Wei Yang1, Dawei Xie2, Amanda H Anderson2, Marshall M Joffe2, Tom Greene3, Valerie Teal2, Chi-yuan Hsu4, Jeffrey C Fink5, Jiang He6, James P Lash7, Akinlolu Ojo8, Mahboob Rahman9, Lisa Nessel2, John W Kusek10, Harold I Feldman2. 1. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Electronic address: weiyang@mail.med.upenn.edu. 2. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3. University of Utah, Salt Lake City, UT. 4. University of California at San Francisco, San Francisco, CA. 5. University of Maryland, Baltimore, MD. 6. Tulane University, New Orleans, LA. 7. University of Illinois at Chicago, Chicago, IL. 8. University of Michigan, Ann Arbor, MI. 9. Case Western Reserve University, Cleveland, OH. 10. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
Abstract
BACKGROUND: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. PREDICTORS: Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. OUTCOMES: Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage. RESULTS: Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. LIMITATIONS: Participants may not be representative of the entire CKD population. CONCLUSIONS: Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.
BACKGROUND: Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race. PREDICTORS: Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors. OUTCOMES: Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage. RESULTS: Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively. LIMITATIONS: Participants may not be representative of the entire CKD population. CONCLUSIONS: Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.
Authors: E J Lewis; L G Hunsicker; W R Clarke; T Berl; M A Pohl; J B Lewis; E Ritz; R C Atkins; R Rohde; I Raz Journal: N Engl J Med Date: 2001-09-20 Impact factor: 91.245
Authors: Jackson T Wright; George Bakris; Tom Greene; Larry Y Agodoa; Lawrence J Appel; Jeanne Charleston; DeAnna Cheek; Janice G Douglas-Baltimore; Jennifer Gassman; Richard Glassock; Lee Hebert; Kenneth Jamerson; Julia Lewis; Robert A Phillips; Robert D Toto; John P Middleton; Stephen G Rostand Journal: JAMA Date: 2002-11-20 Impact factor: 56.272
Authors: Xuelei Wang; Julia Lewis; Lawrence Appel; DeAnna Cheek; Gabriel Contreras; Marquetta Faulkner; Harold Feldman; Jennifer Gassman; Janice Lea; Joel Kopple; Mohammed Sika; Robert Toto; Tom Greene Journal: J Am Soc Nephrol Date: 2006-09-20 Impact factor: 10.121
Authors: B M Brenner; M E Cooper; D de Zeeuw; W F Keane; W E Mitch; H H Parving; G Remuzzi; S M Snapinn; Z Zhang; S Shahinfar Journal: N Engl J Med Date: 2001-09-20 Impact factor: 91.245
Authors: L Y Agodoa; L Appel; G L Bakris; G Beck; J Bourgoignie; J P Briggs; J Charleston; D Cheek; W Cleveland; J G Douglas; M Douglas; D Dowie; M Faulkner; A Gabriel; J Gassman; T Greene; Y Hall; L Hebert; L Hiremath; K Jamerson; C J Johnson; J Kopple; J Kusek; J Lash; J Lea; J B Lewis; M Lipkowitz; S Massry; J Middleton; E R Miller; K Norris; D O'Connor; A Ojo; R A Phillips; V Pogue; M Rahman; O S Randall; S Rostand; G Schulman; W Smith; D Thornley-Brown; C C Tisher; R D Toto; J T Wright; S Xu Journal: JAMA Date: 2001-06-06 Impact factor: 56.272
Authors: Amanda Hyre Anderson; Wei Yang; Chi-yuan Hsu; Marshall M Joffe; Mary B Leonard; Dawei Xie; Jing Chen; Tom Greene; Bernard G Jaar; Patricia Kao; John W Kusek; J Richard Landis; James P Lash; Raymond R Townsend; Matthew R Weir; Harold I Feldman Journal: Am J Kidney Dis Date: 2012-06-02 Impact factor: 8.860
Authors: Harold I Feldman; Lawrence J Appel; Glenn M Chertow; Denise Cifelli; Borut Cizman; John Daugirdas; Jeffrey C Fink; Eunice D Franklin-Becker; Alan S Go; L Lee Hamm; Jiang He; Tom Hostetter; Chi-Yuan Hsu; Kenneth Jamerson; Marshall Joffe; John W Kusek; J Richard Landis; James P Lash; Edgar R Miller; Emile R Mohler; Paul Muntner; Akinlolu O Ojo; Mahboob Rahman; Raymond R Townsend; Jackson T Wright Journal: J Am Soc Nephrol Date: 2003-07 Impact factor: 10.121
Authors: Rupal Mehta; Xuan Cai; Jungwha Lee; Julia J Scialla; Nisha Bansal; James H Sondheimer; Jing Chen; L Lee Hamm; Ana C Ricardo; Sankar D Navaneethan; Rajat Deo; Mahboob Rahman; Harold I Feldman; Alan S Go; Tamara Isakova; Myles Wolf Journal: JAMA Cardiol Date: 2016-08-01 Impact factor: 14.676
Authors: Chi-Yuan Hsu; Vernon M Chinchilli; Steven Coca; Prasad Devarajan; Nasrollah Ghahramani; Alan S Go; Raymond K Hsu; T Alp Ikizler; James Kaufman; Kathleen D Liu; Chirag R Parikh; W Brian Reeves; Mark Wurfel; Michael Zappitelli; Paul L Kimmel; Edward D Siew Journal: JAMA Intern Med Date: 2020-03-01 Impact factor: 21.873
Authors: Jason Lee; Charles E McCulloch; Joseph T Flynn; Joshua Samuels; Bradley A Warady; Susan L Furth; Divya Seth; Barbara A Grimes; Mark M Mitsnefes; Elaine Ku Journal: Clin J Am Soc Nephrol Date: 2020-03-11 Impact factor: 8.237
Authors: Haochang Shou; Jesse Y Hsu; Dawei Xie; Wei Yang; Jason Roy; Amanda H Anderson; J Richard Landis; Harold I Feldman; Afshin Parsa; Christopher Jepson Journal: Clin J Am Soc Nephrol Date: 2017-07-27 Impact factor: 8.237
Authors: Sushrut S Waikar; Anand Srivastava; Ragnar Palsson; Tariq Shafi; Chi-Yuan Hsu; Kumar Sharma; James P Lash; Jing Chen; Jiang He; John Lieske; Dawei Xie; Xiaoming Zhang; Harold I Feldman; Gary C Curhan Journal: JAMA Intern Med Date: 2019-04-01 Impact factor: 21.873
Authors: Michael J Fischer; Jesse Y Hsu; Claudia M Lora; Ana C Ricardo; Amanda H Anderson; Lydia Bazzano; Magdalena M Cuevas; Chi-Yuan Hsu; John W Kusek; Amada Renteria; Akinlolu O Ojo; Dominic S Raj; Sylvia E Rosas; Qiang Pan; Kristine Yaffe; Alan S Go; James P Lash Journal: J Am Soc Nephrol Date: 2016-05-05 Impact factor: 10.121
Authors: Jiang He; Katherine T Mills; Lawrence J Appel; Wei Yang; Jing Chen; Belinda T Lee; Sylvia E Rosas; Anna Porter; Gail Makos; Matthew R Weir; L Lee Hamm; John W Kusek Journal: J Am Soc Nephrol Date: 2015-09-17 Impact factor: 10.121
Authors: Manjula Kurella Tamura; Kristine Yaffe; Chi-Yuan Hsu; Jingrong Yang; Stephen Sozio; Michael Fischer; Jing Chen; Akinlolu Ojo; Jennifer DeLuca; Dawei Xie; Eric Vittinghoff; Alan S Go Journal: Am J Kidney Dis Date: 2016-03-10 Impact factor: 8.860