Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disease that may adversely affect health-related quality of life (HRQoL) in childhood. The relative contributions of age, inflammatory burden, and MEFV mutation type to HRQoL impairment remain incompletely clarified. This cross-sectional study included 100 children with FMF and 70 age- and sex-matched healthy controls. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) child self-report (ages ≥ 8 years) and parent proxy-report forms. PedsQL scores were compared between groups and across age categories and mutation types. Receiver operating characteristic analysis was performed to determine cut-off values for impaired HRQoL, and multivariate logistic regression was used to identify independent predictors. Total and subscale PedsQL scores were significantly lower in children with FMF compared with controls, particularly in the 8–12 and 13–18 age groups (p < 0.001). Strong correlations were observed between child- and caregiver-reported scores. An overall PedsQL total score < 86 was identified as the optimal cut-off for poor HRQoL. In multivariate analysis, age 8–12 years and elevated C-reactive protein levels (> 3 mg/L) were identified as independent predictors of impaired HRQoL. No significant independent association was observed between MEFV mutation subgroups and HRQoL. Conclusion: HRQoL is significantly reduced in children with FMF, particularly in those aged 8–12 years and in patients with evidence of ongoing inflammatory activity. Inflammatory markers rather than mutation type were associated with impaired HRQoL in this cohort. These findings underscore the importance of routine HRQoL assessment in the clinical follow-up of pediatric FMF patients.

Background The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear. Methods We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, na & iuml;ve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA. Results Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFN gamma levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFN gamma secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs. Conclusion This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.

The aim of this prospective study is to investigate the presence of anxiety and depression in children with PMNE and their mothers. This is a cross-sectional study of outpatients who are diagnosed with PMNE at a nephrology clinic. The study included 79 children with PMNE and their mothers (patient group), and 80 randomly selected healthy non-enuretic children and their mothers (control group). Depression and anxiety levels of mothers were measured using the Turkish versions of the Beck Depression Inventory, Beck Anxiety Inventory, and Anxiety Sensitivity Index-3. The Turkish version of the Revised Child Anxiety and Depression Scale-Child Version was used to measure depression and anxiety in children. Patients with PMNE had significantly higher Child Anxiety and Depression Scale scores than controls (p < .001). Beck Depression Inventory, Beck Anxiety Inventory, and The Anxiety Sensitivity Index-3 scores of the mothers of children with PMNE were significantly higher than controls (p < .001 for all). We showed that PMNE was associated with depression and anxiety in mothers and their children. These findings underpin the necessity for clinical screening of anxiety and depression in children with PMNE and their mothers.

BACKGROUND:Alport syndrome (AS) is characterized by progressive kidney disease. There is increasing evidence that renin-angiotensin-aldosterone system (RAAS) inhibition delays chronic kidney disease (CKD) while the effectiveness of immunosuppressive (IS) therapy in AS is still uncertain. In this study, we aimed to analyze the outcomes of pediatric patients with X-linked AS (XLAS) who received RAAS inhibitors and IS therapy.METHODS:Seventy-four children with XLAS were included in this multicenter study. Demographic features, clinical and laboratory data, treatments, histopathological examinations, and genetic analyses were analyzed retrospectively.RESULTS:Among 74 children, 52 (70.2%) received RAAS inhibitors, 11 (14.9%) received RAAS inhibitors and IS, and 11 (14.9%) were followed up without treatment. During follow-up, glomerular filtration rate (GFR) decreased < 60 ml/min/1.73 m2 in 7 (9.5%) of 74 patients (M/F=6/1). In male patients with XLAS, kidney survival was not different between RAAS and RAAS+IS groups (p=0.42). The rate of progression to CKD was significantly higher in patients with nephrotic range proteinuria and nephrotic syndrome (NS), respectively (p=0.006, p=0.05). The median age at the onset of RAAS inhibitors was significantly higher in male patients who progressed to CKD (13.9 vs 8.1 years, p=0.003).CONCLUSIONS:RAAS inhibitors have beneficial effects on proteinuria and early initiation of therapy may delay the progression to CKD in children with XLAS. There was no significant difference between the RAAS and RAAS+IS groups in kidney survival. AS patients presenting with NS or nephrotic range proteinuria should be followed up more carefully considering the risk of early progression to CKD.

Acute tubulointerstitial nephritis (ATIN) is a rare cause of acute kidney injury in children that can lead to chronic kidney disease. The aim of this study was to describe the presenting features, etiology, and clinical characteristics of childhood ATIN, and to evaluate treatment modalities and renal outcomes.

Congenital nephrotic syndrome (CNS) is a rare disorder characterized by massive proteinuria and marked edema manifesting in utero or during the first 3 months of life. CNS can be caused by congenital infections, allo-immune maternal disease or due to the genetic defects of podocyte proteins most commonly NPHS1. Here we present a case of Finnish-type congenital nephrotic syndrome along with feeding problems and abdominal distention which was diagnosed during follow-up as a gastric-duplication cyst with a novel mutation in the nephrin gene. CNS feeding problems are attributed mainly to primary disease but in literature there are case reports of patients with CNS and hypertrophic pyloric stenosis. NPHS1 is also expressed in the stomach tissue. Physicians should be aware of this rare extra-renal manifestation or coincidence of this rare disease.

Aim: The pathogenesis of chronic kidney disease (CKD) remains unknown, but an imbalance between the oxidant and antioxidant defense systems may be a potent trigger of adverse effects in chronic kidney disease (CKD) patients. Measuring thiols in plasma offers an indirect marker of antioxidative defence. This study aimed to determine thiol/disulfide homeostasis as a new indicator of oxidant and antioxidant defence systems in pediatric CKD patients. Material and Methods: This prospective case-control study included 50 pediatric CKD patients (34 non-dialyzed and 16 dialyzed) and 50 gender- and agematched healthy controls. Results: The native thiol, total thiol, and disulfide levels were significantly lower in the CKD group than in the control group (p=0.003, p<0.001, p=0.002, respectively). There was a significant correlation between the glomerular filtration rate. and the native thiol levels and total thiol levels (p=0.003. for each). The native and total thiol levels in the dialyzed patientswere significantly lower than in the non-dialyzedpatients (p<0.001,p=0.002, respectively). Discussion: We observed that the levels of native thiol, total thiol and disulfide in pediatric CKD were lower than in healthy controls, indicating that low thiol levels might be an important factor in the pathogenesis of CKD.

Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro. NEW & NOTEWORTHY Up to now, the role of extracellular vesicles (EVs) in the pathogenesis of steroid-sensitive nephrotic syndrome (NS) has not been studied. Here, we found that relapse NS EVs contain significantly increased active RAC1, induce enhanced podocyte motility, and increase expression of RAC-GTP and phospho-p38 expression in vitro. These results suggest that plasma EVs are biologically active molecules in the pathogenesis of NS.

Objective: We aimed to investigate the efficacy of mycophenolate mofetil (MMF) for maintaining remission and reduce the number of relapses in childhood steroid-sensitive nephrotic syndrome. The effects of MMF on growth and blood pressure parameters were also evaluated. Material and Methods: This retrospective, single-center observational study included patients with steroid-sensitive nephrotic syndrome who were treated using MMF between 2009 and 2019 in the Department of Pediatric Nephrology in our hospital. Results: Ten patients had steroid-dependent nephrotic syndrome; six patients frequently had relapsing nephrotic syndrome in this study. The mean duration of the disease was 93.3 ± 25.0 months and the mean duration of the MMF onset was 33.9 ± 16.7 months after diagnosis. Ten patients showed a 50% or greater reduction in the relapse rate and the prednisolone treatment was discontinued in eight patients for six months or more. Compared to the previous year, before the start of the MMF treatment, there was a 52.7% reduction in the relapse rate and a 36.6% reduction in the cumulative annual dose of steroid after 12 months of MMF treatment. The height z score and the median office systolic blood pressure standard deviation scores of the patients improved after MMF treatment (respectively p = 0.003, p = 0.01). Conclusion: The findings suggest that MMF may lead to decreased relapse rates and cumulative steroid dose, which has a positive effect on growth and blood pressure parameters in steroid-sensitive nephrotic syndrome.

Background Children are one of the most vulnerable groups in conflict zones, especially those with chronic diseases. This study aimed to investigate kidney disease profiles and problems during follow-up in a population of Syrian refugee children residing in Turkey. Methods Syrian refugee children aged between 0 and 18 years were included in the study. Demographic data, diagnosis, particular interventions due to nephrological problems, and problems encountered during follow-up were obtained from all participating pediatric nephrology centers. Results Data from 633 children from 22 pediatric nephrology centers were included. Mean age of the children was 94.8 ± 61.7 months and 375 were male (59%). 57.7% had parental consanguinity and 23.3% had a close relative(s) with kidney disease. The most common kidney diseases were congenital anomalies of the kidney and urinary tract (CAKUT) (31.0%), glomerular disease (19.9%), chronic kidney disease (CKD) (14.8%), and urolithiasis (10.7%). Frequent reasons for CAKUT were nonobstructive hydronephrosis (23.0%), vesico-ureteral reflux (18.4%), and neurogenic bladder (15.8%). The most common etiology of glomerular diseases was nephrotic syndrome (69%). Ninety-four children had CKD, and 58 children were on chronic dialysis. Six children had kidney transplantation. Surgical intervention was performed on 111 patients. The language barrier, lack of medical records, and frequent disruptions in periodic follow-ups were the main problems noted. Conclusions CAKUT, glomerular disease, and CKD were highly prevalent in Syrian refugee children. Knowing the frequency of chronic diseases and the problems encountered in refugees would facilitate better treatment options and preventive measures.

Dent disease is a rare X-linked recessive tubular disorder, characterized by the triad of low molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis.It is caused by mutations in the CLCN5 gene or OCRL gene.Thirty to 80% of affected males develop end-stage kidney disease between the ages of 30 and 50 years.Some children were reported to present with isolated persistent proteinuria and a part of these patients were diagnosed as having focal segmental glomerulosclerosis with kidney biopsy.Although there is no specific treatment, treatment of proteinuria and hypercalciuria is thought to delay the progression of the disease.For this reason, awareness of the disease findings and early diagnosis are important.In this case report, we present a boy followed-up with isolated persistent proteinuria and then diagnosed as having Dent disease with mutation analysis that showed c.328_330delT (p.Phe110Trpfs27*) in the CLCN5 gene.The importance of researching low-molecular-weight proteinuria and considering Dent disease in the differential diagnosis of children presenting with isolated persistent proteinuria has been emphasized.

Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype–phenotype correlations, and determine prognosis of AS in children. A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed. Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival. We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications.

CD80 (also known as B7‐1) is a co‐stimulatory molecule that is expressed in biopsies and also excreted in urine in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). CD80 is inhibited by the cytotoxic T‐lymphocyte‐associated‐antigen 4 (CTLA4), which is mainly expressed on regulatory T cells (Tregs). Ineffective circulating Treg response is involved in the pathogenesis of nephrotic syndrome. In this study, we evaluated CD80 expression and infiltrating Tregs in children with MCD and FSGS.

BACKGROUND:The aim of this study was to identify the cut-offs of postnatal anteroposterior renal pelvic diameter (APRPD), according to the urinary tract dilation (UTD) classification system, to identify the predictors of final diagnosis of UTD and the need for surgery.METHODS:A total of 260 infants (336 renal units) with prenatally detected UTD were prospectively evaluated on serial ultrasonography by the same radiologist. Additional voiding cystourethrography and scintigraphy was done according to the clinical algorithm.RESULTS:Prenatal and postnatal APRPD in patients with transient dilation were significantly lower than in those with urinary tract anomalies (UTA). On follow up, the slope of decrease in APRPD was significantly higher in transient dilation compared with UTA. APRPD 10 mm at first-month ultrasonography, predicted UTA with a sensitivity of 83.1%, and specificity of 71.1%. On multivariate analysis the likelihood of surgical intervention and final diagnosis were predicted independently by the UTD system risk group.CONCLUSIONS:Careful ultrasonography evaluation can avoid unnecessary testing in patients with transient or clinically insignificant dilation. The UTD classification system is valid for evaluation of postnatal hydronephrosis and is reliable in predicting the need for surgical intervention.

Aim: Chronic kidney disease is associated with some hematologic changes such as decreased platelet production, platelet dysfunction and thrombocytosis. The inflammatory markers increase in chronic kidney disease. Mean platelet volume, the ratio of neutrophil count to lymphocyte count, and the ratio of platelet count to lymphocyte count are indicative of inflammation. Erythrocyte stimulating agents can increase platelet count and thrombotic events. We aimed to determine the relationship between the use of erythrocyte stimulating agents and mean platelet volume, the neutrophil/lymphocyte ratio and the platelet/lymphocyte ratio in children with chronic kidney disease in this study. Material and Method: The files of 30 patients diagnosed with chronic kidney disease and treated with erythrocyte stimulating agents between 2013 and 2018 were reviewed retrospectively. Results: The mean age of the patients (16 boys and 14 girls) was 10.6 ± 5.4 years (median 12; 1-17 years). Twelve of them were in pre-dialysis, 9 in hemodialysis and 9 in peritoneal dialysis group. The mean duration of use of erythrocyte stimulating agents was 29.2 ± 34.8 months (median 12.5; 1-127 months). Mean platelet volume values after treatment with erythrocyte stimulating agents in chronic kidney disease patients were significantly higher in all groups. The platelet/lymphocyte ratio values after treatment with erythrocyte stimulating agents were not significant different in all groups. The platelet/lymphocyte ratio had a significant but opposite correlation with mean platelet volume, white cell count and monocyte counts. Mean platelet volume and the neutrophil/lymphocyte ratio measurements were affected by dialysis modality. However the platelet/lymphocyte ratio was not affected. Conclusions: In this small retrospective study, we could not report causality and effect associations in our results. Nevertheless, these simple, cheap, universal methods may be used as the first step in the evaluation of patients by nephrologists.

Lupus anticoagulant hypoprothrombinaemia syndrome (LACHPS) is a rare disorder, defined by the presence of an acquired factor II (FII) deficiency and lupus anticoagulant (LAC) (Rapaport et al. 1960). The main symptom is bleeding that may range from mild mucocutaneous bruises to lifethreatening pulmonary or intracranial haemorrhage. It may occur secondary to systemic lupus erythematosus (SLE), viral infections and drugs (Kim et al. 2014; Komvilaisak et al. 2017). Herein, we report on a 16-year-old girl of LAC-HPS patient associated with SLE who presented with excessive menstrual bleeding, ecchymosis and macroscopic haematuria.

Objective: Renal biopsy plays a crucial role in the diagnosis and treatment of renal diseases. The aim of the present study was to review the reasons leading to biopsy and the pathological diagnoses and to investigate the effectiveness and safety of ultrasound-guided percutaneous renal biopsy in children. Materials and methods: A total of 410 renal biopsies performed in 362 patients between January 2007 and January 2018 at Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research Hospital, Department of Pediatric Nephrology and Rheumatology were retrospectively reviewed. Pathology specimens were evaluated by light and immunofluorescence microscopy. Electron microscopy was performed only on specific occasions. Results: The mean age of the patients was 10.1 +/- 4.4 years, and 55.2% were males. Nephrotic syndrome (44.5%) was the most common indication for renal biopsy. Hematuria +/- proteinuria (19.9%), acute renal injury (15.7%), chronic renal disease (3.2%), and complex renal manifestations (16.6%) were the following indications. The overall complication rate was 8%, and the most common of which was perirenal hematoma (7.5%). The most common histopathological diagnosis was primary glomerulopathy (56.6%). Among primary glomerulopathies, focal segmental glomerulosclerosis was the leading diagnosis (16.5%), followed by mesangioproliferative glomerulonephritis (7.7%) and IgA nephropathy (7.7%). The second most common histological diagnosis was manifestations secondary to systemic diseases (30.9%), among which Henoch-Schonlein purpura (12.4%) and lupus (9.1%) were the leading causes. Conclusion: Renal biopsy is a safe and effective procedure in the diagnosis and treatment of childhood kidney diseases.

Giriş: Herediter ateş sendromlarından biri olarak sınıflandırılan PFAPA (Periodic fever, apthous stomatitis, pharyngitis and cervical adenitis) sendromu , periyodik ateş, farenjit, servikal lenfadenit ve stomatit ile seyretmektedir. PFAPA sendromu ekartasyon tanısı olup, hastalığın bulguları çocukluk çağında sık görülen bakteriyel tonsillit, viral üst solunum yolu enfeksiyonu ile örtüşmektedir. H astalığın ataklarına özgül laboratuvar belirteci bulunmamaktadır. Bu çalışmanın amacı tekrarlayan ateş ve tonsillit atakları nedeniyle PFAPA sendromu ön tanısı ile yönlendirilen hastaların izlemde aldıkları tanıları ve PFAPA atağı ile bakteriyel ve viral tonsillit arasında laboratuvar değerlerindeki farkları ortaya koymaktır. Metod: Bu çalışmaya PFAPA şüphesi ile yönlendirilen toplam 69 çocuk dahil edilmiştir. Bu hastalar en az 2 atak sırasında tek bir hekim tarafından değerlendirilerek, PFAPA sendromu tanısı almıştır. Ateş atakları düzenli aralıklarla tekrarlamayan ve diğer hastalık bulguları olan hastalar tekrarlayan tonsillofarenjit olarak değerlendirilmiştir. PFAPA hastalarının laboratuvar değerleri (lökosit, eritrosit sedimentasyon hızı, C reaktif protein ve prokalsitonin), Grup A beta hemolitik streptokok geçiren 9 hasta ve viral tonsillit geçiren 15 hasta ile karşılaştırılmıştır. Sonuçlar: Tekrarlayan tonsillofarenjit tanısı alan 23 hastadan ikisi mutasyon analizi ile ailevi Akdeniz ateşi (AAA), biri gastroözafajiyel reflü tanısı almış; kalan 20 hastanın ise 15’inin takiplerinde ateşi hiç olmamış, beşinin ise tanı kriterlerinde belirtildiği gibi düzenli aralıklarla tekrarlayan ateşleri gözlenmemiştir. İzlemde PFAPA tanısı alan 46 hasta ile tekrarlayan tonsillit tanısı alanlar karşılaştırıldığında, PFAPA tanısı alan hastaların ailelerinde istatistiksel anlamlı olarak daha fazla tekrarlayan tonsillit hikayesi mevcuttu (%60,9) (p=0.041) ve yakınmalarının başlangıç yaşı daha küçüktü (p=0.022). PFAPA hastaları ile Grup A streptokok tonsilliti geçiren hastalar ile karşılaştırıldığında prokalsitonin seviyelerinde anlamlı fark saptanmazken (p=0.053), PFAPA atağında sedimentasyon daha yüksek, lökosit sayısı daha düşük saptandı (p değerleri 0.021 ve <0,01). Tartışma: Beş yaşın altında tekrarlayan ateş ve farenjit nedeniyle başvuran hastalarda, atak özelliklerinin ve atak aralıklarının değerlendirilmesi PFAPA tanısının doğru konulması açısından önemlidir. Hastaların aile hikayesi, tekrarlayan farenjit ve ailevi Akdeniz ateşi açısından mutlaka sorgulanmalıdır. Prokalsitonin seviyelerinde PFAPA atağı ve bakteriyel tonsillit arasında farklılık saptanmamıştır.