Ian E McCoy1, Jesse Y Hsu2, Joseph V Bonventre3, Chirag R Parikh4, Alan S Go5, Kathleen D Liu6, Ana C Ricardo7, Anand Srivastava8, Debbie L Cohen9, Jiang He10, Jing Chen10,11, Panduranga S Rao12, Chi-Yuan Hsu. 1. Division of Nephrology, University of California San Francisco, San Francisco, California ian.mccoy@ucsf.edu. 2. Division of Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Division of Renal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 4. Division of Nephrology, Johns Hopkins University, Baltimore, Maryland. 5. Division of Research, Kaiser Permanente Northern California, Oakland, California. 6. Division of Nephrology, University of California San Francisco, San Francisco, California. 7. Division of Nephrology, University of Illinois, Chicago, Illinois. 8. Division of Nephrology, Northwestern University, Chicago, Illinois. 9. Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Department of Epidemiology, Tulane University, New Orleans, Louisiana. 11. Division of Nephrology, Tulane University, New Orleans, Louisiana. 12. Division of Nephrology, University of Michigan, Ann Arbor, Michigan.
Abstract
BACKGROUND: Some markers of inflammation-TNF receptors 1 and 2 (TNFR1 and TNFR2)-are independently associated with progressive CKD, as is a marker of proximal tubule injury, kidney injury molecule 1 (KIM-1). However, whether an episode of hospitalized AKI may cause long-term changes in these biomarkers is unknown. METHODS: Among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study, we identified 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥1.5). For each AKI hospitalization, we found the best matched non-AKI hospitalization (unique patients), using prehospitalization characteristics, including eGFR and urine protein/creatinine ratio. We measured TNFR1, TNFR2, and KIM-1 in banked plasma samples collected at annual CRIC study visits before and after the hospitalization (a median of 7 months before and 5 months after hospitalization). RESULTS: In the AKI and non-AKI groups, we found similar prehospitalization median levels of TNFR1 (1373 pg/ml versus 1371 pg/ml, for AKI and non-AKI, respectively), TNFR2 (47,141 pg/ml versus 46,135 pg/ml, respectively), and KIM-1 (857 pg/ml versus 719 pg/ml, respectively). Compared with matched study participants who did not experience AKI, study participants who did experience AKI had greater increases in TNFR1 (23% versus 10%, P<0.01), TNFR2 (10% versus 3%, P<0.01), and KIM-1 (13% versus -2%, P<0.01). CONCLUSIONS: Among patients with CKD, AKI during hospitalization was associated with increases in plasma TNFR1, TNFR2, and KIM-1 several months after their hospitalization. These results highlight a potential mechanism by which AKI may contribute to more rapid loss of kidney function months to years after the acute insult.
BACKGROUND: Some markers of inflammation-TNF receptors 1 and 2 (TNFR1 and TNFR2)-are independently associated with progressive CKD, as is a marker of proximal tubule injury, kidney injury molecule 1 (KIM-1). However, whether an episode of hospitalized AKI may cause long-term changes in these biomarkers is unknown. METHODS: Among adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study, we identified 198 episodes of hospitalized AKI (defined as peak/nadir inpatient serum creatinine values ≥1.5). For each AKI hospitalization, we found the best matched non-AKI hospitalization (unique patients), using prehospitalization characteristics, including eGFR and urine protein/creatinine ratio. We measured TNFR1, TNFR2, and KIM-1 in banked plasma samples collected at annual CRIC study visits before and after the hospitalization (a median of 7 months before and 5 months after hospitalization). RESULTS: In the AKI and non-AKI groups, we found similar prehospitalization median levels of TNFR1 (1373 pg/ml versus 1371 pg/ml, for AKI and non-AKI, respectively), TNFR2 (47,141 pg/ml versus 46,135 pg/ml, respectively), and KIM-1 (857 pg/ml versus 719 pg/ml, respectively). Compared with matched study participants who did not experience AKI, study participants who did experience AKI had greater increases in TNFR1 (23% versus 10%, P<0.01), TNFR2 (10% versus 3%, P<0.01), and KIM-1 (13% versus -2%, P<0.01). CONCLUSIONS: Among patients with CKD, AKI during hospitalization was associated with increases in plasma TNFR1, TNFR2, and KIM-1 several months after their hospitalization. These results highlight a potential mechanism by which AKI may contribute to more rapid loss of kidney function months to years after the acute insult.
Authors: Junichi Ishigami; Jonathan T Taliercio; Harold I Feldman; Anand Srivastava; Raymond R Townsend; Debbie L Cohen; Edward J Horwitz; Panduranga Rao; Jeanne Charleston; Jeffrey C Fink; Ana C Ricardo; James Sondheimer; Teresa K Chen; Myles Wolf; Tamara Isakova; Lawrence J Appel; Kunihiro Matsushita Journal: J Am Soc Nephrol Date: 2020-06-23 Impact factor: 10.121
Authors: Lowell J Lo; Alan S Go; Glenn M Chertow; Charles E McCulloch; Dongjie Fan; Juan D Ordoñez; Chi-yuan Hsu Journal: Kidney Int Date: 2009-07-29 Impact factor: 10.612
Authors: Marco Colombo; Erkka Valo; Stuart J McGurnaghan; Niina Sandholm; Luke A K Blackbourn; R Neil Dalton; David Dunger; Per-Henrik Groop; Paul M McKeigue; Carol Forsblom; Helen M Colhoun Journal: Diabetologia Date: 2019-06-20 Impact factor: 10.122
Authors: Sarah J Schrauben; Hsiang-Yu Chen; Eugene Lin; Christopher Jepson; Wei Yang; Julia J Scialla; Michael J Fischer; James P Lash; Jeffrey C Fink; L Lee Hamm; Radhika Kanthety; Mahboob Rahman; Harold I Feldman; Amanda H Anderson Journal: PLoS Med Date: 2020-12-11 Impact factor: 11.069
Authors: Mary Hannan; Sajid Ansari; Natalie Meza; Amanda H Anderson; Anand Srivastava; Sushrut Waikar; Jeanne Charleston; Matthew R Weir; Jonathan Taliercio; Edward Horwitz; Milda R Saunders; Katherine Wolfrum; Harold I Feldman; James P Lash; Ana C Ricardo Journal: Clin J Am Soc Nephrol Date: 2020-11-11 Impact factor: 8.237
Authors: Areef Ishani; Jay L Xue; Jonathan Himmelfarb; Paul W Eggers; Paul L Kimmel; Bruce A Molitoris; Allan J Collins Journal: J Am Soc Nephrol Date: 2008-11-19 Impact factor: 14.978
Authors: Ian E McCoy; Jesse Y Hsu; Joseph V Bonventre; Chirag R Parikh; Alan S Go; Kathleen D Liu; Ana C Ricardo; Anand Srivastava; Debbie L Cohen; Jiang He; Jing Chen; Panduranga S Rao; Anthony N Muiru; Chi-Yuan Hsu Journal: BMC Nephrol Date: 2022-09-13 Impact factor: 2.585