Portal de Periódicos da CAPES

The Impact of Erythropoietin on Short- and Long-Term Kidney-Related Outcomes in Neonates of Extremely Low Gestational Age. Results of a Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial

2021; Elsevier BV; Volume: 232; Linguagem: Inglês

10.1016/j.jpeds.2021.01.031

1097-6833

David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick D. Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Sandra E. Juul, Bryan A. Comstock, Rajan Wadhawan, Dennis E. Mayock, Sherry E. Courtney, Tonya Robinson, Kaashif A. Ahmad, Ellen Bendel‐Stenzel, Mariana Baserga, Edmund F. LaGamma, L. Corbin Downey, Raghavendra Rao, Nancy Fahim, Andrea Lampland, Ivan D. Frantz, Janine Y. Khan, Michael Weiss, Maureen Gilmore, Robin K. Ohls, Nishant Srinivasan, Jorge Perez, Victor McKay, Phuong T. Vu, Patrick J. Heagerty, Billy Thomas, Nahed O. ElHassan, Sarah B. Mulkey, Philip Dydynski, Vivek K. Vijayamadhavan, Neil Mulrooney, Bradley A. Yoder, Jordan S. Kase, Jennifer Check, Semsa Gogcu, Erin Osterholm, Sara E. Ramel, Catherine M. Bendel, Cheryl A. Gale, T. Neville George, Michael Georgieff, Tate Gisslen, Sixto F. Guiang, Anne M. Hall, Dana E. Johnson, K. Pfister, Heather Podgorski, Kari E. Roberts, Erin C. Stepka, Melissa L. Engel, Heidi Kamrath, Johannah M. Scheurer, Angela Hanson, Katherine M. Satrom, Susan Pfister, Ann Simones, Erin Plummer, Elizabeth Zorn, Camilia R. Martin, Deirdre O’Reilly, Nicolas Porta, Catalina Bazacliu, Jonathan Williams, Dhanashree Rajderkar, Frances J. Northington, Raul Chavez‐Valdez, Sandra Sundquist Beauman, Patel Saurabhkumar, Magaly Diaz-Barbosa, Arturo Serize, Jorge Jordán, Debbie Ott, Ariana Franco Mora, Pamela Hedrick, Vicki Flynn, Amy Silvia, Bailey Clopp, John Feltner, Isabella Esposito, Stephanie Hauge, Samantha Nikirk, Andrea Purnell, Emilie Loy, Natalie Sikes, Melanie Mason, Jana McConnell, Tiffany Brown, Henry Harrison, Denise J. Pearson, Tammy Drake, Jocelyn H. Wright, Debra Walden, Annette Guy, Jennifer Nason, Morgan Talbot, Kristen Lee, Sarah Penny, Terri Boles, Melanie Drummond, Katy Kohlleppel, Charmaine Kathen, Brian Kaletka, Shania Gonzales, Cathy Worwa, Molly Fisher, Tyler Richter, Alexander Ginder, Brixen A. Reich, Carrie A. Rau, Manndi C. Loertscher, Laura Bledsoe, Kandace M. McGrath, Kimberlee Weaver Lewis, Jill Burnett, Susan T. Schaefer, Karie Bird, Clare Giblin, Rita Daly, Kristi Lanier, Kelly Warden, Jenna Wassenaar, Jensina Ericksen, Bridget Davern, Mary Pat Osborne, Brittany Gregorich, Neha Talele, Evelyn Obregon, Tiglath Ziyeh, Molly Clarke, Rachel E. Wegner, Palak Patel, Molly Schau, Annamarie Russow, Kelly Curry, Susan Sinnamon, Lisa Barnhart, Charlamaine Parkinson, Sandra Sundquist Beauman, Mary Hanson, Elizabeth Kuan, Conra Backstrom Lacy, Edshelee M. Galvis, Susana Bombino, Denise Martinez, Suzi Bell, Corrie Long, Cathy Longa, Michael Westerveld, Stacy McConkey, Anne E. Hay, Niranjana Natarajan, Shari Gaudette, Sarah Cobb, Gregory Sharp, Elizabeth Schumacher, Leslie Schuschke, Charlotte Frey, Mario Fierro, Lois Gilmore, Pamela Lundequam, Ronald Hoekstra, Anastasia Ketko, Nina Perdue, Sean Cunningham, Kelly Stout, Becky Hall, Galina Morshedzadeh, Betsy Ostrander, Sarah Winter, Lauren Gulley Cox, Jordan S. Kase, Matthew A. Rainaldi, Sarah Hensley, Melissa Morris, Dia Roberts, Semsa Gogcu, Melissa Tuttle, Christopher J. Boys, Solveig Hultgren, Elizabeth I. Pierpont, Nancy Fahim, Tom George, Erin Osterholm, Michael Georgieff, Kelly King, Katherine Bataglia, Cathy Neis, Mark Bergeron, Cristina Miller, Cara Accomando, Jennifer Anne Gavin, Elizabeth Maczek, Susan Marakovitz, Aimee Knorr, Vincent C. Smith, Jane E. Stewart, Marie Weissbourd, Raye‐Ann deRegnier, Nana Matoba, Shelly C. Heaton, Erika M. Cascio, Janet Brady, Suman Ghosh, Jessica Ditto, Mary Leppert, Jean Lowe, Janell Fuller, Tara L. DuPont, Robin K. Ohls, Pamela Kloska, Saurabh Patel, Lauren Carbonell, Anna Maria Patiño‐Fernández, Carmen de Lerma, Susana Bombino, Arturo Serize, Kelly McDonough, Maiana De Cortada, Lacy Chavis, Jane Shannon, Bryan A. Comstock, Patrick J. Heagerty, Mark A. Konodi, Christopher Nefcy, Phuong T. Vu, Karl Kuban, Jean Lowe, T. Michael O’Shea, Manjiri Dighe, Todd L. Richards, Dennis Shaw, Colin Studholme, Christopher Traudt, Roberta A. Ballard, Bryan A. Comstock, Adam L. Hartman, Scott Janis, Sandra E. Juul, Dennis E. Mayock, T. Robin Ohls, Michael O’Shea, Ronnie Guillet, M. Bethany Ball, Hannah C. Glass, Ben Saville, Michael Schreiber,

Chronic Kidney Disease and Diabetes

ObjectiveTo evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.Study designWe performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.ResultsThe prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit.ConclusionsELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA. To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo. We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs. The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values at days 0, 7, 9, and 14). At 22-26 months of cGA, 16% of the cohort had an estimated glomerular filtration rate (eGFR) 30 mg/g, 23% had a systolic blood pressure (SBP) >95th percentile for age, and 40% had a diastolic blood pressure (DBP) >95th percentile for age. SBP >90th percentile occurred less often among recipients of erythropoietin (P < .04). This association remained even after controlling for gestational age, site, and sibship (aOR 0.6; 95% CI 0.39-0.92). We did not find statistically significant differences between treatment groups in eGFR, albumin/creatinine ratio, rates of SBP >95th percentile, or DBP >90th or >95th percentiles at the 2 year follow-up visit. ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.