Biomarkers of Kidney Tubule Health, CKD Progression, and Acute Kidney Injury in SPRINT (Systolic Blood Pressure Intervention Trial) Participants
SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their...
Uloženo v:
| Vydáno v: | American journal of kidney diseases Ročník 78; číslo 3; s. 361 |
|---|---|
| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.09.2021
|
| ISSN: | 1523-6838, 1523-6838 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal eGFR change and risk of acute kidney injury (AKI).
Observational cohort nested in a clinical trial.
2,351 SPRINT participants with eGFR < 60 ml/min/1.73m
at baseline.
Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), alpha-1 microglobulin (α1m) and beta-2 microglobulin (β2m), uromodulin (UMOD), fibroblast growth factor-23 (FGF23), and intact parathyroid hormone (PTH).
Longitudinal changes in eGFR and risk of AKI.
We performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.
From ten biomarkers, EFA generated four factors reflecting tubule injury/repair (NGAL, IL-18 and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (α1m and β2m), and tubule reserve/mineral metabolism (UMOD, FGF23, and PTH). Each SD higher tubule reserve/mineral metabolism factor scores were associated with a 0.58% (0.39%, 0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair (HR per SD higher 1.18 [1.10, 1.37]) and tubule injury/fibrosis factors (HR 1.23 [1.02, 1.48]) were independently associated with future risk of AKI.
The factors require validation in other settings.
EFA allows parsimonious subgrouping of biomarkers into factors which are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes. |
|---|---|
| AbstractList | SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal eGFR change and risk of acute kidney injury (AKI).
Observational cohort nested in a clinical trial.
2,351 SPRINT participants with eGFR < 60 ml/min/1.73m
at baseline.
Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), alpha-1 microglobulin (α1m) and beta-2 microglobulin (β2m), uromodulin (UMOD), fibroblast growth factor-23 (FGF23), and intact parathyroid hormone (PTH).
Longitudinal changes in eGFR and risk of AKI.
We performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.
From ten biomarkers, EFA generated four factors reflecting tubule injury/repair (NGAL, IL-18 and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (α1m and β2m), and tubule reserve/mineral metabolism (UMOD, FGF23, and PTH). Each SD higher tubule reserve/mineral metabolism factor scores were associated with a 0.58% (0.39%, 0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair (HR per SD higher 1.18 [1.10, 1.37]) and tubule injury/fibrosis factors (HR 1.23 [1.02, 1.48]) were independently associated with future risk of AKI.
The factors require validation in other settings.
EFA allows parsimonious subgrouping of biomarkers into factors which are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes. The Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).RATIONALE & OBJECTIVEThe Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal estimated glomerular filtration rate (eGFR) change and risk of acute kidney injury (AKI).Observational cohort nested in a clinical trial.STUDY DESIGNObservational cohort nested in a clinical trial.2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m2 at baseline.SETTING & PARTICIPANTS2,351 SPRINT participants with eGFR < 60 mL/min/1.73 m2 at baseline.Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M) and β2-microglobulin (B2M), uromodulin (UMOD), fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH).EXPOSURELevels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M) and β2-microglobulin (B2M), uromodulin (UMOD), fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone (PTH).Longitudinal changes in eGFR and risk of AKI.OUTCOMELongitudinal changes in eGFR and risk of AKI.We performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.ANALYTICAL APPROACHWe performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression.From 10 biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 1-SD higher tubule reserve/mineral metabolism factor score was associated with a 0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors were independently associated with future risk of AKI (per 1 SD higher, HRs of 1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively).RESULTSFrom 10 biomarkers, EFA generated 4 factors reflecting tubule injury/repair (NGAL, IL-18, and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (A1M and B2M), and tubule reserve/mineral metabolism (UMOD, FGF-23, and PTH). Each 1-SD higher tubule reserve/mineral metabolism factor score was associated with a 0.58% (95% CI, 0.39%-0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair and tubule injury/fibrosis factors were independently associated with future risk of AKI (per 1 SD higher, HRs of 1.18 [95% CI, 1.10-1.37] and 1.23 [95% CI, 1.02-1.48], respectively).The factors require validation in other settings.LIMITATIONSThe factors require validation in other settings.EFA allows parsimonious subgrouping of biomarkers into factors that are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes.CONCLUSIONSEFA allows parsimonious subgrouping of biomarkers into factors that are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes. |
| Author | Bullen, Alexander L Garimella, Pranav S Katz, Ronit Estrella, Michelle M Lee, Alexandra K Ix, Joachim H Shlipak, Michael G Jotwani, Vasantha |
| Author_xml | – sequence: 1 givenname: Alexander L surname: Bullen fullname: Bullen, Alexander L organization: Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA – sequence: 2 givenname: Ronit surname: Katz fullname: Katz, Ronit organization: Department of Obstetrics & Gynecology, University of Washington, Seattle, Washington, USA – sequence: 3 givenname: Vasantha surname: Jotwani fullname: Jotwani, Vasantha organization: Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, CA; Department of Medicine, San Francisco VA Medical Center, San Francisco, CA – sequence: 4 givenname: Pranav S surname: Garimella fullname: Garimella, Pranav S organization: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA – sequence: 5 givenname: Alexandra K surname: Lee fullname: Lee, Alexandra K organization: Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, CA – sequence: 6 givenname: Michelle M surname: Estrella fullname: Estrella, Michelle M organization: Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, CA; Department of Medicine, San Francisco VA Medical Center, San Francisco, CA – sequence: 7 givenname: Michael G surname: Shlipak fullname: Shlipak, Michael G organization: Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, CA; Department of Medicine, San Francisco VA Medical Center, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA – sequence: 8 givenname: Joachim H surname: Ix fullname: Ix, Joachim H email: joix@ucsd.edu organization: Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA. Electronic address: joix@ucsd.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33857535$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkMtKAzEUhoNUtF5ewIVkqWBrLpPpZNnWS4uiRet6yGTOaNppUpOMMG_hIztgBeHAfxbf9y_-I9SzzgJCZ5QMKRH8ejVUq3U5ZITRIemO0T3Up4LxQZrxrPfvP0RHIawIIZKn6QE65DwTI8FFH31PjNsovwYfsKvwgykttHjZFE0NeAaqjh9XePpwgxfevXsIwTh7hZUt8Vg3Ef6EuV01vsXG4tfFy_xpiS9e2xBdbTSe1M6Vnd65jYeOjOC_wMauCC-9UfUlXigfjTZbZWM4QfuVqgOc7vIYvd3dLqezwePz_Xw6fhxoMWJxoClkpCKyrBilSvOCUS4SWUpRsbQoJBVQEVKOUpqkHQayUFIUispMVVpIzY7RxW_v1rvPBkLMNyZoqGtlwTUhZ4ImQjI-Sjr0fIc2xQbKfOtNN1mb_63IfgBSvnfa |
| CitedBy_id | crossref_primary_10_3389_fendo_2022_956186 crossref_primary_10_3390_jcm13071881 crossref_primary_10_1016_j_ebiom_2023_104635 crossref_primary_10_1093_ndt_gfab308 crossref_primary_10_1016_j_cotox_2022_03_005 crossref_primary_10_1007_s10157_023_02445_8 crossref_primary_10_1007_s11906_025_01328_5 crossref_primary_10_1002_jimd_12672 crossref_primary_10_1093_ndt_gfad131 crossref_primary_10_1016_j_xkme_2024_100846 crossref_primary_10_1053_j_ajkd_2021_03_016 crossref_primary_10_1016_j_ajt_2024_09_016 crossref_primary_10_1186_s12967_022_03706_y crossref_primary_10_3389_fendo_2023_1102634 crossref_primary_10_3389_fmed_2022_840801 crossref_primary_10_3390_ijms231810293 crossref_primary_10_3389_fimmu_2023_1303076 crossref_primary_10_1080_0886022X_2022_2079524 crossref_primary_10_1161_CIRCHEARTFAILURE_123_011751 crossref_primary_10_1097_QAD_0000000000003705 crossref_primary_10_1016_j_jtherbio_2022_103433 crossref_primary_10_1007_s13300_023_01502_5 crossref_primary_10_2215_CJN_0000000676 crossref_primary_10_1016_j_jacc_2023_07_012 crossref_primary_10_1111_jch_14911 crossref_primary_10_3390_toxins13060380 crossref_primary_10_15252_emmm_202114146 crossref_primary_10_1159_000531946 crossref_primary_10_1161_JAHA_122_028146 crossref_primary_10_3389_fcvm_2021_760152 crossref_primary_10_1080_14737159_2024_2379355 |
| ContentType | Journal Article |
| Copyright | Copyright © 2021. Published by Elsevier Inc. Published by Elsevier Inc. |
| Copyright_xml | – notice: Copyright © 2021. Published by Elsevier Inc. – notice: Published by Elsevier Inc. |
| DBID | NPM 7X8 |
| DOI | 10.1053/j.ajkd.2021.01.021 |
| DatabaseName | PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1523-6838 |
| ExternalDocumentID | 33857535 |
| Genre | Journal Article |
| GroupedDBID | --- --K .1- .FO 0R~ 1B1 1P~ 23M 4.4 457 4G. 53G 5GY 5RE 7-5 AAEDT AAEDW AALRI AAWTL AAXUO ABCQX ABFRF ABJNI ABLJU ABOCM ACGFO ACGFS ADBBV AEFWE AENEX AEVXI AFCTW AFRHN AFTJW AITUG AJUYK AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ BELOY CS3 EBS EFJIC EX3 F5P FDB GBLVA K-O KOM L7B M41 MO0 NPM O9- OE- P2P PC. PI~ ROL SEL SES SJN SSZ TWZ UNMZH WOW XH2 YCW Z5R 7X8 AAFWJ ACVFH ADCNI APXCP EFKBS |
| ID | FETCH-LOGICAL-c572t-c1e80f09df211ac3b213549d95f26bb915ef00d76146f09e9ba95ba198afc59c2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 40 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000686900900009&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1523-6838 |
| IngestDate | Mon Sep 29 05:34:45 EDT 2025 Thu Jan 02 22:56:20 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| License | Copyright © 2021. Published by Elsevier Inc. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c572t-c1e80f09df211ac3b213549d95f26bb915ef00d76146f09e9ba95ba198afc59c2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/8384678 |
| PMID | 33857535 |
| PQID | 2514592374 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2514592374 pubmed_primary_33857535 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-09-01 |
| PublicationDateYYYYMMDD | 2021-09-01 |
| PublicationDate_xml | – month: 09 year: 2021 text: 2021-09-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | American journal of kidney diseases |
| PublicationTitleAlternate | Am J Kidney Dis |
| PublicationYear | 2021 |
| SSID | ssj0009366 |
| Score | 2.5336494 |
| Snippet | SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we... The Systolic Blood Pressure Intervention Trial (SPRINT) compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 361 |
| Title | Biomarkers of Kidney Tubule Health, CKD Progression, and Acute Kidney Injury in SPRINT (Systolic Blood Pressure Intervention Trial) Participants |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33857535 https://www.proquest.com/docview/2514592374 |
| Volume | 78 |
| WOSCitedRecordID | wos000686900900009&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LaxsxEBZNU0IuTdI8midT6CGBbGKtrN3VKThpTIyx8cEB34weI7DTalOvXei_yE-OtLvGuQQKvei0gkX6pJnRfPMNId_RZIoyhZFGZaJmYjHKysEkVCWopZK6bDaR9vvZaCQG9YNbUdMql3dieVGbXIc38mtvh5vceyNp8-b5dxS6RoXsat1CY42sM-_KBEpXOlqphQtW5iq9iWJRkrGsLprxuLueXsnpU1AKjWkl20nfdzFLU9Pe-t-f3CafaycTWhUqdsgHdF_IRq9Oo--Sl9tJ_ivwcmYF5Ba6E-PwLwwXavEToSpMuoS77g8YBPZWpdxxCdIZaOnFHJcTOm7qdwQmDkpSxRDOg_55EBqG28CHh6r2cIbQecOshGHA_AUMZM3odvNijzy274d3D1HdmiHSPI3nkaaYNWxDGOsDSKmZiinzkaYR3MaJUoJytI2GSb3xT_xnKJQUXEkqMmk1FzreJx9d7vArAYWppLGloVKlaXw0ZhhPLEXDpU6tVIfk23Ktxx76IZ8hHeaLYrxa7UNyUG3Y-LnS6Bj7yNs7oowf_cPsY7IZcFAxx07IuvUHH0_JJ_1nPilmZyWm_Ngf9F4B-a_Y_A |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Biomarkers+of+Kidney+Tubule+Health%2C+CKD+Progression%2C+and+Acute+Kidney+Injury+in+SPRINT+%28Systolic+Blood+Pressure+Intervention+Trial%29+Participants&rft.jtitle=American+journal+of+kidney+diseases&rft.au=Bullen%2C+Alexander+L&rft.au=Katz%2C+Ronit&rft.au=Jotwani%2C+Vasantha&rft.au=Garimella%2C+Pranav+S&rft.date=2021-09-01&rft.issn=1523-6838&rft.eissn=1523-6838&rft.volume=78&rft.issue=3&rft.spage=361&rft_id=info:doi/10.1053%2Fj.ajkd.2021.01.021&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1523-6838&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1523-6838&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1523-6838&client=summon |