Neonatal Acute Kidney Injury Research Articles

ACUTE KIDNEY INJURY IN PRETERM NEONATES: PERINATAL RISK FACTORS

Introduction. Acute kidney injury (AKI) is the most threatening sign of the syndrome of multiple organ failure in critically sick neonates, especially under conditions of their preterm birth. The frequency of AKI diagnosis among patients at neonatal resuscitation units constitutes from 18 to 70 %. AKI in neonates is associated with a high risk of mortality, continuous hospitalization, unfavourable early and late consequences. Objective: to determine perinatal risk factors promoting formation of AKI in critically sick preterm neonates. Materials and methods. A retrospective analysis of findings from exchange prenatal records, case histories of labor and development of newborns was made in 46 critically sick preterm neonates evaluated by the modified NEOMOD scale more than 7 points. І group of the study included 23 infants with AKI signs, ІІ group of the study – 23 babies without AKI signs. AKI was diagnosed in neonates according to the recommendations of the International Group of Experts “Kidney Disease: Improving Global Outcomes” modified by J. G. Jetton and D. J. Askenazi (2015). In order to determine correlation between perinatal risk factors and AKI formation in children, a logistic regressive analysis was performed with calculation of odds ratio (OR) and its 95 % confidence interval (95 % CІ).Results. In the course of the study there was no statistical significance found concerning any separate unfavourable factor of anamnesis, somatic and gynecological maternal pathology associated with the formation of AKI in preterm neonates, though a tendency to higher frequency of their birth from mothers aged older than35, in case of infertility and cardio-vascular maternal pathology. Development of AKI in preterm neonates was found to be associated with the threat of spontaneous abortion available (OR 4.68; 95 % CІ 1.28-16.98, р=0.0189), threat of preterm labor (OR 5.64; 95 % CІ 1.31-24.32, р = 0,0203), anemia of mother (OR 5.31; 95 % CІ 1.49-18.84, р = 0.0097), as well as lacking of antenatal prevention of respiratory distress-syndrome (OR 4.68; 95 % CІ 1.29-16.98, р = 0.0189).Statistically higher associations of AKI were demonstrated in infants born earlier than physiological term of gestation, with intracranial hemorrhages (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451), early neonatal sepsis (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451), anemia (OR 6.75; 95 % CІ 1.26-36.03, р = 0.0254), hemorrhagic syndrome (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451) and decreased tolerance to food (OR 3.56; 95 % CІ 1.05-12.05, р = 0.0417). Statistically significant associations of AKI formation were found in critically sick preterm neonates with indications to fresh frozen blood (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451), erythrocytes (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451), loop diuretics (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451) and antibacterial drugs of carbapenems group (OR 5.6; 95 % CІ 1.04-30.21, р = 0.0451). Conclusions. AKI formation in critically sick preterm neonates is of a multifactor etiology, which is more associated with unfavourable development of gestational period, lack of antenatal steroid prevention of RDS, development of multiple organ failure after birth, and administration of potentially nephrotoxic therapeutic complex. Further studies will enable to create a comprehensive algorithm to predict AKI development in patients at the intensive care units considering possible perinatal risk factors.

Perinatal lipocalin-2 profile at the extremes of fetal growth

Background Lipocalin-2 (LCN-2) has been identified as an osteoblast-secreted hormone regulating immunity, inflammation and metabolic homeostasis and has emerged as a diagnostic and prognostic biomarker for acute kidney injury in neonates. We investigated the impact of fetal growth on antepartum maternal serum, cord serum and breast milk LCN-2 concentrations and the associations of the latter with perinatal parameters. Methods Maternal serum, cord serum and breast milk LCN-2 concentrations were measured by ELISA in samples from 80 mothers who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by customized weight centiles. LCN-2 concentrations were associated with birth weight, customized centile, gender, maternal age and delivery mode. Results Antepartum maternal serum LCN-2 concentrations were significantly higher in women delivering AGA infants compared to the other two groups. Cord blood LCN-2 concentrations were significantly higher compared to maternal ones; furthermore, they were significantly elevated in the IUGR group compared to the LGA one (p = .019). Lowest concentrations were detected in breast milk, which did not differ between the three growth groups. A negative correlation was documented between cord blood LCN-2 concentrations and customized centiles (r: −0.304, p = .007). Conclusions The higher cord serum LCN-2 concentrations, compared to maternal ones, may point to its fetal origin and potential role in intrauterine growth. The negative correlation of cord LCN-2 concentrations with customized centiles, possibly implies reduced nephron endowment/subclinical kidney damage in IUGR neonates. The extremely low LCN-2 breast milk concentrations could imply that the secretion of LCN-2 from maternal circulation to breast milk is not influenced by factors leading to intrauterine growth pathology.

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.

DOZ047.111: Acute kidney injury in esophageal atresia

Abstract Background Oesophageal atresia (OA) is characterized by a significant morbidity during the neonatal period. Affected infants are exposed to multiple potentially nephrotoxic factors, predisposing them to acute kidney injury (AKI), which is associated with poorer outcomes. Children who survive neonatal AKI are at risk of long-lasting renal complications (including chronic kidney disease and hypertension). Aims The purpose of this study is to investigate AKI prevalence in infants with OA and identify potential contributing factors. Methods Retrospective analysis was conducted on clinical records of patients with OA between 2017 and 2018 in a single referral centre. AKI severity was defined according to established international pRIFLE criteria (Risk of renal dysfunction, kidney Injury, Failure or Loss of kidney function and End-stage renal disease) based on change in serum creatinine and urine output during hospitalization collected 5 days after birth. Risk factors, (including potentially nephrotoxic medications, significant infection, urine output, blood pressure), and outcome data (length of hospitalization, duration of intubation) were recorded. Statistical analysis was performed using Graphpad. Results Thirty-nine OA cases were identified; 6 were excluded for lack of data and 33 were included in the study group. Eighteen (55%), who developed AKI (pRIFLE category Risk or Injury), were compared with 15 patients (45%) with no AKI. AKI was significantly higher in infants with long-gap OA (P = 0.02), significantly associated with vancomycin administration (P = 0.03), with the use of three or more antibiotics during hospitalization (P = 0.0005), and with postoperative muscle paralysis (P = 0.001). Infants with OA and AKI experienced longer mechanical ventilation (P = 0.004) and hospital stay (P = 0.003). No significant association was found with hypotension, or steroid exposure. Incomplete recording of urine output prevented stratification of AKI based on this parameter. Conclusions OA, particularly more severe cases, are at risk of AKI. Renal function should be routinely assessed, during hospitalization and follow-up. Focusing on prevention and avoiding prolonged courses of nephrotoxic medications may improve outcome.

Гостре пошкодження нирок у новонароджених після хірургічної корекції патології дуги аорти

Гостре пошкодження нирок у новонароджених після хірургічної корекції патології дуги аорти

Neonatal acute kidney injury in a tertiary care hospital in Kashmir, Jammu and Kashmir, India

Background: Acute kidney injury (AKI) is a common entity in neonates admitted to the neonatal intensive care unit (NICU). Neonatal AKI is associated with increased morbidity and mortality and a greater risk of chronic kidney disease among the affected ones in future. Objectives: The objectives of this study were to study the incidence and outcome of neonatal AKI in our NICU. Materials and Methods: This single-center retrospective study included all infants who were admitted in a tertiary care hospital, J and K, from June 2013 to May 2014. Neonates, who had known congenital kidney diseases or if they did not survive beyond the first 48 h of life or had a hospital stay for <24 h, were excluded from the study. AKI was defined according to the kidney disease: Improving global outcomes criteria. Both AKI and non-AKI neonates were followed up until NICU discharge. Outcomes studied included mortality and length of NICU stay. Results: A total of 1439 neonates were studied among whom 72.89% (1049/1439) were normal weight, 11.46% (165/1439) were low birth weight, and 15.63% (225/1439) were very low birth weight. Of 1436 studied, 72% (1036) were term babies and 28% (403) were preterm babies. Perinatal asphyxia accounted for 43% (620/1439), seconded by neonatal sepsis 31.6% (455/1439) as a cause of NICU admission. Incidence of neonatal AKI in our study was 8.33% (120/1439). Mortality rate among the neonatal AKI patients was 34.1% (41/120). Conclusion: Our study shows an incidence of 8.3% among the NICU patients with a high mortality rate of 34.1%, implying a heightened awareness and very close monitoring of renal function during hospitalization and after discharge in such infants.

Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review

ObjectiveTo compare the efficacy and safety of theophylline or aminophylline for prevention of acute kidney injury (AKI) in neonates and children.DesignSystematic review and meta-analysis with application of Grading of Recommendations,...

Application of continuous renal replacement therapy in treatment of neonatal acute kidney injury

Objective To explore the efficacy of continuous renal replacement therapy (CRRT) in the treatment of neonatal acute kidney injury (AKI). Methods Totally 17 critically ill neonates treated with CRRT were selected who were hospitalized at Department of Neonatology, Shanghai Children′s Hospital, Children′s Hospital Affiliated to Shanghai Jiaotong University, from June 2012 to June 2017, and among them there were 15 cases with AKI, and the clinical data of these 15 patients were retrospectively analyzed, while 15 AKI neonates were treated with CRRT combined with conventional treatment.The model for CRRT was continuous veno-venous hemofiltration dialysis (CVVHDF) in 13 cases, plasma exchange (PE) in 2 cases.The changes of blood pressure(BP), renal function, electrolyte, acid-base balance index and hemodynamic indicators were analyzed respectively before CRRT treatment, 12 h, 24 h, 48 h after treatment and by the end of CRRT treatment.The efficacy of CRRT treatment was evaluated in these 15 AKI neonates. Results Gestational age of 15 AKI newborns was 33+ 4- 40+ 1 weeks, admission day age was 2-28 days, birth weight was 2.25-4.00 kg.Primary diseases were severe asphyxia in 6 cases, neonatal septicemia in 5 cases, congenital hereditary metabolic disease in 2 cases, traumatic asphyxia in 1 case, and liver failure in 1 case.CRRT treatment persisted for 49-190 hours.BP value[(50.8±6.57) mmHg(1 mmHg=0.133 kPa)] could reach normal level after 12 h CRRT treatment, and blood pH value (7.31±0.25) increased significantly after 12 h CRRT treatment, while blood K+ [(5.51±1.86) mmol/L], urea nitrogen (BUN)[(9.5±3.7) mmol/L], creatinine(Cr)[(93±14) μmol/L] significantly decreased after 12 h CRRT treatment, and reached the normal range[K+ (4.78±2.95) mmol/L, BUN (7.5±2.1) mmol/L, Cr (54±13) μmol/L] after 24 h treatment, but urine volume[(0.8±0.2) mL/(kg·h)] significantly increased after 24 h treatment.Partial pressure of oxygen/fraction of inspired oxygen reached 200 mmHg after 12 h treatment and more than 300 mmHg after 24 h treatment.CRRT treatment of 15 AKI neonates turned out to be effective. Conclusions CRRT can effectively improve the internal environment of AKI neonates and reduce the death rate of neonatal AKI, which can provide an effective adjuvant treatment measures for the treatment of AKI neonates. Key words: Continuous renal replacement therapy; Kidney injury; Infant, newborn; Efficacy; Safety

Urinary NGAL and KIM-1 Are the Early Detecting Biomarkers of Preterm Infants with Acute Kidney Injury

Background: Acute kidney injury (AKI) is common in neonates. However, early diagnosis is difficult. Different biomarkers for early diagnosis of AKI, such as NGAL, KIM-1, Cys-C, IL-18, β2-microglobulin have been proposed. But regarding premature infant, there is very little research that has been reported. Objectives: To investigate the role of urinary NGAL and Kim-1 biomarkers for early diagnosis of AKI in premature neonates. Methods: Eighty cases were divided into experimental group (60 cases) and controls group (20 cases). Of 60 cases, 24 patients met the criteria for AKI group; the remaining 36 were non-AKI group. Blood and urine samples, 1 ml each, were collected from all subjects at first day, second day, third day and seventh day of life. Urine NGAL and KIM-1 were measured by ELISA. Results: The urinary NGAL and KIM-1 are significantly higher in AKI group than Non-AKI group and normal control group in the first three days. They present earlier than classical Scr. Conclusion: Urinay NGAL and Kim-1 are beneficial biomarkers for the early diagnosis of AKI in preterm neonates.

Chronic kidney disease following twin-to-twin transfusion syndrome-long-term outcomes.

Amongst other sequelae, acute kidney injury (AKI) is a well-recognised post-natal complication of twin-to-twin transfusion syndrome (TTTS). Despite this, there has been a lack of data reporting long-term renal outcomes. Our aim was to report the long-term renal outcomes of infants born with TTTS. We performed a retrospective case note review of all infants referred to our centre between 1998 and 2018 with a primary diagnosis of TTTS. Subjects with confirmed TTTS were divided into a chronic kidney disease (CKD) group and a non-CKD group for comparison. Twenty-six infants with TTTS were included for analysis. Eight (31%) subjects developed CKD. Within the CKD group, 50% went on to require long-term renal replacement therapy (RRT) of whom all underwent renal transplantation. For subjects who had neonatal AKI, cumulative survival rate before RRT at 5 and 10years was 79% and 70%, respectively. Subjects with CKD had a significantly higher incidence of AKI in the neonatal period and were more likely to be the donor twin. Gestational age at birth, gender, antenatal interventions and comorbidities did not affect long-term renal outcome between the two groups. This is the first long-term follow-up study demonstrating that CKD progressing to the need for RRT can develop after TTTS. Donor-twin status and neonatal AKI associated with adverse long-term outcomes warranting long-term surveillance in this group.

Late onset neonatal acute kidney injury: results from the AWAKEN Study.

Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d). The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor. Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection. Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.

An Update on Neonatal and Pediatric Acute Kidney Injury

The purpose of this review is to highlight the major advances of pediatric and neonatal acute kidney injury (AKI) research over the last 5 years with particular interest in describing renal physiology, the definition of AKI, risk factors, epidemiology, interventions, and outcomes. The utilization of standardized definitions of AKI has revolutionized our understanding of the incidence and impact of AKI. This has culminated in the seminal Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in critically ill children (AWARE), and Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) publications in pediatric and neonatal AKI, respectively. These studies have clearly shown an independent association of AKI with mortality in critically ill children and neonates. Recent work aimed at the prevention of AKI has demonstrated that nephrotoxic medication-induced AKI occurs commonly and can be prevented with protocolized renal function monitoring. This review also highlights advances in the early identification of patients at risk for the development of AKI via scoring systems (renal angina index), functional tests (furosemide stress test), or novel biomarkers. Furthermore, fluid overload has clearly been shown to impact outcomes in those with the most severe forms of AKI requiring renal replacement therapy. Recent single-center studies have highlighted that children with AKI are at increased risk of chronic kidney disease. The incidence and adverse impact of AKI on outcomes across critically ill pediatric and neonatal populations have been clearly established The importance of fluid overload in children with severe AKI requiring renal replacement therapy is clear. Children with AKI are at increased risk of chronic kidney disease and require long-term outpatient follow-up. As the impact of AKI has become clear, efforts have shifted to prevention of nephrotoxic-induced AKI, early identification, risk stratification (renal angina), and the development of novel biomarkers.

Subclinical acute kidney injury is associated with adverse outcomes in critically ill neonates and children

BackgroundResearch on acute kidney injury (AKI) has focused on identifying early biomarkers. However, whether AKI could be diagnosed in the absence of the classic signs of clinical AKI and whether the condition of subclinical AKI, identified by damage or functional biomarkers in the absence of oliguria or increased serum creatinine (sCr) levels, is clinically significant remains to be elucidated in critically ill children. The aims of the study were to investigate the associations between urinary cystatin C (uCysC) levels and AKI and mortality and to determine whether uCysC-positive subclinical AKI is associated with adverse outcomes in critically ill neonates and children.MethodsIn this prospective cohort study, uCysC levels were serially measured during the first week after intensive care unit (ICU) admission in a heterogeneous group of patients (n = 510) presenting to a tertiary neonatal and pediatric ICU. The diagnosis of neonatal AKI that developed during the first week after admission was based on neonatal KDIGO criteria or sCr >1.5 mg/dL, and pediatric AKI was based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The term “uCysC(−)” or “uCysC(+)”, indicating the absence or presence of tubular injury, was defined by the optimal peak uCysC cutoff value for predicting ICU mortality.ResultsThe initial and peak uCysC levels were significantly associated with AKI and mortality, and had an area under the receiver operating characteristic curve of 0.76 and 0.81, respectively, for predicting mortality. At the optimal cutoff value of 1260 ng/mg uCr, the peak uCysC displayed sensitivity of 79.2% and specificity of 72.3% for predicting mortality. Among all patients, 130 (25.5%) developed uCysC(+)/AKI(−) status during the first week after admission. The adjusted odds ratio for patients with uCysC(+)/AKI(−) status in association with an increased risk of mortality compared with that for patients with uCysC(−)/AKI(−) was 9.34 (P < 0.001). Patients with uCysC(+)/AKI(−) spent 2.8 times as long in the ICU as those with uCysC(−)/AKI(−) (P < 0.001).ConclusionsBoth initial and peak uCysC levels are associated with AKI and mortality and are independently predictive of mortality in critically ill neonates and children. Subclinical AKI may occur without detectable loss of kidney function, and uCysC-positive subclinical AKI is associated with worse clinical outcomes in this population.

Tubular dysfunction in extremely low birth weight survivors.

Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia. Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22-32) and 745g (range 316-999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-β-D-glucosaminidase-to-creatinine ratio (NAG/Cr), β2 microglobulin-to-creatinine ratio (β2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4-6years later. Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, β2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine β2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and β2m/Cr remained similar or increased. Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.

Maternal and environmental risk factors for neonatal AKI and its long-term consequences.

Acute kidney injury (AKI) is a common and life-threatening complication in critically ill neonates. Gestational risk factors for AKI include premature birth, intrauterine growth restriction and low birthweight, which are associated with poor nephron development and are often the consequence of pre-gestational and gestational factors, such as poor nutritional status. Our understanding of how to best optimize renal development and prevent AKI is in its infancy; however, the identification of pre-gestational and gestational factors that increase the risk of adverse neonatal outcomes and the implementation of interventions, such as improving nutritional status early in pregnancy, have the potential to optimize fetal growth and reduce the risk of preterm birth, thereby improving kidney health. The overall risk of AKI among critically ill and premature neonates is exacerbated postnatally as these infants are often exposed to dehydration, septic shock and potentially nephrotoxic medications. Strategies to improve outcomes - for example, through careful evaluation of nephrotoxic drugs - may reduce the incidence of AKI and its consequences among this population. Management strategies and updated technology that will support neonates with AKI are greatly needed. Extremely premature infants and those who survive an episode of AKI should be screened for chronic kidney disease until early adulthood. Here, we provide an overview of our current understanding of neonatal AKI, focusing on its relationship to preterm birth and growth restriction. We describe factors that prevent optimal nephrogenesis during pregnancy and provide a framework for future explorations designed to maximize outcomes in this vulnerable population.

Advances in diagnostic criteria and biomarkers for neonatal acute kidney injury

Acute kidney injury (AKI) has a high incidence in neonates. A variety of perinatal factors may contribute to neonatal AKI, resulting in short- and long-term adverse outcomes, including chronic kidney disease. Early diagnosis and timely treatment can significantly improve the outcomes of these babies. Diagnostic criteria for AKI in adults and children are inapplicable to neonates due to the specific pathophysiological characteristics in newborns. In addition, current diagnosis criteria for neonatal AKI are still inconsistent. These all make it more difficult to diagnose neonatal AKI accurately. New biomarkers for kidney injury, such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and interleukin-18, have been found valuable for early and accurate diagnosis and prognosis of neonatal AKI. However, more studies are required to clarify the influencing factors, diagnostic values and clinical significance of those biomarkers. Key words: Acute kidney injury; Biomarkers; Incidence; Infant, newborn

Timing and effectiveness of continuous renal replacement therapy for neonatal acute kidney injury

Objective To investigate the timing and efficacy of continuous renal replacement therapy (CRRT) in neonatal acute kidney injury (AKI). Methods Nineteen AKI neonates treated with CRRT were enrolled during hospitalization in the Department of Neonatology of the Children's Hospital of Shanghai from June 2011 to June 2018. Their clinical data were retrospectively analyzed. According to their baseline renal function, these neonates were divided into two groups using an improved RIFLE (Risk, Injury, Failure, Loss and End-stage renal disease) standard: AKI stage 1-2 group and AKI stage 3 group. CRRT included continuous veno-venous hemodiafiltration (CVVHDF) and plasma exchange (PE). Several parameters included blood pressure (BP), renal function, electrolyte, blood gas and hemodynamic indicators were analyzed before, 12 h, 24 h, and 48 h after the initiation of CRRT and at the end of CRRT. Changes in neonatal renal function before, 24 h after the initiation of CRRT and at the end of CRRT were compared between the two groups. Efficacy of CRRT was evaluated, and clinical outcomes were analyzed. Kruskal-Wallis H-test or t-test was applied for statistic analysis. Results (1) Among the 19 neonates with AKI, there were 12 in stage 1-2 and seven in stage 3. Seventeen cases were treated with CVVHDF, and the other two underwent plasma exchange. The duration of CRRT was 49-190 h with an average of (89.2±33.9) h. (2) After 12 h of CRRT, the blood pressure of all 19 AKI neonates returned to normal (40-60 mmHg, 1 mmHg=0.133 kPa) and was maintained at that level during the treatment. The blood pH value also increased to a normal range (7.35-7.45) at the same time. The oxygenation index reached 200 mmHg after 12 h of CRRT and rose to over 300 mmHg after 24 h. The levels of serum potassium, urea nitrogen, and creatinine decreased significantly after 12 h of CRRT and reached the normal range after 24 h of CRRT. After 24 h of CRRT, the urine volume significantly increased. (3) Serum levels of urea nitrogen and creatinine in neonates with AKI stage 1-2 decreased significantly after 24 h of CRRT. At any time points before and after CRRT (24 h before, 24 h after and at the end of CRRT), serum levels of urea nitrogen and creatinine in AKI stage 3 neonates were higher than those in AKI stage 1-2 neonates [urea nitrogen: (15.8±4.1) mmol/L vs (10.2±5.1) mmol/L, (11.5±2.4) mmol/L vs (6.3±2.3) mmol/L, (9.8±2.1) mmol/L vs (5.1±2.2) mmol/L, t=2.468, 2.226 and 2.171, respectively; creatinine: (184±32) μmol/L vs (152±26) μmol/L, (110±35) μmol/L vs (87±25) μmol/L, (63±12) μmol/L vs (44±9) μmol/L, t= 2.404, 2.423 and 3.972, respectively; all P<0.05]. (4) Venous catheterization was successful in the 19 AKI neonates. Three cases were complicated with thrombocytopenia, two with obstruction and two with hypotension during CRRT. Complications such as hypothermia, hemorrhage, thrombosis, and infection were not reported. (5) Among the 19 AKI neonates, 12 (including five of severe asphyxia, five of septic sepsis and two of inherited metabolic disorders and in metabolic crisis) were cured and discharged. The other seven cases (two in stage 1-2 and five in stage 3) lived through the oliguria stage but died after their family members gave up the treatment. Conclusions CRRT is a safe and effective management for neonatal AKI. The optimal opportunity for CRRT treatment in AKI neonates should be at stage 1-2. Key words: Acute kidney injury; Renal replacement therapy; Infant, newborn; Treatment outcome

Diagnosis of Acute Kidney Injury in Neonates: Can Urinary Biomarkers Help?

Diagnosing acute kidney injury (AKI) in a diverse population of newborns is challenging. Current definitions of AKI focus on changes in serum creatinine and urine output both of which are subject to maturational and physiological change in newborn populations. Changes in serum creatinine reflect a significant loss of renal function and are a late marker of AKI. This article summarises the current literature related to the use of urinary biomarkers for diagnosing AKI in newborn populations. There is a growing body of evidence that supports the use of novel urinary biomarkers for both diagnosing and predicting the occurrence of neonatal AKI. The possibility of an earlier, pre-clinical diagnosis of kidney damage affords opportunities for researchers and clinicians to develop strategies aimed at reducing the severity of kidney injury. Future definitions of AKI will likely incorporate these non-invasive and early markers of kidney injury as either adjuncts or alternatives to measures of the change in kidney function (i.e. serum creatinine). Further research needs to demonstrate a relationship between AKI diagnosed using novel biomarkers and important long-term adverse clinical outcomes such as hypertension and/or chronic kidney disease. In addition, studies which use urine biomarkers criteria to enrol infants that show improved process of care or important clinical outcomes will be needed before they are adapted into clinical care.

Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis.

Serum and urinary NGAL represent candidate biomarkers with high performance in the prediction of acute kidney injury in newborns with perinatal asphyxia. Before NGAL can be widely used in clinical practice, future large prospective studies are needed to define the optimal cutoffs and accurately determine which levels are suggestive of post-asphyxial acute kidney injury. What is Known: • Acute kidney injury is a major cause of morbidity and mortality in perinatal asphyxia. • Current markers are insufficient in predicting post-asphyxial acute kidney injury. What is New: • Area under the curve for serum and urinary neutrophil gelatinase-associated lipocalin is 0.818 and 0.899, respectively. • Neutrophil gelatinase-associated lipocalin is a useful marker for detecting asphyxiated neonates at risk of developing acute kidney injury.

Renal Support Therapy for Neonates: Challenges, Opportunities, and Growing Awareness

Recent reports of new dialysis machines designed for infants, data suggesting improved outcomes for patients starting chronic dialysis as neonates, and increased awareness of neonatal acute kidney injury (AKI) have all intensified interest in the successful provision of dialysis to neonates. The purpose of this review is to summarize research on neonatal renal support therapy (RST) published in the last year (2017) and to highlight both the active areas of investigation as well as the ongoing knowledge gaps and opportunities for future research. Recent studies cover a breadth of topics related to neonates with both AKI and chronic kidney disease requiring dialysis. New research comes from both single centers and large international cohorts. Topics include survival outcomes, infant hemodialysis, and differences between neonatologists’ and nephrologists’ attitudes about neonatal RST. Survival rates for neonates supported with RST are improving, but still are worse than those for older patients. Increased attention to this issue and the development of novel machines designed specifically for neonates will likely lead to increased RST use and better outcomes. Additional data about the right timing for interventions, strategies to decrease complications, and best practices to improve the care for these complex patients is much needed.