Amira Peco-Antić

Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

Introduction Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). Materials and methods We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). Results Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of

Detection of acute kidney injury in premature asphyxiated neonates by serum neutrophil gelatinase-associated lipocalin (sNGAL)--sensitivity and specificity of a potential new biomarker.

8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was

Oxidative status parameters in children with urinary tract infection

5959.35/QALY. Conclusions Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.

Dilation of the Renal Artery in an Infant: 5 Years Later

Introduction Acute kidney injury (AKI) is common in neonatal intensive care units (NICU). In recent years, every effort is made for early detection of AKI. Our hypothesis was that serum neutrophil gelatinase-associated lipocalin (sNGAL) may be a reliable screening test for early diagnosis of AKI in premature neonates after perinatal asphyxia. Therefore, our aim was to assess the diagnostic accuracy of sNGAL for AKI in premature asphyxiated neonates. Materials and methods AKI was defined in the third day of life (DOL 3) as a serum creatinine (sCr) increase ≥ 26.5 μmol/L from baseline (the lowest previous sCr). According to the increase of sCr, AKI patients were divided in AKIN1 (sCr increase up to 1.9 baseline) and AKIN2 (sCr increase from 2.0 to 2.9 baseline). sNGAL levels were measured on DOL 1, 3 and 7. Results AKI was diagnosed in 73 (0.676) of 108 enrolled premature asphyxiated neonates. Sixty one patients (0.836) were classified in AKIN1 and 12 patients (0.164) in AKIN2. sNGAL reached the maximal concentrations on DOL 1 within 4 hours after admission to NICU, being higher in AKI compared with no-AKI group (160.8 ± 113.1 vs. 87.1 ± 81.6; P < 0.001) as well as in AKIN2 compared with AKIN1 group (222.8 ± 112.9 vs. 147.8 ± 109.9; P < 0.001). The best areas under the receiver operating characteristic curves (AUC) for prediction of AKI were 0.72 [95% (0.62-0.80) P < 0.001] on DOL1 at 2h and 0.72 [95% (0.63-0.80) P < 0.001] at 4th hour after admission respectively. The corresponding sNGAL cutoff concentrations were 84.87 ng/mL (sensitivity 69.0% and specificity 71.9%) and 89.43 ng/mL (sensitivity 65.7% and specificity 74.3%). Conclusions In premature asphyxiated neonates sNGAL measured within the first 4 hours of DOL 1 is predictive of the occurrence and severity of AKI. Therefore, plasma levels of NGAL may be used for early diagnosis of AKI in these patients.

Prevalence of Hypertension in Children with Early-Stage ADPKD

Introduction: Urinary tract infection (UTI) is one of the most common bacterial infectious diseases in children. The aim of this study was to determine the total prooxidant and antioxidant capacity of children with UTI, as well as changes of oxidative status parameters according to acute inflammation persistence and acute kidney injury (AKI) development. Materials and methods: The patients enrolled in the study comprised 50 Caucasian children (median age was 6 months) with UTI. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), inflammation marker C-reactive protein (CRP) and renal function parameters urea and creatinine were analyzed in patient’s serums. Results: According to duration of inflammation during UTI, TAS values were significantly higher (0.99 vs. 0.58 mmol/L, P = 0.017) and OSI values were significantly lower (0.032 vs. 0.041 AU, P = 0.037) in the subjects with longer duration of inflammation than in the subjects with shorter duration of inflammation. We did not find significant difference in basal values of oxidative status parameters according to AKI development. Conclusions: OSI values could detect the simultaneous change of TAS and TOS due to change in the oxidative-antioxidant balance during the recovery of children with UTI. TAS and OSI as markers of oxidative stress during UTI are sensitive to accompanying inflammatory condition. Further investigations are needed to evaluate whether TAS, TOS and OSI could be used to monitor disease severity in children with UTI.

Association of paraoxonase 1 and oxidative stress with acute kidney injury in premature asphyxiated neonates

A 5-month-old infant with a solitary pelvic kidney presented with severe cardiorespiratory distress and hypertension (220/ 160 mm Hg) that was unresponsive to four antihypertensive medications. A critical ostial renal artery stenosis (near the aortic bifurcation) was treated via the left axillary artery with 3-mm and later 4-mm diameter balloon angioplasty (Figures 1 and 2, arrows). Antihypertensive therapy was gradually tapered nd finally completely stopped by 12 months after dilation. At age 5.5 years, the child is normotensive, is free of medications, and has normal renal function. Follow-up angiography, performed because of anomalous drainage from the portal vein into the lower caval vein (Abernethy malformation), showed no stenosis of the renal artery and good flow into the solitary kidney (Figure 3, arrow).

Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents

BACKGROUND AND OBJECTIVES Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. RESULTS Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P=0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P=0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P=0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P=0.10). CONCLUSIONS These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.

Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome

OBJECTIVES Acute kidney injury (AKI) is defined as a decrease in glomerular filtration rate with an increase in serum creatinine (sCr). Perinatal asphyxia (PNA) may be etiological factor for AKI with oxidative stress also implicated. Paraoxonase 1 (PON1) activity has been reported to be decreased in renal disease. The aim of our study was to evaluate paraoxonase 1 (PON1) activity and oxidative stress during the first hours and first days of life and to determine if these parameters could discriminate neonates having AKI from those who do not. METHODS Serum samples at different time points after birth were obtained from 64 preterm newborns with PNA (45 defined as having AKI, 19 as non-AKI). Clinical markers, sCr, total oxidant status (TOS), total antioxidant status (TAS) and PON1 activity were measured. RESULTS The AKI group had more newborns with hypoxic ischemic encephalopathy, significantly higher serum creatinine (sCr) at 3 and 7d, total antioxidant status (TAS) at 7d; decreased PON1 at 4h, 6h and 7d than the non-AKI group. Within the AKI group, significant positive correlations were found between PON1 activity at 2h and TAS at 2h, PON1 activity at 4h and base deficit (BD); whereas negative correlations between PON1 activity at 2h and ΔsCr (at 24h and at 3d), PON1 activity at 7d and ΔsCr (at 24h and 3d). Oxidative stress status parameters indicated excellent discriminative potential at 4h, 6h and 7d. CONCLUSIONS AKI neonates were characterised by a marked decrease in PON1 activity. PON1 activity may be an important factor for discrimination of newborns having AKI from those that do not.

Acute oliguric renal failure in hypoxic neonates born at full term

Abstract Background: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. Methods: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. Results: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = −0.423; p = 0.025) in the group with hypertension. Conclusions: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.