Ismail Dursun

Introduction: We aimed to evaluate the clinical and genetic characteristics and clinical course of children with persistent proteinuria associated with CUBN variants. Methods: Forty-eight children with CUBN variants from 15 pediatric nephrology centers were included. Patients’ characteristics, serum creatinine, albumin, hemoglobin, vitamin B12 levels, urinalysis, spot urine protein/creatinine (uPCR), microalbumin/creatinine (uACR), beta-2 microglobulin/creatinine (uBMCR) ratios, estimated glomerular filtration rates (eGFRs), treatments, kidney biopsies, and genetic findings were evaluated. Results: All patients had normal serum albumin and creatinine and preserved eGFR. There was no significant change in eGFR between the first and last visits ( p = 0.15), whereas uPCR was lower at the last visit ( p = 0.001). Kidney biopsy was performed in 13 (27%); light microscopy was normal in all except one patient with focal segmental glomerulosclerosis (FSGS). Thirty-five patients (72.9%) had ACEi/ARB therapy, which was discontinued in 21 patients without subsequent worsening of proteinuria. Overall, 26 distinct CUBN variants were identified, predominantly in the C-terminal region. The most frequent variant was c.10102A > G (p.Met3368Val). Variant types included 15 (57.7%) missense, 7 (27%) nonsense, 3 (11.5%) splicing, and 1 (3.8%) frameshift variants. Conclusions: In this multicenter, large pediatric cohort, proteinuria associated with CUBN variants generally followed a benign course over short to mid-term follow-up even without sustained ACEi/ARB therapy. Embedding targeted CUBN testing into the evaluation of children with asymptomatic proteinuria and normal kidney function may reduce unnecessary kidney biopsies and prolonged medication, while improving family counseling. We outline a stepwise care pathway → early genetic screening → conservative monitoring with periodic eGFR and proteinuria assessment → consideration of ACEi/ARB discontinuation and recommend prospective validation and cost-effectiveness studies.

Key Points: Among 72 patients with childhood-onset ANCA-associated vasculitis, kidney transplant survival was good (86%). ANCA-associated vasculitis relapse occurred in 8 patients (11%), a median of 71 months after transplantation and resulted in graft failure in only one case. Positive ANCA at the time of transplantation did not predict graft failure but was associated with a higher risk of relapse and worse graft function. Background: ANCA-associated vasculitis (AAV) is rare in children, and results in kidney failure in up to one third of cases. There is very limited knowledge on kidney transplantation in childhood-onset AAV. We assessed kidney transplantation outcomes and prognostic factors in a multicenter cohort of patients with childhood-onset AAV. Methods: Patients diagnosed with AAV during childhood (≤18 years) who received a kidney transplant were included in this retrospective study. We determined patient and graft survival, rates of chronic graft dysfunction (defined as eGFR 2 for ≥3 months) and AAV relapse, and assessed determinants of outcome with logistic regression models. Patients were matched 1:2 for age, sex, and era of transplantation with non-AAV recipients from the Hospital for Sick Children in Toronto, Canada, and their graft survival was compared. Results: We included 72 patients, of whom 53 (74%) had microscopic polyangiitis and 19 (26%) granulomatosis with polyangiitis. Their median age (interquartile range at the time of diagnosis and transplantation was 12 (9–14) and 14 (12–16) years, respectively. After a median post-transplant follow-up of 53 months (interquartile range, 25–97), 70 patients (97%) were alive, 62 (86%) had a functioning graft, 28 (39%) had developed chronic graft dysfunction, and 8 (11%) had experienced AAV relapse. Graft survival was comparable between AAV and non-AAV recipients. Acute rejection was the only independent predictor of graft failure (hazard ratio [HR], 12.11; 95% confidence interval [CI], 1.19 to 122.49). Positive ANCA at the time of transplantation was significantly associated with a chronic graft dysfunction (HR, 4.16; 95% CI, 1.71 to 10.13) and AAV relapse (HR, 23.1; 95% CI, 2.67 to 200.28). Conclusions: Patients with childhood-onset AAV show good overall and graft survival after kidney transplantation and a low rate of post-transplant relapse. Further studies are warranted to confirm whether positive ANCA at the time of transplantation is associated with poorer graft outcomes.

Altay D, et al. Pediatr Gastroenterol Hepatol Nutr. 2026 Jan;29(1):55-61. https://doi.org/10.5223/pghn.2026.29.1.55

Background Hypertension (HT) is an important risk factor in patients with congenital anomalies of the kidney and urinary tract (CAKUT), independent of the existing anomaly in childhood. This study aimed to investigate masked hypertension and/or blood pressure profiles in different subgroups with a normal glomerular filtration rate (GFR). Methods The study included participants from seven different pediatric nephrology centers in Türkiye. Ambulatory blood pressure monitoring (ABPM) was performed on patients aged 5–18 years, diagnosed with CAKUT, with a GFR above 100 ml/min/m², and normal office blood pressure measurements. Validated Mobil-O-Graph or Spacelabs devices were used in all centers. Results In total, 118 healthy control data and 322 patients with CAKUT were evaluated, consisting of 73 (22.7%) with agenesis, 79 (24.5%) with cystic dysplasia, 92 (28.6%) with vesicoureteral reflux, 18 (5.6%) with UPJ (ureteropelvic junction) obstruction, and 60 (18.6%) with other conditions. In all CAKUT patients, daytime systolic blood pressure (SBP) and both day and nighttime diastolic blood pressure (DBP) loads were significantly higher compared to the healthy control group (p < 0.05). Nocturnal hypertension was identified in 58 (18%) of 322 children, whereas none of the control group presented hypertension. Children with cystic dysplasia had the highest nighttime hypertension proportions (22.7%) when compared to other subgroups. All data revealed higher total systolic–diastolic SDS and total mean SDS in the cystic dysplasia subgroup (p < 0.05). Conclusions The findings underscore the importance of blood pressure monitoring in the follow-up of patients with CAKUT, especially those with cystic dysplasia, even in the absence of GFR decline. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Background Early identification of AKI is crucial to lowering morbidity and mortality in pediatric intensive care units (PICU). Dickkopf-3(DKK3) is a glycoprotein produced by stressed tubular epithelium, plays role in Wnt/β-catenin pathway and demonstrates tubulointerstitial damage. The aim of this study to investigate the possible role of urinary DKK3 in detecting AKI before creatinine elevation in PICU and whether elevated urinary DKK3 is associated with worse outcomes. Methods 117 patients were included in the study. Urine DKK3 levels were measured on PICU admission. Patients who developed AKI and those who did not during the 10-days follow-up were compared in terms of urine DKK3 levels, clinical and laboratory variables. Univariate and multiple binary logistic regression analyses were performed to examine risk factors for the development of AKI and mortality. Results Forty-two (35.8%) patients experienced AKI and 39(33%) patients died. Median urine DKK3 level was statistically significantly higher in patients developing AKI (p < 0.001). In multivariate logistic regression model, only LogDKK3/Cr (AOR:3.619; 95%CI:1.478–8.876) was independently associated with AKI. The predictors of mortality by logistic regression model, PELOD (AOR:1.115; 95% CI:1.026–1.212) and LogDKK3/Cr (AOR:3.914; 95%CI:1.397–10.961) were independently associated with mortality. Urine DKK3/Cr more than 63311 pg/ml increases the risk of AKI 5.547 times (95% CI:1.618–19.022, p = 0.006) and more than 86963 pg/ml increases the risk of mortality 5.569 times (95% CI:1.329–22.499, p = 0.019). Conclusions Urine DKK3 is a useful biomarker in predicting the development of AKI according to KDIGO SCr for patients in PICU and high levels are a risk factor for AKI and mortality.

Background/Objectives: Eculizumab is a first-line treatment for atypical hemolytic uremic syndrome (aHUS), and patients undergoing eculizumab therapy may become more susceptible to infection caused by Neisseria meningitidis (Nm). While meningococcal vaccination is required for patients undergoing eculizumab therapy, there is limited knowledge about meningococcal carriage in children with aHUS. We aimed to evaluate (1) the prevalence of Nm carriage, (2) serogroup distribution, and (3) the immunization status of children undergoing eculizumab treatment for aHUS. Methods: The Meningo-aHUS study is a prospective, multi-center study evaluating meningococcal carriage in children and adolescents in Türkiye receiving eculizumab for aHUS. We noted the age, gender, daycare, school, or university attendance, passive smoking status, previous infection and antibiotic use, and previous immunization history, including meningococcal vaccines, from the medical records of those children with aHUS. We collected nasopharyngeal samples, tested them for Nm using real-time polymerase chain reaction, and performed a serogroup analysis on the positive samples. Results: We collected nasopharyngeal samples from 62 children with aHUS. Out of 62 children, 61 (98.4%) had received at least one dose of the meningococcal vaccine. The median time since the last meningococcal vaccine dose was 15 months (1–59 months). We detected meningococcal carriage in three (4.8%, 95% CI 1.0–13.5) children, and all three strains were non-groupable (NG). No other serogroups were detected. Conclusions: Almost all the children received their risk-group meningococcal immunization, including booster doses. A 4.8% of children with aHUS carried NG meningococci and, no vaccine serogroups were detected. Patients treated with eculizumab remain profoundly susceptible to IMD due to these NG meningococcal strains. The occurrence of breakthrough cases and carriage of Nm, especially NG strains, highlights the significance of maintaining a state of constant alertness, promptly seeking medical attention, and swiftly treating any symptoms that align with IMD, regardless of their vaccination status or antibiotic prophylaxis.