Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents

The chronic kidney disease in children (CKiD) cohort

Bradley A. Warady, Alison G. Abraham, George J. Schwartz, Craig S. Wong, Alvaro Muñoz, Aisha Betoko, Mark Mitsnefes, Frederick J. Kaskel, Larry A. Greenbaum, Robert H. Mak, Joseph Flynn, Marva M. Moxey-Mims, Susan Furth

Research output: Contribution to journalArticle

67 Citations (Scopus)

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 > 2 mg/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 >2 mg/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.

Original languageEnglish (US)
Pages (from-to)878-888
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume65
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

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Kidney Diseases
Chronic Renal Insufficiency
Hypoalbuminemia
Glomerular Filtration Rate
Renal Replacement Therapy
Dyslipidemias
Blood Pressure
Anemia
Creatinine
Proteinuria
Observational Studies
Disease Progression
Proteins
Cohort Studies
Demography
Prospective Studies

Keywords

  • adolescents
  • children
  • chronic kidney disease (CKD)
  • Chronic Kidney Disease in Children (CKiD) Study
  • disease progression
  • disease trajectory
  • end-stage renal disease (ESRD)
  • glomerular filtration rate (GFR)
  • Pediatric
  • proteinuria
  • renal replacement therapy (RRT)
  • risk factor
  • urinary protein-creatinine ratio (UPCR)

ASJC Scopus subject areas

  • Nephrology

Cite this

Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents : The chronic kidney disease in children (CKiD) cohort. / Warady, Bradley A.; Abraham, Alison G.; Schwartz, George J.; Wong, Craig S.; Muñoz, Alvaro; Betoko, Aisha; Mitsnefes, Mark; Kaskel, Frederick J.; Greenbaum, Larry A.; Mak, Robert H.; Flynn, Joseph; Moxey-Mims, Marva M.; Furth, Susan.

In: American Journal of Kidney Diseases, Vol. 65, No. 6, 01.06.2015, p. 878-888.

Research output: Contribution to journalArticle

Warady, BA, Abraham, AG, Schwartz, GJ, Wong, CS, Muñoz, A, Betoko, A, Mitsnefes, M, Kaskel, FJ, Greenbaum, LA, Mak, RH, Flynn, J, Moxey-Mims, MM & Furth, S 2015, 'Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents: The chronic kidney disease in children (CKiD) cohort', American Journal of Kidney Diseases, vol. 65, no. 6, pp. 878-888. https://doi.org/10.1053/j.ajkd.2015.01.008
Warady, Bradley A. ; Abraham, Alison G. ; Schwartz, George J. ; Wong, Craig S. ; Muñoz, Alvaro ; Betoko, Aisha ; Mitsnefes, Mark ; Kaskel, Frederick J. ; Greenbaum, Larry A. ; Mak, Robert H. ; Flynn, Joseph ; Moxey-Mims, Marva M. ; Furth, Susan. / Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents : The chronic kidney disease in children (CKiD) cohort. In: American Journal of Kidney Diseases. 2015 ; Vol. 65, No. 6. pp. 878-888.
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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 > 2 mg/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 >2 mg/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.",
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T1 - Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents

T2 - The chronic kidney disease in children (CKiD) cohort

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AU - Schwartz, George J.

AU - Wong, Craig S.

AU - Muñoz, Alvaro

AU - Betoko, Aisha

AU - Mitsnefes, Mark

AU - Kaskel, Frederick J.

AU - Greenbaum, Larry A.

AU - Mak, Robert H.

AU - Flynn, Joseph

AU - Moxey-Mims, Marva M.

AU - Furth, Susan

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N2 - 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 > 2 mg/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 >2 mg/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.

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KW - chronic kidney disease (CKD)

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KW - glomerular filtration rate (GFR)

KW - Pediatric

KW - proteinuria

KW - renal replacement therapy (RRT)

KW - risk factor

KW - urinary protein-creatinine ratio (UPCR)

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