Background. Congenital anomalies of kidney and urinary tract (CAKUT) are the leading causes of chronic kidney disease (CKD) in childhood. Determining the clinical course, outcome, and prognostic factors of this heterogeneous disease group is important to provide appropriate management and follow-up. Therefore, we aimed to identify the risk factors of CKD in CAKUT and the differences in clinical courses between disease subgroups. Methods. Three hundred patients (M/F: 203/97) divided into 16 CAKUT categories were enrolled in the study. Logistic regression and survival analyses were performed to determine the risk factors for CKD that is defined as estimated GFR (eGFR) lower than 90 ml/min/1.73 m2 for at least 6 months. Results. The median age of the study population at the time of the diagnosis was 0.6 years (IQR; 0.1-4.0 years). Among available prenatal diagnoses (n= 138), hydronephrosis (HN) (n= 83; 60.1%) and multicystic dysplastic kidney (MCDK) (n= 39; 28.2%) were the most frequently encountered ones. A total of 24 patients had CKD, and 13 of them (54.1%) progressed to end stage renal disease (ESRD). Patients with posterior urethral valve (PUV) had CKD and ESRD more frequently when compared to the other diagnostic groups (p < 0.001 for CKD, and p < 0.001 for ESRD). Furthermore, the PUV subgroup progressed to ESRD (median 3.63 years) earlier than the other subgroups. The diagnosis of PUV, proteinuria on the first admission, vesicoureteral reflux, and oligohydramnios were identified as independent predictors for CKD in the multivariate logistic regression analysis. Conclusions. Knowing predictive factors for CKD in patients with CAKUT is valuable for physicians in order to determine appropriate treatment strategies and prognosis.

Düzova A, Gülhan B, Topaloğlu R, Özaltın F, Cengiz AB, Yetimakman AF, Doğru D, Güçer Ş, Beşbaş N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.

Today still there remains some questions about renal transplantation to the ones who had bladder augmentation due to improper bladder dynamics. From a lot of centers the reports with small numbers and short follow up periods are reported. Here we share our experience about the transplantation patients whose bladders were augmented. Between November 1975 and October 2002, 43 pediatric renal transplantations were performed. 3 of these had previous augmentation cystoplasty and the compliance and the capacity of the bladders were increased and transplantations were done from cadaver. Mean follow up time was 17 months (8-24 months). All the patients underwent augmentation cystoplasty before end stage renal disease period. Those patients were undertaken only immunosuppressive treatment. The achieved capacity after augmentation was 100 % (90-110 %) of expected capacity for age. Achieved compliance at capacity more than 7,6 times (5-10) of preaugmentation compliance. Those patients underwent cadaver renal transplantation mean of 47 months (24-60 months) after augmentation cystoplasty. Two of those patients did clean intermittent cathaterization (CIC) 3-6X1 times a day and last one no need of CIC. Those transplanted kidneys were functioning properly with mean creatinin rate of 0,8 mg/dl (0,7-0,9 mg/dl). No surgical complications were observed in any of the cases. Although the case number is limited, with appropriate drainage of augmented bladders, the transplanted kidney is not affected. No infection was encountered due to CIC and no metabolic abnormality was observed. As a result in the cases which bladder dynamics are impaired augmentation and transplantation together increase the quality of life.

ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration.

Background: Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant morbidity and mortality. Its genetic heterogeneity impacts its clinical presentation, progress, and outcome, and there is no consensus on its clinical management.Methods: To identify the characteristics of aHUS in Turkish children, an industry-independent registry was established for data collection that includes both retrospective and prospective patients.Results: In total, 146 patients (62 boys, 84 girls) were enrolled; 53 patients (36.3%) were less than 2 years old at initial presentation. Among the 42 patients (37.1%) whose mutation screening was complete for CFH, CFI, MCP, CFB, C3, DGKE, and CHFR5 genes, underlying genetic abnormalities were uncovered in 34 patients (80.9%). Sixty-one patients (41.7%) had extrarenal involvement. During the acute stage, 33 patients (22.6%) received plasma therapy alone, among them 17 patients (51.5%) required dialysis, and 4 patients (12.1%) were still on dialysis at the time of discharge. In total, 103 patients (70.5%) received eculizumab therapy, 16 of whom (15.5%) received eculizumab as a first-line therapy. Plasma therapy was administered to 84.5% of the patients prior to eculizumab. In this group, renal replacement therapy was administered to 80 patients (77.7%) during the acute period. A total of 3 patients died during the acute stage. A total of 101 patients (77.7%) had a glomerular filtration rate >90 mL/min/1.73 m(2) at the 2-year follow-up.Conclusions: The Turkish aHUS registry will increase our knowledge of patients with aHUS who have different genetic backgrounds and will enable evaluation of the different treatment options and outcomes.

Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver–kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

Background Amyloidosis may complicate autoinflammatory diseases (AID). We aimed to evaluate the renal biopsy findings, and clinical and laboratory parameters in patients with AID-associated amyloidosis who have responded to antiinterleukin 1(IL1) treatment.Methods Two children with systemic juvenile idiopathic arthritis and one with cryopyrin-associated periodic syndrome diagnosed as having reactive amyloidosis were treated with anti-IL1 drugs. The renal histopathological findings at the time of diagnosis of amyloidosis and after the onset of antiIL1 were evaluated according to the amyloid scoring/grading system.Results The median age of disease onset and diagnosis of amyloidosis were 3 and 12 years, respectively. Anakinra was started in all; however, anakinra caused a local cutaneous reaction in one, thus canakinumab was commenced. Proteinuria improved in all. Control renal biopsies were performed a median of 3 years after the first biopsies. The renal amyloid prognostic score did not improve in patient 1, and progressed in patients 2 and 3. The renal amyloid grade progressed in patient 2.Conclusions This is the first series demonstrating progression of renal tissue damage after the improvement of proteinuria with anti-IL 1 in AID-associated amyloidosis. Anti-IL1 drugs are important to prevent further amyloid accumulation; however, new treatment strategies are needed to target the amyloid deposits.

AIM:Familial Mediterranean fever (FMF) results from MEFV gene mutations. E148Q is a variant of unknown significance in MEFV. We aimed to define characteristics of FMF patients homozygous for E148Q, check for other MEFV variants in a subgroup, and compare the characteristics with FMF patients carrying other mutations.METHODS:Thirty FMF patients homozygous for E148Q were reviewed. MEFV variant analysis was performed with strip assay. All MEFV exons were screened by direct DNA sequencing in 14 randomly selected E148Q/E148Q patients. E148Q was also checked in 100 healthy adolescents. We compared the characteristics of FMF patients between three groups: E148Q/E148Q (n = 30), M694V/E148Q (n = 19) and exon 10/exon 10 MEFV mutations (n = 48).RESULTS:Among 30 FMF patients (E148Q/E148Q), the median age at disease onset and diagnosis were 60 (12-168) and 94 (41-196) months, respectively. Fifteen (50%) patients had mild, 14 (46.7%) moderate and one (3.3%) had severe disease. Twenty-two (73.3%) patients had complete, seven (23.3%) had incomplete response to colchicine, while only one was unresponsive. The detected MEFV variants in 14 E148Q/E148Q FMF patients were as follows: R314R (n = 9; 64.3%), E474E (n = 13; 92.9%), Q476Q (n = 13; 92.9%), D510D (n = 13; 92.9%), and P588P (n = 8; 57.1%). The E148Q allele frequency was 6.5% in healthy adolescents. When compared to FMF patients with other MEFV mutations, disease onset was later, disease was less severe and the ratio of patients responding completely to colchicine was higher in E148Q/E148Q patients.CONCLUSION:Patients homozygous for E148Q and negative for other pathogenic MEFV variants may display FMF phenotype and may experience moderate/severe disease activity, although the disease may be milder when compared to FMF patients with other mutations.

Immunoglobulin A vasculitis (IgA-V), formerly known as Henoch–Schönlein purpura (HSP), is the most common small vessel vasculitis in children. In recent years, the role of T cells in the pathogenesis of HSP/IgA-V has become a focus of research.

Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are caused primarily by mutations in genes that encode structural and regulatory proteins of the glomerular filtration barrier. The aim of this study was to determine genotype–phenotype correlations and prognosis in patients with CNS and INS.

Monocyte chemoattractant protein-1 (MCP-1) is a highly specific chemokine for monocytes and plays roles in pathogenesis of various renal diseases. The aim of this study is to investigate the effect of MCP1 2518 A/G polymorphism on the incidence and clinical course of focal segmental glomerulosclerosis (FSGS) in children. MCP1 2518 A/G genotype was identified by PCR-RFLP in 60 biopsy-proven FSGS patients, 76 steroid sensitive nephrotic syndrome (SSNS) patients, and 96 healthy children. MCP-1 levels in urine and serum were measured by ELISA in all patients and the correlations of genotype with MCP-1 levels and clinical outcome were evaluated. The genotype frequencies for MCP1 were similar in all groups. The percentage of patients who develop chronic renal failure was higher in patients with AA allele compared to GA or GG alleles (46% vs. 35% respectively, p<0.01, Odds ratio: 1.59). Serum MCP-1 levels were similar in all groups, whereas urinary MCP-1 levels of the patients with FSGS (1680pg/mg creatinine) were significantly higher than that of patients with SSNS (365pg/mg creatinine, p<0.05) and healthy controls (348pg/mg creatinine; p<0.05). Urinary MCP-1 levels were correlated with the degree of proteinuria in FSGS group (r=0.529, p=0.016). Our results suggest that the AA genotype might be a risk factor for the progression of renal disease in FSGS and MCP1 genotyping may help the physicians to predict prognosis in these patients.

Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5–10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents’/physicians’ global assessment of disease severity and laboratory parameters every 3–6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3–11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4–60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12–16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the largest cohort of colchicine-resistant FMF patients in childhood and adolescence. Anti-IL1 treatment is a safe and effective therapy to control inflammation. The treatment should be modified and decided for each patient on an individual basis.

Tacrolimus is a potent immunosuppressive agent widely used after organ transplantation. In this present study we present eight patients who complained of palpitation after kidney transplantation. Eight out of 31 patients who received tacrolimus after kidney transplantation suffered from tachycardia. Resting electrocardiography, 24 hours Holter monitorization, echocardiography were performed, and serum levels of cardiac troponin T, creatine kinase, CKMB, brain natriuretic peptide and tacrolimus were measured. The median time to palpitation after kidney transplantation was 30 days in seven patients, and one patient complained of palpitation five years after transplantation. Cardiovascular assessment revealed sinus tachycardia in all patients. Beta-blocker was instituted in five patients. After two months all patients were asymptomatic and their pulse rates were within normal limits. Transient sinus tachycardia is a frequent adverse event during tacrolimus therapy in children and young adults, at therapeutic levels. Patients may benefit from beta-blockers.

Our purpose was to assess the relationship between serum fibroblast growth factor 23 (FGF23) and left ventricular function, carotid intima-media thickness (CIMT) and laboratory features in children on peritoneal dialysis (PD). The study population consisted of 17 patients (11 female; median age 7.83 years, range 0.66-17.75) undergoing PD for 22 months (range 2-98). Serum FGF23, serum phosphorus, calcium, intact parathyroid hormone (iPTH), 25(OH) vitamin D, 1,25(OH)2 vitamin D and Kt/V urea, left ventricular mass (LVM) and LVM index (LVMI) were assessed. Median FGF23 level was 29.92 pg/ml (22.7-74.76), phosphorus was 5.2 mg/dl (3.1-9.9), iPTH was 438 pg/ml (16-1446), 25(OH) vitamin D was 11 ng/ml (5-35), 1,25(OH)2 vitamin D was 11 pg/ml (2-106), Kt/V urea was 2.33 (1.01-3.84). FGF23 level was independently associated with Kt/V urea (p<0.001). We found that effective dialysis may be the leading determinant of FGF level, independent from the calcium-phosphorus-PTH axis, in pediatric PD patients.

BACKGROUND:The aim of this study was to describe the incidence and contributory risk factors for thromboembolic complications in children with nephrotic syndrome (NS) and thrombosis.METHODS:Among 188 children with the diagnosis of NS (80 girls; mean age: 12.6 ± 5.4 years) followed up in our hospital for the last 5 years, 17 (9.0 %) children (16 boys) identified as having thromboembolic complications. All 17 children with NS and thrombosis were screened for laboratory risk factors for thrombosis. The diagnosis was confirmed by cranial magnetic resonance imaging, doppler ultrasonography, and echocardiography.RESULTS:Among 17 children with thrombosis, 14 (82.3 %) were found to have focal segmental glomerulosclerosis (FSGS) as underlying pathology by renal biopsy. The mean age of the thrombotic children was 4.5 ± 3.2 years at the diagnosis of NS and that was 7.1 ± 4.9 years at the time of thrombosis. The mean time from NS diagnosis to the first thrombosis development was 2.6 ± 2.3 years. Thrombosis occurred during the first year of NS in 9/17 (52.9 %) children. Most of the children (88.2 %) had venous thrombosis. Among the screened risk factors, high factor VIII level (64.7 %) was the leading factor followed by decreased antithrombin III level (29.4 %). Furthermore, 4 children had central venous catheters and 2 had infection as clinical risk factors for thrombosis.CONCLUSION:In this case series, subtype of FSGS, active disease state of NS, central venous catheters, and some inherited and acquired thrombotic risk factors have been identified as contributory factors for the development of thrombosis in children with NS.

This study was performed to evaluate the role of postnatal ultrasonography (US) in predicting the final diagnosis and need of surgery of antenatal hydronephrosis patients. One hundred and twenty six renal units (RUs) of 76 patients with diagnosis of antenatal hydronephrosis (ANH) were studied. An early postnatal US no later than the first week of life was requested. Voiding cystourethrography (VCUG) and/or diuretic renogram (MAG3) was performed in children who had persistent or worsening hydronephrosis to make a certain diagnose of etiology. US findings of different etiologies, and operated/nonoperated groups are compared. Regarding the renal pelvic anteroposterior diameter in the first week postnatal US; mild, moderate, severe, and no HN was detected in 48 (38.1%), 31 (24.6%), 24 (19.0%), and 23 (18.3%) RUs respectively. Eight RUs with a normal first postnatal US were found to have renal anomaly during follow up and 63% of these were vesicoureteral reflux (VUR). Kidneys with mild or moderate HN were likely to have transient dilatation while severe HN was likely to have obstruction. Postpartum follow-up of AHN is a dynamic process. Follow-up must be planned with optimum period of intervals according to clinic and US findings, to select the right patient for surgery or close follow-up.