Adolescent Kidney Outcomes after Extremely Preterm Birth and Neonatal Acute Kidney Injury: There May be More to the Story.

OBJECTIVE: Among children born extremely preterm (EP), the antecedents of chronic kidney disease (CKD), including neonatal acute kidney injury (nAKI), are not well characterized. STUDY DESIGN: This was a retrospective cohort pilot study. Participants (n = 36) were adolescents born before 28 weeks of gestation enrolled at birth into the extremely low gestational age newborn study, between 2002 and 2004, at the University of North Carolina. Participants were stratified by the primary exposure to nAKI, defined using the modified Kidney Disease Improving Global Outcomes nAKI criteria. Baseline serum creatinine (SCr) was defined as the lowest SCr after 48 to 72 postnatal hours. The primary outcome was an abnormal kidney profile during adolescence, defined as having one or more of these outcomes: elevated blood pressure (>120/80 mm Hg), microalbuminuria (urine microalbumin/creatinine >30 µg/g), or an abnormal kidney volume measured by ultrasound (total kidney volume corrected for body surface area <10th%ile for age). RESULTS: Half of the participants had a history of nAKI. Thirteen had stage 1 nAKI, four had stage 2, and one had stage 3 nAKI. At 15 years of age, 50% were overweight/obese, 31% had elevated blood pressure (BP), 11% had abnormal kidney volumes, and 17% had microalbuminuria. The relative risk for having an abnormal kidney profile during adolescence among participants with a history of nAKI was 0.63 (95% confidence interval: 0.3-1.3, p = 0.2). CONCLUSION: In this sample of adolescents born EP, a history of nAKI was not associated with elevated BP, microalbuminuria, or abnormal kidney volume. Future studies are needed in larger samples to better characterize the relationship between nAKI and CKD in EP-born children. KEY POINTS: · Extremely preterm birth is associated with acute kidney injury.. · Extremely preterm birth is associated with chronic kidney disease.. · Neonatal acute kidney injury after extremely preterm birth was not associated with kidney outcomes..

From premature birth to premature kidney disease: does accelerated aging play a role?

As the limits of fetal viability have increased over the past 30 years, there has been a growing body of evidence supporting the idea that chronic disease should be taken into greater consideration in addition to survival after preterm birth. Accumulating evidence also suggests there is early onset of biologic aging after preterm birth. Similarly, chronic kidney disease (CKD) is also associated with a phenotype of advanced biologic age which exceeds chronologic age. Yet, significant knowledge gaps remain regarding the link between premature biologic age after preterm birth and kidney disease. This review summarizes the four broad pillars of aging, the evidence of premature aging following preterm birth, and in the setting of CKD. The aim is to provide additional plausible biologic mechanisms to explore the link between preterm birth and CKD. There is a need for more research to further elucidate the biologic mechanisms of the premature aging paradigm and kidney disease after preterm birth. Given the emerging research on therapies for premature aging, this paradigm could create pathways for prevention of advanced CKD.

Severe Fetal CAKUT (Congenital Anomalies of the Kidneys and Urinary Tract), Prenatal Consultations, and Initiation of Neonatal Dialysis.

INTRODUCTION: Pediatric nephrology prenatal consultations for congenital anomalies of the kidney and urinary tract (CAKUT) and criteria for kidney replacement therapy initiation in neonatal end-stage kidney disease (ESKD) are not well described. We evaluated pediatric nephrology approaches to prenatal CAKUT counseling and neonatal dialysis initiation. METHODS: A 35-question Qualtrics survey was distributed via the North American Pediatric Renal Trials and Collaborative Studies email list between January and March 2021. Thirty-nine pediatric nephrology centers completed the survey. RESULTS: All but one responding center (n = 38) provide prenatal CAKUT consultations and neonatal dialysis, with wide variability in reported multispecialty involvement. Nearly half (47%) of centers utilize written/unwritten criteria for offering neonatal dialysis. The most common contraindications to neonatal dialysis were parental refusal (61%), contraindication to access placement by surgeons (55%), and birth weight (BW) contraindication (55%, with < 1,500 g being the most common BW contraindication). Overall, 79% of centers reported caring for < 5 neonates with ESKD in the past year, 61% use hemodialysis therapies prior to peritoneal dialysis in neonates requiring dialysis, and 100% transition to peritoneal dialysis by hospital discharge. CONCLUSION: Many pediatric nephrology programs provide prenatal CAKUT consultations and neonatal dialysis, but with variability in practice approach. Further multicenter research regarding prenatal consultations and neonatal dialysis outcomes is necessary to further improve care delivery to this population.

Mortality Risk Factors among Infants Receiving Dialysis in the Neonatal Intensive Care Unit.

OBJECTIVES: To identify risk factors associated with mortality for infants receiving dialysis in the neonatal intensive care unit (NICU). STUDY DESIGN: In this retrospective cohort study, we extracted data from the Pediatrix Clinical Data Warehouse on all infants who received dialysis in the NICU from 1999 to 2018. Using a Cox proportional hazards model with robust SEs we estimated the mortality hazard ratios associated with demographics, birth details, medical complications, and treatment exposures. RESULTS: We identified 273 infants who received dialysis. Median gestational age at birth was 35 weeks (interquartile values 33-37), median birth weight was 2570 g (2000-3084), 8% were small for gestational age, 41% white, and 72% male. Over one-half of the infants (59%) had a kidney anomaly; 71 (26%) infants died before NICU hospital discharge. Factors associated with increased risk of dying after dialysis initiation included lack of kidney anomalies, Black race, gestational age of <32 weeks, necrotizing enterocolitis, dialysis within 7 days of life, and receipt of paralytics or vasopressors (all P < .05). CONCLUSION: In this cohort of infants who received dialysis in the NICU over 2 decades, more than 70% of infants survived. The probability of death was greater among infants without a history of a kidney anomaly and those with risk factors consistent with greater severity of illness at dialysis initiation.

Eculizumab exposure in children and young adults: indications, practice patterns, and outcomes-a Pediatric Nephrology Research Consortium study.

BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.

Severe acute kidney injury in neonates with necrotizing enterocolitis: risk factors and outcomes.

BACKGROUND: To study the risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis. METHODS: Retrospective chart review of 202 neonates with necrotizing enterocolitis (NEC) (Bell stage >IIa) from 2013 to 2018. AKI was defined as per-modified neonatal Kidney Disease: Improving Global Outcomes criteria. Demographic, clinical, and outcome data were compared between neonates without severe AKI (stage 0 and 1 AKI) and those with severe AKI (stage 2 and 3 AKI). RESULTS: Severe AKI occurred in 66/202 (32.6%) of neonates after NEC diagnosis and after 61/104 (58.7%) of surgical NEC diagnoses. On adjusted model, surgical NEC [adjusted odds ratio (aOR) = 30.6; 95% confidence interval (CI) = 8.9, 130.6], outborn [aOR = 3.9; 95% CI = 1.54, 11.0], exposure to antenatal steroids [aOR = 3.0; 95% CI = 1.1, 8.9], and positive blood culture sepsis [aOR = 3.5; 95% CI = 1.3, 10.0] had increased odds for severe AKI. Those with severe AKI required longer hospitalization [124 days (interquartile range (IQR) 88-187) vs. 82 days (IQR 42-126), p < 0.001]. CONCLUSIONS: Severe AKI is common in neonates with NEC who require surgical intervention, are outborn, have positive blood culture sepsis, and receive antenatal steroids. Severe AKI is associated with a significantly longer length of hospitalization. IMPACT: Neonates with NEC, who are transferred from outside hospitals, require surgical NEC management, and/or have a positive blood culture at NEC onset are at the highest odds for severe (stages 2 and 3) AKI. Assessment of urine output is important for patients with NEC. Without it, 11% of those with severe AKI would have been misdiagnosed using serum creatinine alone. Kidney-protective strategies in the pre-, peri-, and postoperative period may improve the morbidity and mortality associated with severe AKI in neonates with NEC.

Albuminuria, Hypertension, and Reduced Kidney Volumes in Adolescents Born Extremely Premature.

Background: Premature birth is associated with decreased nephron number and an increased risk for chronic kidney disease (CKD). To inform the development of guidelines for kidney follow up of children born prematurely, we undertook a study of individuals born extremely preterm, with the aim of characterizing the prevalence and predictors of microalbuminuria, elevated blood pressure, and/or abnormal kidney volume in adolescence. Methods: Study participants (n = 42) were born before 28 weeks of gestation and were enrolled at birth in the Extremely Low Gestational Age Newborns (ELGAN) study. When participants were 15 years old, we obtained 2 manual blood pressures, a spot urine microalbumin measurement, and sonographic measurements of kidney length and volume. Results: Of the 42 participants, 60% were male, 52% were Caucasian (18% Hispanic), and 43% were African-American. Their median age was 15 (IQR 15, 15.3) years. In 33.3% of the cohort, blood pressure was elevated (>120/80 mmHg). Microalbuminuria (>30 mg/g) was present in 11.9% of the cohort, and kidney volume below the 10th percentile of normative data was present in 14%. Twenty-one (50%) of the sample had at least one kidney abnormality (microalbuminuria, elevated blood pressures, and/or kidney hypoplasia); these individuals were more likely to have experienced neonatal hypotension [55% vs. 17% among those with no kidney abnormality, p = 0.02]. Conclusions: Half of adolescents in this subset of ELGAN cohort have at least one risk factor of kidney disease (reduced kidney volume, microalbuminuria, and/or elevated blood pressures) at 15 years of age. This study suggests the importance of monitoring kidney outcomes in children after extremely preterm birth, especially those with a history of neonatal hypotension.

Renal replacement therapies for infants and children in the ICU.

PURPOSE OF REVIEW: Pediatric acute kidney injury (AKI) in critically ill patients is associated with increased morbidity and mortality. Emerging data support that the incidence of pediatric AKI in the ICU is rising. For children with severe AKI, renal replacement therapy (RRT) can provide a lifesaving supportive therapy. The optimal timing to deliver and modality by which to deliver RRT remain a point of discussion within pediatric (and adult) literature. This review discusses the use of RRT for pediatric patients in the ICU. We discuss the most recent evidence-based methods for RRT with a focus on continuous RRT. RECENT FINDINGS: The feasibility of dialyzing the smallest infants and more medically complex children in the ICU is dependent on the advancements in dialysis access and circuit technology. At present, data indicate that upward of 27% of children in the ICU develop AKI and 6% require RRT. Newer dialysis modalities including prolonged intermittent hemodialysis and continuous flow peritoneal dialysis as well as newer dialysis technologies such as the smaller volume circuits (e.g., Cardio-Renal Pediatric Dialysis Emergency Machine, Newcastle Infant Dialysis and Ultrafiltration System) have made the provision of dialysis safer and more effective for pediatric patients of a variety of sizes. SUMMARY: Renal replacement in the ICU requires a multidisciplinary team approach that is facilitated by a pediatric nephrologist in conjunction with intensivists and skilled nursing staff. Although mortality rates for children on dialysis remain high, outcomes are improving with the support of the multidisciplinary team and dialysis technology advancements.

End-stage kidney disease in infancy: an educational review.

An increasing number of infants with end-stage kidney disease (ESKD) are surviving and receiving renal replacement therapy (RRT). Unique clinical issues specific to this age group of patients influence their short- and long-term outcomes. This review summarizes current epidemiology, clinical characteristics, ethical dilemmas, management concerns, and outcomes of infants requiring chronic dialysis therapy. Optimal care during infancy requires a multidisciplinary team working closely with the patient's family. Nutritional management, infection prevention, and attention to cardiovascular status are important treatment targets. Although mortality rates remain higher among infants on dialysis compared to older pediatric dialysis patients, outcomes have improved over time. Most importantly, infants who subsequently receive a kidney transplant are now experiencing graft survival rates that are comparable to older pediatric patients.

Outcomes of infants receiving chronic peritoneal dialysis: an analysis of the USRDS registry.

BACKGROUND: Outcome data for infants on chronic peritoneal dialysis (CPD) is limited and has been based primarily on the analyses of voluntary entry registry data. In contrast, the United States Renal Data Systems (USRDS) collects data on all infants with end-stage kidney disease (ESKD) on chronic dialysis in the USA. We aimed to describe the clinical characteristics of this population and to determine the associated patient mortality. METHODS: The USRDS database was reviewed retrospectively for data on infants who initiated CPD at ≤ 12 months of age from 1990 to 2014. Infants were categorized into four groups, CPD initiation age (≤ 1 month of age or neonates and > 1-12 months of age or older infants) and initiation era (1990-1999 and 2000-2014). RESULTS: A total of 1723 infants (574 neonates and 1149 older infants) were identified. Overall, 20.9% of infants (147 neonates and 213 older infants) died on dialysis during the follow-up. The most commonly identified causes of death on dialysis were cardiorespiratory disease (25.8%) and infection (22.8%). There was an increased risk for mortality in all infants who initiated CPD in the earlier initiation era (1990-1999) vs the later era (2000-2014) (aHR of 1.95), for females vs males (aHR 1.43), and for those with a primary diagnosis of cystic kidney diseases vs congenital anomalies of the kidney and urinary tract (CAKUT) (aHR 1.84). In 2000-2014, patient survival at 1 and 5 years was 86.8% and 74.6% for those who initiated CPD as neonates and 89.6% and 79.3% for those who did so as older infants. CONCLUSIONS: In this large cohort of infants who received chronic peritoneal dialysis over more than two decades, the probability of survival after initiating CPD in the first year of life has significantly improved. There is no difference in the probability of death for neonates compared to older infants. However, the mortality rate remains substantial in association with multiple risk factors.