Acute Kidney Injury In Preterm Infants Research Articles

Factors associated with acute kidney injury among preterm infants administered vancomycin: a retrospective cohort study

BackgroundVancomycin (VCM) is a widely used antibiotic for the treatment of gram-positive microorganisms, with some nephrotoxic effects. Recent studies have suggested that piperacillin-tazobactam (TZP) aggravates VCM-induced nephrotoxicity in adults and adolescents. However, there is a lack of research investigating these effects in the newborn population. Therefore, this study investigates whether the concomitant use of TZP with VCM use increases the risk of acute kidney injury (AKI) and to explore the factors associated with AKI in preterm infants treated with VCM.MethodsThis retrospective study included preterm infants with birth weight < 1,500 g in a single tertiary center who were born between 2018 and 2021 and received VCM for a minimum of 3 days. AKI was defined as an increase in serum creatinine (SCr) of at least 0.3 mg/dL and an increase in SCr of at least 1.5 times baseline during and up to 1 week after discontinuation of VCM. The study population was categorized as those with or without concomitant use of TZP. Data on perinatal and postnatal factors associated with AKI were collected and analyzed.ResultsOf the 70 infants, 17 died before 7 postnatal days or antecedent AKI and were excluded, while among the remaining participants, 25 received VCM with TZP (VCM + TZP) and 28 VCM without TZP (VCM—TZP). Gestational age (GA) at birth (26.4 ± 2.8 weeks vs. 26.5 ± 2.6 weeks, p = 0.859) and birthweight (750.4 ± 232.2 g vs. 838.1 ± 268.7 g, p = 0.212) were comparable between the two groups. There were no significant differences in the incidence of AKI between groups. Multivariate analysis showed that GA (adjusted OR: 0.58, 95% CI: 0.35–0.98, p = 0.042), patent ductus arteriosus (PDA) (adjusted OR: 5.23, 95% CI: 0.67–41.05, p = 0.115), and necrotizing enterocolitis (NEC) (adjusted OR: 37.65, 95% CI: 3.08–459.96, p = 0.005) were associated with AKI in the study population.ConclusionsIn very low birthweight infants, concomitant use of TZP did not increase the risk of AKI during VCM administration. Instead, a lower GA, and NEC were associated with AKI in this population.

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

The association of rs187238, rs19465518 and rs1946519 IL-8 polymorphisms with acute kidney injury in preterm infants.

BackgroundInterleukin 18 (IL-18) promoter polymorphisms (−656G > T, −607C > A, and −137G > C) affect serum IL- 18 (sIL-18) levels and are associated with renal injury.PurposeThis study aimed to determine the diagnostic utility of sIL-18 and urine IL-18 (uIL-18) as biomarkers for acute kidney injury (AKI) and analyse the association of IL-18 polymorphisms to AKI in preterm infants.MethodsBlood and urine samples were collected from 56 preterm infants with AKI and 56 without AKI to measure serum creatinine (SCr), sIL-18, and uIL-18. Genotyping of polymorphisms was performed and analysed, with AUC-ROCs analysis used to evaluate the diagnostic utility of s-/uIL-18 levels.ResultsThe median sIL-18 and uIL-18 levels were significantly higher than those without AKI. For a cutoff of >132 pg/mL, the sIL-18 expression had sensitivity and specificity of 80.36% and 60.71%, respectively, while for uIL-18, a cutoff of >900.7 pg/mL had sensitivity and specificity of 51.79% and 78.57%, respectively. The odds ratio of sIL-18 and uIL-18 to predict AKI in preterm infants was 5.89 (95%CI:2.31–15.02) and 4.15 (95%CI:1.58–10.89), respectively. The polymorphisms −137G > C and −656G > T were significantly associated with sIL-18 expression.ConclusionSerum and urine IL-18 levels are risk factors for and a moderate predictor of AKI in preterm infants.

Effect of ibuprofen for hemodynamically significant patent ductus arteriosus closure on the development of acute kidney injury in preterm infants

Premature infants with hemodynamically significant patent ductus arteriosus (HSPDA) have a high risk of developing acute kidney injury (AKI) due to renal hypoperfusion and use of ibuprofen for duct closure. The aim of the study was to evaluate the effect of ibuprofen for the closure of HSPDA on the development of AKI in preterm infants depending on high dose of the drug on the first day of life. 40 preterm infants with HSPDA who were admitted for observation on the first day of life were examined. To close the ductus arteriosus, infants received restrictive therapy. In addition, 32 (80,0%) preterm infants on the first day of life were prescribed ibuprofen: 19 infants – in high dose (20 mg/kg), 13 infants – in standard dose (10 mg/kg). Clinical examination and treatment of preterm infants was carried out according to the generally accepted methods. Echocardiography with Doppler was performed at 5-11 hours of life and then daily to determine the size and hemodynamic significance of patent ductus arteriosus. Diagnosis and stratification of the severity of AKI were performed according to the criteria of neonatal modification of KDIGO, for which the concentration of serum creatinine and diuresis were studied. According to the results of the study, it was established that the frequency of AKI on the third and fifth days of life in preterm infants with HSPDA, who received ibuprofen in a high dose (20 mg/kg) on the first day, was 73.7% and 84.2%, respectively, which is 2.2 (OR=5.6; CI: 1,43-21,95; р&lt;0.02) and 2.5 (OR=10.67; CI: 2.31-49.31; р&lt;0.002) times, more often than in infants without such therapy. High dose of ibuprofen on the first day of life in preterm infants with HSPDA are most often associated with the development of stage I AKI on the third or fifth day of life, which was temporary in one third of patients. The use of a high-dose ibuprofen for HSPDA closure on the first day of life in preterm infants was significantly more often associated with foci of infection in the mother, large duct size and furosemide use.

Прогнозування ранньої діагностики гострого пошкодження нирок у недоношених дітей з гемодинамічно значущою відкритою артеріальною протокою

The development of acute kidney injury (AKI) in preterm infants with hemodynamically significant patent ductus arteriosus (HSPDA) is an additional burden on homeostatic mechanisms, leading to loss of fluid, electrolyte balance, and acid-base disturbance and increasing the risk of mortality by 50%. Therefore, early detection of AKI in preterm infants with HSPDA is extremely important in terms of improving treatment outcomes. Purpose — to create, evaluate and further analyze the binary logistic regression model of AKI on the background of HSPDA in premature infants. Materials and methods. The group of study participants consisted of 40 premature babies with HSPDA, who were admitted for treatment on the first day of life to the Department of Anesthesiology and Neonatal Intensive Care at MI «Dnepropetrovsk Regional Children's Clinical Hospital» Dnepropetrovsk Regional Council». On the third to fifth day of life, 23 (57.5%) patients were diagnosed with AKI. Clinical and laboratory examination included obstetric history, gestational age, weight, physical examination, clinical analysis of blood and urine, arterial blood oxygen saturation, biochemical methods — examination of urea, serum and urine creatinine, serum and urine sodium, serum potassium. The concentration index of creatinine, fractional excretion of sodium, glomerular filtration rate (GFR) according to the Schwartz formula were calculated. Instrumental methods of examination included echocardiography with Doppler, ultrasound Doppler of renal vessels, renal spectroscopy in the near infrared region. In order to preliminarily determine the diagnostic potential of some clinical'anamnestic and laboratory data, the parameters of the sample with AKI and the sample without this pathology were compared: in the case of interval scale the Mann–Whitney U-test was used, in the case of categorical scale — χ2-test or Fisher's exact test. Spearman's rank correlation was used to form the optimal set of input variables for regression modeling. The method of binary logistic regression was used to develop a diagnostic model of AKI development on the background of HSPDA in premature infants. Results. At the stage of exploratory data analysis (several dozen parameters of clinical and biochemical analysis of blood and urine, renal hemodynamics, renal oxygenation and therapeutic measures on the first day), as well as clinical and anamnestic data, it was found that AKI has a significant relationship with 14 interval ( maximum blood flow velocity in the interlobar renal artery, minimum blood flow velocity in the interlobar renal artery, resistance index in the interlobar renal artery, maximum blood flow velocity in the main renal artery, diameter of the open arterial duct, renal oxygenation, fractional renal tissue extraction of oxygen, serum creatinine, GFR, creatinine concentration index, urinary sodium, fractional sodium excretion, urine protein, diastolic blood pressure) and 9 nominal values (the size of the patent ductus arteriosus on the first day of more than 2 mm, ibuprofen therapy at a dose of 20 mg/kg on the first day, ibuprofen therapy on the first day of life, furosemide treatment, history of renal disease in the mother, chronic foci of infection in the mother, hypertension of pregnancy, threat of abortion, necrotizing enterocolitis in the patient on the first day of life). Conclusions. The most significant predictors of AKI development in premature infants with HSPDA are the parameter of maximum blood flow velocity in the interlobar renal artery, HSPDA diameter greater than 2 mm and serum creatinine level on the first day of life. The sensitivity of the AKI logistic regression model, in which HSPDA diameter and serum creatinine level are used as explanatory variables, is 91%, specificity — 88%, overall accuracy — 90%. Replacement of serum creatinine in the logit function for the maximum blood flow velocity in the interlobar renal artery allows to increase the sensitivity of the model up to 96%, and the overall accuracy up to 93%. The study was conducted in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of parents of children was obtained for the research. The authors were declare no conflict of interest. Key words: hemodynamically significant patent ductus arteriosus, premature infants, acute kidney injury, prediction of early diagnosis.

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.

Acute kidney injury in the newborn infant: classification, causes and epidemiology

In the article are presented classifications, causes and epidemiology of acute kidney injury (AKI) in newborns, unsolved problems. Neonatal AKI classifications proposed by Acute Kidney Injury Network (2007), JG Jetton, DJ Askenazi (2012), modifications from NKC, KDIGO, and AWAKEN (2016), AKI Workshop (2017) are discussed. The results of the international assessment Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN), JG Jetton et al (2016, 2017) are discussed. Of the 2022 babies, 605 (30 %) had the status of AKI: in 48 % of the 273 preterm neonates with gestatoinal age 22-29 weeks; 18 % of 916 preterm neonates with gestatoinal age 29-36 weeks; in 37 % of 833 neonates with gestatoinal age after 36 weeks. The risk factors for the development of early AKI in preterm infants include low gestational age and very low birth weight. According to international epidemiological studies, the development of AKI in premature newborns is the main and independent risk factor for mortality and the formation of chronic kidney disease. The absence of multicenter epidemiological studies of acute kidney damage in newborns in our country is still an unsolved problem. The solution of the problem facing the national neonatology should be aimed at ensuring a unified approach to the classifications of acute kidney damage, on studying epidemiology, features of development, course, and outcome of acute kidney damage of various etiologies, on developing algorithms for prevention, diagnosis and treatment in term and preterm infants.

Patent ductus arteriosus is associated with acute kidney injury in the preterm infant.

This study aimed to test the hypothesis that a patent ductus arteriosus (PDA) is independently associated with acute kidney injury (AKI) in neonates ≤ 28weeks gestation. Preterm infants with echocardiographic diagnosis of moderate-large PDA at age ≤ 30days were studied retrospectively. AKI, the primary outcome, was defined and staged according to serum creatinine using Kidney Disease Improving Global Outcomes (KDIGO) neonatal criteria. Its association with the timing and duration of PDA, non-steroidal anti-inflammatory drugs (NSAIDs) and other nephrotoxic exposures, gestational age, and other covariates was evaluated using mixed-effects logistic regression models. Acute Kidney Injury occurred in 49% (101/206) of infants. Moderate-to-large PDA was associated with any-stage AKI (OR 5.31, 95% CI 3.75 to 7.53), stage 1 (mild) AKI (OR 4.86, 95% CI 3.12 to 7.56), and stages 2-3 (severe) AKI (OR 10.9, 95% CI 5.70 to 20.8). NSAID treatment added additional risk for mild AKI (OR 2.45, 95% CI 1.61 to 3.71). Severe AKI was less likely when NSAID treatment was effective (OR 0.45, 95% CI 0.21 to 0.97) but not when ineffective (OR 1.63, 95% CI 0.76 to 3.50). Moderate-to-large PDA was strongly associated with all stages of AKI in preterm infants ≤ 28weeks of gestational age. Effective NSAID treatment decreased the risk of severe but not mild AKI. These differential effects reflect the balance between the renal benefits of PDA closure and the risk of NSAID toxicity.

Low Renal Oxygen Saturation at Near-Infrared Spectroscopy on the First Day of Life Is Associated with Developing Acute Kidney Injury in Very Preterm Infants

Background: Acute kidney injury (AKI) is a frequent complication in preterm infants, and the identification of early markers of renal hypoperfusion is a chief challenge in neonatal intensive care units. Objectives: To describe the association between early markers of cardiovascular function and renal perfusion with AKI occurrence in a cohort of preterm infants < 32 weeks’ gestation. Methods: 128 infants were prospectively included from birth to discharge. During the first day of life, we assessed cardiovascular function, systemic and organ blood flow by Doppler ultrasound, and monitored cerebral and renal regional oxygen saturation (rSO₂) using near-infrared spectroscopy (NIRS). These measures were analyzed in relation to developing AKI and serum creatinine (SCr) peak from day 2 to 7 of life. Results: 12 of 128 infants presented with AKI (9.4%). SCr peak was 155.3 ± 30.2 µmol/L in infants with AKI versus 82.0 ± 16.5 in non-AKI infants (p < 0.001). Among all measures of cardiovascular function and renal perfusion, low mean cerebral and renal rSO₂ during the first day of life and a low resistive index at renal artery Doppler were significantly associated with developing AKI. After adjustment for possible confounding factors, low renal rSO₂ on the first day of life remained associated with a high SCr peak from day 2 to 7 of life. Conclusion: Low renal rSO₂ values during the first day of life correlate with developing AKI in preterm infants < 32 weeks’ gestation. NIRS monitoring of renal function during adaptation seems promising, and its very early use after birth to detect kidney hemodynamic dysfunction deserves further investigations.

Early urinary biomarkers of acute kidney injury in preterm infants.

Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

Can peritoneal dialysis be used in preterm infants with congenital diaphragmatic hernia?

Peritoneal dialysis (PD) is considered as the most common form of renal replacement therapy for newborns including preterms with acute kidney injury (AKI). Although there are several reports describing successful PD performed for AKI in preterm infants, there is no data describing the use of PD to treat AKI in preterm newborns with congenital diaphragmatic hernia (CDH), which is one of the contraindications for PD.We present a preterm newborn with CDH, truncus arteriosus and AKI treated with PD and emphasize that PD may be successfully performed with caution even in cases of contraindications when other renal replacement therapies cannot be used.