Bradley A Warady1, Alison G Abraham2, George J Schwartz3, Craig S Wong4, Alvaro Muñoz2, Aisha Betoko2, Mark Mitsnefes5, Frederick Kaskel6, Larry A Greenbaum7, Robert H Mak8, Joseph Flynn9, Marva M Moxey-Mims10, Susan Furth11. 1. Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, MO. Electronic address: bwarady@cmh.edu. 2. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 3. University of Rochester, Rochester, NY. 4. University of New Mexico/Children's Hospital, Albuquerque, NM. 5. Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 6. Children's Hospital at Montefiore, New York, NY. 7. Emory University and Children's Healthcare of Atlanta, Atlanta, GA. 8. University of California at San Diego, La Jolla, CA. 9. Seattle Children's Hospital, Seattle, WA. 10. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 11. The Children's Hospital of Philadelphia, Philadelphia, PA.
Abstract
BACKGROUND: Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. STUDY DESIGN: Prospective multicenter observational cohort study. SETTING & PARTICIPANTS: 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. PREDICTORS: Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. OUTCOMES: Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). RESULTS: 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. LIMITATIONS: Small number of events in glomerular patients and use of internal cross-validation. CONCLUSIONS: Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.
BACKGROUND: Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. STUDY DESIGN: Prospective multicenter observational cohort study. SETTING & PARTICIPANTS: 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. PREDICTORS: Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. OUTCOMES: Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). RESULTS: 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. LIMITATIONS: Small number of events in glomerular patients and use of internal cross-validation. CONCLUSIONS: Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.
Authors: Jérôme Rossert; Adeera Levin; Simon D Roger; Walter H Hörl; Bruno Fouqueray; Cristiana Gassmann-Mayer; Dieter Frei; William M McClellan Journal: Am J Kidney Dis Date: 2006-05 Impact factor: 8.860
Authors: Susan L Furth; Stephen R Cole; Jeffrey J Fadrowski; Arlene Gerson; Christopher B Pierce; Manju Chandra; Robert Weiss; Frederick Kaskel Journal: Pediatr Nephrol Date: 2006-11-21 Impact factor: 3.714
Authors: Nora Voormolen; Marlies Noordzij; Diana C Grootendorst; Ivo Beetz; Yvo W Sijpkens; Jeannette G van Manen; Elisabeth W Boeschoten; Roel M Huisman; Raymond T Krediet; Friedo W Dekker Journal: Nephrol Dial Transplant Date: 2007-05-21 Impact factor: 5.992
Authors: Susan L Furth; Stephen R Cole; Marva Moxey-Mims; Frederick Kaskel; Robert Mak; George Schwartz; Craig Wong; Alvaro Muñoz; Bradley A Warady Journal: Clin J Am Soc Nephrol Date: 2006-07-19 Impact factor: 8.237
Authors: Joseph T Flynn; Mark Mitsnefes; Christopher Pierce; Steven R Cole; Rulan S Parekh; Susan L Furth; Bradley A Warady Journal: Hypertension Date: 2008-08-25 Impact factor: 10.190
Authors: George J Schwartz; Alvaro Muñoz; Michael F Schneider; Robert H Mak; Frederick Kaskel; Bradley A Warady; Susan L Furth Journal: J Am Soc Nephrol Date: 2009-01-21 Impact factor: 10.121
Authors: Jürgen Floege; Robert H Mak; Bruce A Molitoris; Giuseppe Remuzzi; Pierre Ronco Journal: Nat Rev Nephrol Date: 2015-09-29 Impact factor: 28.314
Authors: Na Ri Kang; Yo Han Ahn; Eujin Park; Hyun Jin Choi; Seong Heon Kim; Heeyeon Cho; Min Hyun Cho; Jae Il Shin; Joo Hoon Lee; Young Seo Park; Hae Il Cheong; Hee Gyung Kang; Il-Soo Ha; Young Sook Kwack; Kyoung Hee Han Journal: Pediatr Nephrol Date: 2019-06-20 Impact factor: 3.714
Authors: Darcy K Weidemann; Alison G Abraham; Jennifer L Roem; Susan L Furth; Bradley A Warady Journal: Am J Kidney Dis Date: 2020-01-24 Impact factor: 8.860
Authors: Ellen R Brooks; Shannon Haymond; Alfred Rademaker; Christopher Pierce; Irene Helenowski; Rod Passman; Faye Vicente; Bradley A Warady; Susan L Furth; Craig B Langman Journal: Pediatr Nephrol Date: 2017-12-07 Impact factor: 3.714
Authors: Denver D Brown; Jennifer Roem; Derek K Ng; Kimberly J Reidy; Juhi Kumar; Matthew K Abramowitz; Robert H Mak; Susan L Furth; George J Schwartz; Bradley A Warady; Frederick J Kaskel; Michal L Melamed Journal: Clin J Am Soc Nephrol Date: 2020-05-28 Impact factor: 8.237
Authors: Anthony A Portale; Myles S Wolf; Shari Messinger; Farzana Perwad; Harald Jüppner; Bradley A Warady; Susan L Furth; Isidro B Salusky Journal: Clin J Am Soc Nephrol Date: 2016-08-25 Impact factor: 8.237