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.

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.

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.

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.

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.

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.

Demographic and clinical characteristics of children with autosomal dominant polycystic kidney disease: a single center experience

Background/aim: In children with autosomal dominant polycystic kidney disease (ADPKD), clinical manifestations range from severe neonatal presentation to renal cysts found by chance. We aimed to evaluate demographic, clinical, laboratory findings, and genetic analysis of children with ADPKD. Materials and methods: We evaluated children diagnosed with ADPKD between January 2006 and January 2019. The diagnosis was established by family history, ultrasound findings, and/or genetic analysis. The demographic, clinical, and laboratory findings were evaluated retrospectively. Patients <10 years and ≥10 years at the time of diagnosis were divided into 2 groups and parameters were compared between the groups. Results: There were 41 children (M/F: 18/23) diagnosed with ADPKD. The mean age at diagnosis was 7.2 ± 5.1 (0.6­16.9) years and the follow-up duration was 59.34 ± 40.56 (8­198) months. Five patients (12%) were diagnosed as very early onset ADPKD. All patients had a positive family history. Genetic analysis was performed in 29 patients (PKD1 mutations in 21, PKD2 mutations in 1, no mutation in 3). Cysts were bilateral in 35 (85%) of the patients. Only one patient had hepatic cysts. No valvular defect was defined in 12 patients detected. Only 1 patient had hypertension. None of them had chronic kidney disease. No difference could be demonstrated in sex, laterality of the cysts, maximum cyst diameter, cyst or kidney enlargement, follow-up duration, or GFR at last visit between Groups 1 and 2. Conclusion: The majority of children with ADPKD had preserved renal functions and slight cyst enlargement during their follow-up. However, they may have different renal problems deserving closed follow-up.

Successful Management of a Rare Cause of Hemolytic Uremic Syndrome With Eculizumab in a Child.

BACKGROUND: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. It very rarely coexists with acute lymphoblastic leukemia (ALL) emerging before, simultaneously, or after the diagnosis has been made, and management of the patient may be difficult. CASE: We present the case of a 7-year-old boy who was diagnosed with HUS and initially managed by hemodialysis (HD). Thereafter, HUS progressed, and neurological findings developed. The patient was treated with eculizumab, agressive blood pressure control, and antiepileptic drugs. At the fifth month of follow-up, the patient was diagnosed with acute B-cell lymphoblastic leukemia with fever, bone pain, hepatosplenomegaly, and pancytopenia. After initiation of ALL treatment, he had no episodes of HUS, despite cessation of eculizumab. CONCLUSION: In conclusion, eculizumab may be a treatment of choice to prevent further systemic damage in recurrent HUS episodes of patients with borderline changes in the bone marrow until ALL is constantly diagnosed.

Cyclosporine causes no hearing defect in paediatric patients with nephrotic syndrome.

OBJECTIVE: We aimed to evaluate the ototoxicity of cyclosporine A (CsA) in children with nephrotic syndrome (NS). DESIGN: Data of paediatric patients with NS followed in paediatric nephrology department were evaluated retrospectively, and hearing functions were evaluated by pure tone audiometry (PTA) and transient evoked otoacoustic emissions (TEOAEs). Age, gender, type of NS, duration and cumulative doses of immunosuppressives were noted. STUDY SAMPLE: The patients who had received CsA (n: 16) and immunosuppressives other than CsA (n: 13) for at least 6 months formed two patient groups and healthy cases formed a control group (n: 20). Children with known previous hearing defect, inner ear trauma or surgery, recurrent otitis media and those using hearing aid were excluded. RESULTS: Gender, age at first clinical presentation, laboratory tests and number of relapses were similar between the groups. No hearing loss was defined in PTA at frequencies of 250, 500, 1000, 2000, 4000 and 8000 Hz. The results of TEOAEs were similar between the groups and compatible with normal hearing. CONCLUSIONS: CsA is not responsible for permanent sensorineural hearing loss in children with NS, and there is no sufficient evidence to consider routine hearing assessment in children with NS treated with CsA.