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

Research output: Contribution to journalArticlepeer-review

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

ASJC Scopus subject areas

  • Internal Medicine

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