Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction

A case-control study

William R. Zhang, Timothy E. Craven, Rakesh Malhotra, Alfred K. Cheung, Michel Chonchol, Paul Drawz, Mark J. Sarnak, Chirag Parikh, Michael G. Shlipak, Joachim H. Ix

Research output: Contribution to journalArticle

Abstract

Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown. Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial). Design: Nested case-control study within SPRINT. Setting: Adults with hypertension without baseline kidney disease. Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group. Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes. Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95% CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti- chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, β2-microglobulin, α 1-microglobulin, YKL-40, and uromodulin. Limitation: Biomarker measurements were available only at baseline and 1 year. Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury.

Original languageEnglish (US)
Pages (from-to)610-618
Number of pages9
JournalAnnals of Internal Medicine
Volume169
Issue number9
DOIs
StatePublished - Nov 6 2018

Fingerprint

Chronic Renal Insufficiency
Case-Control Studies
Biomarkers
Blood Pressure
Kidney
Uromodulin
Albumins
Creatinine
Wounds and Injuries
Interleukin-18
Chemokine CCL2
Renal Circulation
Kidney Diseases
Random Allocation
Glomerular Filtration Rate
Odds Ratio
Hypertension
Control Groups
Incidence

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Zhang, W. R., Craven, T. E., Malhotra, R., Cheung, A. K., Chonchol, M., Drawz, P., ... Ix, J. H. (2018). Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction: A case-control study. Annals of Internal Medicine, 169(9), 610-618. https://doi.org/10.7326/M18-1037

Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction : A case-control study. / Zhang, William R.; Craven, Timothy E.; Malhotra, Rakesh; Cheung, Alfred K.; Chonchol, Michel; Drawz, Paul; Sarnak, Mark J.; Parikh, Chirag; Shlipak, Michael G.; Ix, Joachim H.

In: Annals of Internal Medicine, Vol. 169, No. 9, 06.11.2018, p. 610-618.

Research output: Contribution to journalArticle

Zhang, WR, Craven, TE, Malhotra, R, Cheung, AK, Chonchol, M, Drawz, P, Sarnak, MJ, Parikh, C, Shlipak, MG & Ix, JH 2018, 'Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction: A case-control study', Annals of Internal Medicine, vol. 169, no. 9, pp. 610-618. https://doi.org/10.7326/M18-1037
Zhang, William R. ; Craven, Timothy E. ; Malhotra, Rakesh ; Cheung, Alfred K. ; Chonchol, Michel ; Drawz, Paul ; Sarnak, Mark J. ; Parikh, Chirag ; Shlipak, Michael G. ; Ix, Joachim H. / Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction : A case-control study. In: Annals of Internal Medicine. 2018 ; Vol. 169, No. 9. pp. 610-618.
@article{848486865d4148e19d8677c545934d2b,
title = "Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction: A case-control study",
abstract = "Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown. Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial). Design: Nested case-control study within SPRINT. Setting: Adults with hypertension without baseline kidney disease. Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group. Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes. Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95{\%} CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti- chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, β2-microglobulin, α 1-microglobulin, YKL-40, and uromodulin. Limitation: Biomarker measurements were available only at baseline and 1 year. Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury.",
author = "Zhang, {William R.} and Craven, {Timothy E.} and Rakesh Malhotra and Cheung, {Alfred K.} and Michel Chonchol and Paul Drawz and Sarnak, {Mark J.} and Chirag Parikh and Shlipak, {Michael G.} and Ix, {Joachim H.}",
year = "2018",
month = "11",
day = "6",
doi = "10.7326/M18-1037",
language = "English (US)",
volume = "169",
pages = "610--618",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "9",

}

TY - JOUR

T1 - Kidney damage biomarkers and incident chronic kidney disease during blood pressure reduction

T2 - A case-control study

AU - Zhang, William R.

AU - Craven, Timothy E.

AU - Malhotra, Rakesh

AU - Cheung, Alfred K.

AU - Chonchol, Michel

AU - Drawz, Paul

AU - Sarnak, Mark J.

AU - Parikh, Chirag

AU - Shlipak, Michael G.

AU - Ix, Joachim H.

PY - 2018/11/6

Y1 - 2018/11/6

N2 - Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown. Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial). Design: Nested case-control study within SPRINT. Setting: Adults with hypertension without baseline kidney disease. Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group. Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes. Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95% CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti- chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, β2-microglobulin, α 1-microglobulin, YKL-40, and uromodulin. Limitation: Biomarker measurements were available only at baseline and 1 year. Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury.

AB - Background: Whether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown. Objective: To compare changes in kidney damage biomarkers between incident CKD case participants and matched control participants as well as between case participants in the intensive (<120 mm Hg) versus the standard (<140 mm Hg) SBP management groups of SPRINT (Systolic Blood Pressure Intervention Trial). Design: Nested case-control study within SPRINT. Setting: Adults with hypertension without baseline kidney disease. Participants: Case participants (n = 162), who developed incident CKD during trial follow-up (128 in the intensive and 34 in the standard group), and control participants (n = 162) without incident CKD, who were matched on age, sex, race, baseline estimated glomerular filtration rate, and randomization group. Measurements: 9 urinary biomarkers of kidney damage were measured at baseline and at 1 year. Linear mixed-effects models were used to estimate 1-year biomarker changes. Results: Higher concentrations of urinary albumin, kidney injury molecule-1, and monocyte chemoattractant protein-1 at baseline were significantly associated with greater odds of incident CKD (adjusted odds ratio per doubling: 1.50 [95% CI, 1.14 to 1.98], 1.51 [CI, 1.05 to 2.17], and 1.70 [CI, 1.13 to 2.56], respectively). After 1 year of blood pressure intervention, incident CKD case participants in the intensive group had significantly greater decreases in albumin-creatinine ratio (ACR), interleukin-18, anti- chitinase-3-like protein 1 (YKL-40), and uromodulin than the matched control participants. Compared with case participants in the standard group, those in the intensive group had significantly greater decreases in ACR, β2-microglobulin, α 1-microglobulin, YKL-40, and uromodulin. Limitation: Biomarker measurements were available only at baseline and 1 year. Conclusion: Incident CKD in the setting of intensive SBP lowering was accompanied by decreases, rather than elevations, in levels of kidney damage biomarkers and thus may reflect benign changes in renal blood flow rather than intrinsic injury.

UR - http://www.scopus.com/inward/record.url?scp=85056153068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056153068&partnerID=8YFLogxK

U2 - 10.7326/M18-1037

DO - 10.7326/M18-1037

M3 - Article

VL - 169

SP - 610

EP - 618

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 9

ER -