Background: This study by the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) was designed to determine the incidence, risk factors, current management strategies, and outcomes of antibody-mediated rejection (ABMR) in pediatric kidney transplant recipients (pKTR). Methods: We performed an international, multicenter, longitudinal cohort study of data reported to the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. Three hundred thirty-seven pKTR from 21 European centers were analyzed. Clinical outcomes, including kidney dysfunction, rejection, HLA donor-specific antibodies, BK polyomavirus-associated (BKPyV) nephropathy, and allograft loss, were assessed through 5 years post-transplant. Results: The cumulative incidence of de novo donor-specific class I HLA antibodies (HLA-DSA) post-transplant was 4.5% in year 1, 8.3% in year 3, and 13% in year 5; the corresponding data for de novo class II HLA-DSA were 10%, 22.5%, and 30.6%, respectively. For 5 years post-transplant, the cumulative incidence of acute ABMR was 10% and that of chronic active ABMR was 5.9%. HLA-DR mismatch and de novo HLA-DSA, especially double positivity for class I and class II HLA-DSA, were significant risk factors for ABMR, whereas cytomegalovirus (CMV) IgG negative recipient and CMV IgG negative donor were associated with a lower risk. BKPyV nephropathy was associated with the highest risk of graft dysfunction, followed by ABMR, T-cell mediated rejection, and older donor age. Conclusions: This study provides an estimate of the incidence of de novo HLA-DSA and ABMR in pKTR and highlights the importance of BKPyV nephropathy as a strong risk factor for allograft dysfunction. Graphical

Malnutrition is frequent in children with chronic kidney disease (CKD). Apart from undernutrition and protein energy wasting (PEW), overnutrition prevalence is rising, resulting in fat mass accumulation. Sedentary behavior and unbalanced diet are the most important causal factors. Both underweight and obesity are linked to adverse outcomes regarding renal function, cardiometabolic risk and mortality rate. Muscle wasting is the cornerstone finding of PEW, preceding fat loss and may lead to fatigue, musculoskeletal decline and frailty. In addition, clinical data emphasize the growing occurrence of muscle mass and strength deficits in patients with fat mass accumulation, attributed to CKD-related wasting processes, reduced physical activity and possibly to obesity-induced inflammatory diseases, leading to sarcopenic obesity. Moreover, children with CKD are susceptible to abdominal obesity, resulting from high body fat distribution into the visceral abdomen compartment. Both sarcopenic and abdominal obesity are associated with increased cardiometabolic risk. This review analyzes the pathogenetic mechanisms, current trends and outcomes of malnutrition patterns in pediatric CKD. Moreover, it underlines the importance of body composition assessment for the nutritional evaluation and summarizes the advantages and limitations of the currently available techniques. Furthermore, it highlights the benefits of growth hormone therapy and physical activity on malnutrition management.

Background: This study investigates the effect of chronic kidney disease (CKD) stage on fatigue and health-related quality of life (HRQoL) in the pediatric population. Material and Methods: The PedsQL (Pediatric Quality of Life Inventory) Multidimensional Fatigue Scale (subcategories: general, sleep/rest, and cognitive fatigue) and HRQoL Generic Core Scales (subcategories: physical, emotional, social, and school functioning) questionnaires were completed by 30 patients aged from 7 to 18 years old with CKD stage 2–4, CKD stage 5 on dialysis (CKD 5D), and kidney transplantation (KTx), as well as their parents. Results: Both low “Total Fatigue” and “Total HRQoL” scores were reported in 16.7% of patients. “Sleep/Rest Fatigue”, “Emotional Functioning”, and “School functioning” were the lowest scored subcategories. CKD 5D/KTx patients presented lower “Sleep/Rest Fatigue” (p = 0.022) and, more frequently, low “School Functioning” scores (p = 0.029). The “Total HRQoL” score was correlated to the “Total Fatigue” score (rs = 0.625, p < 0.001). A low “Sleep/Rest Fatigue” score was associated with low “Physical Functioning”, “School Functioning”, and “Total HRQoL” scores (p = 0.016, p = 0.001, and p = 0.047 respectively). Parents’ HRQoL score was lower than patients’ score on “Physical Functioning” (p = 0.040) and “School Functioning” subcategories (p = 0.045). Conclusions: Fatigue and disturbed HRQoL are mostly observed in CKD 5D and KTx pediatric patients, and are associated with sleep disorders and school dysfunction. Fatigue affects HRQoL, which is perceived as more deteriorated by the patients’ parents.

Background: Acute pyelonephritis (APN) in pediatric patients may lead to kidney scarring and is one of the main causes of permanent kidney damage. The incidence of kidney scarring after one febrile urinary tract infection (UTI) is reported to range from 2.8 to 15%, with the percentage rising to 28.6% after ≥ 3 febrile UTIs. Corticosteroids may have a role in the reduction of kidney scar formation and urine cytokine levels. The possible benefit of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN has been recently examined in randomized controlled trials (RCTs). Objectives: The aim of this meta-analysis was to provide a summary of the current literature about the efficacy and safety of adjuvant corticosteroid administration in the reduction of kidney scar formation in children with APN. Data sources: An extensive literature search through major databases (PubMed/MEDLINE and Scopus) was carried out for RCTs from inception until October 12, 2022, investigating the efficacy and safety of adjuvant corticosteroids in preventing kidney scarring in children with APN. A risk ratio with 95% CI was used for dichotomous outcomes. Results: In total, 5 RCTs with 918 pediatric patients with APN were included in the study. Adjuvant corticosteroid treatment revealed a statistically significant reduction in kidney scarring (95% CI 0.42–0.95, p = 0.03), without increasing the risk of adverse events like bacteremia, prolonged hospitalization, or recurrence of UTI. Limitations: There were limitations regarding sample size (n = 498 children), different classes of corticosteroids (methylprednisolone or dexamethasone), different routes of corticosteroid administration (intravenous or oral), and different day courses (3-day or 4-day course). Conclusions: Adjuvant corticosteroid administration seems to have a beneficial effect on kidney scar reduction in children with APN. Future studies should focus on the evaluation of the efficacy and safety of corticosteroids in kidney scarring reduction after APN to strengthen the results of our study. Graphical

Congenital anomalies of the urinary tract, and particularly of obstructive nephropathy such as ureteropelvic junction obstruction (UPJO) in infants, can later lead to chronic kidney disease and hypertension. Fundamental questions regarding underlying mechanisms remain unanswered. The aim of the present study was to quantitate the systemic amino acids metabolome in 21 UPJO infants requiring surgery (Group A) and 21 UPJO infants under conservative treatment (Group B). Nineteen healthy age-matched infants served as controls (Group C). Serum amino acids involved in several pathways and representative metabolites, including the L-arginine-derived nitric oxide (NO) metabolites nitrite and nitrate and the lipid peroxidation biomarker malondialdehyde (MDA) were measured by gas chromatography–mass spectrometry (GC–MS) methods using their stable-isotope labeled analogs as internal standards after derivatization to their methyl esters N-pentafluoropropionic amides (amino acids) and to their pentafluorobenzyl derivatives (nitrite, nitrate, MDA). The concentrations of the majority of the biomarkers were found to be lower in Group A compared to Group B. Statistical analysis revealed clear differentiation between the examined study groups. Univariate statistical analysis highlighted serum homoarginine (q = 0.006), asymmetric dimethylarginine (q = 0.05) and malondialdehyde (q = 0.022) as potential biomarkers for UPJO infants requiring surgery. Group A also differed from Group B with respect to the diameter of the preoperative anterior–posterior renal pelvis (AP) as well as regarding the number and extent of inverse correlations between AP and the serum concentrations of the biomarkers. In Group A, but not in Group B, the AP diameter strongly correlated with hydroxy-proline (r = −0.746, p = 0.0002) and MDA (r = −0.754, p = 0.002). Our results indicate a diminished amino acids metabolome in the serum of UPJO infants requiring surgery comparing to a conservative group.