Kathleen D Liu1, Wei Yang2, Alan S Go3, Amanda H Anderson2, Harold I Feldman2, Michael J Fischer4, Jiang He5, Radhakrishna R Kallem2, John W Kusek6, Stephen R Master7, Edgar R Miller8, Sylvia E Rosas9, Susan Steigerwalt10, Kaixiang Tao2, Matthew R Weir11, Chi-Yuan Hsu12. 1. Department of Medicine, University of California, San Francisco, San Francisco, CA. 2. Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA. 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA. 4. Department of Medicine, Jesse Brown VAMC and University of Illinois Hospital and Health Sciences System, Chicago, IL. 5. Department of Epidemiology, Tulane University, New Orleans, LA. 6. The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. 7. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA. 8. Department of Medicine, Johns Hopkins University, Baltimore, MD. 9. Department of Medicine, Joslin Diabetes Center & Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 10. St. Claire Specialty Physicians, St. John Hospital & Medical Center, Detroit, MI. 11. Department of Medicine, University of Maryland, Baltimore, MD. 12. Department of Medicine, University of California, San Francisco, San Francisco, CA; Division of Research, Kaiser Permanente Northern California, Oakland, CA. Electronic address: hsuchi@medicine.ucsf.edu.
Abstract
BACKGROUND: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). STUDY DESIGN: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. SETTING & PARTICIPANTS: 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. PREDICTOR: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. OUTCOMES: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. MEASUREMENTS: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). RESULTS: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. LIMITATIONS: Urine NGAL was measured only once. CONCLUSIONS: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.
BACKGROUND:Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria). STUDY DESIGN: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study. SETTING & PARTICIPANTS: 3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m(2) enrolled from June 2003 through August 2008. PREDICTOR: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. OUTCOMES: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011. MEASUREMENTS: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). RESULTS: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. LIMITATIONS: Urine NGAL was measured only once. CONCLUSIONS: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.
Authors: Carmen A Peralta; Ronit Katz; Joseph V Bonventre; Venkata Sabbisetti; David Siscovick; Mark Sarnak; Michael G Shlipak Journal: Am J Kidney Dis Date: 2012-06-30 Impact factor: 8.860
Authors: W D Rosamond; A R Folsom; L E Chambless; C H Wang; P G McGovern; G Howard; L S Copper; E Shahar Journal: Stroke Date: 1999-04 Impact factor: 7.914
Authors: Edward R Smith; Darren Lee; Michael M Cai; Laurie A Tomlinson; Martin L Ford; Lawrence P McMahon; Stephen G Holt Journal: Nephrol Dial Transplant Date: 2013-01-16 Impact factor: 5.992
Authors: Axel C Carlsson; Anders Larsson; Johanna Helmersson-Karlqvist; Lars Lind; Erik Ingelsson; Tobias E Larsson; Johan Sundström; Johan Arnlöv Journal: Eur J Heart Fail Date: 2012-12-07 Impact factor: 15.534
Authors: Johanna Helmersson-Karlqvist; Anders Larsson; Axel C Carlsson; Per Venge; Johan Sundström; Erik Ingelsson; Lars Lind; Johan Arnlöv Journal: Atherosclerosis Date: 2013-01-18 Impact factor: 5.162
Authors: Neil J Glassford; Antoine G Schneider; Shengyuan Xu; Glenn M Eastwood; Helen Young; Leah Peck; Per Venge; Rinaldo Bellomo Journal: Intensive Care Med Date: 2013-08-06 Impact factor: 17.440
Authors: Mark J Sarnak; Andrew S Levey; Anton C Schoolwerth; Josef Coresh; Bruce Culleton; L Lee Hamm; Peter A McCullough; Bertram L Kasiske; Ellie Kelepouris; Michael J Klag; Patrick Parfrey; Marc Pfeffer; Leopoldo Raij; David J Spinosa; Peter W Wilson Journal: Circulation Date: 2003-10-28 Impact factor: 29.690
Authors: Kathleen D Liu; Wei Yang; Amanda H Anderson; Harold I Feldman; Sevag Demirjian; Takayuki Hamano; Jiang He; James Lash; Eva Lustigova; Sylvia E Rosas; Michael S Simonson; Kaixiang Tao; Chi-yuan Hsu Journal: Kidney Int Date: 2013-01-23 Impact factor: 10.612
Authors: Helen V Alderson; James P Ritchie; Sabrina Pagano; Rachel J Middleton; Menno Pruijm; Nicolas Vuilleumier; Philip A Kalra Journal: Clin J Am Soc Nephrol Date: 2016-11-16 Impact factor: 8.237
Authors: Morgan E Grams; Wei Yang; Casey M Rebholz; Xue Wang; Anna C Porter; Lesley A Inker; Edward Horwitz; James H Sondheimer; L Lee Hamm; Jiang He; Matthew R Weir; Bernard G Jaar; Tariq Shafi; Lawrence J Appel; Chi-Yuan Hsu Journal: Am J Kidney Dis Date: 2017-03-30 Impact factor: 8.860
Authors: Jing Chen; Joshua D Bundy; L Lee Hamm; Chi-Yuan Hsu; James Lash; Edgar R Miller; George Thomas; Debbie L Cohen; Matthew R Weir; Dominic S Raj; Hsiang-Yu Chen; Dawei Xie; Panduranga Rao; Jackson T Wright; Mahboob Rahman; Jiang He Journal: Hypertension Date: 2019-04 Impact factor: 10.190
Authors: Elaine Ku; Wei Yang; Charles E McCulloch; Harold I Feldman; Alan S Go; James Lash; Nisha Bansal; Jiang He; Ed Horwitz; Ana C Ricardo; Tariq Shafi; James Sondheimer; Raymond R Townsend; Sushrut S Waikar; Chi-Yuan Hsu Journal: Am J Kidney Dis Date: 2019-11-12 Impact factor: 8.860
Authors: Meyeon Park; Chi-Yuan Hsu; Alan S Go; Harold I Feldman; Dawei Xie; Xiaoming Zhang; Theodore Mifflin; Sushrut S Waikar; Venkata S Sabbisetti; Joseph V Bonventre; Josef Coresh; Robert G Nelson; Paul L Kimmel; John W Kusek; Mahboob Rahman; Jeffrey R Schelling; Ramachandran S Vasan; Kathleen D Liu Journal: Clin J Am Soc Nephrol Date: 2017-03-02 Impact factor: 8.237
Authors: Elaine Ku; Dawei Xie; Michael Shlipak; Amanda Hyre Anderson; Jing Chen; Alan S Go; Jiang He; Edward J Horwitz; Mahboob Rahman; Ana C Ricardo; James H Sondheimer; Raymond R Townsend; Chi-Yuan Hsu Journal: J Am Soc Nephrol Date: 2015-11-24 Impact factor: 10.121
Authors: Nisha Bansal; Charles E McCulloch; Feng Lin; Arnold Alper; Amanda H Anderson; Magda Cuevas; Alan S Go; Radhakrishna Kallem; John W Kusek; Claudia M Lora; Eva Lustigova; Akinlolu Ojo; Mahboob Rahman; Cassianne Robinson-Cohen; Raymond R Townsend; Jackson Wright; Dawei Xie; Chi-Yuan Hsu Journal: Hypertension Date: 2017-07-03 Impact factor: 10.190