Search Results (30)

Background and Objectives: The long-term renal and cardiovascular effects of neonatal acute kidney injury (AKI) in preterm infants remain unclear. This study investigated whether neonatal AKI leads to persistent subclinical kidney injury and blood pressure changes in school-aged children born preterm. Methods: In this prospective cohort, preterm-born children (≤35 weeks’ gestation) with (n = 19) and without (n = 38) neonatal AKI were evaluated at 7–12 years. A term-born control group (n = 44) was included for biomarker comparison. Assessments included perinatal data, anthropometry, office and ambulatory blood pressure monitoring (ABPM), and renal ultrasonography. Kidney function was evaluated using serum creatinine (sCr), cystatin C, and estimated glomerular filtration rate (eGFR). Tubular injury was assessed using urinary kidney injury molecule-1/Cr (KIM-1/Cr), neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr), and trefoil factor 3/Cr (TFF3/Cr) ratios, as well as serum TFF3. Results: Conventional kidney function markers were similar among groups. However, the AKI group had higher serum cystatin C, lower cystatin C–based eGFR, and elevated urinary KIM-1/Cr and NGAL/Cr compared to no-AKI and term controls. Serum TFF3 was also higher in the AKI group. ABPM revealed higher nocturnal systolic blood pressure and blood pressure load in the AKI group. Kidney size did not differ between preterm subgroups. Conclusions: Neonatal AKI in preterm infants is associated with subtle alterations and potential renal stress or injury at school age, detectable only with sensitive biomarkers and ABPM. Further prospective studies are needed to validate these biomarkers and determine their role in predicting long-term outcomes in preterm infants with neonatal AKI. Full article

Sepsis-associated acute kidney injury (S-AKI) represents a significant health problem associated with adverse outcomes. Our study aimed to assess the value of serum cystatin-C (sCysC) and TNF-α (rs361525) in combination for diagnosing S-AKI patients and predicting their adverse outcomes. The study included 100 critically ill neonates and 100 controls. Patients were categorized into an S-AKI group and a non-AKI group. TNF-α (−238, rs361525) genotyping was performed using RT-PCR, and sCysC was assessed using ELISA. Our study showed a fundamental difference in the genotype frequencies of TNF-α (−238, rs361525) and SNP between S-AKI and non-AKI patients. Furthermore, there was a significant relationship between cystatin C and TNF-α (−238, rs361525), where cystatin C was higher in patients with AA alleles than in patients with GA and GG alleles. Combining GA + AA genotypes with elevated serum cystatin-C levels can serve as a potential diagnostic and prognostic biomarker for AKI development in this population. The GA/AA genotypes independently predicted S-AKI risk (OR = 6.64, p < 0.001). At the same time, elevated sCysC (>9.4 mg/L) emerged as a sensitive biomarker (AUC = 0.848) and independent predictor of adverse outcomes. Collectively, these findings contribute to the growing field of personalized medicine and represent a strategic advantage, enabling prevention-focused care rather than the treatment of established disease. Full article

Background: Neonates, particularly those born prematurely or with low birth weight, face an elevated risk of developing Acute Kidney Injury (AKI) due to various factors. Perinatal and maternal considerations, often linked to preterm delivery, contribute to this heightened risk. Methods: A retrospective study of neonates admitted to the intensive care unit at a single Israeli Hospital who were diagnosed as having AKI. The study includes follow-up data on these children. Results: During the study period, 971 neonates were admitted to the Pediatric Intensive Care Unit (PICU), and 47 cases had a documented diagnosis of AKI. Thirty-four of them had available long-term data and were included in this analysis. A total of 13 out of 26 subjects with available blood pressure measurements had high blood pressure for their age percentile compatible with the definition of hypertension, and 6 out of 34 (17.6%) had proteinuria. Conclusions: These findings underscore the importance of increased clinical awareness and structured long-term follow-up for neonates who experience AKI. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

In neonates, estimation of the glomerular filtration rate is problematic, and assessment of renal impairment is challenging. Serum creatinine is a widely used marker, and urine output is an important vital parameter monitored in intensive care settings, particularly in unwell neonates. However, the rapid changes after birth with adaptation to the extrauterine environment is a unique situation in which absolute serum creatinine is not a reliable indicator of renal function. A rise in serum creatinine from the previous value during the neonatal period can be a result of worsening renal function in neonates but is dependent on many other factors. In addition, urine output can be difficult to measure in sick neonates during their intensive care stay. Despite a high prevalence of acute kidney injury (AKI) in preterm and/or unwell infants, the current definitions are not straightforward and do not take postnatal adaptation processes into account. The management of AKI is challenging in very young and small patients because the assessment of fluid status as well as balancing nutritional needs with fluid restriction can be problematic. The Australian Neonatal Medicines Formulary provides advice on drug dosing in the face of reduced renal function in neonates. Predictors (or long-term outcome, or recovery) after AKI diagnosis are still poorly described. Therefore, the diagnosis of neonatal AKI needs to be documented and transferred to the paediatrician responsible for the follow-up of the child. This educational review aims to give a perspective on neonatal kidney function and AKI, the relation of fluid balance and creatinine, the management of neonatal AKI and the consequences for drug dosing and long-term outcomes. Full article

Background/Objectives: Precision medicine is a state-of-the-art medicine tactic that tailors information about people’s genes, environment, and lifestyle to aid the prevention, diagnosis, and treatment of various diseases to provide an overview of the currently available knowledge and applicability of precision medicine in the diagnosis of different cases admitted to the NICU, such as encephalopathies, respiratory distress syndrome of prematurity, hemodynamic instability, acute kidney injury, sepsis, and hyperbilirubinemia. Methods: The authors searched databases, such as PubMed and PubMed Central, for the terms neonatal “precision medicine”, “personalized medicine”, “genomics”, and “metabolomics”, all related to precision medicine in the diagnosis of neonatal illness. The related studies were collected. Results: The review highlights the diagnostic approach that serves to implement precision medicine in the NICU and provide precision diagnosis, monitoring, and treatment. Conclusions: In this review, we projected several diagnostic approaches that provide precision identification of health problems among sick neonates with complex illnesses in the NICU; some are noninvasive and available in ordinary healthcare settings, while others are invasive or not feasible or still in ongoing research as machine learning algorithms. Future studies are needed for the wide implementation of artificial intelligence tools in the diagnosis of neonatal illnesses. Full article

Background/Objectives: Hemolysis has been associated with acute kidney injury (AKI) in infants and neonates after surgery involving cardiopulmonary bypass (CPB). Erythrocyte hemolysis and subsequent end-organ injury have been shown to be a complex process involving the liberation of multiple molecules that mediate the loss of nitric oxide and oxidative damage. This study assesses the association of multiple products of erythrocyte hemolysis with the evolution of AKI in neonates and infants undergoing CPB surgery. Methods: Blood and urine samples were collected at multiple time points before and after CPB and stored within an institutional biorepository. Twenty-one patients with AKI were matched with twenty-one non-Aki patients based on demographic and case complexity data. Results: Samples were analyzed for cell-free hemoglobin, heme, non-transferrin-bound iron, haptoglobin, hemopexin, and nitrite/nitrate. NGAL and KIM-1 were measured to index AKI. Cell-free hemoglobin was higher, haptoglobin was lower, and haptoglobin:hemoglobin ratio was lower in AKI compared to non-AKI patients. Conclusions: AKI in neonates and infants after CPB is associated with a pre and postoperative decrease in serum haptoglobin. These results confirm the need for future studies to prevent injury from hemolysis during CPB and potentially identify at-risk patients with decreased haptoglobin levels before surgery if delay is an option. Full article

Background: Acute kidney injury (AKI) is common in neonates with increased mortality and longer hospitalization. Few studies have evaluated AKI outcomes in relation to serum creatinine dynamics in neonates from the first day of life. Methods: We performed an observational, retrospective, single-center study on newborns admitted to the “Louis Turcanu” Emergency County Hospital for Children between 2014 and 2022. The cohort comprised 1106 neonates with their serum creatinine values recorded on the first day of life and at least another measurement taken at between days 2 and 7. We evaluated the outcomes of serum creatinine trends in relation to mortality, hospitalization and progression to chronic kidney disease. Results: Overall, 23.4% (259) of babies had an ascending trend of serum creatinine and on day 1 had higher urea levels, lower hemoglobin and thrombocytes, lower serum proteins and higher degrees of inflammation compared to the ones with descending trends. An ascending serum creatinine level trend was associated with increased neonatal AKI (nAKI) risk in the first seven days of 12.93 times and an increased overall nAKI risk of 4.07 times. Ascending creatinine trends independently increased mortality in the entire cohort by 1.92 times and by 4.65 times in the subgroup of patients without AKI. In the crude analysis, an ascending creatinine trend increased the risk of chronic kidney disease by 8.74 times and, in an adjusted model, only nAKI was an independent risk factor (8.57 times). Conclusions: Neonates are a high-risk population with prolonged hospitalization regardless of serum creatinine trend. Our study emphasizes the importance of monitoring serum creatinine trends in at-risk newborns, especially those with ascending serum creatinine trends in the first week of life. Only the ascending serum creatinine trend was independently associated with an increased risk of nAKI development and mortality. nAKI is a risk factor for progression to chronic kidney disease. Full article

Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care. Full article

Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the “Pius Brînzeu” Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals. Full article

This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted. Full article

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease. Full article

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain’s adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO₂ was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO₂ and PvO₂; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO₂ and SvO₂. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO₂ steps, but predominantly by hypoxemia at FiO₂ < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO₂ steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia. Full article

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children’s hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups (p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere’s test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass. Full article

Acute kidney injury (AKI) in neonates is associated with increased morbidity and mortality. Theophylline (a methylxanthine) has been shown to prevent neonatal AKI but is seldom used due to its unfavorable profile. Caffeine, another methylxanthine, is utilized ubiquitously to treat apnea of prematurity, but there are no randomized trials evaluating its efficacy in preventing neonatal AKI. This literature review aims to summarize the existing research pertaining to the relationship between caffeine and neonatal AKI. The review was conducted using Pubmed, Embase, Google Scholar, and Cochrane. Inclusion criteria incorporated empirical studies, being published in English, and being available electronically. All eight studies identified were included. Seven studies found caffeine-exposed premature neonates had lower rates of AKI than caffeine-unexposed neonates. Four found reduced AKI severity with caffeine exposure. One study included term neonates and did not find a difference in the AKI rate between caffeine-exposed and non-exposed babies. Limitations include exclusively observational studies, short study periods, heterogenous definitions of prematurity, and a lack of assessment of dose–effect relationships. In conclusion, premature neonates exposed to caffeine appear to have lower rates and potentially less severe AKI. Further research is needed before caffeine can be considered for use in the primary prevention of neonatal AKI. Full article