TY - JOUR
T1 - Growth pattern of kidney cyst number and volume in autosomal dominant polycystic kidney disease
AU - Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)
AU - Bae, Kyongtae T.
AU - Zhou, Wen
AU - Shen, Chengli
AU - Landsittel, Douglas P.
AU - Wu, Zhiyuan
AU - Tao, Cheng
AU - Chapman, Arlene B.
AU - Torres, Vicente E.
AU - Yu, Alan S.L.
AU - Mrug, Michal
AU - Bennett, William M.
AU - Harris, Peter C.
N1 - Funding Information:
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, and 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 TranslationalSciencesClinicalandTranslationalScienceAwardsateach 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). D.P. Landsittel reports grants from NIDDK R01 grant to the University of Pittsburgh.
Funding Information:
Dr. Bae is a consultant to Kadmon and Otsuka. Dr. Chapman is a Steering Committee member for Otsuka Pharmaceuticals. Dr. Harris reports grants from Otsuka Pharmaceuticals, outside the submitted work. Dr. Mrug reports grants, personal fees and nonfinancial support from Otsuka, grants, personal fees and nonfinancial support from Sanofi, personal fees from ClearView Healthcare Partners, personal fees from Decision Resources Group Consulting, personal fees from CLARION Healthcare, outside the submitted work; and serves as the PKD Foundation Scientific Advisory Committee Chair. Dr. Torres reports grants and other from Otsuka Pharmaceuticals, during the conduct of the study; grants and other from Palladio Biosciences, other from Mironid, grants and other from Sanofi Genzyme, other from Vertex, grants from Acceleron Pharma Inc., grants from Regulus Therapeutics, and grants from Palladio Biosciences, outside the submitted work. Dr. Yu reports other from Regulus Therapeutics and personal fees from Sanofi,outsidethesubmittedwork.Dr.Bennett,Dr.Landsittel,Dr.Shen, Dr. Tao, Dr. Wu, and Dr. Zhou have nothing to disclose.
PY - 2019/6/7
Y1 - 2019/6/7
N2 - Background and objectives To evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease. Design, setting, participants, & measurements Kidney cyst number and cyst volume were measured from serial magnetic resonance images, giving a maximum follow-up of 14.23 years, from 241 patients with autosomal dominant polycystic kidney disease (15-46 years old at baseline). The growth pattern was analyzed, in association with sex, age, height-adjusted total kidney volume, and genotype, using linear mixed models of repeated measurements and tests of interactions with age (as a time-dependent covariate) to assess rates of change over time. Models were also fit using Irazabal class. Genotypic groups were characterized as either (1) PKD1 truncating, PKD1 nontruncating, and PKD2 pluspatients withnomutation detected; or (2) in combination with PKD1 mutation strength groups. Results Imaging and genetic data were collected (at least one visit) for 236 participants. The mean heightadjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit, while the mean height-adjusted total cyst volume increased exponentially from 305 to 770 ml. Height-adjusted total kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were all highly correlated over time. Female participants and participantswith larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. PKD1 was associated with significant increases in both cyst number and volume at a given age, but genotype did not significantly affect the rate of growth. Conclusions Both height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth.
AB - Background and objectives To evaluate the growth pattern of kidney cyst number and cyst volume in association with kidney size, demographics, and genotypes in autosomal dominant polycystic kidney disease. Design, setting, participants, & measurements Kidney cyst number and cyst volume were measured from serial magnetic resonance images, giving a maximum follow-up of 14.23 years, from 241 patients with autosomal dominant polycystic kidney disease (15-46 years old at baseline). The growth pattern was analyzed, in association with sex, age, height-adjusted total kidney volume, and genotype, using linear mixed models of repeated measurements and tests of interactions with age (as a time-dependent covariate) to assess rates of change over time. Models were also fit using Irazabal class. Genotypic groups were characterized as either (1) PKD1 truncating, PKD1 nontruncating, and PKD2 pluspatients withnomutation detected; or (2) in combination with PKD1 mutation strength groups. Results Imaging and genetic data were collected (at least one visit) for 236 participants. The mean heightadjusted total cyst number increased exponentially over time from a baseline value of 762 to 1715 at the last clinic visit, while the mean height-adjusted total cyst volume increased exponentially from 305 to 770 ml. Height-adjusted total kidney volume, height-adjusted total cyst number, and height-adjusted total cyst volume were all highly correlated over time. Female participants and participantswith larger height-adjusted total kidney volume at baseline showed smaller rates of change in the log of height-adjusted total cyst number and cyst volume. PKD1 was associated with significant increases in both cyst number and volume at a given age, but genotype did not significantly affect the rate of growth. Conclusions Both height-adjusted total cyst number and height-adjusted total cyst volume increased exponentially and more than doubled over 14.23 years of follow-up. Compared with PKD2 plus no mutation detected, PKD1 was associated with a greater cyst number and volume at a given age, but no significant difference in the rate of growth.
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U2 - 10.2215/CJN.10360818
DO - 10.2215/CJN.10360818
M3 - Article
C2 - 31088850
AN - SCOPUS:85067634805
VL - 14
SP - 823
EP - 833
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
SN - 1555-9041
IS - 6
ER -