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.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluation of urinary haptoglobin level as a biomarker of diabetic nephropathy in children with type 1 diabetes.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a common endocrine disease in children. Early recognition of complications of T1DM is important for preventing long-term morbidity and mortality. We aimed to investigate whether urinary haptoglobin level is a biomarker of diabetic nephropathy in children with T1DM. METHODS: Ninety T1DM patients, aged between 2-18 years, and 60 healthy age-matched children were included in the study. Glycosylated hemoglobin (HbA1c), spot urine creatinine, microalbumin, protein and haptoglobin levels of all cases were measured and compared. Correlations between HbA1c level, duration of diabetes, spot urine microalbumin/creatinine (uACR), protein/creatinine (uPCR), and haptoglobin/creatinine (uHCR) ratios in the T1DM group were evaluated. RESULTS: T1DM and control groups were homogeneous in terms of age, sex, and anthropometric measurements. uACR was higher in the T1DM group than in the control group (14 mg/g vs. 6 mg/g) while uHCR was not elevated in T1DM patients. Nevertheless, uHCR was higher in the microalbuminuria group when compared to the normoalbuminuria group. In the T1DM group, moderate positive correlations between uPCR with uACR and uHCR, and weak correlation between uACR and uHCR were found (r = 0.60, p < 0.001; r = 0.55, p < 0.001; r = 0.24, p = 0.03, respectively). No significant relationship was found between diabetes duration, HbA1c levels and uACR, uPCR, and uHCR. CONCLUSIONS: Although uHCR in the T1DM group was similar to the control group, uHCR was higher in the microalbuminuria group than in the normoalbuminuria group. These results show that the uHg level could be a biomarker of diabetic nephropathy, but not earlier than albuminuria in the disease course. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

SERPINB11 variant-related liver injury in STEC-HUS: case reports and literature review.

BACKGROUND: Liver damage is uncommon in Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). Herein, we present two cases with a diagnosis of STEC-HUS that progressed to liver damage, with findings presumably related to the SERPINB11 gene c.268G > T (p.Glu90Ter) variant. CASE-DIAGNOSIS/TREATMENT: Two boys aged 3 and 2 years, respectively, were referred to our clinic with a preliminary diagnosis of STEC-HUS. The patients had low hemoglobin, thrombocyte, and haptoglobin levels but high levels of lactic dehydrogenase, urea, creatinine, and schistocytes in peripheral smears. Escherichia coli O157:H7 was detected in their stool samples. The patients underwent hemodialysis, plasma exchange, and supportive treatments. Meanwhile, cholestasis developed in the patients, resulting in elevated total bilirubin levels. During the follow-up period, kidney function recovered completely; however, liver function did not improve, and one patient developed chronic liver damage. Gene mutations that may cause liver damage were investigated, and c.268G > T (p.Glu90Ter) homozygous and heterozygous variants were detected in exon 9 of the SERPINB11 gene in the patients. CONCLUSIONS: Our patients presented with kidney impairment and liver malfunction. Hepatic involvement in STEC-HUS may result from ischemia, hemolysis, and endothelial damage in the hepatic vessels. Liver injury in STEC-HUS cases may be associated with the homozygous SERPINB11 gene c.268G > T (p.Glu90Ter) variant.

COVID-19 in pediatric patients undergoing chronic dialysis and kidney transplantation.

The study aims to present the incidence of COVID-19 in pediatric patients undergoing renal replacement therapy (RRT) and to compare the severity and outcomes of the disease between the dialysis and kidney transplant (KTx) groups. This multicenter observational study was conducted between 1 April and 31 December 2020 in Istanbul. Members of the Istanbul branch of the Turkish Pediatric Nephrology Association were asked to report all confirmed cases of COVID-19 who were on RRT, as well as the number of prevalent RRT patients under the age of 20. A total of 46 confirmed cases of COVID-19 were reported from 12 centers, of which 17 were dialysis patients, and 29 were KTx recipients. Thus, the incidence rate of COVID-19 was 9.3% among dialysis patients and 9.2% among KTx recipients over a 9-month period in Istanbul. Twelve KTx recipients and three dialysis patients were asymptomatic (p = 0.12). Most of the symptomatic patients in both the dialysis and KTx groups had a mild respiratory illness. Only two patients, one in each group, experienced a severe disease course, and only one hemodialysis patient had a critical illness that required mechanical ventilation. In the entire cohort, one hemodialysis patient with multiple comorbidities died.Conclusion: While most cases are asymptomatic or have a mild disease course, pediatric patients undergoing dialysis and a kidney transplant are at increased risk for COVID-19. What is Known: • In adult population, both dialysis patients and kidney transplant recipients are at increased risk for severe illness of COVID-19 and have higher mortality rate. • Children with kidney transplantation are not at increased risk for COVID-19 and most have mild disease course. • Data on children on dialysis are scarce. What is New: • Pediatric patients undergoing dialysis and kidney transplantation have an increased risk for COVID-19. • Most patients undergoing renal replacement therapy either on dialysis or transplanted develop asymptomatic or mild COVID-19 disease with a favorable outcome.

Serum copeptin as a biomarker of hypertension in children with obesity.

BACKGROUND: Hypertension (HT) in obesity has been reported frequently in children in recent years. The role of copeptin and uric acid here are not well known. We aimed to investigate the relationship between HT and serum copeptin and uric acid levels in children with obesity. METHODS: We included 80 children with obesity who were admitted to our hospital between April 2018 and September 2018. The patients were separated into two groups: hypertensive and non-hypertensive. Serum copeptin levels were measured using the enzyme-linked immunosorbent assay. RESULTS: Copeptin levels were significantly higher in patients with HT than in those without (p = 0.0001). In addition, serum uric acid levels in patients with HT were significantly higher, while the serum potassium levels were significantly lower (p = 0.01) than in those without HT (p = 0.001). In correlation analyses, a positive correlation was detected between blood sodium and copeptin levels (p = 0.037). CONCLUSIONS: Hypertensive children with obesity had higher serum copeptin and uric acid and lower blood potassium levels. Moreover, copeptin levels were positively correlated with blood sodium levels. Thus, in addition to copeptin, serum uric acid, potassium, and sodium levels may be important in the diagnosis and follow-up of children with HT.

COVID-19 in pediatric nephrology centers in Turkey.

BACKGROUND: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. METHODS: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. RESULTS: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10-15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. DISCUSSION: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients' susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage.

Evaluation of S100A12 protein levels in children with familial Mediterranean fever

Background/aim: Familial Mediterranean fever (FMF), the most common autoinflammatory disease in children, is characterized by recurrent febrile episodes. FMF is known to progress with chronic inflammation, particularly during attack periods. This study aimed to investigate the relationship of S100A12, an inflammatory marker, with attacks and inflammatory events in FMF patients. Materials and methods: The study included 57 patients diagnosed with FMF, 43 in an attack-free period and 14 in an attack period, and 31 healthy children as the control group. Only white blood cell (WBC) count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and S100A12 level were analyzed in the control group. In addition, serum amyloid A (SAA), and fibrinogen levels were measured, and a mutation analysis was performed in the patient group. The results were compared among the attack-free period, acute attack FMF and control groups. Results: The mean age of patients and control group was 10 (2.5­18) and 9.5 (2.5­16) years, respectively. The CRP (p = 0.001), S100A12 (p = 0.003) and ESR (p= 0.001) values differed significantly between the FMF and control groups. S100A12 level (p = 0.027), WBC count (p = 0.003), CRP level (p = 0.0001), ESR (p = 0.004), and fibrinogen level (p = 0.001) differed significantly between the acute attack and attack-free period groups. SAA level (p = 0.05), ESR (p = 0.001), fibrinogen level (p = 0.001), WBC count (p = 0.001), and S100A12 level (p = 0.027) were higher in M694V homozygous FMF patients than in other FMF patients. Conclusion: Patients with FMF had higher S100A12 levels than the control group, while the mean S100A12 concentration was higher in acute attack period patients than in attack-free period patients. S100A12 level might be an important indicator in the monitoring of chronic inflammation in patients with FMF.

P-Wave Changes Associated with Chiari Network in the Right Atrium.

The Chiari network (CN) is a mobile, net-like structure occasionally present in the right atrium, near the opening of the inferior vena cava and coronary sinus. While typically asymptomatic, it may contribute to thromboembolism or right atrial pathologies. Here, we hypothesized that existing differences in P-wave morphology on electrocardiograms (ECG) may be associated with atrial conduction changes. Seventy-one children with a CN were recruited and matched to 60 healthy controls. P-wave duration, P-wave amplitude, P dispersion (Pd), QRS, PR, QT, and QTc (calculated with Bazett formula) intervals were measured and compared. Between the control and the patient groups, the mean P-wave duration was 78.1 ms and 88.7 ms, P amplitude was 1.3 mm and 1.1 mm, and Pd was 18.9 and 35.5 ms, respectively. These differences were statistically significant across all measurements (p < 0.05). Atrial conduction may be affected in patients with CN, and these patients may then develop atrial arrhythmia.

Aetiological evaluation of chest pain in childhood and adolescence.

BACKGROUND: Chest pain, as a common cause of hospital admissions in childhood, necessitates detailed investigations due to a wide range of differential diagnoses. In this study, we aimed to determine the distribution of diseases causing chest pain in children and investigate the clinical characteristics of children with chest pain. METHODS: This study included 782 patients aged between 3 and 18 years who presented to a paediatric cardiology outpatient clinic with chest pain between April 2017 and March 2018. Aetiological causes and demographic features of the patients were analysed. RESULTS: Most prevalent causes of chest pain were musculoskeletal system (33%) and psychogenic (28.4%) causes. Chest pain due to cardiac reasons was seen in eight patients (1%). Diseases of musculoskeletal and gastrointestinal systems and psychogenic disorders were significantly more common in male and female patients, respectively (p < 0.001 for all). In winter, patients' age and the number of patients with ≥12 years were higher than those in other seasons (p < 0.001). Most of the parents (70.8%) and patients (90.2%) thought that chest pain in their children was caused by cardiac causes. CONCLUSION: Most of the diagnoses for chest pain in childhood period are benign and include the musculoskeletal system and psychogenic diseases. Although chest pain due to cardiac diseases is rare, a comprehensive analysis of medical history, detailed physical examination and cardiac imaging with echocardiography is needed to reach more accurate diagnoses.

Evaluation of Continuous Renal Replacement Therapy and Therapeutic Plasma Exchange, in Severe Sepsis or Septic Shock in Critically Ill Children.

Background and objective: Severe sepsis and septic shock are life-threatening organ dysfunctions and causes of death in critically ill patients. The therapeutic goal of the management of sepsis is restoring balance to the immune system and fluid balance. Continuous renal replacement therapy (CRRT) is recommended in septic patients, and it may improve outcomes in patients with severe sepsis or septic shock. Therapeutic plasma exchange (TPE) is another extracorporeal procedure that can improve organ function by decreasing inflammatory and anti-fibrinolytic mediators and correcting haemostasis by replenishing anticoagulant proteins. However, research about sepsis and CRRT and TPE in children has been insufficient and incomplete. Therefore, we investigated the reliability and efficacy of extracorporeal therapies in paediatric patients with severe sepsis or septic shock. Materials and methods: We performed a multicentre retrospective study using data from all patients aged <18 years who were admitted to two paediatric intensive care units. Demographic data and reason for hospitalization were recorded. In addition, vital signs, haemogram parameters, and biochemistry results were recorded at 0 h and after 24 h of CRRT. Patients were compared according to whether they underwent CRRT or TPE; mortality between the two treatment groups was also compared. Results: Between January 2014 and April 2019, 168 septic patients were enrolled in the present study. Of them, 47 (27.9%) patients underwent CRRT and 24 underwent TPE. In patients with severe sepsis, the requirement for CRRT was statistically associated with mortality (p < 0.001). In contrast, the requirement for TPE was not associated with mortality (p = 0.124). Conclusion: Our findings revealed that the requirement for CRRT in patients with severe sepsis is predictive of increased mortality. CRRT and TPE can be useful techniques in critically ill children with severe sepsis. However, our results did not show a decrease of mortality with CRRT and TPE.

Allergic sensitization in kidney transplanted patients - Is it a result of immunosuppressive agents or the sensitization of living donor?

BACKGROUND: Allergic sensitization has been reported increasingly in organ transplant recipients. However, the pathogenesis of this sensitization has still not been clearly understood. OBJECTIVE: The aim of this study was to evaluate allergic sensitization in kidney transplanted children and adolescents under immunosuppressive treatment. METHODS: Twenty seven kidney-transplanted subjects were studied by standardized interviews from the International Study of Asthma and Allergies in Childhood criteria, skin prick test (SPT) and measurement of specific immunoglobulin E (s-IgE). Patients were considered to have allergic sensitization when presenting a positive SPT and/or s-IgE >0.35 kUA/l to at least one of the tested allergens. Patients with a history of allergic diseases accompanied by sensitization were accepted as allergic. We also performed SPT on the living donors of the allergic groups. RESULTS: Seven patients (25.9%) were found to be sensitized to ≥1 common inhalant and 3 subjects (11.1%) additionally reported a corresponding present history of allergic diseases. All of the living donors' sensitized patients were allergic. New-onset post-transplantation food allergy was not documented in any patients. CONCLUSIONS: This study supports the concept that not only immunosuppressant agents but also sensitization of living donors could be a significant contributor to allergic sensitization in kidney recipients.

Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1, and L-FABP.

BACKGROUND: Reflux nephropathy is the most serious complication of vesicoureteral reflux (VUR). The aim of this study was to assess the role of urinary levels of neutrophil-gelatinase-associated lipocalin (NGAL),kidney injury molecule-1 (KIM-1), and liver-type fatty-acid-binding protein (L-FABP) in the early diagnosis of reflux nephropathy in patients with VUR. METHODS: This study assessed 123 patients with primary VUR and 30 healthy children as a control group. The children were divided into five groups: Group A, patients with VUR and renal parenchymal scarring (RPS); Group B, patients with VUR and without RPS; Group C, patients with RPS and resolved VUR; Group D, patients with resolved VUR and without RPS; Group E, healthy reference group. RESULTS: Median urinary NGAL (uNGAL)/Creatinine (Cr) was significantly higher in patients with than those without RPS and the control group (p = 0.0001). Median uKIM-1/Cr was similar in all groups (p = 0.417). Median uL-FABP/Cr was significantly higher in patients with RPS than in the reference group (p < 0.05). CONCLUSIONS: Urinary NGAL levels may be used as a noninvasive diagnostic marker for predicting renal scarring in reflux nephropathy.

Magnetic resonance imaging based kidney volume assessment for risk stratification in pediatric autosomal dominant polycystic kidney disease.

Introduction: In the pediatric context, most children with autosomal dominant polycystic kidney disease (ADPKD) maintain a normal glomerular filtration rate (GFR) despite underlying structural kidney damage, highlighting the critical need for early intervention and predictive markers. Due to the inverse relationship between kidney volume and kidney function, risk assessments have been presented on the basis of kidney volume. The aim of this study was to use magnetic resonance imaging (MRI)-based kidney volume assessment for risk stratification in pediatric ADPKD and to investigate clinical and genetic differences among risk groups. Methods: This multicenter, cross-sectional, and case-control study included 75 genetically confirmed pediatric ADPKD patients (5-18 years) and 27 controls. Kidney function was assessed by eGFR calculated from serum creatinine and cystatin C using the CKiD-U25 equation. Blood pressure was assessed by both office and 24-hour ambulatory measurements. Kidney volume was calculated from MRI using the stereological method. Total kidney volume was adjusted for the height (htTKV). Patients were stratified from A to E classes according to the Leuven Imaging Classification (LIC) using MRI-derived htTKV. Results: Median (Q1-Q3) age of the patients was 6.0 (2.0-10.0) years, 56% were male. There were no differences in sex, age, height-SDS, or GFR between the patient and control groups. Of the patients, 89% had PKD1 and 11% had PKD2 mutations. Non-missense mutations were 73% in PKD1 and 75% in PKD2. Twenty patients (27%) had hypertension based on ABPM. Median htTKV of the patients was significantly higher than controls (141 vs. 117 ml/m, p = 0.0003). LIC stratification revealed Classes A (38.7%), B (28%), C (24%), and D + E (9.3%). All children in class D + E and 94% in class C had PKD1 variants. Class D + E patients had significantly higher blood pressure values and hypertension compared to other classes (p > 0.05 for all). Discussion: This study distinguishes itself by using MRI-based measurements of kidney volume to stratify pediatric ADPKD patients into specific risk groups. It is important to note that PKD1 mutation and elevated blood pressure were higher in the high-risk groups stratified by age and kidney volume. Our results need to be confirmed in further studies.

Non-dipping phenomenon in children with monosymptomatic nocturnal enuresis.

PURPOSE: Monosymptomatic nocturnal enuresis is a common disorder seen in childhood, and many factors play a role in its etiopathology to varying degrees. The aim of our study was to investigate the possible association between nocturnal enuresis and 24-h blood pressure profiles of enuretic children. METHODS: A total of 45 children ranging in age from 6 to 15 years with monosymptomatic nocturnal enuresis and 22 age-matched healthy controls were enrolled in our study. The blood pressure measurement was made at 30-min intervals during a 24-h period via an ambulatory blood pressure measurement device. Both groups underwent medical tests that included a complete blood count, blood biochemistry profile, urinalysis and blood renin-aldosterone levels, and all study subjects received an abdominal ultrasound. RESULTS: Statistically significant high nocturnal blood pressure levels were observed in our patients with monosymptomatic nocturnal enuresis compared with the control group (p < 0.05). The mean values of the day-to-night difference (dipping) in the systolic and diastolic blood pressure of the patients were significantly lower than those of control group (p < 0.05). CONCLUSION: Nocturnal enuresis should not only be accepted as a urinary system disorder. Possible systemic causative factors have to be examined, especially in patients that are resistant to first-line therapy. Based on the results of our study, we deduce that one of the factors that plays a role in the pathogenesis of enuresis nocturna is a non-dipping blood pressure profile (the "non-dipping" phenomenon).

Blood pressure and heart rate monitoring in children and adolescent with Still's vibratory murmur.

BACKGROUND: Innocent heart murmur is common in healthy infants, children and adolescents. Although most cases are not pathologic, a murmur may be the manifestation of cardiovascular disease. It may also cause or be an indicator of blood pressure (BP) and heart rate (HR) changes. OBJECTIVE: This study aimed to document changes in BP and HR in children with Still's vibratory murmur (SVM). METHODS: This study included 226 children with SVM, and the control group included 138 healthy children that were age-, height- and weight-balanced. Patient files and our hospital registry system were retrospectively investigated for laboratory findings and electrocardiography and echocardiography results. In addition, we prospectively performed 24-h ambulatory BP monitoring in both groups. RESULTS: There were no statistically significant differences in 24-h, daytime and nighttime systolic BP, 24-h and nighttime diastolic BP and nighttime HR between the patient and control groups (P = ns). However, daytime diastolic BP, mean HR and daytime HR were significantly higher in patient group (P = 0.009, 0.039 and 0007, respectively). CONCLUSIONS: We believe that in the presence of a higher HR and a higher aortic diastolic BP, which may induce hemodynamic changes in the left ventricle, flow turbulence through the aortic valve may increase, increasing the probability of hearing a murmur. ambulatory BP monitoring could be useful to obtain a better picture of these parameters during the 24-h period.

Using urinary neutrophile gelatinase-associated lipocalin for prognosticate renal dysfunction in children with familial Mediterranean fever the study design: a pilot study.

BACKGROUND: The most important finding that affects the prognosis in Familial Mediterranean Fever is renal amyloidosis. The aim of the present study was to analyze neutrophil gelatinase-associated lipocalin levels in the urine, and to investigate whether it may be used as an early marker for renal involvement. METHODS: Forty attack-free children followed by diagnosis of Familial Mediterranean Fever with age range of 5 and 18 years, and 38 healthy children with similar ages and genders were enrolled into the study. Hemogram, sedimentation, C-reactive protein, urine analysis, creatinine in the spot urine, microalbumin and urinary neutrophil gelatinase-associated lipocalin levels were analyzed and evaluated statistically in the patients and controls. RESULTS: There was not any statistically significant difference between the patient and control groups for age, gender, height and body weight. Although there was not any clinical sign of attack in the patient group, sedimentation, C-reactive protein and fibrinogen levels were significantly higher than the control group (p = 0.002, p = 0.023, and p = 0.006, respectively). Similarly, urinary neutrophil gelatinase-associated lipocalin level and urinary creatinine ratio were significantly higher in the patient group (p = 0.0001, p = 0.011, respectively). We found a positive correlation between uNGAL level and uNGAL/uCr ratio and number of attacks per year in FMF patients (r = 0.743, p = 0.001 and r = 0.516, p = 0.001; respectively). CONCLUSIONS: Detection of significantly higher levels of urinary neutrophil gelatinase-associated lipocalin level and urinary neutrophil gelatinase-associated lipocalin level to creatinine ratio were suggested as urinary neutrophil gelatinase-associated lipocalin level as a non-invasive marker for renal involvement better than microalbumin.

The relationship between body fat ratio and blood pressure in school-age children.

Hypertension (HTN) and obesity prevalences are rising in childhood and it is important to evaluate associations of these situations. The objective of this study is to investigate the relationship between HTN and body fat ratios (BFR) in children. This cross-sectional study was conducted among 134 participants who were directed to pediatric nephrology outpatient clinic with the prediagnosis of primary HTN. Weight, height, body fat ratio, blood pressure, and ambulatory blood pressure monitor (ABPM) was carried out for all the participants. Of the participants, 70 of them were diagnosed as hypertension with ABPM and included in the patient group, 64 of them had elevated office blood pressure (BP) but normotensive according to ABPM were included in the control group. Body fat ratio (BFR) levels of the patient group were higher than the control group (p < 0.05). There were significant linear correlation between night systolic blood pressure (SBP), night diastolic blood pressure (DBP), night mean arterial pressure (MAP), and BFR in the patient group (p < 0.05). There was a negative correlation between BFR and dipper (p = 0.022; p < 0.05) in the patient group. There was no correlation between BFR and blood pressures or dipper in the control group. According to our results BFR levels have significant association with HTN. According to our findings high BFR especially effects night BP, pulses, nondipping, and nighttime values can be evaluated only with ABPM. For prevention of HTN in children, caution should be given to monitor and lower BFR values.

The role of endothelium-derived hyperpolarizing factor in children with familial mediterranean fever.

OBJECTIVE: Familial Mediterranean Fever is an autoinflammatory disease characterized by inflammatory attacks in serous tissues often accompanied by endothelial dysfunction. This study aimed to evaluate the effect of endothelium-derived hyperpolarizing factor, which is an indicator of endothelial dysfunction in children with familial Mediterranean fever. METHODS: This study include 57 children with familial Mediterranean fever and 31 children as healthy controls. Blood samples were collected from all participants to measure their endothelium-derived hyperpolarizing factor, complete blood count and C-reactive protein. In addition, inflammatory markers, mutation analyses, and microalbuminuria were examined only in the patient group. RESULTS: The mean age of the patient group was 9.8 ± 4.0 (2.5-18) years, while the mean age of control group was 9.5 ± 3.9 (2.5-16) years (p=0.808). Study group had significantly higher C-reactive protein levels and systolic and diastolic blood pressures and lower endothelium-derived hyperpolarizing factor values than the control group (p=0.0001, p=0.002, p=0.035 and p=0.009, respectively). CONCLUSION: Low levels of endothelium-derived hyperpolarizing factor, high levels C-reactive protein and high blood pressure in patients with familial Mediterranean fever can be attributed to the changes in the endothelium resulting from subacute inflammation.