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.

Clinical Characteristics of Children With Acute Tubulointerstitial Nephritis: A Single-Center Experience.

OBJECTIVE: Acute tubulointerstitial nephritis (ATIN) is an infiltration of the kidney interstitium with inflammatory cells. Medications are most frequently blamed for the etiology. Patients may present with non-specific signs and symptoms. Therefore, the diagnosis of ATIN is often delayed. In this study, clinical characteristics, treatment protocols, and outcomes of children diagnosed with ATIN were presented. METHODS: This is a retrospective study based on the data of 18 patients diagnosed with ATIN between 2017 and 2022 at Gazi University. Patients were divided into two groups: steroid-treated (n=13) and non-steroid-treated (n=5). Clinical features and laboratory evaluations were compared between the groups. RESULTS: The mean age of the patients was 14.4±2.6 years, and the great majority were girls (88.9%, n=16). ATIN was mostly medication-related (n=17, 94.4%). Steroids were started in one-third of patients using non-steroidal anti-inflammatory drugs. Steroids were started in 45.4% of the patients with eosinophilia, 75% of those with pyuria, 66.6% of those with hematuria, and half of the patients with increased kidney echogenicity. The kidney functions returned to normal ranges in all patients. In steroid-treated patients, although recovery times for serum creatinine were longer (7.2±2.5 vs. 71.2±100.7 days), blood eosinophil count reached normal values more rapidly (5.4±2.3 vs. 3.1±1.0 days). CONCLUSION: ATIN can be associated with diverse clinical presentations. The first and most important step of treatment is to discontinue the medication responsible for the etiology. Steroid treatment improves eosinophilia more rapidly. However, randomized controlled studies are needed to determine further treatment steps and establish a more definite treatment protocol.

Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in the Evaluation of Acute Rejection and Chronic Allograft Nephropathy in Children With Kidney Transplantation.

OBJECTIVES: Neutrophil-to-lymphocyte ratio and platelet (thrombocyte)-to-lymphocyte ratio have become accepted markers of inflammation in recent years and are used to assess disease activity in some diseases. In this study, we investigated the relationship between these values and acute rejection attacks, as well as their role in determining chronic allograft nephropathy, in follow-up of pediatric kidney transplant recipients. MATERIALS AND METHODS: Our study included 58 kidney transplant recipients (age 5-18 years) with at least 5-year follow-up at our center. Patients with history of secondary transplant, concomitant malignancy, and shorter follow-up were excluded. Medical history and laboratory parameters pretransplant and at 1, 3, and 6 months and 1, 2, 3, 4, and 5 years posttransplant, as well as kidney biopsy reports, were reviewed. RESULTS: Both neutrophil-to-lymphocyte (P = .003) and thrombocyte-to-lymphocyte (P = .002) ratios were significantly higher during acute rejection attacks. Although both values were higher in patients with chronic allograft nephropathy at 5 years posttransplant, differences were not statistically significant (P = .69 and P = .55). When patients with and without chronic allograft nephropathy within 5 years were compared, those who developed chronic allograft nephropathy had significantly higher neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios at all periods in the first 2 and 4 years posttransplant, respectively. Among patients who had acute rejection attacks, those who subsequently developed chronic allograft nephropathy had higher neutrophil-tolymphocyte ratio in the first 3 years posttransplant, with higher thrombocyte-to-lymphocyte ratio at all posttransplant periods. CONCLUSIONS: This is the first study on neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios in pediatric kidney transplant recipients. Our results indicated that both values can be useful and easily accessible markers in acute rejection diagnosis and determining chronic allograft nephropathy development risk, which are 2 major causes of kidney graft loss posttransplant. Pediatric studies with larger populations are needed to support our findings.

Results of native and transplant kidney biopsies of children in a single center over a 15 years period.

Renal biopsy is an important diagnostic procedure in pediatric nephrology. This study retrospectively investigates the indications, results and complications in a single tertiary children's hospital in Turkey. We evaluated the native and transplant kidney biopsies in Gazi University Pediatric Nephrology Department between 2001 and 2015. A total of 196 biopsies (144 natives and 52 transplants) were included into the study. The mean age of the patients was respectively 10.8 ± 3.5, 13.9 ± 1.5 years. The main indication for a biopsy was non-nephrotic proteinuria with or without hematuria (n= 35), followed by steroid-resistance nephrotic syndrome (SRNS) (n = 34) and Henoch-Schönlein purpura (HSP)-related proteinuria (n = 20) for native kidneys. We found that focal segmental glomerulosclerosis (FSGS) (11.7%) was the most common histopathologic diagnosis for native kidneys, but acute cellular rejection (7.6%) was the most common histopathologic diagnosis for transplant kidneys. The complication rate in our study was founded 6.6% totally. Different complication rates were found in other studies; however, we think that this difference comes from the inspecting methodology of the complications. Hence, we wanted to share our own experience in the context of other studies in the literature.

¿Puede usarse el receptor soluble de transferrina para diagnosticar anemia ferropénica y evaluar la respuesta al hierro en lactantes con desnutrición aguda moderada? / Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

Objetivo. Evaluar la eficacia del receptor soluble de transferrina (RST) en el diagnóstico de la anemia ferropénica (AF) y en la evaluación de la respuesta al hierro en los lactantes con desnutrición aguda moderada (DAM). Población y métodos. Se reclutó a lactantes con valores de hemoglobina (Hb) inferiores a los valores umbrales de anemia para su edad y con anemia hipocrómica/microcítica observada en el frotis de sangre periférica. La DAM se definió como un puntaje Z de peso/estatura de entre < -2 y -3. Se compararon los valores del hemograma, los parámetros férricos y el RST entre 41 lactantes con DAM y anemia (grupo DA), 32 lactantes con anemia sin DAM (grupo A) y controles saludables (n= 30). Una vez completado el tratamiento de la anemia y la desnutrición, se repitieron las evaluaciones. Resultados. Además de los índices hematológicos compatibles con AF, los valores de hierro sérico (Fe) y saturación de transferrina (ST) eran significativamente menores, mientras que el valor de transferrina era significativamente mayor en los grupos DA y A en comparación con los controles (p < 0,001). Los valores de ferritina y proteína C-reactiva (PCR) eran significativamente más elevados en el grupo DA (p < 0,05 para la ferritina, p < 0,01 para la PCR). El valor medio del RST fue similar en ambos grupos (DA y A) (p > 0,05) y significativamente mayor que en los controles (p < 0,001). Después del tratamiento con hierro, el RST disminuyó en los grupos DA y A (p < 0,001) a valores similares a los observados en los controles. El RST se correlacionó negativamente con la Hb durante todo el estudio (grupo DA: r= -0,350, p < 0,05; grupo A: r= -0,683, p < 0,01). Conclusiones. Dado que los valores del RST en los grupos DA y A disminuyeron después del tratamiento con hierro, consideramos que este parámetro no estuvo afectado por la DAM ni la inflamación y puede usarse, por sí solo, para detectar la AF y supervisar la respuesta al tratamiento en los lactantes con DAM.

Objective. To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Population and methods. Infants withhemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Results. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p <0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased inboth MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). Conclusions. As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition? / ¿Puede usarse el receptor soluble de transferrina para diagnosticar anemia ferropénica y evaluar la respuesta al hierro en lactantes con desnutrición aguda moderada?

OBJECTIVE: To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). POPULATION AND METHODS: Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. RESULTS: Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p 0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased in both MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). CONCLUSIONS: As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

Evaluar la eficacia del receptor soluble de transferrina (RST) en el diagnóstico de la anemia ferropénica (AF) y en la evaluación de la respuesta al hierro en los lactantes con desnutrición aguda moderada (DAM).

Changing trends in pediatric renal biopsies: analysis of pediatric renal biopsies in national nephrology registry data.

Renal biopsy is the gold standard method for determining the diagnosis, treatment, and prognosis in children with renal disease. This study aims to evaluate the histopathological features of pediatric renal biopsies obtained from the national nephrology registry in the last two decades. Data recorded in the Turkish Society of Nephrology Registry System (TSNRS) in 1991 as well as in between 2001 and 2010 were analyzed. A total of 3892 biopsies were recorded; with the least number in 1991 (total 103 biopsies from 17 centers) and the highest number in 2008 (total 654 biopsies from 23 centers). Glomerular diseases constituted the main group in the registry (62.64%), followed by systemic diseases (20.06%). Focal and segmental glomerulosclerosis (FSGS) and Henoch-Schönlein purpura (HSP) nephritis (IgA vasculitis) were the most common glomerular and systemic diseases, respectively. Overall prevalence of renal amyloidosis and membranous nephropathy (MN) was quite low (1.87% and 1.56%, respectively) in all periods. Compared to 1991, there was an increasing trend in the frequencies of certain disorders including hemolytic uremic syndrome (HUS), IgA nephropathy, and HSP nephritis; and there was a decrease in acute proliferative glomerulonephritis (GN) in 2008. As well as demonstrating the etiologies of renal diseases which can only be identified by renal biopsies, this study provides important information regarding the changing patterns of histopathological findings due to better management of pediatric renal diseases over the years in Turkey.

The Association Between Plasma Ferritin Level and Simple Febrile Seizures in Children.

INTRODUCTION: We conducted this study to determine the role of iron deficiency (ID) as a risk factor for simple febrile seizure (SFS) in 6- to 60-month-old children. MATERIALS AND METHODS: In this case-control study 100 children aged 6 to 60 months with febrile seizure (FS) (study group) and 100 febrile children without seizures (control group) admitted to Pediatric Departments of Kecioren Training and Research Hospital in between June 2014 and March 2015 were evaluated. Complete blood count, serum iron, plasma ferritin, and total iron binding capacity analyses were performed in children with FS and were compared with controls. RESULTS: Ferritin level was significantly lower in the study group than controls (P<0.05). Compared with the onset of the study (first day), ferritin levels of the study group significantly decreased at the 10th day (P<0.05). At the onset, we were not able to determine ID in 18% of children because of fever. CONCLUSIONS: There was a relationship between low plasma ferritin level and SFS. Low plasma ferritin level may be a risk factor for the development of SFS. For preventing the FS attacks, treatment of present ID and oral supplementary iron therapy should be initiated for children with SFS who have a low plasma ferritin.

Influence of body mass index on pediatric urolithiasis.

OBJECTIVE: In recent years, there has been increased incidence of urolithiasis in children. Changing nutritional patterns and sedentary lifestyles predispose to urolithiasis, as well as to the global rise in obesity. It has been established that the prevalence of high body mass index (BMI) is increasing in the pediatric population. The aim of the present study was to incorporate 24-h urine metabolic analysis results with BMI values to evaluate the tendency towards stone formation in children. METHODS: Eighty-four children were recruited to the study, stratified into three BMI categories as low, normal, or upper. All patients were evaluated with 24-h urine analysis results. Patients with a secondary cause of stone formation such as hyperparathyroidism, cystinuria, primary hyperoxaluria, inflammatory bowel disease, cystic fibrosis, history of prematurity and/or use of drug, recurrent urinary tract infection, and urinary tract anomaly were excluded. Additionally, it was ensured that none of the patients were taking specific medication or diet that could alter their acid-base metabolism and calcium, oxalate, and uric acid levels. RESULTS: Mean BMI of patients was 21.6 ± 2.9 kg/m(2). LBMI was found in 52 (61.9%), N-BMI in 20 (23.8%), and U-BMI in 12 (14.3%) of the patients. No significant differences were present between the three groups for stone sizes and numbers. The patients' characteristics and 24-h urine parameters for BMI groups are presented in the Table. DISCUSSION: In the literature, several studies have focused on the relationship between obesity and pediatric urinary stone disease. However, only a few evaluated the urinary metabolic analysis in pediatric patients. We have encountered different results from mainly adult studies and some pediatric studies. Our study shows that U-BMI children are not under greater risk for urolithiasis than the other groups. An important portion of our study group was in the L-BMI group; nevertheless we cannot conclude that having a low BMI predisposes to urolithiasis based on the urinary metabolic evaluation as well as the stone sizes and numbers. The N-BMI group has increased risk factors for urolithiasis rather than the other groups, according to results of 24-h urine analysis. CONCLUSION: The results of our study indicate that BMI itself could not be considered as a separate and definite risk factor for urolithiasis development in children. Although the mechanisms and causative factors for urinary stone formation are better defined in adults, further studies investigating these parameters in children are warranted.

The evaluation of bone metabolism in children with renal transplantation.

This study aims to evaluate BMD and bone biomarkers and to investigate the effects of immunosuppressives on bone disease after RTx. Thirty-three RTR aged 16.7 ± 3.7 yr and healthy controls (n = 32) were enrolled. There was no difference between pre-RTx BMD and BMD at the time of study (45.9 ± 30.9 months after RTx), while both values were lower than controls (p < 0.01 and p < 0.05, respectively). Worst BMD scores were obtained at sixth month after RTx (-0.2 ± 0.9) and best at fourth year (1.4 ± 1.3). 25-hydroxy-(OH) vitamin D and OPG were higher in RTR (p < 0.001). BMD z scores negatively correlated with OPG and cumulative CS doses at the time of study (r = -0.344, p < 0.05 and r = -0.371, p < 0.05, respectively). Regression analysis revealed OPG as the only predictor of BMD (ß -0.78, 95% CI -0.004 to -0.013, p < 0.001). The increase in OPG, a significant predictor of BMD, could either be secondary to graft dysfunction or for protection against bone loss. CS doses should be minimized to avoid their untoward effects on bone metabolism.

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay.

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n=17), regular hemodialysis patients (HD) (n=15), and those that received kidney transplants (Tx) (n=17), comprised the study group. They were compared with age- and gender-matched healthy children (n=20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean ± SD) (5.22 ± 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 ± 1.23), (4.91 ± 1.35), and (5.79 ± 1.94), respectively, vs the healthy children (2.74 ± 2.91) (p<0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p<0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy.

Micronucleus frequencies in peripheral blood lymphocytes of children with chronic kidney disease.

One of the crucial adverse effects of chronic kidney disease (CKD) and its treatment is an elevated cancer risk. There are no data on cytogenetic effects in children with CKD or children undergoing dialysis or those who have received a transplant. In this study, cytogenetic effects in children with CKD in pre-dialysis (PreD) stage, on regular haemodialysis (HD) and transplanted (Tx) compared with a control group of healthy children has been investigated using the cytokinesis-blocked micronucleus (CBMN) assay and fluorescence in situ hybridisation (FISH) combined with CBMN (CBMN-FISH) in peripheral blood lymphocytes. The results revealed a significant increase (P < 0.001) in micronucleus (MN) frequencies [mean ± SD (n)] in the PreD, HD and Tx groups versus the control group [CBMN assay; 9.19 ± 2.61 (16), 9.07 ± 4.86 (15), 6.12 ± 5.33 (17) versus 1.60 ± 0.99 (20), respectively]. Moreover, centromere negative micronucleus (C- MN) and centromere positive micronucleus (C+ MN) frequencies were significantly higher in each subgroup children (PreD, HD and Tx) than in the control group (P < 0.01) although children in Tx group had lower C- MN frequencies than PreD and lower C+ MN frequencies than PreD and HD groups (P < 0.05). Additionally, MN frequencies in mononuclear cells, nucleoplasmic bridges and nuclear buds in binucleated cells were increased in children with CKD (P < 0.001, P < 0.001, P > 0.05, respectively). The nuclear division index significantly decreased in Tx group relative to the control, PreD and HD groups (P < 0.001). Associations between cytogenetic parameters and creatinine or blood urea nitrogen were found (P < 0.05). To provide longer and better life expectancy of children with CKD and treatment modes, further research is needed to better understand and avoid these effects.

Gestational diabetes and gestational impaired glucose tolerance in 1653 teenage pregnancies: prevalence, risk factors and pregnancy outcomes.

STUDY OBJECTIVE: The aim of this study was to determine the prevalence of gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT) in adolescent pregnancies, associated risk factors, and pregnancy complications. DESIGN: Retrospective study. SETTINGS: Community-based teaching hospital. PARTICIPANTS: Results of 1653 pregnant women age ≤ 19 years in 2005-2007 were reviewed. INTERVENTION: All pregnant women screened with 50-g glucose challenge test (GCT) and patients with a GCT result ≥ 140 mg/dl underwent a 3-hour 100-g oral glucose tolerance test (OGTT). MAIN OUTCOME MEASURES: GDM was diagnosed with at least two abnormal results and GIGT was diagnosed with one abnormal result. GDM and GIGT cases were evaluated for the presence of any associated risk factors and effects of presence of risk factors on pregnancy outcomes. RESULTS: The prevalence of GDM was 0.85% (95% CI, 0.41-1.29), GIGT was 0.5% (95% CI, 0.15-0.81) and GDM+GIGT was 1.35% (95% CI, 0.78-1.88) by Carpenter and Coustan criteria. 68% of patients had at least one of the risk factors including body mass index ≥ 25, family history of diabetes and polycystic ovary syndrome (PCOS). Only 9.1% (n = 2) of them required insulin for glucose regulation during pregnancy with 9.1% (n = 2) macrosomia rate. All patients were primiparous and cesarean delivery rate was 27.3% (n = 6). We could not find any effect of presence of risk factors on pregnancy outcomes in GDM and GIGT cases. CONCLUSION: We demonstrated that GDM and GIGT are strongly associated with high BMI before pregnancy, PCOS, and family history of diabetes. Since GDM is a state of prediabetes, it is important to diagnose in adolescent pregnancies considering their life expectancy to take preventive measures to avoid diabetes mellitus.