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

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.

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

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.

[Aminoglycoside trough levels in neonates].

INTRODUCTION: Drug safety depends on trough levels. OBJECTIVE: Objective of the study was to measure gentamicin and amikacin trough levels in neonates and to identify risk groups by gestational and postnatal age. METHODS: Gentamicin and amikacin were applied according to the clinical practice guidelines. Trough levels (mg/l) were determined using fluorescence polarization immunoassay methodology. Target trough levels were <2 mg/l for gentamicin, and <10 mg/l for amikacin. Patients were divided in 3 groups by gestational age: I < or =32, II 33-36, and III > or =37 gestational weeks and, by postnatal age, in 2 groups: < or =7 and >7 days. RESULTS: Out of 163 neonates, 111 were receiving gentamicin and 52 amikacin. Mean amikacin trough level was 7.8 +/- 4.8 mg/l and, in group 110.5 +/- 4.9 mg/l, which was above the target range and significantly higher than in group II (LSD, p < 0.05). In the amikacin group, 26 patients were 7 and less, and 26 more than 7 days old, without significant differences in trough levels between the groups. In the gentamicin group, 52.3% of neonates had trough values within the target range. Gentamicin trough level in group I was above the trough range, 3.7 +/- 1.8, 2.3 +/- 1.5 in group II and, 1.8 +/- 1.4 mg/l in group III. The difference in trough levels among the groups was highly significant (F = 9.015, p < 0.001, chi2 = 17.576, p < 0.001). Further analysis revealed that differences between groups I and II (LSD, p = 0.002) and between I and III (LSD, p = 0.000) were highly significant. CONCLUSION: Obtained gentamicin and amikacin trough levels are high. Inverse correlation has been confirmed between trough level and gestational age, with highly significant difference, and the risk group has been identified. There is obviously a need to change the dosing regimen in terms of those with extended intervals, particularly for neonates of the lowest gestational age, along with pharmacokinetic measurements.

[Acute oliguric renal failure in hypoxic neonates born at full term]. / Oligurijska akutna insuficijencija bubrega kod hipoksicnog novorodjenceta rodjenog u terminu.

INTRODUCTION: Acute renal failure (ARF) is a frequent clinical condition in neonatal intensive care units (NICU). The leading cause of neonatal ARF is perinatal asphyxia (PS). The aim of this study was to examine the relationship between the degree of PS and the severity of ARF in term neonates. METHODS: A prospective survey of 31 term neonates with Ps and but without congenital malformations or sepsis was performed in NICU of the regional Hospital of Gynaecology and Obstetrics in Belgrade (average number of deliveries about 6000 per year). ARF was diagnosed in the first 7 days of life when plasma creatinine was above 133 mumol/L for at least 48 hours while maternal renal function was normal. The degree of PS was determined according to Apgar score (AS) at 1 min. The severe PS was defined as AS < 3 and moderate PS as AS 4-6. RESULTS: Twenty neonates (64%) had oliguric ARF with urine output of 0.37 +/- 0.16 ml/kg/h while the others had nonoliguric ARF with urine output of 2.4 +/- 0.7 ml/kg/h. Most of neonates with oliguric ARF (65%) had severe perinatal asphyxia while in those with nonoliguric ARF moderate perinatal asphyxia predominated (73%). DISCUSSION: During hypoxic-ischaemic events many organs are injured, and the most vulnerable ones are kidneys and central nervous system. Our results showed a strong connection between perinatal asphyxia and A, which was in accordance with the results of other studies. Neonates with severe perinatal asphyxia had serious impairment of renal function, which was confirmed with strong correlation between Apgar score and plasma creatinine. In neonates with oliguric ARF, but not in those with nonliguric ARF, the highly positive linear correlations were found between AS and urinary output (r = 0.77; p < 0.01), plasma creatinine (r = 0.78; p < 0.01), fractional excretion of sodium (r = 0.76; p < 0.01), and index of renal failure (r = 0.80; p < 0.01). Only in oliguric neonates with severe perinatal asphyxia (31%) the outcome was fatal. CONCLUSION: We conclude that in tgerm neonates with severe perinatal asphyxia oliguric ARF was the predominant type of ARF. There is a good prediction of the severity of oliguric ARF according to the degree of perinatal asphyxia determined by Apgar score at 1 min.