renal transplantation and examine potential barriers within the process.MethodsCross-sectional, multicentre, observational study where paediatric nephrology centres in the UK were requested to provide data on transplantation plans for all children (<18 years) with end-stage kidney disease (ESKD).Results308 children with ESKD were included in this study from 12 out of 13 UK paediatric nephrology centres. 139 (45%) were being prepared for living donor transplantation and 82 (27%) were listed for deceased donor transplantation. The most common cited factors delaying transplantation from occurring in children were disease factors (36%), donor availability (27%) and size of the child (20%). Psychosocial factors were listed as a barrier in 19% of children.ConclusionsIn this study we have documented the main barriers to renal transplantation in children. Some identified factors may be modifiable through local or national intervention, including donor availability and patient psychosocial factors.
Background Intravenous fluid administration is an essential part of perioperative care for children receiving a kidney transplant. There is a paucity of evidence to guide optimal perioperative fluid management. This study aimed to identify the volume of perioperative fluids administered across 5 UK paediatric kidney transplant centres and explore associations between fluid volume administered, graft function, and fluid-related adverse events. Methods Data were collected from five UK paediatric kidney transplant centres on perioperative fluid volumes administered, and incidence of pulmonary oedema, systemic hypertension, and requirement for intensive care support. Children < 18 years of age who received a kidney-only transplant between 1st January 2020 and 31st December 2021 were included. Results Complete data from 102 children were analysed. The median total volume of fluid administered in 72 h was 377 ml/kg (IQR 149 ml/kg) with a high degree of variability. A negative relationship between total fluid volume administered and day 7 eGFR was noted (p < 0.001). Association between urine volume post-transplant and day 7 eGFR was also negative (p < 0.001). Adverse events were frequent but no significant difference was found in the fluid volume administered to those who developed an adverse event, vs those who did not. Conclusions This study describes a high degree of variability in perioperative fluid volumes administered to children receiving kidney transplants. Both fluid volume and urine output were negatively associated with short-term graft function. These data contrast traditional interpretation of high urine output as a marker of graft health, and highlight the need for prospective clinical trials to optimise perioperative fluid administration for this group. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information
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