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Improving the quality of neonatal acute kidney injury care: neonatal-specific response to the 22nd Acute Disease Quality Initiative (ADQI) conference

Abstract

With the adoption of standardized neonatal acute kidney injury (AKI) definitions over the past decade and the concomitant surge in research studies, the epidemiology of and risk factors for neonatal AKI have become much better understood. Thus, there is now a need to focus on strategies designed to improve AKI care processes with the goal of reducing the morbidity and mortality associated with neonatal AKI. The 22nd Acute Dialysis/Disease Quality Improvement (ADQI) report provides a framework for such quality improvement in adults at risk for AKI and its sequelae. While many of the concepts can be translated to neonates, there are a number of specific nuances which differ in neonatal AKI care. A group of experts in pediatric nephrology and neonatology came together to provide neonatal-specific responses to each of the 22nd ADQI consensus statements.

Introduction

Acute kidney injury (AKI) is common in critically ill neonates and is associated with adverse outcomes including mortality and multiple measures of morbidity [1,2,3,4,5,6,7,8,9,10,11]. The impact of neonatal AKI on long-term kidney function is still being elucidated, but studies suggest AKI incurs risk above that of other, known chronic kidney disease (CKD) risk factors [12,13,14,15,16,17,18,19,20,21,22]. Despite these associations, care pathways, standard quality metrics/indicators, and strategies designed to optimize AKI care in neonates are lacking [23, 24].

The 22nd Acute Disease Quality Initiative (ADQI) conference was convened to provide a framework for care improvement in adults at risk for AKI. This group identified best practices in “prevention, identification, and care of patients with AKI” across the spectrum of health care settings. Their comprehensive recommendations were published in 2019 [25,26,27], providing much-needed guidance to support the delivery of high-quality AKI care. More importantly, it highlighted the role that quality improvement efforts have in the care of patients at risk for and with AKI.

Although many of the ADQI 22 recommendations can be directly applied to neonates, there are unique aspects to neonatal physiology and care processes that differ from adults necessitating a nuanced approach. Given the success that AKI care improvement processes have shown in adults, a multidisciplinary group of neonatal and pediatric nephrology providers was convened to provide neonatal-specific context and comments to each of the 22nd ADQI consensus statements. We recommend these guidelines be applied not only to the neonatal period but include the whole NICU hospitalization. The overarching goal of this report is to encourage and enable providers to develop a meaningful quality improvement kidney health program in their NICU. Understanding the best strategies to reduce the short and long-term consequences of AKI in neonates [28,29,30] through quality improvement should be studied and shared across the world.

Community health care standards for AKI

Question 1: What are the roles and responsibilities of clinicians and health care systems in AKI risk monitoring and mitigation?

Consensus Statement A. Health care systems and professionals should identify populations and patients at risk of AKI and implement monitoring and preventive interventions to decrease the incidence of AKI.

Consensus Statement B. A minimum set of baseline risk factors and acute exposures should be considered for AKI risk stratification.

Neonatal patients, (age 0–28 days), can develop AKI in the community if they are born at home, or after their initial hospital discharge. At the community level, caregivers should identify maternal and neonatal factors known to increase the risk of neonatal AKI. Maternal factors can be divided into three different time frames: pregestational, gestational, and the peripartum period (Table 1) [31]. In an analysis of the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) study, a 24-center multinational observational cohort of infants admitted between January 1, 2014, to March 31, 2014, who were <14 days of age and received at least 48 h of intravenous fluids, Charlton et al. found that 21% of the neonates developed AKI during the first postnatal week at a mean age of 2.8 days [5], suggesting that maternal factors and perinatal events contributed significantly to AKI. They also found that among babies who met study criteria and were admitted to a referral NICU, the odds of being outborn was higher than being inborn.

Table 1 Maternal risk factors for neonatal AKI.

The two biggest risk factors for neonatal AKI, premature birth, and low birth weight, fall into all three time frames [8]. Both of these risk factors increase AKI risk through a common pathway: impaired nephrogenesis and reduced nephron endowment, which leads to impaired renal tubular function (with associated fluid and electrolyte balance dysregulation and dehydration) and low glomerular filtration rate (GFR) [31]. Both of these effects limit renal reserve that help maintain GFR during acute stressful events like the inability to feed appropriately and diarrhea, both of which can cause significant dehydration and lead to AKI, especially in resource-poor environments. Other common AKI risk factors include dehydration in neonates with high insensible water loss, certain medication combinations like vancomycin and piperacillin–tazobactam, and neonates with shock from either adrenal hyperplasia or congenital heart disease. These are not an exhaustive list of risk factors, but just a few common situations in which interventions, therapeutics, and screening can prevent or change the course of AKI.

Developing strategies aimed to mitigate maternal factors that lead to neonatal AKI before delivery may be critical to improving outcomes. We support ongoing community strategies targeting the prevention of preterm birth and fetal growth restriction, as these are the most important risk factors for neonatal AKI. Awareness and early identification of dehydration in neonates who are not feeding well, and/or have excessive stool losses is imperative. Strategies for primary prevention should target not only neonatologists and pediatricians but also family medicine, obstetric, and maternal-fetal medicine providers.

Question 2: How should AKI high-risk populations be monitored?

Consensus Statement A. Populations/patients at high risk for developing AKI should have a Kidney Health Assessment (KHA) at least every 12 months to define and modify their AKI risk profile.

Consensus Statement B. High-risk patients have another KHA at least 30 days before AND again 2–3 days after a planned exposure that carries AKI risk.

Consensus Statement C. Clinicians should review a patient’s KHA immediately after an unplanned acute exposure that carries AKI risk.

These adult-based recommendations suggest that at-risk patients should have a Kidney Health Assessment (KHA) yearly, and before or during an illness/procedure known to carry a high risk of AKI. The group agrees that a neonatal (nKHA) assessment should target neonates at high risk for AKI (Table 2). With regards to timing, with the neonatal period being 28 days, the yearly recommendation does not apply. We believe that a routine nKHA should be performed within 48 hours of birth in high-risk neonates. We also suggest that high-risk neonates have periodic assessments, weekly for the first month, then monthly until the patient is ready for discharge. The group agrees that the nKHA assessment should be undertaken before high-risk procedures, surgeries, and exposure to nephrotoxic medications known to be associated with AKI (Table 3). This assessment could help determine if appropriate preventive measures should be implemented (i.e., hydration before high-risk events). The group agrees with the adult recommendation that a repeat nKHA should occur 48–72 h after high-risk procedures, surgeries, exposures, and more often as necessary. A clinician with the appropriate training and context should review the nKHA immediately after it is performed in association with a high-risk event.

Table 2 High-risk neonates.
Table 3 High-risk procedures and states.

The components of this assessment were operationalized as ABCDD, including (1) AKI history, (2) Blood pressure determination, (3) Creatinine measurement, (4) Drug list review, and (5) Dipstick of urine. Although we agree in principle with the KHA, we suggest that the nKHA only include: AKI history, Blood Pressure measurement according to the American Academy of Pediatrics (AAP) guidelines [32], Creatinine measurement and Drug list review (or ABCD evaluation, Fig. 1). The group believes that the urinalysis should not be mandatory in neonatal patients for both clinical and biological reasons. Pragmatically, a clean sample is difficult to obtain in neonates via bag collection technique and sampling. Biologically, many premature neonates and term neonates during the first few weeks have high rates of physiologic transient proteinuria and even asymptomatic transient hematuria [33,34,35]. Although we do not recommend urine analysis, the assessment of specific gravity or urine osmolality may have a role in the management of AKI to determine if the neonate can concentrate urine which may help assist in development of a fluid management strategy [36].

Fig. 1: ABCD evaluation and 4Ms.
figure1

KHA and response. KHA includes AKI history, BP, CKD, serum creatinine level, Drug list and urine dipstick (ABCD). Exposures include nephrotoxic medications, imaging, surgery, sickness (NISS). KHR (4Ms) that encompasses medication review to withhold unnecessary medications, the minimization of nephrotoxic exposures, messaging the health care team and patient to alert the high risk of AKI, and monitoring for AKI and its consequences. Reprinted from Acute Disease Quality Initiative (ADQI) [25], with permission.

Question 3: How can AKI preventive strategies be implemented within high-risk populations?

Consensus Statement A. KHA should be followed by a Kidney Health Response (KHR) after acute exposure to risk factors of AKI.

Consensus Statement B. We suggest raising awareness of the definition, signs, symptoms, and acute exposures associated with AKI among clinicians and high-risk patients/populations.

Consensus Statement C. We suggest enhanced coordination between all stakeholders to monitor the rate, causes, and outcomes of AKI to identify variations in care and outcomes across and between the populations.

We strongly agree with these strategies to prevent AKI in neonates. The 22nd ADQI report underscores the fact that the KHA is a snapshot of the current state of kidney health, and assessment and evaluation of the changes over time are invaluable to making an appropriate “kidney health response” (KHR). The KHR focuses on “the 4Ms” (1) Medication adjustment, (2) Minimize exposures, (3) Message care team and patient, and (4) Monitor (Fig. 1).

In the absence of proven treatments for established AKI, preventive strategies are the foundation for AKI care in neonates. Coordinated multidisciplinary efforts to build awareness and educate the neonatal care community on issues related to neonatal AKI (definition, signs/symptoms, high-risk exposures, and high-risk populations) are greatly needed. We propose that partnerships between the pediatric nephrology and the neonatology communities (i.e., the Neonatal Kidney Collaborative www.babykidney.org) will have the highest impact on educating our workforce. The involvement and engagement of general pediatricians, newborn hospitalists, neonatal nurse practitioners, physician assistants, and neonatologists will be central to efforts designed to decrease the burden of AKI. Furthermore, on an individual level, pediatric nephrologists should make themselves available for consultation before high-risk procedures in high-risk populations to optimize pre-exposure care.

Primary prevention of AKI during a hospital encounter

Question 1: How and when should the risk for AKI be identified among hospitalized patients?

Consensus Statement A. Patients at hospital admission should be screened for the risk of AKI.

Consensus Statement B. All patients at risk for AKI should at least have an assessment of serum creatinine, urine dipstick analysis, and urine output measurement.

Consensus Statement C. All hospitalized patients should have periodic risk reassessment using appropriate clinical or electronic models before and after risk exposure or change in clinical status.

Neonates admitted to the NICU who have risk factors (Tables 1 and 2) or are undergoing events that carry additional risk for AKI (Table 3), should have an initial assessment for AKI before and then repeated evaluations as the event continues (i.e., necrotizing enterocolitis (NEC), treatment for hemodynamically significant patent ductus arteriosus (PDA)). As with any illness, early recognition and implementation of mitigation strategies are critical to improving outcomes. One thing that is unique about neonates is their length of hospitalization. Neonates may have AKI around the time of birth or NICU admission but remain at risk for AKI during a hospitalization that may last months. Thus, we believe that identification of high-risk events, with periodic assessment for AKI during these events, may improve outcomes. Development of simple, practical risk assessment scoring systems similar to those developed for children and adults may be useful [37,38,39]. A recent adaptation of the Nephrotoxic Injury Negated by Just-in-time Action (NINJA) program has been effective in reducing the rates of AKI in neonates in the NICU [40]. Incorporation of these systems into the electronic medical record (EMR) may be beneficial.

During high-risk events (Table 3), we agree with the 22nd ADQI report that a serum creatinine (SCr) should be obtained, and urine output be monitored. Recognizing the challenges and risks of blood draws and urine output assessment in neonates, a consensus approach has been developed by an expert panel as part of the planning for a multicenter observational study. Neonatology and nephrology investigators from the 15 participating centers have discussed, vetted, and found consensus on the minimum standard of care for SCr/UOP assessments in neonates admitted to the NICU as follows:

  1. 1.

    During the first week after birth, neonates who are expected to require respiratory support, blood pressure support, or intravenous antibiotics for >3 or more days, should have an AKI assessment (SCr and UOP) on days 2, 3, and 4 after birth.

  2. 2.

    SCr and UOP should be performed on the day of and the following 2 days of a high-risk event (major surgical procedure, hypotension requiring vasopressors, hemodynamically significant PDA, high nephrotoxic exposure, and patients with necrotizing enterocolitis).

  3. 3.

    The frequency of assessments should be tailored to the individual patient and disease and repeated as conditions change and risk escalates.

We do not agree with the ADQI group recommendation that a urinalysis should be obtained during all high-risk neonatal AKI events due to concerns about high false-positive rates previously mentioned. A urinalysis and other tests should be considered in the appropriate clinical scenario (i.e., evaluation for urinary tract infection, evaluation for renal vein thrombosis) where it is likely to provide actionable data and/or assist with differential diagnosis.

The ADQI group did not recommend trending of fluid balance but based on mounting evidence regarding the negative impact of fluid overload in critically ill patients [2, 41], the group strongly recommends that all neonatal patients at risk for AKI have a careful assessment of their current fluid status. Particularly in neonates, using daily weights to define fluid balance is an excellent approximation of net fluid loss or gain consistent with the previously published work in neonates ≥36 weeks gestation [41].

Leveraging the EMR to allow for the timely diagnosis of AKI is an important opportunity to improve care delivery, risk assessment, and neonatal AKI evaluation. The goals of these alert systems are not only to enhance provider awareness but also to reduce AKI severity and duration. EMR systems have been successful in pediatric patients [42,43,44], but the benefits of these AKI alert tools in neonates remain to be determined.

Question 2: What core preventive measures should be considered as a target for QI projects?

Consensus Statement A. Early correction or mitigation of context-specific modifiable risk factors of AKI should be considered for all high-risk patients.

We agree that a neonatal-specific AKI care bundle should be developed and tested with the goal of decreasing the rates and severity of AKI. Such a bundle would be centered around risk assessment, identification of AKI early in the disease process, mitigation of modifiable risk factors, treating reversible conditions (i.e. renal hypoperfusion, bladder outlet obstruction), and monitoring for preventable complications (Table 4). We recognize that different strategies and bundles may be required for different patient populations (i.e., premature patients vs. cardiac patients) and clinical scenarios (i.e., nephrotoxic medication exposure, congenital diaphragmatic hernia, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO) and NEC). Working with subspecialty teams who understand and can balance the pros and cons of interventions in the context of holistic patient care will be essential to the development and successful implementation of such neonatal care bundles.

Table 4 Neonatal AKI bundle.

Question 3: What are the quality indicators for assessing risk of AKI?

Consensus Statement A. The quality indicators for AKI prevention in the hospital should include (1) proportion of patients screened for AKI risk, (2) proportion of identified AKI high-risk patients, (3) proportion of AKI high-risk exposures among all hospitalized population and all high-risk patients, (4) proportion of patients who received an appropriate intervention around a high-risk exposure, and (5) proportion of patients who developed AKI among all admissions.

Consensus Statement B. The quality indicators should be reviewed and utilized to identify areas of improvement and action.

We believe these statements also apply to neonates. The stated metrics can be utilized to monitor practices, determine the effectiveness of interventions, identify benchmarks for care, and develop institutional quality improvement goals centered around neonatal AKI reduction. Using these metrics, multiple studies have shown that surveillance programs designed to identify and mitigate risk in patients receiving nephrotoxic medications decreased rates of AKI, reduced costs, and improved outcomes in children and adults [37,38,39, 45]. As an example, the Baby NINJA project demonstrated a sustained >50% reduction in AKI rates following implementation of a QI process. Importantly, reduction of AKI using the Baby NINJA QI process has only been done in one level IV NICU and must be validated in other NICUs. As of May 2020, ten pediatric hospitals are now using these metrics to track quality improvement efforts to reduce hospital-acquired nephrotoxic medication associated neonatal AKI as part of the Solutions for Patient Safety collaborative and within the Baby NINJA Collaborative. These metrics should be considered in other critically ill newborns with other risk factors for AKI.

Multicenter neonatal studies have demonstrated that there are significant differences in AKI epidemiology across institutions [8], perhaps due to differences in patient populations or clinical practices. However, in the AWAKEN study, sites that measured SCr more often had much higher rates of AKI than sites who measured it infrequently, suggesting that data acquisition may be a major contributor to differences [46]. Thus, we believe that capturing rates of SCr monitoring is essential for understanding AKI prevalence at the population level. It is important to understand baseline institutional AKI rates prior to implementing interventions designed to improve outcomes. Further development, validation, and use of such metrics utilizing the comprehensive quality improvement methodology outlined in Fig. 2 are needed to help identify opportunities for care improvement.

Fig. 2: Quality improvement methodology.
figure2

Seven steps needed to be taken for a successful quality improvement project. Reprinted from Acute Disease Quality Initiative (ADQI) [25], with permission.

Secondary prevention of AKI

Question 1: What are the key considerations for developing quality programs that evaluate contributors to an episode of AKI?

Consensus Statement A. For each patient diagnosed with AKI during hospitalization, the goal is recovery to baseline kidney function in the shortest period of time with a minimum number of complications. This is best achieved by timely and accurate diagnosis and management of AKI.

Consensus Statement B. QI surrounding the diagnostic evaluation of AKI should attempt to maximize the proportion of patients who undergo a context-appropriate and timely evaluation while avoiding unnecessary testing.

We agree with the statements above as they relate to secondary prevention of neonatal AKI. The secondary prevention of AKI encompasses a two-pronged approach aimed at the mitigation of AKI severity and the prevention of AKI complications. Secondary preventive measures that are designed to halt progression include strategies designed to alleviate potentially reversible causes of AKI, such as hypovolemia, low oncotic pressure, urinary obstruction, and intra-abdominal hypertension. Strategies (i.e. limiting nephrotoxic medications in patients with AKI, optimizing hemodynamics) designed to reduce AKI during high-risk events should also be implemented. After a timely diagnosis of AKI, quality improvement measures aimed at reducing the severity and duration of AKI episodes should focus on potentially modifiable factors and limiting consequences (i.e., hyperkalemia, fluid overload, acidosis) throughout their hospitalization.

The development, implementation, and dissemination of a “Neonatal Preventive AKI Bundle” is a meaningful goal for the neonatal nephrology community. The efforts to develop context-specific AKI bundles efforts have been successful in adults [47,48,49,50,51,52], but data are just now becoming available in the neonatal community [53]. These bundles would focus on education, risk assessment, timely diagnosis, interventions, mitigating consequences, and therapeutic monitoring. Again, leveraging the EMR may allow clinicians timely recognition of AKI, and evaluation of critical metrics.

Question 2: What are the key considerations for developing QI programs focused on limiting the duration and severity of AKI?

Consensus Statement A. QI programs should include the implementation and reporting of the proportion of patients that receive timely and diagnosis-appropriate interventions.

We agree that quality improvement programs should not only develop the process for care but should also capture consistency in the application of standardized care processes. These include measures of the frequency of AKI assessment (i.e., percent of high-risk patients for whom a SCr is measured), timely diagnosis, appropriate interventions of strategies designed to reduce AKI. These data should be made available to all stakeholders.

Question 3: What are the key considerations for developing QI programs focused on reducing the complications of AKI?

Consensus Statement A. Quality indicators for prevention of avoidable AKI-related complications include monitoring, reporting the context-specific adverse events (to patient advocates, clinicians, administrators, and regulatory bodies), and implementation of risk reduction strategies.

Emerging data suggest that the consequences of AKI, such as fluid overload, electrolyte, and acid/base perturbations, and hypertension, are common and associated with poor outcomes across the age spectrum. There have been a few neonatal studies showing the negative impact of fluid overload and AKI [2, 41]. Quality improvement programs designed to limit neonatal fluid overload in the context of a patient who is at risk for AKI are needed. Further studies are needed in neonatal patients to determine optimal fluid balance during the birth transition and during high-risk AKI events. Strategies to reduce other consequences of AKI (such as hyperkalemia, acidosis) should be studied as they may lead to an improvement in outcomes. Once more research on the complications and consequences has been performed and more clearly delineated, then larger neonatal regulatory bodies can utilize this information to implement risk reduction strategies.

Kidney replacement therapy quality indicators

Question 1: How should the quality of acute renal replacement therapy be monitored, evaluated, and reported?

Consensus Statement A. Quality indicators should integrate structure, process, and outcome indicators for each therapeutic modality.

We agree with the 22nd ADQI report that the incorporation of quality indicators should be part of programs that provide acute kidney replacement therapy to neonates. Kidney replacement therapy (KRT) in neonates has been challenging due to a lack of technology for small patients. Our group did not address the modality and timing of therapy, but the group holds a strong opinion that programs should use quality improvement methodologies to ensure safe and high-quality care to neonates who receive kidney support therapy. Peritoneal dialysis (PD), hemodialysis (HD), and continuous kidney replacement therapy (CKRT) have been used for decades to support neonates with kidney failure, and determination on which therapy is used is driven by patient characteristics, institutional resources, and provider experience. Extracorporeal therapies pose the neonate at a much higher risk of hemodynamic instability due to the large extracorporeal volume when using tubing and filters designed for adults.

Furthermore, the error rates on fluid delivery devices and fluid removal pumps pose much higher relative error rates. Recent use of machines with small circuits have mitigated these risks and are beginning to shift the practice of neonatal kidney support in some programs [54,55,56]. As these machines continue to be incorporated into NICUs around the world, it will be critical to document and institute QI tools to track, improve, and evolve this therapy.

Neonatal CKRT should be viewed like any other complex, high-risk procedure. Each program must have outlined policies and procedures, clearly defined roles and responsibilities for all team members, assure adequate training, develop procedure checklists, institute timeouts prior to initiation, and perform continuous quality improvement assessments. All programs should integrate structural, process, and outcome measures within the context of a quality improvement framework. Programs should focus on the most important elements that will capture the strengths and weaknesses of the program and may include processes to optimize the initiation of therapy, assess the efficiency of therapy, evaluate provider skills, and evaluate patient safety [57]. Quality improvement in CKRT should seek to optimize the timing of the initiation, evaluate safety events, and optimize the efficiency of therapy. QI data are also important to justify the need for neonatal-specific technologies.

Question 2: What are the minimum structure quality indicators that should be implemented for acute KRT?

Consensus Statement A. Structural quality indicators should specifically target clinician, nursing, and allied health professionals’ capacity and expertise for providing acute KRT and identify a responsible team to implement and report quality metrics for acute KRT services.

We agree with this statement. We believe the delivery of acute KRT for critically ill neonates and infants is a partnership between nephrologists and neonatologists (or intensivists) due to the complexity of the procedure, disease processes, and goals of care. Programs that provide acute KRT in neonate must have a sound infrastructure.

The program should have a dedicated multidisciplinary team with the necessary skills and equipment to provide acute KRT to neonates. This team should have physician and nursing champions who have allocated administrative time to enable them to develop and maintain the program [57]. At a minimum, this includes developing procedures, policies, educational curricula, as well as determining appropriate quality indicators, data collection, data analysis, and program evaluation [57, 58]. The team should incorporate other physicians, advanced practice providers, clinical nurse specialists, bedside nurses, clinical pharmacists, and dietitians with specific education and expertise in AKI care. A successful program must adequately train providers of care, which include training in prescribing therapies to physicians and nurse providers, as well as training the personnel who will initiate and maintain the therapy.

Fundamental to care of the critically ill neonate who needs acute KRT, institutions must determine whether care should be provided in the NICU or whether it is in the child’s best interest to transfer to a location within the hospital (i.e., PICU) who has the training and skills to provide care. If the institution does not have the training or equipment to provide acute KRT, they should consider transferring the patient to a hospital that does.

Question 3: What are the minimum process quality indicators that should be implemented for the provision of acute KRT?

Consensus Statement A. Process quality indicators should incorporate methodologies that lead to standardized protocols and procedures, allowing for increased efficiency and consistency in care and safety, and should be specific to each KRT modality.

We agree with this statement. Process measures assess and evaluate the delivery of care for all forms of acute KST (PD, HD, and CRRT). A focus on standardization and elimination of practice variation within providers is necessary to deliver safe, efficient kidney replacement care. Standard practice protocols and procedures should be developed using current evidence-based and identified best practices. Policies, protocols, and procedures should guide practices along the continuum of AKI care from initial consultation to discontinuation of therapy.

For both PD and extracorporeal therapies, we recommend that complications, safety events, filter life, and vascular access metrics (i.e., the proportion of catheters/treatment, number of catheter revisions, infection, adherence to placement guidelines) be incorporated into the process of care evaluations [59]. Weight-based guidelines should be utilized to recommend the size and location of vascular access [60] and cuffed, tunneled catheters should be considered for both PD and extracorporeal therapies if the duration of therapy is expected to be prolonged.

The optimal timing for the initiation of acute KRT remains an active area of research in other populations but has not been explored in neonates. We recommend that quality initiatives should include measurement of fluid overload status and AKI staging at the time of therapy initiation [61, 62]. The initiation of acute PD and extracorporeal therapies should be done according to the established practices associated with all critical procedures. These practices include performing a “timeout” using a checklist to review the prescribed procedure, review of prescription, vital sign goals, and first and second treatments for vital sign changes. Additionally, at each neonatal extracorporeal therapy initiation procedure, a provider (physician, physician assistant, or nurse practitioner from critical care and nephrology) should be present.

Question 4: What are the minimum outcome indicators that should be implemented for the provision of acute KRT?

Consensus Statement A. Outcome quality indicators should include patient-centered outcomes, including clinician and patient satisfaction, mortality, and quality of life among survivors; dialysis liberation rates; and health-economic outcomes.

We agree with this statement. Institutions should track system outcome measures and neonatal-specific metrics should include neurological outcomes as well as parental understanding and satisfaction.

Tertiary prevention of AKI short- and long-term complications

Question 1: How should the appropriate post-AKI care be measured?

Consensus Statement A. Health care systems need to quantitate the proportion of patients who need post-AKI follow-up, those who receive any post-AKI follow-up, and evaluate the quality of care for those who received post-AKI follow-up.

Programs should seek to optimize follow-up as the final step in the care of neonatal patients following an AKI episode. Efforts should be made to ensure that follow-up visits are arranged, and that critical clinical information is communicated with outpatient providers. At the most basic level, problem lists should be updated and reviewed for accuracy as it relates to AKI episodes. This ensures providers can recognize those at risk for future episodes of AKI, especially those who have previously experienced multiple AKI episodes. Follow-up care may require the development of specific AKI follow-up clinics at busier pediatric institutions. At a minimum, the following groups warrant follow-up by pediatric nephrologists 3 months after discharge: those with a history severe AKI (stage 2, stage 3, or kidney support therapy), multiple episodes of AKI, long-duration AKI events (>7 days), and children with other risk factors for CKD (i.e., congenital heart disease, extreme prematurity, and very low birth weight). Further research and cost analysis is needed to determine which providers (PCP, NICU follow-up clinics, Pediatric Nephrologists), which tests, and what frequency of follow-up in high-risk infants is needed after AKI. Unique to neonates, studying if a AKI recovery (versus progression to CKD) affects neurodevelopmental outcomes and quality of life is needed.

Question 2: What are the key elements of an appropriate post-AKI care bundle?

Consensus Statement A . Quality indicators should at least include structure (needed personnel and resources), process for follow-up (who and by whom, what, where, when, why, and how), and outcome indicators (CKD progression, continued or new need for dialysis, mortality, etc.)

To ensure adequate follow-up, neonates and infants at high risk for CKD, as described above, should have the initial follow-up performed by a pediatric nephrologist or other appropriate care providers within 3 months of the discharge, as recommended by the KDIGO guidelines [60]. This follow-up should include kidney function and blood pressure measurements. Subsequent duration of follow-up should be determined based on the presence and risk for subsequent CKD, availability of local resources, and willingness for primary care physicians to follow patients at risk for CKD. Follow-up studies of neonatal AKI have shown that kidney dysfunction can be detected as early as 2 years of age [12, 13], but there is a need for further large-scale research studies to determine the optimal timing and locations of follow-up for neonates at risk for CKD.

Summary statement

Neonatal AKI is now well defined and has been identified as an important contributor to neonatal morbidity and mortality. The 22nd ADQI Consensus Statement has provided valuable recommendations on how systematic changes can impact positively the care of all patients with AKI. To further clarify how these recommendations can be applied to neonates, we provide a parallel response to each statement from the perspective of neonatal clinical care. We recognize that few NICU programs are currently engaged in AKI QI programs, but we urge the community to begin so that the quality of care for neonates with and at risk for AKI can begin to improve. We propose that each NICU establish its own neonatal AKI QI approach utilizing available resources and teams. We recommend that each NICU implement the elements from this report, which they believe are most important and feasible.

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Acknowledgements

We acknowledge Drs. Ravi Mehta, John Kellum, and Claudio Ronco for their leadership and vision in leading the ADQI collaborative. Furthermore, we are indebted to all of the members of the 22nd ADQI meeting who worked together to develop and articulate the importance of quality improvement in the field of AKI.

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All authors have participated in the concept and design; analysis and interpretation of data; drafting and revising of the manuscript, and they have approved the manuscript as submitted here.

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Correspondence to Matthew W. Harer.

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The authors have no quality improvement related conflicts of interest to report that would have affected the writing of this publication. For AKI-related research, MZ is a member of the AKI adjudication committee for an industry sponsored study on NGAL as an AKI biomarker (Bioporto Inc.) DJA is consultant for Baxter, CHF solutions, Bioporo, and Medtronic. RKB is a consultant for Baxter, Biomerieux and BioPorto.

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Harer, M.W., Selewski, D.T., Kashani, K. et al. Improving the quality of neonatal acute kidney injury care: neonatal-specific response to the 22nd Acute Disease Quality Initiative (ADQI) conference. J Perinatol 41, 185–195 (2021). https://doi.org/10.1038/s41372-020-00810-z

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