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Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials.

Abstract
The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.
AuthorsMaría V Irazabal, Laureano J Rangel, Eric J Bergstralh, Sara L Osborn, Amber J Harmon, Jamie L Sundsbak, Kyongtae T Bae, Arlene B Chapman, Jared J Grantham, Michal Mrug, Marie C Hogan, Ziad M El-Zoghby, Peter C Harris, Bradley J Erickson, Bernard F King, Vicente E Torres, CRISP Investigators
JournalJournal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 26 Issue 1 Pg. 160-72 (Jan 2015) ISSN: 1533-3450 [Electronic] United States
PMID24904092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2015 by the American Society of Nephrology.
Topics
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Clinical Trials as Topic
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Image Processing, Computer-Assisted
  • Kidney (pathology)
  • Kidney Failure, Chronic (diagnosis, mortality, pathology)
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Patient Selection
  • Polycystic Kidney, Autosomal Dominant (diagnosis, mortality, pathology)
  • Tomography, X-Ray Computed

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