TY - JOUR
T1 - Baseline total kidney volume and the rate of kidney growth are associated with chronic kidney disease progression in Autosomal Dominant Polycystic Kidney Disease
AU - Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)
AU - Yu, Alan S.L.
AU - Shen, Chengli
AU - Landsittel, Douglas P.
AU - Harris, Peter C.
AU - Torres, Vicente E.
AU - Mrug, Michal
AU - Bae, Kyongtae T.
AU - Grantham, Jared J.
AU - Rahbari-Oskoui, Frederic F.
AU - Flessner, Michael F.
AU - Bennett, William M.
AU - Chapman, Arlene B.
N1 - Funding Information:
This paper is dedicated to the memory of Dr. Jared J. Grantham, who passed away while this manuscript was being prepared. Dr. Grantham was a founding investigator of CRISP and its scientific and moral compass and was a key intellectual driving force in developing the studies described in this paper. The CRISP study is supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (DK056943, DK056956, DK056957, DK056961), and by R01 DK113111. This study was also supported in part by the NIDDK through P30 grants to the Kansas PKD Research and Translation Core Center (DK106912) and the Mayo Translational PKD Center (DK090728), by the National Center for Research Resources General Clinical Research Centers at each institution (RR000039, Emory University; RR00585, Mayo College of Medicine; RR23940, Kansas University Medical Center; RR000032, University of Alabama at Birmingham), and the National Center for Advancing Translational Sciences Clinical and Translational Science Awards at each institution (RR025008 and TR000454, Emory; RR024150 and TR000135, Mayo College of Medicine; RR033179 and TR000001, Kansas University Medical Center; RR025777, TR000165, and TR001417, University of Alabama at Birmingham; RR024153 and TR000005, University of Pittsburgh School of Medicine). The investigators are indebted to the study coordinators in CRISP.
Funding Information:
VET, PCH, and MM have received research funding from Otsuka Pharmaceuticals. FFR-O is a consultant for Keryx and Kadmon and has received research funding from Otsuka and Genzyme. ABC is a consultant for Otsuka, Pfizer, and Sanofi and has received research funding from Boston Scientific, Kadmon, and Otsuka. All the other authors declared no competing interests.
Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2018/3
Y1 - 2018/3
N2 - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study (a prospective, multicenter, observational analysis of 241 patients with ADPKD initiated in 2000), baseline height-adjusted total kidney volume (htTKV) was shown to be associated with development of CKD stage 3 after eight years of follow-up. Here we conducted an extended study and found that in a multivariable logistic regression model, baseline htTKV was shown to be a strong, independent predictor for the development of CKD after a median follow-up of 13 years. The odds ratio of reaching each CKD stage per 100 mL/m increment in htTKV was 1.38 (95% confidence interval 1.19-1.60) for stage 3, 1.42 (1.23-1.64) for stage 4, and 1.35 (1.18-1.55) for stage 5 or ESRD. Baseline htTKV was also associated with relative decreases in the glomerular filtration rate of 30%, and 57% or more. Moreover, the rate of change in htTKV was negatively correlated with the slope of the glomerular filtration rate. While ADPKD genotype was also associated with CKD outcomes, it was not an independent prognostic factor after adjusting for htTKV. Thus, baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD. These findings support the use of total kidney volume as a prognostic and potentially monitoring biomarker in ADPKD.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study (a prospective, multicenter, observational analysis of 241 patients with ADPKD initiated in 2000), baseline height-adjusted total kidney volume (htTKV) was shown to be associated with development of CKD stage 3 after eight years of follow-up. Here we conducted an extended study and found that in a multivariable logistic regression model, baseline htTKV was shown to be a strong, independent predictor for the development of CKD after a median follow-up of 13 years. The odds ratio of reaching each CKD stage per 100 mL/m increment in htTKV was 1.38 (95% confidence interval 1.19-1.60) for stage 3, 1.42 (1.23-1.64) for stage 4, and 1.35 (1.18-1.55) for stage 5 or ESRD. Baseline htTKV was also associated with relative decreases in the glomerular filtration rate of 30%, and 57% or more. Moreover, the rate of change in htTKV was negatively correlated with the slope of the glomerular filtration rate. While ADPKD genotype was also associated with CKD outcomes, it was not an independent prognostic factor after adjusting for htTKV. Thus, baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD. These findings support the use of total kidney volume as a prognostic and potentially monitoring biomarker in ADPKD.
KW - ADPKD
KW - chronic kidney disease
KW - glomerular filtration rate
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UR - http://www.scopus.com/inward/citedby.url?scp=85042350648&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2017.09.027
DO - 10.1016/j.kint.2017.09.027
M3 - Article
C2 - 29290310
AN - SCOPUS:85042350648
SN - 0085-2538
VL - 93
SP - 691
EP - 699
JO - Kidney international
JF - Kidney international
IS - 3
ER -