极低出生体重早产儿动脉导管未闭的治疗

目的探讨极低出生体重早产儿有临床表现的动脉导管未闭的治疗方法方法 本研究为前瞻性队列研究.2008年1月1日至2010年12月31日间出生体重＜1500 g的确诊有临床表现的动脉导管未闭早产儿78例,其中42例采用口服吲哚美辛治疗者作为治疗组,36例未治疗者为对照组.观察吲哚美辛的疗效、副作用以及对早产儿的近远期预后.结果治疗组及对照组在性别比例、胎龄、动脉导管直径、合并心力衰竭、败血症、新生儿呼吸窘迫综合征、脑室内出血的差异均无统计学意义(P均＞0.05).治疗组治疗后动脉导管关闭33例,关闭率为78.6%,高于对照组,自发关闭9例,关闭率25.0%,差异有统计学意义(χ2=22.39,P=0.000).治疗组治疗前后的血肌酐、血小板差异无统计学意义(P均＞0.05).治疗组较对照组有较少的脑室内出血发生比例(z=1.167,P=0.030)、较短的总用氧时间[分别为(8.0±5.5) d和(13.3±9.3) d,t=2.225,P=0.032]及住院时间[(39.0±7.7) d和(43.6±10.6) d,t=2.229,P=0.029],且支气管肺发育不良、坏死性小肠结肠炎的发生情况组间差异无统计学意义(P均＞0.05).治疗组中有5例药物治疗失败后使用胸腔镜钳闭动脉导管,术后3例发生肺部感染,1例出现胸腔积液,无死亡及气胸发生.结论极低出生体重早产儿有临床表现的动脉导管未闭应积极干预,口服吲哚美辛可有效关闭动脉导管,胸腔镜钳闭动脉导管可作为药物治疗失败后的一种选择.

Abstract：

Objective To investigate the treatment of symptomatic patent ductus arteriosus (PDA) in very low birth weight preterm infants. Methods From January 1, 2008 to December 31, 2010, 78 very low birth weight preterm infants (birth weight＜1500 g) were diagnosed as symptomatic PDA. Among which, 42 cases administered orally with indomethacin (0.2 mg/kg, every 12 hrs for three times) were taken as treatment group, while five cases in this group who failed to indomethacin treatment were interrupted with video-assisted thoracoscopic surgery. And 36 cases who did not receive treatment for ductus arteriosus were taken as control group. The clinical outcomes, complications and prognosis of these patients were observed. Results There were no significant differences between the gentle percentage, gestational age, diameter of ductus arteriosus, rate of complicated with heart failure, sepsis, neonatal respiratory distress syndrome and intraventricular hemorrhage of two groups (P>0.05, respectively). The ductus arteriosus closed in 33 patients of treatment group (78.6%) and in nine patients of control group (25.0%)(χ2=22.39,P=0.000). There were no significant differences in serum creatinine level and platelet count between before and after the treatment in treatment group(P>0.05). Compared with control group, the treatment group had lower incidence of intraventricular hemorrhage (z=1.167, P=0.030), shorter duration of oxygen therapy [(8.0±5.5) d vs (13.3±9.3) d, t=2.225, P=0.032] and shorter hospital stay [(39.0±7.7) d vs (43.6±10.6) d, t=2.229, P=0.029]; while the incidence of bronchopulmonary dysplasia and necrotizing enterocolitis were similar (P>0.05). The five cases of PDA who received video-assisted thoracoscopic surgery were successfully interrupted with no residual shunt left, while three of them had lung infections and one had pleural effusion, but no pneumothorax and infant death associated with surgery occurred. Conclusions Symptomatic PDA of very low birth weight preterm infants should be treated actively. Oral indomethacin was an effective and safe method to cure the PDA in these infants. Surgical ligation under video-assisted thoracoscopic surgery after failure of indomethacin treatment might be a good option.     

Efficacy and safety of rectal ibuprofen for patent ductus arteriosus closure in very low birth weight preterm infants

Background: To compare rectal ibuprofen with oral ibuprofen for the closure of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants.

Study design and subjects: In a prospective, randomized study, 72 VLBW infants who had hsPDA received either rectal or oral ibuprofen. The plasma concentration of ibuprofen and renal functions were determined in both groups by the high-performance liquid chromatography (HPLC) method and cystatin-C (cys-C), respectively.

Results: The hsPDA closure rate of the group that received rectal ibuprofen was similar to oral ibuprofen (86.1% versus 83.3%) after the first course of the treatment (p?=?0.745). A statistically significant difference was identified between the mean plasma cys-C levels before and after treatment in both the rectal and oral ibuprofen groups (p?=?0.004 and pp?>?0.05 for all values).

Conclusions: Rectal ibuprofen is as effective as oral ibuprofen for hsPDA closure in VLBW infants. The rise in the cys-C level with rectal and oral treatment shows that patients with borderline renal function should be evaluated and followed closely.     

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

BACKGROUND: Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA). OBJECTIVE: To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with that of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected. METHODS: Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender. RESULTS: Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients. CONCLUSION: In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.     

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

BACKGROUND: Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA). OBJECTIVE: To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with that of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected. METHODS: Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender. RESULTS: Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients. CONCLUSION: In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.     

Fluid regimens in the first week of life may increase risk of patent ductus arteriosus in extremely low birth weight infants.

BACKGROUND: High fluid volumes may increase neonatal morbidity. However, evidence supporting fluid restriction is inconclusive and restricting fluids may restrict caloric intake. OBJECTIVE: To determine if higher fluid intake was associated with increased risk of patent ductus arteriosus (PDA) or bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. STUDY DESIGN: A total of 204 ELBW (170 ml kg(-1) day(-1)) in the first days of life is associated with increased risk of PDA.     

Antenatal exposure to magnesium sulfate and the incidence of patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVE: Magnesium sulfate (MgSO(4)) is the most commonly used tocolytic agent in the US and is also employed as a prophylactic agent against seizures in pre-eclamptic women. MgSO(4) crosses the placenta and its concentration in the newborn usually exceeds that of maternal levels. The purpose of this study was to explore the relationship between antenatal exposure to MgSO(4) and the incidence of patent ductus arteriosus (PDA) in extremely low birth weight infants. STUDY DESIGN: A total of 954 neonates with birth weights between 500 and 1000 g, born at the University of Miami/Jackson Memorial Hospital between January 1995 and December 2004 and surviving for more than 3 days, were followed until death or discharge from the hospital. The incidence of PDA in infants exposed to MgSO(4) was compared with those not exposed and comparisons were also made between infants exposed to different maternal doses of MgSO(4). RESULTS: The incidence of PDA was significantly higher in the group of infants exposed to MgSO(4) compared with the unexposed control group (67 vs. 60%, P<0.018). When stratified by gestational age the differences were significant only in the group of infants with a gestational age of >or=26 weeks (58 vs. 49%, P<0.039). Logistic regression analysis to adjust for co-variables indicated an increased risk of PDA with higher doses of MgSO(4) (odds ratio 1.33 confidence interval (CI) 1.12 to 1.58, per 50 g of MgSO(4)). CONCLUSION: Antenatal exposure to MgSO(4) is associated with a higher risk of PDA in extremely low birth weight infants and this effect is more significant and dose-related in more mature infants.     

Fluid management during the first postnatal day in very low birth weight neonates and rates of patent ductus arteriosus requiring treatment

Purpose: Previous studies have suggested an association between high maintenance fluid volumes during the first several postnatal days and patent ductus arteriosus (PDA) requiring treatment in very low birth weight (VLBW) neonates. However, no studies have specifically examined fluid administration during the first postnatal day with regard to PDA-related outcomes. We seek to determine whether additional intravenous fluid administration beyond prescribed goals during the first postnatal day is associated with PDA requiring treatment.

Materials and methods: Retrospective data were collected from neonates with birth weight <1250?g. Infants receiving fluids beyond initially documented goals, stratified by relative degree of additional fluids, were compared to those receiving no additional intravenous fluids for the primary outcome of PDA requiring treatment and secondarily for other neonatal morbidities.

Results: Two hundred VLBW neonates were included. Controlling for birth weight and gestational age, fluid administration beyond prescribed goals during the first postnatal day was not associated with increased PDA requiring treatment. Additionally, no statistically significant associations between additional fluids and secondary outcomes were observed.

Conclusions: No significant relationship between fluid volumes during the first postnatal day and PDA requiring treatment were observed. Further prospective analysis of early fluid management in VLBW neonates is warranted.     

Nutrition in very very low birth weight infants

The VVLBW infant's limited nutritional reserves, high requirements for normal growth and development, and gastrointestinal immaturity pose a particularly challenging nutritional problem. Given the potential consequences of inadequate or inappropriate nutritional management, we are obligated to make nutrition a high priority in the overall care of VVLBW infants.     

Catheter-based closure of the patent ductus arteriosus in lower weight infants

Risks associated with drug therapy and surgical ligation have led health care providers to consider alternative strategies for patent ductus arteriosus (PDA) closure. Catheter-based PDA closure is the procedure of choice for ductal closure in adults, children, and infants ≥6 kg. Given evidence among older counterparts, interest in catheter-based closure of the PDA in lower weight (<6 kg) infants is growing. Among these smaller infants, the goals of this review are to: (1) provide an overview of the procedure; (2) review the types of PDA closure devices; (3) review the technical success (feasibility); (4) review the risks (safety profile); (5) discuss the quality of evidence on procedural efficacy; (6) consider areas for future research. The review provided herein suggests that catheter-based PDA closure is technically feasible, but the lack of comparative trials precludes determination of the optimal strategy for ductal closure in this subgroup of infants.     

Outcome of very very low birth weight infants

This review of the literature and selected unpublished data documents normal early outcome in 50 to 81 per cent of tiny infants. Educational outcome described by a few studies is less encouraging, with only 32 to 36 per cent considered normal. Each study investigated the contribution of different perinatal, environmental, or social variables, therefore it is difficult to determine which has most impact on neurodevelopmental outcome.     

Echocardiographic assessment of patent ductus arteriosus in very low birthweight infants over time: prospective observational study

Background: We aimed to determine the echocardiographic parameters that can predict the presence of patent ductus arteriosus (PDA) and haemodynamically significant ductus arteriosus (HSDA) at different time points.

Methods: Echocardiogram was performed on postnatal days 3 and 7(D3-Echo and D7-Echo, respectively) in 71 very low birthweight infants with a median gestational age of 28.0 weeks. We first assessed the correlation between D3-Echo findings among infants with ductal patency and persistent ductal patency on D7-Echo. We subsequently assessed the correlation between D7-Echo findings and ultimate need for PDA treatment.

Results: Forty-nine (69.0%) infants had ductal patency on D3-Echo, and 32(65.3%) of these had persistent PDA on D7-Echo. Twenty of the latter (62.5%) underwent PDA treatment at a median chronological age of 19 days. PDA treatment was significantly correlated with DA size and DA peak-systolic-to-end-diastolic velocity(S/D) ratio on D3- and D7-Echo. Receiver operating characteristic curve analysis revealed that DA size?≥2.040?mm and S/D ratio?≥2.016 had fair sensitivity, specificity, and predictive values for PDA treatment.

Conclusion: The significance of different echocardiographic parameters associated with future ductal patency or HSDA depends on the time of assessment. DA size and S/D ratio on day 7 are two reliable indicators of the need for future PDA treatment.     

An epidemiologic study of very low and very very low birth weight infants

VVLBW infants constitute only 1 per cent of the total births, but account for 60 per cent of the NMR and 40 per cent of the IMR. While improved technology and refinements in care continue to improve survival for VVLBW infants, questions regarding the lower limits of viability must be considered. The medical community can rightly take credit for improvement in outcome of infants with weight and gestations so small that, just a decade ago, they were considered nonviable; however, an excruciatingly slow pace of decline in the prematurity rate is an agonizing fact. Can anything be done to prevent prematurity and avoid its devastating consequences on the family and society? The recent French experience suggests the answer could be "yes." A similar experience also has been reported in the United States. Although VLBW NMR is a major fraction of total IMR, nearly one quarter of first-year deaths occur in infants who are over 2500 gm at birth. That the postneonatal death of normal birth weight infants is only next in magnitude to the neonatal death of VLBW infants further points to the need for developing preventive child health programs encompassing periods before and during the pregnancy, through the immediate peripartum period, and well into infancy and childhood. Neither a woman's pregnancy experience nor the concerns of the health community end with her taking a baby home.     

Oral ibuprofen in early curative closure of patent ductus arteriosus in very premature infants

Intravenous indomethacin and intravenous ibuprofen are widely used for the treatment of patent ductus arteriosus (PDA) in premature infants. Intravenous indomethacin may lead to renal impairment, enterocolitis, and intraventricular hemorrhage. Intravenous ibuprofen was shown to be as effective and to cause fewer side effects. If ibuprofen is effective intravenously, it will probably be effective orally, too. This study was conducted to test oral ibuprofen in early curative closure of PDA in very premature infants hoping for a better tolerance and the same efficacy as intravenous ibuprofen. Forty very premature infants (mean gestational age: 29.4 +/- 1 to 2 weeks [range: 26 to 31.5 weeks]; mean weight: 1237.2 +/- 198 g [range: 650-1770 g]) with PDA and respiratory distress were studied prospectively. They received, while between 48 and 96 hours old, oral ibuprofen at a dose of 10 mg/kg, followed, if needed, at 24-hour intervals by one or two additional doses of 5 mg/kg each. Color Doppler echography of the heart, brain, and abdomen were performed before treatment and after each dose administration. Ductal closure, early outcome (1 week after treatment), and late outcome were recorded. Thirty-eight patients (95%) achieved pharmacological closure. Two patients did not respond to the treatment: One required surgical ligation of the ductus, and the other patient received and well tolerated ductal shunting. Twenty-four patients were treated with one dose of oral ibuprofen, 10 were treated with two doses, and 6 were treated with three doses. Early outcome showed no case of renal impairment, no significant differences in serum creatinine levels, nine cases (22.5%) of intraventricular hemorrhage, three cases (7.5%) of necrotizing enterocolitis, and two cases (5%) of gastrointestinal bleeding. Late outcome showed 15 cases (37.5%) of nosocomial sepsis, 3 cases (7.5%) of chronic lung disease, 2 cases (5%) of periventricular leukomalacia, and 17 cases of death. In this study, oral ibuprofen was effective and well tolerated for early curative closure of PDA in very premature infants. Nevertheless, larger randomized comparative studies with pharmacokinetics measures are warranted.     

Pros and cons of patent ductus arteriosus ligation: hemodynamic changes and other morbidities after patent ductus arteriosus ligation

Although surgical ligation of a persistent patent ductus arteriosus resolves the adverse hemodynamic consequences of the systemic-to-pulmonary shunt and may confer some long-term benefits, it is also associated with both immediate and long-term negative effects. The population that benefits from or is harmed by the procedure is not clearly defined. Although indiscriminate ligation of the patent ductus arteriosus in all patients is not supported by the available information, the recent suggestion declaring the ductus harmless is not supported either. As we await the results of appropriately designed randomized control studies to define the indications for ligation, we must use clinical and echocardiographic indicators of a hemodynamically significant ductus arteriosus and thoughtful assessment of each individual patient to help guide us in addressing this complex problem.     

147例极低和超低出生体重儿胃肠道内喂养的影响因素

目的 分析影响极低出生体重儿(very low birth weight infant,VLBWI)和超低出生体重儿(extremely low birth weight infant,ELBWI)胃肠道内喂养的相关因素.方法 对147例出院前达到足量胃肠道内喂养,即奶量达到120 ml/(kg·d)的VLBWI和ELBWI的临床资料进行回顾性研究,分析影响胃肠道内喂养的相关因素.对服从双变量正态分布的资料,采用Pearson法进行相关性分析,否则采用Spearman法进行相关性分析;应用t检验进行单因素分析;应用多元线性回归探讨达足量胃肠道内喂养时间的影响因素.结果 147例研究对象的平均胎龄(31.0±2.0)周;平均出生体重(1246±185)g;达到足量胃肠道内喂养的时间为(24.4±10.5)d.单因素分析显示出生体重(r=-0.477,P=0.000)、胎龄(r=-0.405,P=0.000)、机械通气时间(r=0.393,P=0.000)、开奶日龄(r=0.318,P=0.000)、开奶量(r=-0.263,P=0.001)、第3天奶量(r=-0.412,P=0.000)及第7天奶量(r=-0.592,P=0.000)、新生儿呼吸窘迫综合征(t=3.368,P=0.001)、血糖异常(t=3.285,P=0.001)、败血症(t=3.244,P=0.001)、脐静脉置管(t=3.571,P=0.000)、应用氨茶碱(t=4.341,P=0.000)、光疗(t=3.054,P=0.003)与达到足量喂养时间相关.多元线性回归分析显示出生体重(t=4.175,P=0.000)、开奶日龄(t=2.851,P=0.005)、应用氨茶碱(t=2.231,P=0.027)、光疗(t=2.852,P=0.005)、败血症(t=3.895,P=0.000和第7天奶量(t=7.332,P=0.000)与达到足量喂养时间相关.结论 VLBWI和ELBWI的喂养不但受消化道成熟程度影响,还受其他胃肠道外相关因素的影响,因此应综合考虑临床各方面的具体情况,正确实施胃肠道内喂养.

Abstract：

Objective To summarize and analyze the impact factors on enteral feeding in very low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI). Methods A retrospective study was carried out in VLBWI and ELBWI who had achieved full enteral feeding prior to discharge. The impact factors correlated to the time of achieving full enteral feeding were analyzed. If the data underwent bi-variable normal distribution, they were analyzed with Pearson correlation test; otherwise they would be analyzed with Spearman correlation test. T test was used for single factor analysis and multiple linear regression analysis was carried out to determine the significant risk factors associated with the time of achieving full enteral feeding. Results One hundred and forty-seven infants with mean gestational age of (31.0±2.0) weeks, mean birth weight of (1246±185) g and mean time of achieving full enteral feeding of (24. 4± 10. 5) days were admitted. With the single factor analysis, it was found that birth weight (r=- 0. 477, P = 0. 000), gestational age (r = - 0. 405, P= 0. 000), mechanical ventilation duration (r= 0. 393, P = 0. 000), the time began to enteral feeding (r = 0. 318, P = 0. 000), initial milk volume (r = - 0. 263, P = 0. 001 ), the milk volume on the third day (r= -0. 412, P=0. 000) and the seventh day (r= -0. 592, P=0. 000),neonatal respiratory distress syndrome (t = 3. 368, P = 0. 001), umbilical catheterization (t = 3. 571,P=0. 000), abnormal blood glucose level (t=3. 285, P=0. 001), aminophylline using (t=4. 341,P=0. 000), phototherapy (t=3. 054, P=0. 003) and sepsis (t=3. 244, P=0. 001) were correlated to the time of achieving full enteral feeding. Multiple linear regression showed that the birth weight (t=4. 175, P= 0. 000), the time began to enteral feeding (t= 2. 851, P = 0. 005), aminophylline using (t=2. 231, P=0. 027), sepsis (t=3. 895, P=0. 000), phototherapy (t=2. 852, P=0. 005)and the milk volume on the seventh day (t= 7. 332, P=0. 000) were significantly correlated with the time of achieving full enteral feeding. Conclusions The enteral feeding of VLBWI and ELBWI was not only influenced by maturity of gastrointestinal tract, but also by other parenteral correlation factors. Multiple factors associated with all around clinical conditions should be considered when providing enteral feeding for VLBWI and ELBWI.     

The patent ductus arteriosus in term infants, children, and adults

During fetal life, the ductus arteriosus is a normal and essential structure that connects the pulmonary artery to the distal aortic arch, permitting right ventricular ejection into the aorta. After birth, with commencement of pulmonary blood flow and a 2-ventricle circulation, a variety of physiological and biochemical signals normally result in complete closure of the ductus. Persistent patency of the ductus arteriosus may impair systemic cardiac output and result in deleterious effects on the cardiovascular system and lungs. Although surgery is still the treatment of choice for most premature infants with patent ductus arteriosus (PDA), transcatheter techniques have largely supplanted surgery for closure of PDA in children and adults. This article is a review of the PDA in term infants, children, and adults, with focus on the clinical manifestations and management.     

Nephrotoxic medication exposure in very low birth weight infants

Abstract

Objective: To quantify exposure to potentially nephrotoxic medications among very low birth weight (VLBW) infants and determine the relationship of nephrotoxic medication exposure to acute kidney injury (AKI) in this vulnerable population.

Methods: We reviewed 107 VLBW infants who survived to discharge from April 2011 to March 2012 and measured exposure to the following nephrotoxic medications: acyclovir, amikacin, amphotericin B, gentamicin, ibuprofen, indomethacin, iohexol, tobramycin and vancomycin. Acute kidney injury was determined by the KDIGO guidelines.

Results: Exposure to ≥1 nephrotoxic medication occurred in 87% of infants. The most common exposures were gentamicin (86%), indomethacin (43%) and vancomycin (25%). There was an inverse linear relationship between birth weight and nephrotoxic medications received per day (R^2?=?0.169, p?<?0.001). Infants with AKI received more nephrotoxic medications per day than those who did not (0.24 versus 0.15; p?=?0.003).

Conclusions: VLBW infants are frequently exposed to nephrotoxic medications, receiving approximately two weeks of nephrotoxic medications before discharge or 1 for every 6?d of hospitalization. The greatest exposure occurred among the smallest, most immature infants and those who experienced AKI.