Immature granulocytes as biomarkers of inflammation in children with predialysis chronic kidney disease.

BACKGROUND: Chronic inflammation in patients with predialysis chronic kidney disease (CKD) is quite common. We aimed to investigate the relationship of the percentage of immature granulocytes (IG%) and immature granulocyte count (IGC) with inflammation in children with predialysis CKD. METHODS: The data from children with stage 2-4 CKD and a control group of healthy children were evaluated retrospectively. A highly-sensitive C-reactive protein (hs-CRP) level above 5 mg/dL was considered the presence of inflammation. The IGCs were calculated in the white cell differential channel of the Sysmex XN-9000 using the fluorescent flow cytometry method. The IG% was expressed as percentage of total leucocyte concentration. RESULTS: The data from 57 patients (30 stage 2 CKD, 15 stage 3 CKD, 12 stage 4 CKD) and 46 controls were analyzed. hs-CRP levels, IG%, IGC, white blood cell (WBC) and neutrophil counts, and neutrophil-to-lymphocyte ratio (NLR) were higher in patients than the control group (p < 0.000, p < 0.000, p < 0.000, p = 0.001, p = 0.002, p < 0.000, respectively). Both IG% and IGC were positively correlated with hs-CRP, WBC and neutrophil counts, and NLR (r = 0.485, p < 0.000; r = 0.379, p = 0.004; r = 0.543, p < 0.000; r = 0.628, p < 0.000 for IG%; r = 0.379, p = 0.004; r = 0.351, p = 0.007; r = 0.525, p < 0.000; r = 0.601, p < 0.000 for IGC, respectively). A ROC analysis of the relationship between IGC, IG%, and inflammation showed IGC and IG% had predictive value for the presence of inflammation (cut-off value: 0.035 × 106/mL, AUC: 0.799 ± 0.061, sensitivity: 74.2%, specifity: 63%, p < 0.001 for IGC; cut-off value: 0.45%, AUC: 0.838 ± 0.056, sensitivity: 70.8%, specifity: 67.3%, p = 0.001 for IG%). CONCLUSIONS: Immature granulocytes may be used as a biomarker of inflammation in children with predialysis CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis.

OBJECTIVES: Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. MATERIALS AND METHODS: PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). CONCLUSION: The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

Diagnostic Values of Immature Granulocytes Detected by the Sysmex XN 9000 Hematology Analyzer in Children with Urinary Tract Infections.

Immature granulocytes (IGs) are used as markers of infection and systemic inflammation. We aimed to investigate the diagnostic value of IGs in children with urinary tract infections (UTIs). Children with their first UTIs were included in this observational study. Blood samples were obtained before antibiotic therapy. The blood analysis was repeated 2 weeks after the treatment ended. In total, 194 children (95 with febrile UTI, 58 with cystitis, and 41 controls) were included. The percentage of IGs (IG%) and IG count (IGC) measured at the time of admission were higher in the patients with febrile UTI than in the patients with cystitis and the controls (P = 0.000). The IGC and IG% after treatment were higher in patients with renal scarring than in those without scarring (P = 0.012 and P = 0.021, respectively). Cox's regression analysis showed the significant associations of renal scarring with both IGC and IG% (hazard ratio: 8.181, P = 0.002; hazard ratio: 5.106, P = 0.033, respectively). Both IGC and IG% were positively associated with severe vesicoureteral reflux (VUR) [odds ratio (OR): 22.235, P = 0.025; OR: 15.597, P = 0.038, respectively]. In conclusion, the IG% and IGC, which can be easily measured in a routine complete blood count without the need for additional effort, could be used as biomarkers for predicting febrile UTI, renal scarring, and severe VUR in children.

Relation of serum irisin levels to obesity and non-alcoholic fatty liver disease.

BACKGROUND: Irisin is a newly defined myokine which is induced by exercise, which stimulates white fat cells to have the characteristics of brown adipose tissue cell. It thereby causes thermogenesis, energy and weight loss and improvement in insulin sensitivity. These effects of irisin suggest that it may be associated with obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). METHODS: The aim of the present study was to determine the relationship of serum irisin levels in obese children with NAFLD. A total of 60 pubertal obese adolescents (age range: 11-18 yrs) as well as age and sex matched 28 healthy children were included in the study. Thirty of obese patients had NAFLD. RESULTS: The median irisin levels were lower in the obese patients both with and without NAFLD when compared with the control group. NAFLD group had a higher BMI than obese controls, however, the irisin levels were not different between these groups. The irisin levels were negatively correlated with BMI, BMI SDS, waist, hip and arm circumferences, waist/hip ratio, triceps-biceps skinfold thickness and AST, ALT levels in the all study groups. However, it was positively correlated with BMI, BMI SDS and waist and hip circumference in the entire obese group and positively with BMI SDS in the NAFLD subgroup. CONCLUSIONS: Consequently, circulating irisin levels are lower in obese adolescents and negatively correlated with body adiposity. In NAFLD patients, it may be related to steatosis and may decrease with liver damage.

Oxidative Status and Thiol/Disulfide Homeostasis Are Changed During 75 g Oral Glucose Tolerance Test over a Five-Hour Period.

BACKGROUND: Oral glucose loading may affect oxidative status during oral glucose tolerance test (OGTT). We aimed to investigate how oxidant and antioxidant markers and thiol/disulfide parameters change during OGTT. METHODS: OGTT was performed to 42 volunteers who were considered risk of type 2 diabetes and were divided into three groups (normoglycemic, prediabetes, diabetes) according glucose levels during OGTT. Glucose, insulin, c-peptide, total antioxidant status (TAS), total oxidant status (TOS), total thiol and native thiol were investigated with auto-anaylzer for five-hours period. RESULTS: Decrease of TAS and increase of TOS levels began with the increase in glucose and insulin levels. The increase of TAS started at third hour and reached the highest levels at fifth hour. OSI levels were higher at fourth hour than fasting and first hours in normoglycemic and diabetes groups. In the prediabetic group, TAS were higher than the other groups, TOS peak was at the second hour (p < 0.05). Native thiol and total thiol levels showed variable course during OGTT, both parameters increased at the end of the process (p < 0.05). Disulfide levels showed an increase trend but it was not statistically different in normoglycemic and diabetes groups. In prediabetes group, second hour disulfide level was lower than fasting state and disulfide was significantly increased at third, fourth and fifth hours and fifth hour disulfide level was also higher than fasting. CONCLUSION: Oxidative stress parameters and thiol/disulfide balance were found to deteriorate within five-hours after glucose loading in all groups. These results indicates that oxidative stress occurs during OGTT.

Serum Presepsin, Proadrenomedullin andTriggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as Biomarkers for the Diagnosis of Acute Pyelonephritis.

OBJECTIVE: To investigate the diagnostic values of serum presepsin, proadrenomedullin (proADM) and triggering receptor expressed on myeloid cells-1 (TREM-1) levels in children with acute pyelonephritis and lower urinary tract infection. METHODS: Peripheral venous blood and urine samples were obtained before starting antibiotic therapy at the time of admission in all patients. Serum TREM-1, presepsin and proADM concentrations were determined by the enzyme-linked immunosorbent assay method. RESULTS: 82 children (38 acute pyelonephritis, 24 lower urinary tract infection, 20 controls) were enrolled. Serum proADM and TREM-1 levels were higher in patients with acute pyelonephritis than those of lower urinary tract infection and controls (P=0.001 and P<0.001, respectively). Both serum proADM and TREM-1 levels had predictive value for diagnosis of acute pyelonephritis (P=0.006 and P<0.001, respectively). ROC analysis showed that proADM and TREM-1 had positive predictive values for diagnosis of acute pyelonephritis (AUC=0.830, P=0.003; and AUC=0.843, P<0.001, respectively). CONCLUSIONS: Serum proADM and TREM-1 levels could serve as early biomarkers for the diagnosis of acute pyelonephritis in children.

Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney.

INTRODUCTION: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. METHODS: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. RESULTS: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). CONCLUSIONS: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

Transforming Growth Factor-Beta 1 and Endoglin Levels in Congenital Solitary Functioning Kidney.

INTRODUCTION: Glomerular hyperfiltration leads to hypertension, microalbuminuria, and impaired renal function in children with congenital solitary functioning kidney (cSFK). The purpose of this study was to investigate the associations between serum transforming growth factor ß-1 (TGF) and endoglin levels and hypertension, renal function or microalbuminuria in children with cSFK. MATERIALS AND METHODS: 63 patients and 36 controls were included in the study. Serum endoglin and TGF-ß1 level was measured using ELISA commercial kits. RESULTS: Serum TGF-ß1 and endoglin levels were higher in patients than those of controls (P = 0.04 and P < 0.001, respectively). The prevalence of hypertension was found to be 45.6%. There was a positive association between endoglin levels and the presence of masked hypertension (odds ratio: 1.121, P = 0.04). TGF-ß1 and endoglin levels were positively associated with microalbuminuria (OR: 1.17, P = 0.04; OR: 1.836, P = 0.01). ROC curve analysis showed that serum endoglin and TGF-ß1 levels had predictive value for microalbuminuria (cut-off value: 4.86 ng/mL, sensitivity: 94.7%, specificity: 54.5%, area under the curve ± standard error [AUC ± SE]: 0.888 ± 0.025, P = 0.01 for endoglin; cut-off value 561.24 pg/mL, sensitivity: 89.5%, specificity: 73%, AUC ± SE: 0.995 ± 0.334, P = 0.02 for TGF-ß1). There were no significant relationships between glomerular filtration rate and serum TGF-ß1 or endoglin levels. CONCLUSIONS: Endoglin and TGF-ß1 may play an important role in the pathophysiology of microalbuminuria in cSFK. Endoglin may have a role in the development of hypertension in children with cSFK.

Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney / Níveis de hepcidina, netrina-1, lipocalina associada a gelatinase neutrofílica e ligante de quimiocina C-C motif na urina do rim displásico multicístico

ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.