Browsing by Author "Menon, Shina"
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Item Acute Kidney Injury and Bronchopulmonary Dysplasia in Premature Neonates Born Less than 32 Weeks’ Gestation(Thieme, 2020-02) Starr, Michelle C.; Boohaker, Louis; Eldredge, Laurie C.; Menon, Shina; Griffin, Russell; Mayock, Dennis E.; Li, Linzi; Askenazi, David; Hingorani, Sangeeta; Pediatrics, School of MedicineObjective: This study aimed to evaluate the association between acute kidney injury (AKI) and bronchopulmonary dysplasia (BPD) in infants born <32 weeks of gestational age (GA). Study design: Present study is a secondary analysis of premature infants born at <32 weeks of GA in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) retrospective cohort (n = 546). We stratified by gestational age and used logistic regression to determine association between AKI and moderate or severe BPD/mortality. Results: Moderate or severe BPD occurred in 214 of 546 (39%) infants, while death occurred in 32 of 546 (6%); the composite of moderate or severe BPD/death occurred in 246 of 546 (45%). For infants born ≤29 weeks of gestation, the adjusted odds ratio (OR) of AKI and the primary outcome was 1.15 (95% confidence interval [CI] = 0.47-2.86; p = 0.76). Infants born between 29 and 32 weeks of gestation with AKI had four-fold higher odds of moderate or severe BPD/death that remained after controlling for multiple factors (adjusted OR = 4.21, 95% CI: 2.07-8.61; p < 0.001). Conclusion: Neonates born between 29 and 32 weeks who develop AKI had a higher likelihood of moderate or severe BPD/death than those without AKI. Further studies are needed to validate our findings and evaluate mechanisms of multiorgan injury.Item Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates(American Medical Association, 2023-08-01) Starr, Michelle C.; Griffin, Russell L.; Harer, Matthew W.; Soranno, Danielle E.; Gist, Katja M.; Segar, Jeffrey L.; Menon, Shina; Gordon, Lindsey; Askenazi, David J.; Selewski, David T.; Pediatrics, School of MedicineImportance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, setting, and participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main outcomes and measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.Item Acute Kidney Injury is Associated with Poor Lung Outcomes in Infants Born ≥32 Weeks of Gestational Age(Thieme, 2020-01) Starr, Michelle C.; Boohaker, Louis; Eldredge, Laurie C.; Menon, Shina; Griffin, Russell; Mayock, Dennis; Askenazi, David; Hingorani, Sangeeta; Pediatrics, School of MedicineObjective: This study aimed to evaluate the association between acute kidney injury (AKI) and lung outcomes in infants born ≥32 weeks of gestational age (GA). Study design: Secondary analysis of infants ≥32 weeks of GA in the assessment of worldwide acute kidney injury epidemiology in neonates (AWAKEN) retrospective cohort (n = 1,348). We used logistic regression to assess association between AKI and a composite outcome of chronic lung disease (CLD) or death at 28 days of age and linear regression to evaluate association between AKI and duration of respiratory support. Results: CLD occurred in 82/1,348 (6.1%) infants, while death occurred in 22/1,348 (1.6%); the composite of CLD/death occurred in 104/1,348 (7.7%). Infants with AKI had an almost five-fold increased odds of CLD/death, which remained after controlling for GA, maternal polyhydramnios, multiple gestations, 5-minute Apgar's score, intubation, and hypoxic-ischemic encephalopathy (adjusted odds ratio [OR] = 4.9, 95% confidence interval [CI]: 3.2-7.4; p < 0.0001). Infants with AKI required longer duration of respiratory support (count ratio = 1.59, 95% CI: 1.14-2.23, p = 0.003) and oxygen (count ratio = 1.43, 95% CI: 1.22-1.68, p < 0.0001) compared with those without AKI. Conclusion: AKI is associated with CLD/death and longer duration of respiratory support in infants born at ≥32 weeks of GA. Further prospective studies are needed to elucidate the pathophysiologic relationship.Item Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference(Springer, 2024) Starr, Michelle C.; Barreto, Erin; Charlton, Jennifer; Vega, Molly; Brophy, Patrick D.; Bignall, O. N. Ray, II; Sutherland, Scott M.; Menon, Shina; Devarajan, Prasad; Arikan, Ayse Akcan; Basu, Rajit; Goldstein, Stuart; Soranno, Danielle E.; ADQI 26 workgroup; Pediatrics, School of MedicineBackground: In the past decade, there have been substantial advances in our understanding of the pathobiology of pediatric acute kidney injury (AKI). In particular, animal models and studies focused on the relationship between kidney development, nephron number, and kidney health have identified a number of heterogeneous pathophysiologies underlying AKI. Despite this progress, gaps remain in our understanding of the pathobiology of pediatric AKI. Methods: During the 26th Acute Disease Quality Initiative (ADQI) Consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations for opportunities to advance translational research in pediatric AKI. The current state of research understanding as well as gaps and opportunities for advancement in research was discussed, and recommendations were summarized. Results: Consensus was reached that to improve translational pediatric AKI advancements, diverse teams spanning pre-clinical to epidemiological scientists must work in concert together and that results must be shared with the community we serve with patient involvement. Public and private research support and meaningful partnerships with adult research efforts are required. Particular focus is warranted to investigate the pediatric nuances of AKI, including the effect of development as a biological variable on AKI incidence, severity, and outcomes. Conclusions: Although AKI is common and associated with significant morbidity, the biologic basis of the disease spectrum throughout varying nephron developmental stages remains poorly understood. An incomplete understanding of factors contributing to kidney health, the diverse pathobiologies underlying AKI in children, and the historically siloed approach to research limit advances in the field. The recommendations outlined herein identify gaps and outline a strategic approach to advance the field of pediatric AKI via multidisciplinary translational research.Item Artificial Intelligence for AKI!Now: Let’s Not Await Plato’s Utopian Republic(American Society of Nephrology, 2021-11-18) Soranno, Danielle E.; Bihorac, Azra; Goldstein, Stuart L.; Kashani, Kianoush B.; Menon, Shina; Nadkarni, Girish N.; Neyra, Javier A.; Pannu, Neesh I.; Singh, Karandeep; Cerda, Jorge; Koyner, Jay L.; Pediatrics, School of MedicineItem Association of delayed cord clamping with acute kidney injury and two-year kidney outcomes in extremely premature neonates: a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT)(Research Square, 2024-07-19) Harer, Matthew; Zapata, Henry; Todurkar, Namrata; Favel, Kristen; Griffin, Russell; Starr, Michelle; Charlton, Jennifer; McAdams, Ryan; Askenazi, David; Kulkarni, Tapas; Menon, Shina; Mammen, Cherry; Pediatrics, School of MedicineBackground: Delayed cord clamping (DCC) occurs in most preterm births. Objective: Evaluate the association of DCC with acute kidney injury (AKI) and two-year kidney outcomes. Methods: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates born 240/7 to 276/7 weeks' gestation. AKI and two year kidney outcomes were compared in neonates with DCC (≥30 seconds after delivery) to those with early cord clamping (ECC) (<30 seconds after delivery). Results: The incidence and severity of AKI did not differ between the DCC and ECC groups (aOR 1.17 [95%CI 0.76-1.80]). At two years corrected age, DCC was associated with a 4.5-fold times increased adjusted odds of eGFR <90 mL/min/1.73m2. No significant associations were noted between DCC and albuminuria or elevated BP. Conclusions: DCC was not associated with decreased neonatal AKI, but was associated with higher adjusted odds of eGFR <90 mL/min/1.73m2 at two years.Item Association of Fluid Balance With Short- and Long-term Respiratory Outcomes in Extremely Premature Neonates: A Secondary Analysis of a Randomized Clinical Trial(American Medical Association, 2022-12-01) Starr, Michelle C.; Griffin, Russell; Gist, Katja M.; Segar, Jeffrey L.; Raina, Rupesh; Guillet, Ronnie; Nesargi, Saudamini; Menon, Shina; Anderson, Nekayla; Askenazi, David J.; Selewski, David T.; Pediatrics, School of MedicineImportance: Extremely low gestational age neonates are at risk of disorders of fluid balance (FB), defined as change in fluid weight over a specific period. Few data exist on the association between FB and respiratory outcomes in this population. Objective: To describe FB patterns and evaluate the association of FB with respiratory outcomes in a cohort of extremely low gestational age neonates. Design, setting, and participants: This study is a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3 placebo-controlled randomized clinical trial of erythropoietin in extremely premature neonates conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 874 extremely premature neonates born at 24 to 27 weeks' gestation who were enrolled in the PENUT study. Secondary analysis was performed in November 2021. Exposures: Primary exposure was peak FB during the first 14 postnatal days. The FB was calculated as percent change in weight from birth weight (BW) as a surrogate for FB. Main outcomes and measures: The primary outcome was mechanical ventilation on postnatal day 14. The secondary outcome was a composite of severe bronchopulmonary dysplasia (BPD) or death. Results: A total of 874 neonates (449 [51.4%] male; mean [SD] BW, 801 [188] g; 187 [21.4%] Hispanic, 676 [77.3%] non-Hispanic, and 11 [1.3%] of unknown ethnicity; 226 [25.9%] Black, 569 [65.1%] White, 51 [5.8%] of other race, and 28 [3.2%] of unknown race) were included in this analysis. Of these 874 neonates, 458 (52.4%) received mechanical ventilation on postnatal day 14, and 291 (33.3%) had severe BPD or had died. Median peak positive FB was 11% (IQR, 4%-20%), occurring on postnatal day 13 (IQR, 9-14). A total of 93 (10.6%) never decreased below their BW. Neonates requiring mechanical ventilation at postnatal day 14 had a higher peak FB compared with those who did not require mechanical ventilation (15% above BW vs 8% above BW, P < .001). On postnatal day 3, neonates requiring mechanical ventilation were more likely to have a higher FB (5% below BW vs 8% below BW, P < .001). The median time to return to BW was shorter in neonates who received mechanical ventilation (7 vs 8 days, P < .001) and those with severe BPD (7 vs 8 days, P < .001). After adjusting for confounding variables, for every 10% increase in peak FB during the first 14 postnatal days, there was 103% increased odds of receiving mechanical ventilation at postnatal day 14 (adjusted odds ratio, 2.03; 95% CI, 1.64-2.51). Conclusions and relevance: In this secondary analysis of a randomized clinical trial, peak FB was associated with mechanical ventilation on postnatal day 14 and severe BPD or death. Fluid balance in the first 3 postnatal days and time to return to BW may be potential targets to help guide management and improve respiratory outcomes.Item Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement(American Medical Association, 2022-09-01) Goldstein, Stuart L.; Akcan-Arikan, Ayse; Alobaidi, Rashid; Askenazi, David J.; Bagshaw, Sean M.; Barhight, Matthew; Barreto, Erin; Bayrakci, Benan; Bignall, Orville N. R.; Bjornstad, Erica; Brophy, Patrick D.; Chanchlani, Rahul; Charlton, Jennifer R.; Conroy, Andrea L.; Deep, Akash; Devarajan, Prasad; Dolan, Kristin; Fuhrman, Dana Y.; Gist, Katja M.; Gorga, Stephen M.; Greenberg, Jason H.; Hasson, Denise; Heydari Ulrich, Emma; Iyengar, Arpana; Jetton, Jennifer G.; Krawczeski, Catherine; Meigs, Leslie; Menon, Shina; Morgan, Jolyn; Morgan, Catherine J.; Mottes, Theresa; Neumayr, Tara M.; Ricci, Zaccaria; Selewski, David; Soranno, Danielle E.; Starr, Michelle; Stanski, Natalja L.; Sutherland, Scott M.; Symons, Jordan; Tavares, Marcelo S.; Wong Vega, Molly; Zappitelli, Michael; Ronco, Claudio; Mehta, Ravindra L.; Kellum, John; Ostermann, Marlies; Basu, Rajit K.; Pediatric ADQI Collaborative; Pediatrics, School of MedicineImportance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.Item Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative(Elsevier, 2024) Starr, Michelle C.; Gist, Katja M.; Zang, Huaiyu; Ollberding, Nicholas J.; Balani, Shanthi; Cappoli, Andrea; Ciccia, Eileen; Joseph, Catherine; Kakajiwala, Aadil; Kessel, Aaron; Muff-Luett, Melissa; Santiago Lozano, María J.; Pinto, Matthew; Reynaud, Stephanie; Solomon, Sonia; Slagle, Cara; Srivastava, Rachana; Shih, Weiwen V.; Webb, Tennille; Menon, Shina; Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) Collaborative; Pediatrics, School of MedicineRationale & objective: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival. Study design: Retrospective multicenter cohort study. Setting & participants: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases). Exposure: CKRT for acute kidney injury or volume overload. Outcomes: Death before intensive care unit (ICU) discharge. Analytical approach: Descriptive statistics. Results: Median age was 8.8 years (IQR, 1.6-15.0), and median weight was 26.8 (IQR, 11.6-55.0) kg. CKRT was initiated a median of 2 (IQR, 1-6) days after ICU admission and lasted a median of 6 (IQR, 3-14) days. The most common CKRT modality was continuous venovenous hemodiafiltration. Citrate anticoagulation was used in 62%, and the internal jugular vein was the most common catheter placement location (66%). 629 participants (64.1%) survived at least until ICU discharge. CKRT dose, filter type, and anticoagulation were similar in those who did and did not survive to ICU discharge. There were apparent practice variations by institutional ICU size. Limitations: Retrospective design; limited representation from centers outside the United States. Conclusions: In this study of children and young adults receiving CKRT, approximately two thirds survived at least until ICU discharge. Although variations in dialysis mode and dose, catheter size and location, and anticoagulation were observed, survival was not detected to be associated with these parameters. Plain-language summary: In this large contemporary epidemiological study of children and young adults receiving continuous kidney replacement therapy in the intensive care unit, we observed that two thirds of patients survived at least until ICU discharge. However, patients with comorbidities appeared to have worse outcomes. Compared with previously published reports on continuous kidney replacement therapy practice, we observed greater use of continuous venovenous hemodiafiltration with regional citrate anticoagulation.Item Documentation of acute kidney injury at discharge from the neonatal intensive care unit and role of nephrology consultation(Springer Nature, 2022) Chmielewski, Jennifer; Chaudhry, Paulomi M.; Harer, Matthew W.; Menon, Shina; South, Andrew M.; Chappell, Ashley; Griffin, Russell; Askenazi, David; Jetton, Jennifer; Starr, Michelle C.; Neonatal Kidney Collaborative; Pediatrics, School of MedicineObjective: To investigate whether NICU discharge summaries documented neonatal AKI and estimate if nephrology consultation mediated this association. Study design: Secondary analysis of AWAKEN multicenter retrospective cohort. Exposures: AKI severity and diagnostic criteria. Outcome: AKI documentation on NICU discharge summaries using multivariable logistic regression to estimate associations and test for causal mediation. Results: Among 605 neonates with AKI, 13% had documented AKI. Those with documented AKI were more likely to have severe AKI (70.5% vs. 51%, p < 0.001) and SCr-only AKI (76.9% vs. 50.1%, p = 0.04). Nephrology consultation mediated 78.0% (95% CL 46.5-109.4%) of the total effect of AKI severity and 82.8% (95% CL 70.3-95.3%) of the total effect of AKI diagnostic criteria on documentation. Conclusion: We report a low prevalence of AKI documentation at NICU discharge. AKI severity and SCr-only AKI increased odds of AKI documentation. Nephrology consultation mediated the associations of AKI severity and diagnostic criteria with documentation.