Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT
Rationale & Objective: Among individuals with chronic kidney disease (CKD), higher blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with greater risk of CKD progression. Their associations with risk of cardi...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Kidney Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590059525000603 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849702334886576128 |
|---|---|
| author | Nicholas Wettersten Ronit Katz Simon B. Ascher Rebecca Scherzer Alexander L. Bullen Teresa K. Chen Kasey Campos Pranav S. Garimella Michelle M. Estrella Michael G. Shlipak Joachim H. Ix |
| author_facet | Nicholas Wettersten Ronit Katz Simon B. Ascher Rebecca Scherzer Alexander L. Bullen Teresa K. Chen Kasey Campos Pranav S. Garimella Michelle M. Estrella Michael G. Shlipak Joachim H. Ix |
| author_sort | Nicholas Wettersten |
| collection | DOAJ |
| description | Rationale & Objective: Among individuals with chronic kidney disease (CKD), higher blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with greater risk of CKD progression. Their associations with risk of cardiovascular disease (CVD) and all-cause mortality in individuals with CKD remain uncertain. Study Design: An observational cohort study. Setting & Participants: Systolic Blood Pressure Intervention Trial participants with hypertension and CKD (eGFR <60 mL/min/1.73 m2) but without diabetes. Predictors: Plasma KIM-1, TNFR-1, and TNFR-2. Outcomes: A composite CVD outcome (acute coronary syndrome/myocardial infarction, stroke, heart failure, and CVD death) and all-cause mortality. Analytic Approach: Cox proportional hazards models, adjusting for CVD risk factors, eGFR, and urine albumin-to-creatinine ratio. Results: Total of 2,350 participants with a mean age of 73 ± 9 years, eGFR of 46 ± 10 mL/min/1.73m2 and 25% prevalence of CVD. Over more than 3 years follow-up, 293 CVD events (12%) and 160 deaths (7%) occurred. Higher KIM-1, TNFR-1, and TNFR-2 were associated with higher risk of the composite CVD outcome after adjusting for CVD risk factors, but associations were no longer significant after adjusting for eGFR and urine albumin-to-creatinine ratio (KIM-1: HR = 1.13, 95% CI, 0.99-1.30; TNFR-1: HR = 1.03, 95% CI, 0.72-1.46; TNFR-2: HR = 0.98, 95% CI, 0.76-1.26). In contrast, in fully adjusted models, higher plasma KIM-1 and TNFR-1, but not TNFR-2, were associated with higher risk of all-cause mortality (KIM-1: HR = 1.23, 95% CI, 1.01-1.49; TNFR-1: HR = 2.09, 95% CI, 1.14-3.83; TNFR-2: HR = 1.19, 95% CI, 0.85-1.66). Limitations: No individuals with diabetes or stroke. Conclusions: In individuals with hypertension and nondiabetic CKD, associations of higher plasma KIM-1, TNFR-1, and TNFR-2 concentrations with CVD events were not independent of eGFR and albuminuria, whereas higher levels of plasma KIM-1 and TNFR-1 were independently associated with greater risk of all-cause mortality. Plain-Language Summary: Blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with progression of kidney disease. We evaluated if these biomarkers were associated with risk of cardiovascular events and all-cause mortality in individuals without diabetes with hypertension and chronic kidney disease from the Systolic Blood Pressure Intervention Trial adjusting for relevant risk factors and biomarkers. We found none of the biomarkers were associated with risk of cardiovascular events, whereas KIM-1 and TNFR-1 were associated with risk of all-cause mortality. These findings suggest KIM-1 and TNFR-1 may be useful for risk prediction and emphasize the importance of inflammation as a risk factor for mortality. |
| format | Article |
| id | doaj-art-cb56d72b64674666bbd8189e25d0706e |
| institution | DOAJ |
| issn | 2590-0595 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney Medicine |
| spelling | doaj-art-cb56d72b64674666bbd8189e25d0706e2025-08-20T03:17:40ZengElsevierKidney Medicine2590-05952025-07-017710102410.1016/j.xkme.2025.101024Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINTNicholas Wettersten0Ronit Katz1Simon B. Ascher2Rebecca Scherzer3Alexander L. Bullen4Teresa K. Chen5Kasey Campos6Pranav S. Garimella7Michelle M. Estrella8Michael G. Shlipak9Joachim H. Ix10Cardiology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Cardiology, Department of Medicine, University of California San Diego, San Diego, CA; Address for Correspondence: Nicholas Wettersten, MD, VA San Diego Healthcare System, Cardiology 4 West, Room 4022 (111A), 3350 La Jolla Village Drive, San Diego, CA 92161.Division of Nephrology, Department of Medicine, University of Washington, Seattle, WADepartment of Internal Medicine, University of California Davis, Sacramento, CA; Kidney Health Research Collaborative, Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CAKidney Health Research Collaborative, Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CANephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CAKidney Health Research Collaborative, Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CA; Nephrology Section, Veterans Affairs San Francisco Healthcare System, San Francisco, CAKidney Health Research Collaborative, Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CADivision of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CANephrology Section, Veterans Affairs San Francisco Healthcare System, San Francisco, CAKidney Health Research Collaborative, Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CANephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CARationale & Objective: Among individuals with chronic kidney disease (CKD), higher blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with greater risk of CKD progression. Their associations with risk of cardiovascular disease (CVD) and all-cause mortality in individuals with CKD remain uncertain. Study Design: An observational cohort study. Setting & Participants: Systolic Blood Pressure Intervention Trial participants with hypertension and CKD (eGFR <60 mL/min/1.73 m2) but without diabetes. Predictors: Plasma KIM-1, TNFR-1, and TNFR-2. Outcomes: A composite CVD outcome (acute coronary syndrome/myocardial infarction, stroke, heart failure, and CVD death) and all-cause mortality. Analytic Approach: Cox proportional hazards models, adjusting for CVD risk factors, eGFR, and urine albumin-to-creatinine ratio. Results: Total of 2,350 participants with a mean age of 73 ± 9 years, eGFR of 46 ± 10 mL/min/1.73m2 and 25% prevalence of CVD. Over more than 3 years follow-up, 293 CVD events (12%) and 160 deaths (7%) occurred. Higher KIM-1, TNFR-1, and TNFR-2 were associated with higher risk of the composite CVD outcome after adjusting for CVD risk factors, but associations were no longer significant after adjusting for eGFR and urine albumin-to-creatinine ratio (KIM-1: HR = 1.13, 95% CI, 0.99-1.30; TNFR-1: HR = 1.03, 95% CI, 0.72-1.46; TNFR-2: HR = 0.98, 95% CI, 0.76-1.26). In contrast, in fully adjusted models, higher plasma KIM-1 and TNFR-1, but not TNFR-2, were associated with higher risk of all-cause mortality (KIM-1: HR = 1.23, 95% CI, 1.01-1.49; TNFR-1: HR = 2.09, 95% CI, 1.14-3.83; TNFR-2: HR = 1.19, 95% CI, 0.85-1.66). Limitations: No individuals with diabetes or stroke. Conclusions: In individuals with hypertension and nondiabetic CKD, associations of higher plasma KIM-1, TNFR-1, and TNFR-2 concentrations with CVD events were not independent of eGFR and albuminuria, whereas higher levels of plasma KIM-1 and TNFR-1 were independently associated with greater risk of all-cause mortality. Plain-Language Summary: Blood levels of kidney injury molecule-1 (KIM-1) and soluble tumor necrosis factor receptors (TNFR-1 and TNFR-2) have been associated with progression of kidney disease. We evaluated if these biomarkers were associated with risk of cardiovascular events and all-cause mortality in individuals without diabetes with hypertension and chronic kidney disease from the Systolic Blood Pressure Intervention Trial adjusting for relevant risk factors and biomarkers. We found none of the biomarkers were associated with risk of cardiovascular events, whereas KIM-1 and TNFR-1 were associated with risk of all-cause mortality. These findings suggest KIM-1 and TNFR-1 may be useful for risk prediction and emphasize the importance of inflammation as a risk factor for mortality.http://www.sciencedirect.com/science/article/pii/S2590059525000603Inflammationkidney injurymortalitycardiovascular riskchronic kidney disease |
| spellingShingle | Nicholas Wettersten Ronit Katz Simon B. Ascher Rebecca Scherzer Alexander L. Bullen Teresa K. Chen Kasey Campos Pranav S. Garimella Michelle M. Estrella Michael G. Shlipak Joachim H. Ix Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT Kidney Medicine Inflammation kidney injury mortality cardiovascular risk chronic kidney disease |
| title | Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT |
| title_full | Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT |
| title_fullStr | Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT |
| title_full_unstemmed | Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT |
| title_short | Association of Plasma KIM-1, TNFR-1, and TNFR-2 With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Chronic Kidney Disease: An Ancillary Analysis of SPRINT |
| title_sort | association of plasma kim 1 tnfr 1 and tnfr 2 with cardiovascular outcomes and all cause mortality in individuals with chronic kidney disease an ancillary analysis of sprint |
| topic | Inflammation kidney injury mortality cardiovascular risk chronic kidney disease |
| url | http://www.sciencedirect.com/science/article/pii/S2590059525000603 |
| work_keys_str_mv | AT nicholaswettersten associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT ronitkatz associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT simonbascher associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT rebeccascherzer associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT alexanderlbullen associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT teresakchen associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT kaseycampos associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT pranavsgarimella associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT michellemestrella associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT michaelgshlipak associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint AT joachimhix associationofplasmakim1tnfr1andtnfr2withcardiovascularoutcomesandallcausemortalityinindividualswithchronickidneydiseaseanancillaryanalysisofsprint |