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Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection

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Abstract

Background

Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications.

Methods

Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model.

Results

Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were >95 % for both the at-risk cohort and those with RLE.

Conclusions

Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

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Acknowledgments

The authors would like to thank the researchers and institutions involved in the conduct of 219C as well as the leadership and participants of the P219/219C protocol team and the 219C iDACS617 Working Group. The authors are grateful for the contributions of Joyce Kraimer, Carol Elgie, Barbara Heckman, Shirley Traite, and Nathan Tryon. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). This project has been funded in whole or in part with Federal funds from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800014C. The authors also thank the individual staff members and sites who have participated in the conduct of this study, as provided in Appendix 1.

James M Oleske MD MPH, Founding Chair and Russell Van Dyke MD, Chair, Mark Abzug MD and John Farley MD; Vice-Chairs, Mary Glen Fowler MD MPH, Michael Brady MD and Wayne Dankner MD; Past Vice-Chairs,

Protocol Team Members (versions 1 and 2 of PACTG-219): Mary Culnane MS CRNP, Elizabeth Hawkins, Lynne Mofenson MD, Yvonne J Bryson, MD, Edward M Connor MD, Lawrence D’Angelo MD MPH, Mark Mintz MD, Karen J O’Donnell PhD, Margaret Oxtoby, MD, Andrea Rubin Hale RN MPH, Richard D Gelber PhD, Steven Gortmaker PhD, William Lenderking PhD, Lynn Marrow, Christina Joy RN MSM, Colleen Clark MPH, Bethann Cunningham MS, Rhoda Sperling MD, Gwendolyn B Scott MD, Courtney Fletcher PharmD, Blake Caldwell MD, Dianne Donovan,

Protocol Team Members (versions 3 and 4 of PACTG-219C): Elizabeth Smith MD, Anne Fresia, Gregory Ciupak, Michelle Eagle PA, Dorothy R Smith MS CPNP, Paul Palumbo MD, John Sleasman MD, James Connor MD, Michael Hughes PhD, Rebecca Oyomopita MSc, George Johnson MD, Andrew Wiznia MD, Nancy Hutton MD, Andrea Kovacs MD, Mary Sawyer MD, Martin Anderson MD, Audrey Rogers PhD MPH, William Borkowsky MD, Jane Lindsey ScD, Jack Moye MD, Myron Levin MD, Marilyn Crain MD MPH, Paul Britto MS, Ruth Toumala MD, Joseph Cervia MD, Eileen Monagham, Kenneth Dominguez MD, Melody Higgins RN MS, George Seage DSc MPH, Denise Gaughan MPH, Phil Gona PhD, William Shearer MD PhD, Lois Howland DPH MS RN, Deborah Storm PhD RN, Kathleen Malee PhD, Wendy Mitchell MD, Carol Gore, Eve Powell, Michelle McConnell MD, Newana Beatty, Susan Brogly PhD, Jennifer Bryant CRA, Miriam Chernoff PhD, Barbara Heckman BS, Dawn English, Edward Handelsman MD, Patrick Jean-Philippe MD, Kathleen Kaiser, Joyce Kraimer MS, Linda Millar, Shirley Traite MSW, Paige Williams PhD, Elizabeth Woods MD MPH, Carol Worrell MD.

iDACS617 Working Group: Charles D. Mitchell, MD, MS, Miriam C. Chernoff, PhD, George R. Seage III, DSc, MPH, Murli U. Purswani, MD, Hans M.L. Spiegel, MD Barbara Heckman., James M. Oleske, MD, MPH, and Warren Andiman, MD

Author information

Authors and Affiliations

  1. Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Miami Miller School of Medicine, Room 286, Batchelor Children’s Research Institute, 1580 NW 10th Avenue, Miami, 33136, FL, USA

    Charles D. Mitchell

  2. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, USA

    Miriam C. Chernoff & George R. Seage III

  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    George R. Seage III

  4. Division of Pediatric Infectious Disease, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Boston, MA, USA

    Murli U. Purswani

  5. HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

    Hans M. L. Spiegel

  6. Division of Pediatric Nephrology, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, USA

    Gaston Zilleruelo & Carolyn Abitbol

  7. Frontier Science and Technology Research Foundation, Amherst, NY, USA

    Barbara Heckman

  8. Department of Pediatrics, Rutgers University/New Jersey Medical School, New Jersey, USA

    Christopher B. Ponce & James M. Oleske

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  1. Charles D. Mitchell
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  2. Miriam C. Chernoff
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  3. George R. Seage III
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  4. Murli U. Purswani
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  5. Hans M. L. Spiegel
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  6. Gaston Zilleruelo
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  7. Carolyn Abitbol
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  8. Barbara Heckman
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for the IMPAACT 219/219C Study Team

Corresponding author

Correspondence to Charles D. Mitchell.

Additional information

HJF is a global organization dedicated to advancing military medical research and is contractor to the National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD

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Appendix I: Participating institutions in the U.S.-based multisite cohort study, PACTG 219/219C, between 1993–2007

Appendix I: Participating institutions in the U.S.-based multisite cohort study, PACTG 219/219C, between 1993–2007

The following institutions and clinical site investigators participated in PACTG 219/219C:

University of New Jersey Medical and Dental School–Department of Pediatrics, Division of Allergy, Immunology & Infectious Diseases: Dr. James Oleske, Dr. Arlene Bardeguez, Dr. Arry Dieudonne, Linda Bettica, Juliette Johnson; Boston Medical Center, Division of Pediatric Infectious Diseases: Dr. Stephen I. Pelton, Dr. Ellen R. Cooper, Lauren Kay, Ann Marie Regan Med; Children’s Hospital LA–Department of Pediatrics, Division of Clinical Immunology & Allergy: Dr. Joseph A. Church, Theresa Dunaway; Long Beach Memorial Medical Center, Miller Children’s Hospital: Dr. Audra Deveikis, Dr. Jagmohan Batra, Susan Marks, Ilaisanee Fineanganofo; Harbor-UCLA Medical Center–Department of Pediatrics, Division of Infectious Diseases: Dr. Margaret A. Keller, Dr. Nasser Redjal, Spring Wettgen, Sheryl Sullivan; Johns Hopkins Hospital & Health System–Department of Pediatrics, Division of Infectious Diseases: Dr. Nancy Hutton, Beth Griffith, Mary Joyner, Carolyn Keifer; University of Maryland Medical Center, Division of Pediatric Immunology & Rheumatology: Dr. Douglas Watson, Dr. John Farley; Texas Children’s Hospital, Allergy & Immunology Clinic: Dr. Mary E. Paul, Chivon D. Jackson, Faith Minglana, Dr. Heidi Schwarzwald; Cook County Hospital: Dr. Kenneth M. Boyer, Dr. Jamie Martinez, Dr. James B. McAuley, Maureen Haak; Children’s Hospital of Columbus, Ohio: Dr. Michael Brady, Dr. Katalin Koranyi, Jane Hunkler, Charon Callaway; University of Miami Miller School of Medicine, Division of Pediatric Immunology & Infectious Disease: Dr. Gwendolyn B. Scott, Dr. Charles D. Mitchell, Dr. Claudia Florez, Joan Gamber; University of California San Francisco School of Medicine, Department of Pediatrics: Dr. Diane W. Wara, Dr. Ann Petru, Nicole Tilton, Mica Muscat; Children’s Hospital & Research Center Oakland, Pediatric Clinical Research Center & Research Lab: Dr. Ann Petru, Teresa Courville, Karen Gold, Katherine Eng; University of California San Diego Mother, Child & Adolescent HIV Program: Dr. Stephen A. Spector, Dr. Rolando M. Viani, Mary Caffery, Kimberly Norris; Duke University School of Medicine–Department of Pediatrics, Children’s Health Center: Margaret Donnelly, Dr. Kathleen McGann, Carole Mathison, John Swetnam; University of North Carolina at Chapel Hill School of Medicine–Department of Pediatrics, Division of Immunology and Infectious Diseases: Dr. Tom Belhorn, Jean Eddleman, Betsy Pitkin; Schneider Children’s Hospital: Dr. Vincent R. Bonagura, Dr. Susan Schuval, Dr. Blanka Kaplan, Dr. Constance Colter; Harlem Hospital Center: Dr. Elaine J. Abrams, Maxine Frere, Delia Calo; New York University School of Medicine, Division of Pediatric Infectious Diseases: Dr. William Borkowsky, Nagamah Deygoo, Maryam Minter, Seham Akleh; Children’s National Medical Center, George Washington University: Diana Dobbins, Deidre Wimbley, Dr. Lawrence D’Angelo, Hans Spiegel; University of Washington School of Medicine–Children’s Hospital and Regional Medical Center: Dr. Ann J. Melvin, Kathleen M. Mohan, Michele Acker, Suzanne Phelps; University of Illinois College of Medicine at Chicago, Department of Pediatrics: Dr. Kenneth C. Rich, Dr. Karen Hayani, Julia Camacho; Yale University School of Medicine–Department of Pediatrics, Division of Infectious Disease: Dr. Warren A. Andiman, Leslie Hurst, Dr. Janette de Jesus, Donna Schroeder; SUNY at Stony Brook School of Medicine, Division of Pediatric Infectious Diseases: Denise Ferraro, Jane Perillo, Michele Kelly; Howard University Hospital, Department of Pediatrics & Child Health: Dr. Sohail Rana, Dr. Helga Finke, Patricia Yu, Dr. Jhoanna Roa; LA County/University of Southern California Medical Center: Dr. Andrea Kovacs, Dr. James Homans, Dr. Michael Neely, Dr. LaShonda Spencer; University of Florida Health Science Center Jacksonville, Division of Pediatric Infectious Disease & Immunology: Dr. Mobeen H. Rathore, Dr. Ayesha Mirza, Kathy Thoma, Almer Mendoza; North Broward Hospital District, Children’s Diagnostic & Treatment Center: Dr. Ana M. Puga, Dr. Guillermo Talero, James Blood, Stefanie Juliano; University of Rochester Medical Center, Golisano Children’s Hospital: Dr. Geoffrey A. Weinberg, Barbra Murante, Susan Laverty, Dr. Francis Gigliotti; Medical College of Virginia: Dr. Suzanne R. Lavoie, Tima Y. Smith; St. Jude Children’s Research Hospital, Department of Infectious Diseases: Dr. Aditya Gaur, Dr. Katherine Knapp, Dr. Nehali Patel, Marion Donohoe; University of Puerto Rico, U. Children’s Hospital AIDS: Dr. Irma L. Febo, Dr. Licette Lugo, Ruth Santos, Ibet Heyer; Children’s Hospital of Philadelphia, Center for Pediatric & Adolescent AIDS: Dr. Steven D. Douglas, Dr. Richard M. Rutstein, Carol A. Vincent, Patricia C. Coburn; St. Christopher’s Hospital for Children/Drexel University College of Medicine: Dr. Jill Foster, Dr. Janet Chen, Dr. Daniel Conway, Dr. Roberta Laguerre; Bronx-Lebanon Hospital Center, Infectious Diseases: Dr. Emma Stuard, Caroline Nubel, Dr. Stefan Hagmann, Dr. Murli Purswani; New York Medical College/Metropolitan Hospital Center: Dr. Mahrukh Bamji, Dr. Indu Pathak, Dr. Savita Manwani, Dr. Ekta Patel; University of Massachusetts Memorial Children’s Medical School, Department of Pediatrics: Dr. Katherine Luzuriaga, Dr. Richard Moriarty; Baystate Health, Baystate Medical Center: Dr. Barbara W. Stechenberg, Dr. Donna J. Fisher, Dr. Alicia M. Johnston, Maripat Toye; Connecticut Children’s Medical Center: Dr. Juan C. Salazar, Kirsten Fullerton, Gail Karas; Medical College of Georgia School of Medicine, Department of Pediatrics, Division of Infectious Disease: Dr. Stuart Foshee, Dr. Chitra S. Mani, Dr. Deniis L. Murray, Dr. Christopher White, University of South Alabama College of Medicine, Southeast Pediatric ACTU: Dr. Mary Y. Mancao, Dr. Benjamin Estrada; LSU Health Sciences Center: Dr. Ronald D. Wilcox; Tulane University Health Sciences Center: Dr. Margarita Silio, Dr. Thomas Alchediak, Cheryl Borne, Shelia Bradford; St. Josephs Hospital and Medical Center

Cooper University Hospital; Children’s Hospital Boston, Division of Infectious Diseases; David Geffen School of Medicine at UCLA, Department of Pediatrics, Division of Infectious Diseases; Children’s Hospital of Orange County; Children’s Memorial Hospital, Department of Pediatrics, Division of Infectious Disease; University of Chicago, Department of Pediatrics, Division of Infectious Disease; Mt. Sinai Hospital Medical Center, Chicago, Women’s & Children’s HIV Program; Columbia University Medical Center; Pediatric ACTU; Incarnation Children’s Center; Cornell University, Division of Pediatric Infectious Diseases & Immunology; University of Miami Miller School of Medicine, Jackson Memorial Hospital; Bellevue Hospital (Pediatric); San Francisco General (Pediatric); Phoenix Children’s Hospital; Metropolitan Hospital Center (N.Y.); University of Cincinnati; SUNY Downstate Medical Center; Children’s Hospital at Downstate; North Shore University Hospital; Jacobi Medical Center, University of South Florida, Department of Pediatrics, Division of Infectious Diseases; Cornell University; Oregon Health & Science University, Department of Pediatrics, Division of Infectious Diseases; Children’s Hospital of the King’s Daughters, Infectious Disease; Lincoln Medical & Mental Health Center; Mt. Sinai School of Medicine, Division of Pediatric Infectious Diseases; Emory University Hospital; San Juan City Hospital; UMDNJ;, Robert Wood Johnson Medical School; Ramon Ruiz Arnau University Hospital; Medical University of South Carolina; SUNY Upstate Medical University, Department of Pediatrics; Wayne State University School of Medicine; Children’s Hospital of Michigan; Children’s Hospital at Albany Medical Center; Children’s Medical Center of Dallas; Children’s Hospital, University of Colorado at Denver and Health Sciences Center, Pediatric Infectious Diseases; Columbus Children’s Hospital; University of Florida College of Medicine, Department of Pediatrics, Division of Immunology, Infectious Diseases & Allergy; University of Mississippi Medical Center; Palm Beach County Health Department; Children’s Hospital LA, Department of Pediatrics, Division of Adolescent Medicine; Vanderbilt University Medical Center, Division of Pediatric Infectious Diseases; Washington University School of Medicine at St. Louis; St. Louis Children’s Hospital; Children’s Hospital & Medical Center; Seattle ACTU; Oregon Health Sciences University; St. Luke’s-Roosevelt Hospital Center; Montefiore Medical Center, Albert Einstein College of Medicine; Children’s Hospital, Washington, D.C.; Children’s Hospital of the King’s Daughters; University of Alabama at Birmingham; Department of Pediatrics, Division of Infectious Diseases; Columbus Regional HealthCare System; The Medical Center, Sacred Heart Children’s Hospital/CMS of Florida; Bronx Municipal Hospital Center/Jacobi Medical Center.

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Mitchell, C.D., Chernoff, M.C., Seage, G.R. et al. Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection. Pediatr Nephrol 30, 153–165 (2015). https://doi.org/10.1007/s00467-014-2909-1

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