Very-early-onset Inflammatory Bowel Disease in an Infant with a Partial RIPK1 Deletion.

The monogenic causes of very-early-onset inflammatory bowel disease (VEO-IBD) have been defined by genetic studies, which were usually related to primary immunodeficiencies. Receptor-interacting serine/threonine-protein kinase-1 (RIPK1) protein is an important signalling molecule in inflammation and cell death pathways. Its deficiency may lead to various clinical features linked to immunodeficiency and/or inflammation, including IBD. Here, we discuss an infant with malnutrition, VEO-IBD, recurrent infections and polyathritis who has a homozygous partial deletion in RIPK1 gene.

Nutcracker syndrome in pediatrics: initial findings and long-term follow-up results.

BACKGROUND: Nutcracker syndrome (NCS) describes a set of symptoms and signs resulting from compression of the left renal vein (LRV). There is a lack of knowledge about its natural course, diagnosis, and management, especially in children. Herein, we present our single-center experience with a large number of patients who have long-term follow-up results. METHODS: All patients with NCS diagnosed between January 2011 and March 2021 were included and their data were obtained retrospectively. RESULTS: A total of 123 NCS patients (85 females) were included. The median age at the time of diagnosis was 12 (IQR 10-14) years, and BMI percentiles were below 5% in 38% of the cases. At the time of diagnosis, two-thirds of the patients were asymptomatic. The most common laboratory finding was nephritic proteinuria (98%), followed by microscopic hematuria (16%). Signs of LRV compression were significantly more evident in upright position Doppler ultrasonography (DUS) examination. All patients have been followed conservatively; hematuria and/or proteinuria resolved in 43 of the 108 patients (40%) within 35.8 ± 25.8 months of follow-up. Control DUS was performed in 52 patients after a mean period of 39.1 ± 21.3 months. The median peak velocity and diameter ratios of the LRV in the upright position were found to be decreased significantly when compared to the initial assessment (p < 0.05). Normal DUS findings were noted in 13 patients at the final evaluation. CONCLUSIONS: In unexplained proteinuria and/or hematuria, NCS should be considered, especially in asthenic adolescents. Our results support conservative management in children as the first-line treatment approach.

Risk factors for recurrence in pediatric urinary stone disease.

BACKGROUND: Children's urinary system stones may develop from environmental, metabolic, anatomical, and other causes. Our objective is to determine the recurrence and prognosis, demographic, clinical, and etiological characteristics of children with urolithiasis. METHODS: Medical records of patients were evaluated retrospectively. Patients' demographic data and medical history, serum/urine biochemical and metabolic analysis, blood gas analysis, stone analysis, imaging findings, and medical/surgical treatments were recorded. RESULTS: The study included 364 patients (male 187). Median age at diagnosis was 2.83 (IQR 0.83-8.08) years. The most common complaints were urinary tract infection (23%) and urine discoloration (12%). Sixty-two percent had a family history of stone disease. At least one metabolic disorder was found in 120 (88%) of 137 patients having all metabolic analyses: hypercalciuria was found in 45%, hypocitraturia in 39%, and hyperoxaluria in 37%. Anatomical abnormalities were detected in 18% of patients. Of 58 stones analyzed, 65.5% were calcium and 20.6% were cystine stones. Stone recurrence rate was 15% (55/364). Older age (> 5 years), family history of stone disease, stone size (≥ 5 mm), and urinary system anatomical abnormalities were significantly associated with stone recurrence (p = 0.027, p = 0.031, p < 0.001, and p < 0.001, respectively). In adjusted logistic regression analysis, stone size ≥ 5 mm (OR 4.85, 95% CI 2.53-9.3), presence of urinary system anatomical abnormalities (OR 2.89, 95% CI 1.44-5.78), and family history of stone disease (OR 2.41, 95% CI 1.19-4.86) had increased recurrence rate. CONCLUSIONS: All children with urolithiasis should be evaluated for factors affecting stone recurrence. Children at higher risk of recurrence need to be followed carefully.

Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

Variable phenotype and genotype of pediatric patients with HNF1B nephropathy.

AIMS: Hepatocyte nuclear factor 1ß (HNF1B) mutations are the most common monogenic cause of congenital anomalies of the kidney and urinary tract (CAKUT). We aimed to investigate clinical and genetic characteristics of patients with HNF1B nephropathy to expand its phenotypic and genetic spectrum. MATERIALS AND METHODS: This retrospective cohort study included 16 unrelated pediatric patients (6 females, 10 males) from 13 families with genetically confirmed HNF1B-related nephropathy. RESULTS: Abnormal prenatal kidney abnormalities were present in 13 patients (81.3%). The most common antenatal kidney abnormality was kidney cysts, which were observed in 8 patients (61.5%). Urinary system abnormalities (vesicoureteral reflux (VUR) and ureteropelvic junction obstruction (UPJO)) were present in 4 patients (25%). HNF1B analysis uncovered missense variants in 4 families (30.8%) as the most common genetic abnormality. In addition, 4 novel pathological variations have been defined. During follow-up, hypomagnesemia and hyperuricemia were observed in 7 (43.8%) and 5 patients (31.3%), respectively. None of the patients with a missense variant had hypomagnesemia. However, 7 out of 12 patients (58.3%) with a non-missense variant had hypomagnesemia (p = 0.09). None of the patients had an HNF1B score below 8, and the mean score was 15.3 ± 4.4. The mean follow-up period was 7.4 ± 5.0 years. While 100% of patients (n = 4) with missense variants were in various stages of CKD (CKD2: 2 patients, CKD3: 2 patients), 25% of those with non-missense variants had CKD (CKD2, 3, and 5; 1 patient, respectively) (p = 0.026). CONCLUSION: Patients with HNF1B-associated disease have concomitant urinary system abnormalities such as VUR or UPJO. Missense variants seem to be the most common pathological variations in HNF1B gene and have higher risk of CKD.

Long Term Follow-Up Of Patients With Nonrefluxing Hydronephrosis.

BACKGOUND: The aim of this study is to examine the long-term prognosis of children with ureteropelvic junction obstruction-like hydronephrosis (UPJO-like HN). PATIENTS AND METHODS: The files of children with hydronephrosis (HN) were analyzed retrospectively. Patients with vesicoureteral reflux (VUR) and other genitourinary anomalies were excluded. The final status of the HN, the need for surgery, and urinary tract infection (UTI) frequency were evaluated. RESULTS: The study included 219 patients with 302 renal units (RU) with HN. Surgery rate was higher in RUs with larger kidney size and parenchymal thinning (p:<0.001 for both). Hydronephrosis resolved in 113 (40.2%) RUs, improved in 66 (23.3%), unchanged in 100 (35.5%) and worsened in 4 (1.4%). The frequency of recovery and improvement was found to be less in RUs with severe HN, large kidney size, and thin parenchyma. The UTI frequency was higher in severe HN group (12.2% vs 30.6% p:<0.001). CONCLUSIONS: Children with mild HN had an excellent prognosis. Although the majority of the patients with high-grade HN had also a good prognosis, it seems important to closely follow up patients with severe HN, increased kidney size, and accompanying parenchymal thinning. Clinicians should be aware of the increased frequency of UTIs in children with severe HN.

Childhood-Onset Sacroiliitis: Causes and Correlation Between Clinical Findings and Magnetic Resonance Imaging.

OBJECTIVE: The aims of this study were to describe disease associations of magnetic resonance imaging (MRI)-confirmed and clinically symptomatic sacroiliitis in pediatric patients with rheumatic diseases and to examine the relationship between patient characteristics and MRI findings of the sacroiliac joint (SIJ). METHODS: Demographic and clinical data were extracted from the electronic medical records of the patients with sacroiliitis followed in the last 5 years. Active inflammatory and structural damage lesions of the SIJ-MRI were examined by the modified Spondyloarthritis Research Consortium of Canada scoring system, and correlation analysis of these results with clinical characteristics was evaluated. RESULTS: A total of 46 symptomatic patients were found to have MRI-proven sacroiliitis of 3 different etiologies: juvenile idiopathic arthritis (JIA) (n = 17), familial Mediterranean fever (FMF) (n = 14), and chronic nonbacterial osteomyelitis (CNO) (n = 8). Seven patients, FMF and JIA (n = 6) and FMF and CNO (n = 1), had a co-diagnosis that might cause sacroiliitis. Although inflammation scores and structural damage lesions did not statistically differ between the groups, capsulitis and enthesitis on the MRI were more frequently detected in the CNO group. There was a negative correlation between symptom onset and inflammation scores of bone marrow edema. Disease composite scores and acute phase reactants were correlated with MRI inflammation scores. CONCLUSIONS: We demonstrated that JIA, FMF, and CNO were the major rheumatic causes of sacroiliitis in children originating from the Mediterranean region. Quantitative MRI scoring tools can be used to assess the inflammation and damage of the SIJ in rheumatic diseases, show discrepancies between them, and have an important correlation with various clinical and laboratory features.

Evaluation of Gastrointestinal System Complaints and Comorbidities in Pediatric Familial Mediterranean Fever Patients.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disease among children. Abdominal pain and various gastrointestinal system (GIS) manifestations may arise directly from FMF or concomitantly with FMF. This study aimed to evaluate GIS complaints and findings other than classic peritonitis attacks in patients with FMF and to interpret concomitant GIS and hepatic disorders in these patients. METHODS: The medical and genetic findings of patients with FMF who attended our clinic between December 2011 and December 2021 were reviewed. Gastrointestinal system symptoms, liver function tests, abdominal images, and endoscopic and histopathological data were extracted from medical records. RESULTS: A total of 576 pediatric patients (female, 52.3%) diagnosed with FMF were included. Among them, almost one-fifth displayed GIS complaints, such as abdominal pain, defecation problems, and dyspepsia, distinct from typical FMF attacks. High serum aminotransferase levels were detected in 18.4% of the patients, with viral infections being the most common cause of moderate/severe hypertransaminasemia. In addition, during follow-up, 26.9% of them were referred to the pediatric gastroenterology department. At least 1 gastroenterological and hepatobiliary disorder was detected in 17.5% of the patients because of organic and functional GIS disorders or hepatobiliary disorders, such as gastroesophageal reflux disease, esophagitis, functional dyspepsia, and inflammatory bowel diseases. CONCLUSION: Various GIS and hepatic disorders can be encountered in children with FMF. The spectrum of these complaints and pathologies can range from frequently observed health problems to more severe diseases.

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients-a CERTAIN registry analysis.

BACKGROUND: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. METHODS: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. RESULTS: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. CONCLUSION: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

Nutcracker syndrome: a potentially underdiagnosed cause of proteinuria in children with familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory disease with an increased risk for secondary amyloidosis. Since lifelong colchicine has been the treatment of choice that prevents renal amyloidosis, non-amyloid kidney diseases are more frequently considered in the differential diagnosis of proteinuria. Nutcracker syndrome (NCS) can be one of the confounding causes. This long-term retrospective study aimed to evaluate the causes of proteinuria in a pediatric cohort of patients with FMF and discuss changing trends in recent years . METHODS: Demographic, clinic, and laboratory data were extracted from electronic medical records of patients with FMF. All urine tests of the study population were reviewed. Patients were evaluated for persistent proteinuria and grouped according to the etiology of proteinuria. RESULTS: A total of 576 patients with FMF were identified with a mean follow-up of 6.3 years in the last 10 years; 8% had persistent proteinuria. The etiology was NCS in 67.5% of the patients with proteinuria, and renal amyloidosis was less commonly encountered (15%) without any new diagnosis for the last 8 years. Non-amyloid kidney diseases were also diagnosed in 17.5% of the patients. Patients with NCS had significantly lower BMI than other patients in the cohort and less subclinical inflammation, higher hemoglobin concentration, and milder levels of proteinuria with normal serum albumin and eGFR than other patients with proteinuria. CONCLUSION: Nutcracker syndrome is the leading cause of proteinuria in children with FMF nowadays, and it should be kept in mind during the evaluation of proteinuria in these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ocular inflammatory diseases in children with familial Mediterranean fever: a true association or a coincidence?

PURPOSE: To describe the characteristics of patients with familial Mediterranean fever (FMF) with concurrent ocular inflammatory disease (OID) and to analyze possible relations between them. METHODS: Clinical data were extracted from electronic medical records. Additionally, the medical literature on OIDs reported in patients with FMF was reviewed. RESULTS: Among 512 pediatric patients with FMF, five cases were found to have OIDs: bilateral anterior chronic uveitis, bilateral panuveitis, recurrent optic neuritis (RON), recurrent orbital myositis (ROM), and acquired Brown's syndrome. The first cases of ROM and acquired Brown's syndrome in FMF have been described in the literature. All cases presented with early-onset typical FMF attacks, carried at least one M694V mutation, and experienced OID while on colchicine. CONCLUSION: Increased frequency of OIDs in FMF as per the pediatric population and relapsing and chronic course of OIDs occasionally with concurrent FMF attacks suggest that this inflammatory syndrome, especially those carrying M694V mutations, may be a predisposing factor for OIDs.

Transplantation in pediatric aHUS within the era of eculizumab therapy.

aHUS is caused by the over-activation and dysregulation of the alternative complement pathway. Data regarding outcomes of pediatric aHUS patients after kidney transplantation are still very scarce. Accordingly, the aim of this study was to describe the clinical findings and outcomes of pediatric aHUS patients after renal transplantation. This is a retrospective, multicenter study including 12 patients from the national registry system. Among the 12 patients, eight had received prophylactic eculizumab and none of those patients (except one) had experienced aHUS recurrence during a median follow-up period of 58.5 (min-max, 4-94) months. Although eculizumab had been started on the day before transplantation in one of them, aHUS recurrence occurred during the transplantation procedure. Eculizumab had been stopped in only one patient who had no complement gene mutation after 35 months of therapy, and recurrence had not been observed during the 19 months of follow-up. In three patients, maintenance doses had been spaced out without any recurrence. One additional patient with anti-CFH antibody received only two doses of eculizumab for transplantation and had been followed for 46 months without aHUS recurrence. The remaining three patients had not received anti-C5 therapy and none of those patients experienced aHUS recurrence during a median follow-up period of 21 (min-max, 9-42) months. Prophylactic eculizumab is a safe and effective treatment for the prevention of aHUS recurrence. Eculizumab interval prolongation, discontinuation, and transplantation without eculizumab prophylaxis can be tried in selected patients with close follow-up.

Chronic non-bacterial osteomyelitis: another disease associated with MEFV gene mutations.

OBJECTIVES: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of unknown aetiology. The relationship between CNO and familial Mediterranean fever (FMF) is not clearly documented so far. This cross-sectional study aims to evaluate the clinical and laboratory characteristics of a cohort of CNO patients within the context of its relationship with FMF and MEFV gene mutations. METHODS: Demographic and clinical data were extracted from electronic medical records of patients with CNO. The MEFV gene analysis was performed for all patients. RESULTS: A total number of 18 patients with CNO with a median follow-up of 36.50 (13.00-84.00) months were included in the study. Five patients (27.8%) were found to have at least one exon 10 mutations (four with M694V and one with M680I). Four of them (22.2%) had homozygous or compound heterozygous mutations of the MEFV gene. Two patients had a previous diagnosis of FMF and developed CNO while FMF was under control. Patients with MEFV mutations had an earlier onset of CNO, higher acute phase reactants, lower haemoglobin concentrations, and a higher number of bone lesions at disease onset with a persistent course of disease more frequently. CONCLUSIONS: Our results demonstrated an increased frequency of MEFV gene mutations in CNO and a more severe disease phenotype of CNO in patients with MEFV gene mutations. Physicians practicing in regions where FMF is prevalent should be aware of this relationship and ask about the symptoms of FMF in detail in patients with CNO. Moreover, FMF should be included in CNO-associated conditions.

COL4A3 mutation is an independent risk factor for poor prognosis in children with Alport syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Graphical abstract.

Sex and age as determinants for high blood pressure in pediatric renal transplant recipients: a longitudinal analysis of the CERTAIN Registry.

BACKGROUND: High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. METHODS: This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. RESULTS: At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. CONCLUSIONS: BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).

Renal Biopsy Prognostic Findings in Children With Atypical Hemolytic Uremic Syndrome.

BACKGROUND: The aim of this study was to investigate the histopathological findings in kidney biopsies in children with atypical hemolytic uremic syndrome (aHUS) and to determine whether specific pathological findings in aHUS have a prognostic value. METHODS: Renal biopsy specimens of 29 patients who were recorded in the national Turkish aHUS registry database were available for review. Histopathological findings were compared with the clinical and laboratory features at the presentation and the final outcome. RESULTS: The mean age at presentation and follow-up period was 4.9 ± 3.9 and 3.9 ± 3.0 years, respectively. The median time interval from the first symptom to biopsy was 10 days. Vascular thrombosis and interstitial fibrosis were significantly related to chronic kidney disease (CKD) requiring dialysis or kidney transplantation during follow-up (5.6-fold, for both). Glomerular necrosis, cortical necrosis, and glomerular sclerosis were markedly associated with CKD without dialysis (6.2-fold, 13.3-fold, and 8.8-fold, respectively). However, presence of endothelial swelling, subendothelial widening, and fragmented erythrocytes was found to be correlated with a favorable final outcome. CONCLUSIONS: Presence of vascular thrombosis, cortical necrosis, and glomerular sclerosis in histopathological evaluation correlated with developing CKD. Chronic changes in the interstitial compartment were also related to poor prognosis, a finding that has been shown for the first time in pediatric aHUS cases.

Multiple intra-cardiac masses: A life-threatening complication of Behçet's disease.

The incidence of multiple intra-cardiac masses is rare, and the differential diagnosis may be challenging sometimes. The most common etiologies of multiple intra-cardiac masses are thrombus, vegetation, and tumors. Intra-cardiac thrombus is more common in patients with central catheters, with a wall-motion abnormality and global hypokinesis. Certain autoimmune disorders may favor the development of intra-cardiac thrombus, and very rarely, multiple thrombi may be seen. Here, a patient with multiple intra-cardiac masses in the right ventricle and diagnosed with Behçet's disease is presented.

The changing resistance patterns of bacterial uropathogens in children.

BACKGROUND: Increased antimicrobial resistance is a problem in managing urinary tract infections (UTI). With this study we assessed the resistance patterns of urinary isolates in children with UTI between January 2017 and January 2018. METHODS: A retrospective cohort study was conducted. Among 5,443 isolates, a total of 776 UTI episodes in 698 patients were included. Patients' gender, age, voiding dysfunction, UTI history, prophylaxis status, and presence of vesicoureteral reflux were noted. Patients were divided into three age groups: group 1 for ages ≤12 months; group 2 for ages 13-60 months; and group 3 for ages >60 months. The susceptibilities of etiologic agents to different antimicrobials were explored. RESULTS: Median age was 54 months (range 1 month-21 years); male to female ratio was 1:5. The most common causative agent was Escherichia coli (83% of the cases), followed by Klebsiella pneumoniae (7.5%). Resistance to ampicillin (62.6%) and co-trimoxazole (39.8%) were remarkable in all isolates. Overall extended-spectrum beta-lactamase (ESBL) positivity was 23.5%. The highest resistance rates, higher ESBL positivity (28.6%), and K. pneumoniae frequency (13.5%) were observed in group 1. Ceftriaxone resistance was significantly low (0.5%) in the ESBL (-) group, which constituted the majority of the isolates. Higher resistance rates were observed among the patients on prophylaxis compared to those off prophylaxis (P < 0.001). CONCLUSION: Ceftriaxone can still be used for empirical treatment; however, initial urine culture results are crucial due to high ESBL positivity. Special consideration must be taken for patients under 1 year of age. Periodical surveillance studies are needed to explore the changing resistance patterns of uropathogens and modify treatment plans.

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease.

BACKGROUND: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. METHODS: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m2. RESULTS: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 µmol/l (8.7) and 17.0 µmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. CONCLUSIONS: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.

Clinical features and disease severity of Turkish FMF children carrying E148Q mutation.

BACKGROUND: Familial Mediterranean fever (FMF) is the most common hereditary monogenic autoinflammatory disease caused by mutations in the MEFV gene. It is controversial whether E148Q alteration is an insignificant variant or a disease-causing mutation. The aim of this study was to evaluate the clinical features and disease severity of FMF patients carrying E148Q mutation. METHODS: Files of FMF patients were retrospectively evaluated. Patients with at least one E148Q mutation were included to the study. The clinical characteristics and disease severity of the patients who were carrying only E148Q mutation were compared with the patients who were compound heterozygous for E148Q and homozygous for M694V mutation. RESULTS: The study group comprised 33 patients who were homozygous or heterozygous for E148Q; 34 with compound heterozygous E148Q mutations and 86 patients who had homozygous M694V mutation. Patients who had only E148Q mutation were found to have the oldest mean age of disease onset and lowest mean disease severity score. Attack frequency and colchicine doses were lower in patients with only E148Q mutation as compared with the other two groups. The frequency of clinical findings such as fever, abdominal pain, arthralgia, and arthritis among the three groups was similar. CONCLUSION: Familial Mediterranean fever patients with only E148Q mutation are presenting with late-onset and milder disease course despite having similar clinical findings as compared with patients who had other mutations. Finally, we imply that E148Q is a mutation and colchicine treatment should be given.