Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

OBJECTIVES: The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). METHODS: Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. RESULTS: One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. CONCLUSION: Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

The Effect of "Unclassified" Blood Pressure Phenotypes on Left Ventricular Hypertrophy.

OBJECTIVE: We aimed to evaluate the clinical significance of the "unclassified" blood pressure phenotypes on left ventricular hypertrophy in children. MATERIALS AND METHODS: All children evaluated with ambulatory blood pressure monitoring in the pediatric nephrology department between October 2018 and January 2021 were included in the study. Prehypertension, normotensive, white coat hypertension, masked hypertension, ambulatory hypertension groups and 2 other groups including increased blood pressure load, normal ambulatory blood pressure measurements, but normal (unclassified group 1) or high (unclassified group 2) office blood pressure measurements were defined according to the American Heart Association 2014 statement. Left ventricular mass index, left ventricular mass index/95 percentile values, and left ventricular hypertrophy ratios were compared between the groups separately to establish the influence of the unclassified cases. RESULTS: A total of 497 children were included. There were 52 cases in normotensive, 47 cases in unclassified group 1, 50 cases in masked hypertension, 79 cases in white coat hypertension, 104 cases in unclassified group 2, and 165 cases in the ambulatory hypertension group. Left ventricular mass index/95 percentile and left ventricular hypertrophy in masked hypertension were significantly higher than normotensive but similar between normotensive and unclassified group 1 groups. Left ventricular hypertrophy was significantly higher in the ambulatory hypertension group compared to white coat hypertension, and similar between white coat hypertension and unclassified group 2 groups. CONCLUSION: Independent of age, we have found that interpretation of blood pressure load not only has a limited predictable effect on left ventricular hypertrophy but also causes a large group of patients to be unclassified. Cite this article as: Kasap-Demir B, Basaran C, Demircan T, et al. The effect of "unclassified" blood pressure phenotypes on left ventricular hypertrophy. Turk Arch Pediatr. 2024;59(1):43-48.

Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

The outcomes of renin-angiotensin-aldosterone system inhibition and immunosuppressive therapy in children with X-linked Alport syndrome.

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.

Pulse Wave Analysis in Obese Children with and without Metabolic Syndrome

Objective: To compare pulse wave analysis (PWA) of obese children with and without metabolic syndrome (MS) with healthy, non-obese children and to evaluate the association between PWA findings and additional risk factors present in children with MS and obesity. Methods: From the obese patients examined between June 2019 and June 2021, 41 patients with MS, 36 obese patients without MS, and 34 healthy non-obese children of similar age and gender were evaluated retrospectively. Anthropometric measurements, biochemical evaluation, 24-hour ambulatory blood pressure (BP) measurement (ABPM), left ventricular mass index (LVMI) and PWA measurements were compared. Results: When the three groups were compared, weight standard deviation score (SDS), height SDS and body mass index SDS were all significantly higher in the MS group (p<0.05). The following measurements were significantly higher in both MS and non-MS obese patients compared to the control group: from ABPM measures, the systolic and mean arterial pressure BP SDSs load; from PWA, the night central systolic BP, 24-hour, day and night pulse pressure values and 24-hour, day and night pulse wave velocity (PWV) rates; and from cardiac evaluations, the LVMI and relative wall thickness measurements (all p<0.05). Furthermore, the 24-hour and daytime central systolic (cSBP) and diastolic BP (cDBP) values were significantly different between the three groups, being the highest in the MS group (p<0.05). Conclusion: Obesity causes higher office, ambulatory and central BP, PWV and LVMI. However our results suggest that additional risk factors associated with MS do not contribute to these parameters, except for 24-hour and daytime cSBP and cDBP values.

Dietary acid load in children with chronic kidney disease: its association with nutritional status and health-related quality of life.

BACKGROUND: This study aimed to determine the dietary acid load of children with chronic kidney disease (CKD) and to evaluate the relationship between dietary acid load, nutritional status, and health-related quality of life (HRQOL). METHOD: A total of 67 children aged 3-18 years with a diagnosis of CKD stages II-V were included in the study. Anthropometric measurements (body weight, height, mid-upper arm circumference, waist, and neck circumference) and 3-day food consumption records were taken to evaluate the nutritional status. The net endogenous acid production (NEAP) score was calculated to determine the dietary acid load. "Pediatric Inventory of Quality of Life (PedsQL)" was used to assess the participants' HRQOL. RESULTS: The mean NEAP was 59.2 ± 18.96 mEq/day. Stunted and malnourished children had significantly higher NEAP than those who were not (p < 0.05). There were no significant differences in terms of HRQOL scores according to NEAP groups. The multivariate logistic regression analysis showed that waist circumference (OR: 0.890, 95% CI: 0.794-0.997), serum albumin (OR: 0.252, 95% CI: 0.068-0.929), and glomerular filtration rate (GFR) (OR: 0.985, 95% CI: 0.970-1.000) were negatively associated with high NEAP. CONCLUSION: This study shows that a diet shifted in an acidic direction in children with CKD and a higher dietary acid load are associated with lower serum albumin, GFR, and waist circumference, but not HRQOL. These results suggest that dietary acid load might affect nutritional status and CKD progression in children with CKD. Future studies with larger samples are needed to confirm these results and to understand underlying mechanisms. A higher resolution version of the Graphical abstract is available as Supplementary information.

Blood pressure parameters affecting ventricular repolarization in obese children.

BACKGROUND: Ventricular repolarization (VR) increases the risk of sudden cardiac death due to ventricular arrhythmia. We aimed to evaluate the blood pressure (BP) parameters affecting VR in obese children. METHODS: Obese (BMI ≥ 95p) and healthy children ≥ 120 cm between January 2017 and June 2019 were included. Demographic and laboratory data, peripheral and central BPs evaluated by a device capable of ambulatory blood pressure monitoring (ABPM), and pulse wave analysis were assessed. Electrocardiographic ventricular repolarization indices, left ventricular mass index (LVMI), and relative wall thickness (RWT) were calculated. RESULTS: A total of 52 obese and 41 control patients were included. Uric acid, triglyceride, total cholesterol, LDL, and ALT values, systolic and diastolic office BPs, 24-h, daytime and nighttime systolic and mean arterial BPs, daytime diastolic BP SDS levels, daytime and nighttime systolic loads, daytime diastolic load, 24-h, daytime and nighttime central systolic and diastolic BPs, and pulse wave velocity values were significantly higher, whereas 24-h, daytime and nighttime AIx@75 were similar between the groups. fT4 levels of obese cases were significantly lower. QTcd and Tp-ed were higher in obese patients. Although RWT was higher in obese cases, LVMI values and cardiac geometry classifications were similar. The independent factors affecting VR in obese cases were younger age and higher diastolic load at night (B = - 2.83, p = 0.010; B = 0.257, p = 0.007, respectively). CONCLUSION: Obese patients have higher peripheral and central BP, arterial stiffness, and higher VR indices that develop before an increase in LVMI. It would be useful to prevent obesity from an early age and follow up nighttime diastolic load to control VR associated sudden cardiac death in obese children. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Influence of Non-E. Coli or Extended-Spectrum ß-Lactamase-Producing Bacterial Growth on the Follow-Up Procedure of Infants with the First Febrile Urinary Tract Infection.

OBJECTIVE: To evaluate the effects of non-E. coli or extended-spectrum ß-lactamase-positive (ESBL-positive) microorganism growth in the first febrile urinary tract infection (UTI) of infants on laboratory findings or renal parenchymal damage presenting the severity of inflammation, anatomic abnormalities defined by imaging studies, and recurrent UTIs in the follow-up period. METHODS: The data of patients aged between 2 and 24 mo and followed up for at least 6 mo with febrile UTI guideline of the authors' pediatric-nephrology clinic, were retrospectively analyzed. Ultrasonography was performed in all the cases at the time of UTI and dimercaptosuccinic-acid (DMSA) at least 4 mo after the infection. Voiding cystourethrography (VCUG) was performed only if ultrasonography findings were abnormal, the uptake deformity was detected in DMSA scan, or the patients experienced recurrent UTIs. The patients were grouped concerning E. coli or non-E. coli and ESBL-PB or non-ESBL-BP growth in the urine cultures. RESULTS: There were 277 infants followed up for 28.55 ± 15.24 (6-86) mo. The causative microorganisms were non-E. coli in 73 (26.4%) and ESBL-PB in 58 (20.9%) cases. CRP values, pyuria, and leukocyte-esterase positivity were significantly higher in UTIs caused by E. coli compared to non-E. coli bacteria. All clinical and laboratory findings were similar between the ESBL-PB and non-ESBL groups, but abnormal ultrasonography findings were more common in non-E. coli group. CONCLUSION: E. coli causes more severe inflammation, but non-E. coli infections are more frequently associated with ultrasound abnormalities. However, ESBL production did not affect either laboratory or radiological findings in the present cohort.

Risk Assessment for Arrhythmia in Pediatric Renal Transplant Recipients.

OBJECTIVES: Renal transplant recipients are at risk for ventricular arrhythmia and sudden death. To assess that risk, we compared the ventricular repolarization markers of pediatric renal transplant recipients with those of healthy children. MATERIALS AND METHODS: We included 30 children and adolescents who were followed for at least 6 months after renal transplant; 30 age- and sex-matched children were included for the control group. Demographic features, medications, and laboratory findings were recorded. Blood pressure measurements, ventricular repolarization indexes including QT dispersion, corrected QT dispersion, T-wave peak-to-end interval dispersion, the T-wave peak-to-end interval∕QT ratio, the T-wave peak-to-end interval∕corrected QT ratio, left ventricular mass index, and relative wall thickness were compared between groups. In addition, the correlations of ventricular repolarization indexes with other variables were evaluated. RESULTS: Blood pressure standard deviation scores, the mean heart rate, QT dispersion, corrected QT dispersion, the T-wave peak-to-end interval∕QT ratio, the T-wave peak-to-end interval/corrected QT ratio, left ventricular mass index, and relative wall thickness values were significantly higher in renal transplant patients, whereas T-wave peak-to-end interval dispersion, ejection fraction, and fractional shortening were similar between groups. Although ventricular repolarization indexes were similar in patients with and without left ventricular hypertrophy, only corrected QT dispersion was significantly higher in patients with hypertension (P = .006). The only variable that significantly predicted prolonged corrected QT dispersion was the systolic blood pressure standard deviation score (P = .005, ß = .403). CONCLUSIONS: Ventricular repolarization anomalies, hypertension, left ventricular hypertrophy, and cardiac geometry irregularity may be observed after renal transplant in pediatric recipients despite acceptable allograft functions and normal serum electrolyte levels. Control of systolic blood pressure would decrease the risk of ventricular repolarization abnormalities, namely, the corrected QT dispersion. Follow-up of cardiovascular risks with noninvasive methods is recommended in all pediatric renal transplant recipients.

Evaluation of Pediatric Patients with a Diagnosis of Ureterocele.

Aim: The presence and clinical importance of vesicoureteric reflux in patients with a double collecting system are being questioned. Therefore, the role of voiding cystourethrography in the management of patients with ureterocele is unclear. This study aimed to evaluate patients with a ureterocele in terms of urinary tract infection (UTI) and vesicoureteral reflux (VUR). Material Methods: The cases who were admitted to the Pediatric Nephrology Clinic of Health Sciences University Tepecik Training and Research Hospital between 2012 and 2022 and were diagnosed with ureterocele were evaluated retrospectively. Demographic, clinical, and laboratory data were obtained from file records. Results: All patients diagnosed with ureterocele and voiding cystourethrography (VCUG) were evaluated. A total of 24 (female 13 (54.2%)) children were included. The reasons for admission were antenatal hydronephrosis in 13 (54.2%) patients, UTI in 9 (37.5%) patients, and incidentally diagnosed ureterocele in 2 (8.3%) patients. Urinary tract infection was observed in 20 patients at admission, recurrent UTI in 21 patients at follow-up, preoperative pyelonephritis in 12 patients. VUR was found in 11 patients, and severe VUR (≥stage 3) was found in 9 patients. Ten patients had ipsilateral hydronephrosis, and 14 patients had a double collecting system. The presence of VUR was found to be associated with female gender, UTI at admission, and recurrent UTI at follow-up (p < 0.05). However, there was no difference between groups with or without VUR in terms of ipsilateral hydronephrosis, scar formation, and the need for surgery (p > 0.05). Conclusions: We could not demonstrate any criteria to select patients to receive VCUG; on the other hand, VUR did not cause more kidney damage. Our study supports the need for more scientific data to determine management in patients with ureterocele.

Epicardial adipose tissue and risk of arrhythmia in nephrotic syndrome.

BACKGROUND: Patients with nephrotic syndrome (NS) are at a high risk of cardiovascular disease, obesity, and dyslipidemia. The aim of this study was to evaluate the formation of epicardial adipose tissue (EAT) and investigate electrocardiographic (ECG) parameters in patients. METHODS: Thirty-two patients aged 0-18 years and 15 control patients were compared. In the patient group, physical examination and laboratory parameters were recorded. Atrial depolarization and ventricular repolarization parameters in ECG were compared between the groups. EAT was evaluated with M-mode measurements on echocardiography. RESULTS: There was no difference between the groups in terms of sex, age, body mass index, systolic and diastolic BP. EAT was found to be significantly higher in the patient group. In ECG evaluations it was determined that atrial depolarization and ventricular repolarization parameters increased in the patient group. CONCLUSIONS: Cardiovascular morbidity and mortality are high in kidney diseases. Measurement and follow-up of EAT and ECG findings as a noninvasive parameter can provide information in NS.

Diffuse Alveolar Hemorrhage as a Life-Threatening Feature of Juvenile Onset Systemic Lupus Erythematosus: A Case-Based Review.

Diffuse alveolar hemorrhage is an uncommon but serious complication of systemic lupus erythematosus (SLE). We reported a 17-year-old boy with idiopathic thrombocytopenic purpura, who admitted with pallor and petechiae. He had Coombs positive hemolytic anemia and thrombocytopenia (hemoglobin 6.2g/dL, platelets 10,000/mm3 and lactate dehydrogenase 1024U/L), cough, tachypnea, and desaturation in the room air. Chest radiograph revealed bilateral diffuse alveolar opacities and computed tomography showed bilateral diffuse alveolar infiltrates and ground-glass opacity consistent with pulmonary hemorrhage. Anti-nuclear antibody (ANA) was 1:640 with positive Ro and anti-phospholipid antibodies, low C3 and C4, but negative anti-double-stranded DNA. He was treated with pulse methylprednisolone followed by tapering doses of steroids and with 6 doses of intravenous cyclophosphamide once every two weeks followed by mycophenolate mofetil. He had no relapse in the following 3 years. The case was reported to emphasise this life-threatening complication of juvenile-onset SLE and we reviewed the literature.

Re-evaluating hypertension in children according to different guidelines: a single-center study.

We aimed to evaluate the agreements between the guidelines used for both office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM). Our secondary aim was to define the best threshold to assess children at risk of left ventricular hypertrophy (LVH). Thresholds proposed by the Fourth Report (FR), European Society of Hypertension (ESH), and American Academy of Pediatrics (AAP) for OBP and the Wühl, ESH, and American Heart Association (AHA) for ABPM were used, and nine different BP phenotype combinations were created. The agreements between the thresholds, the sensitivity of the thresholds, and the BP phenotypes used to predict LVH were determined in 949 patients with different ages and body mass indices (BMIs). The agreements between the guidelines for OBP and ABPM were "good" and "very good" (κ = 0.639; 95% CI, 0.638-0.640, κ = 0.986; 95% CI, 0.985-0.988), respectively. To classify OBP and ABPM into BP phenotypes, we obtained nine different combinations, which had "very good" agreement (κ = 0.880; 95% CI, 0.879-0.880). The sensitivity of AAP for detecting LVH was the highest in <12-year-old obese children (S = 75.8, 95% CI, 56.4-89.7). The sensitivity of ABPM in detecting LVH was similar among different age and BMI groups. The sensitivity of different BP phenotypes tended to be higher in the groups where OBP was evaluated according to AAP. The highest sensitivity was detected in the 13- to 15-year-old normal weight group.(S: 88.8, 95% CI, 51.7-99.7). The AAP guideline is more sensitive and decisive for BP phenotypes to detect LVH, especially in normal-weight children ≤ 15 years, while ABPM thresholds for children have limited effect.

Is coronavirus pandemic-related anxiety higher in children with chronic kidney disease than healthy children?

BACKGROUND: Since the emergence and worldwide spread of the new coronavirus (COVID-19) pandemic, it has caused people to experience adverse psychological effects. This study aimed to assess anxiety levels during COVID-19 in children with chronic kidney disease (CKD), including nephrotic syndrome (NS) and kidney transplantation (Tx). METHODS: A case-controlled, cross-sectional study was conducted with children aged 10-18 years, who had a diagnosis of CKD or NS, or Tx, and followed in our center between April and July 2020. A healthy control group was recruited with age- and gender-matched children. A questionnaire with printed and online versions was designed in three parts: the first addressed demographic characteristics, the second addressed opinions about the pandemic, and the third was the Turkish version of the Revised Child Anxiety and Depression Scale - Child Version. RESULTS: A total of 88 children completed the questionnaire. The patient and control groups were similar in terms of gender, age, household members and history of psychiatric treatment. Both groups stated that coronavirus is a risky disease for children (63.6%), and that they were afraid of contagion (69.3%). Only half of them were receiving realistic and informative answers from family members. In the Revised Child Anxiety and Depression Scale - Child Version, 66% of them received a high score on at least one subscale. The social phobia scores of the control group were higher than those of the patient group, although the proportion of high scores was similar in both groups. The ratio of high-scored participants was higher in CKD patients for panic disorder, and was lower in the immunosuppressive agent group for social phobia. CONCLUSION: The current COVID-19 pandemic is a disaster that children encounter for the first time in their lives. It does not exclusively cause anxiety among children with chronic kidney diseases but also affects healthy children.