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Biomarkers of cardiovascular stress and incident chronic kidney disease.

ABSTRACT: BACKGROUND:Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community. METHODS:Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR <60 mL · min(-1) · (1.73 m(2)) (-1), n = 276], microalbuminuria (urinary albumin to creatinine ratio ?25 mg/g in women and 17 mg/g in men, n = 191), and rapid decline in renal function [decline in eGFR ?3 mL · min(-1) · (1.73 m(2)) (-1) per year, n = 237], were evaluated using multivariable logistic regression; P < 0.006 was considered statistically significant in primary analyses. RESULTS:Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U increase in log-GDF-15, 95% CI 1.6-2.3, P < 0.0001] and rapid decline in renal function (OR, 1.6; 95% CI, 1.3-1.8; P < 0.0001). GDF-15, sST2, and hsTnI had suggestive associations with incident microalbuminuria but did not meet the prespecified P-value threshold after multivariable adjustment. Adding plasma GDF-15 to clinical covariates improved risk prediction of incident CKD: the c-statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net reclassification was 6.3% (95% CI, 2.7-9.9%). CONCLUSIONS:Higher circulating GDF-15 is associated with incident renal outcomes and improves risk prediction of incident CKD. These findings may provide insights into the mechanisms of renal injury.

SUBMITTER: Ho JE

PROVIDER: S-EPMC3972213 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Biomarkers of cardiovascular stress and incident chronic kidney disease.

Ho Jennifer E JE Hwang Shih-Jen SJ Wollert Kai C KC Larson Martin G MG Cheng Susan S Kempf Tibor T Vasan Ramachandran S RS Januzzi James L JL Wang Thomas J TJ Fox Caroline S CS

Clinical chemistry 20130719 11

<h4>Background</h4>Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical outcomes. We examined whether circulating concentrations are related to the development of kidney disease in the community.<h4>Methods</h4>Plasma GDF-15, sST2, and hsTnI concentrations were measured in 2614 Framingham Offspring cohort participants (mean age 57 years, 54% women) at the sixth examination cycle (1995-1998). Association ...[more]

PMID: 23873716

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Project description:BackgroundWhether the increased incidence of chronic kidney disease (CKD) during intensive systolic blood pressure (SBP) lowering is accompanied by intrinsic kidney injury is unknown.ObjectiveTo 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).DesignNested case-control study within SPRINT.SettingAdults with hypertension without baseline kidney disease.ParticipantsCase 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.Measurements9 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.ResultsHigher 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, α1-microglobulin, YKL-40, and uromodulin.LimitationBiomarker measurements were available only at baseline and 1 year.ConclusionIncident 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.Primary funding sourceNational Institute for Diabetes and Digestive and Kidney Diseases.

Project description:Background and objectivesThe matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.Design setting participants and measurementsA community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM]; n = 741; mean age: 77 years) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.ResultsThere was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman ρ = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/creatinine ratio, and the inflammatory markers interleukin 6 and high-sensitivity C-reactive protein (odds ratio for 1 standard deviation [SD] of urinary osteopontin, 1.42, 95% CI 1.00-2.02, p = 0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI 1.14-1.58, p < 0.001, and 1.00, 95% CI 0.79-1.26, p = 0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p < 0.002).ConclusionsHigher urinary osteopontin specifically predicts incident chronic kidney disease, while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remain to be established.

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Biomarkers of cardiovascular stress and incident chronic kidney disease.

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Biomarkers of cardiovascular stress and incident chronic kidney disease.

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