Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

Assessment of left ventricular function by tissue Doppler echocardiography in pediatric chronic kidney disease.

BACKGROUND: Cardiovascular (CV) disease remains the most common cause of mortality in chronic kidney disease (CKD). METHODS: In this cross-sectional study, 43 pediatric patients with CKD were divided into two groups according to their estimated glomerular filtration rate (eGFR): groups 1 and 2 (eGR; 29-75 and 15-29 mL/min/1.73 m(2), respectively). M - mode, conventional pulsed wave Doppler (cPWD) echocardiography and tissue Doppler imaging (TDI) were performed in all patients and 16 healthy controls. Maximal early (E wave) and late (A wave) diastolic flow velocities were assessed by cPWD. Using TDI, the early (E') and late (A') diastolic filling velocities were recorded. Early and late diastoles were evaluated using E' values and E/E' ratios, respectively. RESULTS: Left ventricular hypertrophy (LVH) was determined in 19/43 (44.2%) patients. The E/E' ratio was significantly higher in group 2 than in group 1 and controls. E/E' was found to be positively correlated with left ventricular mass (LVM) index, and negatively with hemoglobin (Hb) levels. Low Hb levels were only independent predictor of E/E' (p = 0.001, ß: -0.470, 95% CI: -0.764; -0.196). E' ratio was significantly lower in both patient groups compared to the controls. CONCLUSIONS: LVH and diastolic dysfunction are already present in early stages of CKD. Treatment of risk factors, such as anemia, is important to improve the clinical outcome.

Clinical evaluation of R202Q alteration of MEFV genes in Turkish children.

To date, over 200 alterations have been reported in Mediterranean fever (MEFV) genes, but it is not clear whether all these alterations are disease-causing mutations. This study aims to evaluate the clinical features of the children with R202Q alteration. The medical records of children with R202Q alteration were reviewed retrospectively. A total of 225 children, with 113 males, were included. Fifty-five patients were heterozygous, 30 patients were homozygous for R202Q, and 140 patients were compound heterozygous. Classical familial Mediterranean fever (FMF) phenotype was present in 113 patients: 2 heterozygous and 7 homozygous R202Q, 46 double homozygous R202Q and M694V, and 58 compound heterozygous. The main clinical characteristics of the patients were abdominal pain in 71.5 %, fever in 37.7 %, arthralgia/myalgia in 30.2 %, arthritis in 10.2 %, chest pain in 14.6 % and erysipelas-like erythema in 13.3 %. The frequency of abdominal pain was significantly lower in patients with homozygous R202Q alteration (p = 0.021), whereas patients with heterozygous R202Q mutations, though not statistically significant, had a higher frequency of arthralgia/myalgia (40.0 %, p = 0.05). R202Q alteration of the MEFV gene leads to symptoms consistent with FMF in some cases. This alteration may be associated with a mild phenotype and shows phenotypic differences other than the common MEFV mutations.

Epstein-Barr virus infection in children with renal transplantation: 17 years experience at a single center.

OBJECTIVES: The aim of this study was to detect the frequency, time of occurrence, management and outcome of Epstein-Barr virus (EBV) infection and related complications in pediatric renal transplant recipients. METHODS: Pediatric renal allograft recipients transplanted between August 1994 and December 2011 at our hospital was evaluated retrospectively. The patients were divided into two groups; Groups 1 and 2 were composed of patients transplanted before and after November 2007, respectively, when plasma EBV DNA levels were periodically measured. RESULTS: The study included 166 children, 89 (53.6%) boys, with a mean age of 12.2 ± 3.8 years. Prior to transplantation, 144 patients (86.7%) were EBV seropositive. Within a median follow-up period of 36 months, 11 of 22 seronegative children (50%) developed primary EBV infection. EBV reactivation was observed in 23 of 144 children (15.9%). Two patients with primary infection developed post-transplant lymphoproliferative disorder, one of whom died. Elevated serum creatinine levels or graft loss were not observed in any patient with EBV reactivation. CONCLUSIONS: EBV DNA monitoring by PCR in high-risk pediatric renal transplant recipients will provide early diagnosis and treatment of EBV infections.

Circulating endothelial cells in pediatric renal transplant recipients.

BACKGROUND: An increase in the number of circulating endothelial cells (CEC) indicates endothelial damage and the risk of cardiovascular disease. The aim of our study was to investigate the association of CEC with various clinical parameters in pediatric renal transplant recipients. METHODS: CEC, defined as CD45(-)CD146(+), were enumerated by flow cytometry from the peripheral blood of 50 pediatric renal transplant recipients and 20 healthy controls. Clinical parameters, including renal function tests, fasting blood glucose, serum cholesterol and triglyceride, cyclosporine A (CsA) (trough and 2nd-hour) and tacrolimus (tac) trough blood levels and their association with CEC numbers were analyzed. RESULTS: CEC numbers of patients were higher than those of controls (respectively, 128 ± 89 cells/ml (42-468 cells/ml), 82 ± 33 cells/ml (32-137 cells/ml), p = 0.024). There was a statistically significant negative correlation between CEC numbers and glomerular filtration rate (GFR) (r = -0.300, p = 0.012). There was also a statistically positive association between CEC numbers and transplant duration as well as cyclosporine trough level (respectively, r = 0.397, p = 0.004, r = 0.714, p = 0.004). CEC numbers in patients on tac and CsA were similar (p = 0.716). CONCLUSIONS: Our results demonstrate that renal transplant recipients with high CsA trough blood level, longer transplant duration, and lower GFR, are at greater risk of developing endothelial damage.

MEFV gene mutations in Turkish children with juvenile idiopathic arthritis.

UNLABELLED: Mutations of the Mediterranean fever (MEFV) gene, which encodes pyrin protein, leads to familial Mediterranean fever (FMF) and a connection between MEFV mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV mutations in children with juvenile idiopathic arthritis (JIA). In this study, children with JIA, who had no typical symptoms of FMF, were screened for the mutations in exons 2 and 10 of the MEFV gene by direct sequencing. A total of 96 children, 56 girls (58.3%), with a median age of 11 years (2-18 years) were included. Patients were classified according to JIA subgroups as oligoarthritis in 43 (44.8%), rheumatoid factor-negative polyarthritis in 22 (22.9%), rheumatoid factor-positive polyarthritis in 2 (2.1%), systemic arthritis in 12 (12.5%) patients, enthesitis-related arthritis in 16 (16.7%), and psoriatic arthritis 1 (1.04%). A total of 31 children (32.3%) had MEFV mutations: 25 heterozygous, 2 homozygous, and 4 compound heterozygous. There were 22 (11.4%) exon 10 mutations (M694V, R761H, K695R, V726A, R653H) and 15 (7.8%) exon 2 mutations (E148Q, G304R, E148V, T267I). The allele frequencies of MEFV mutations were found to be 19.27%, which is higher than the general population [p = 0.03, (odds ratio (OR):1.93, 95% confidence interval (CI): 1.09-3.41)]. MEFV mutation carrier rates were significantly higher in antinuclear antibody (ANA) negative than in ANA positive patients [p = 0.01, (OR: 0.25, 95% CI: 0.085-0.74)] and in males than in females [p = 0.001, (OR: 0.197, 95% CI: 0.078-0.495)]. Also, there was a statistically significant difference between the MEFV mutation carrier rates and the subgroups of JIA (p = 0.005). CONCLUSION: These findings suggest that mutations of the MEFV gene may be responsible for rheumatic diseases other than FMF, and patients with JIA especially males, ANA negatives, and ERA subgroups should be screened for MEFV gene mutations in countries where FMF is frequent.

Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schönlein purpura without FMF symptoms.

Familial Mediterranean fever (FMF) has been reported more frequently in patients presenting with Henoch-Schönlein purpura (HSP) than in the general population. But, there is no clear knowledge about MEFV mutations in patients with HSP. We investigated the prevalence of MEFV mutations in children with HSP and without FMF whether these mutations have any effect on the disease course or complications. A total of 76 children with HSP who had no typical symptoms of FMF were screened for the mutations in exon 2 and exon 10 of the MEFV gene. Eleven of 76 patients (14.4 %) were heterozygous (E148Q in 5, M694V in 4, M680I in 1, E148V in 1), 5 (6.6 %) were homozygous (M694V/M694V in 4, V726A/V726A in 1), and 2 (2.6 %) were compound heterozygous (E148Q/M694V mutations in 1 and L110P/E148Q mutations in 1). Altogether, 7 patients carried 2 mutated MEFV alleles (9.2 %), which was higher than that observed in the general Turkish population (1 %). No significant differences in joint, gastrointestinal, renal involvement, or subcutaneous edema, and also acute phase reactants including leukocyte count, erythrocyte sedimentation rate, and serum C-reactive protein concentration were found between the groups. The prevalence of the two allele-MEFV mutations in patients with HSP was found higher than that of the general population. However, it seems that MEFV gene mutations may not have any effect on the clinical presentation of HSP.