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 R. Parikh, Michael G. Shlipak, Joachim H. Ix

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28 Scopus citations

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
Externally publishedYes

Bibliographical note

Funding Information:
Disclosures: Mr. Craven reports grant support from NIH/ NHLBI/NIDDK during the conduct of the study. Dr. Cheung reports grant support from NIH during the conduct of the study. Dr. Sarnak serves on the steering committee for an ane- mia treatment study funded by Akebia; funds for his involvement are payed to Tufts Medical Center. Dr. Shlipak reports grant support from Cricket Health and TAI Diagnostics outside the submitted work. Dr. Ix reports grant support from NIDDK during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/Conflict OfInterestForms.do?msNum=M18-1037.

Funding Information:
Grant Support: This ancillary study was supported by grant R01DK098234 from the NIDDK to Drs. Ix and Shlipak. Mr. Zhang is supported by grant TL1TR001871 from NIH/National Center for Advancing Translational Sciences (NCATS). The SPRINT study is funded by the NIH, including the National Heart, Lung, and Blood Institute (NHLBI); NIDDK; National Institute on Aging; and National Institute of Neurological Disorders and Stroke, under contracts HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200 900048C, and HHSN268200900049C and Inter-Agency Agreement A-HL-13-002-001. It also is partly supported with resources and use of facilities through the U.S. Department of Veterans Affairs. The SPRINT investigators are supported by the following NCATS-funded Clinical and Translational Science Awards: Case Western Reserve University, UL1TR 000439; Ohio State University, UL1RR025755; University of Pennsylvania, UL1RR024134 and UL1TR000003; Boston University, UL1RR025771; Stanford University, UL1TR000093; Tufts University, UL1RR025752, UL1TR000073 and UL1TR 001064; University of Illinois, UL1TR000050; University of Pittsburgh, UL1TR000005; University of Texas Southwestern, 9U54TR000017-06; University of Utah, UL1TR000105-05; Vanderbilt University, UL1 TR000445; George Washington University, UL1TR000075; University of California, Davis, UL1 TR000002; University of Florida, UL1 TR000064; University of Michigan, UL1TR000433; Tulane University, Centers of Biomedical Research Excellence Award P30GM103337, National Institute of General Medical Sciences; and Wake Forest University, UL1TR001420.

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