TY - JOUR
T1 - Associations of Biomarkers of Kidney Tubule Health, Injury, and Inflammation with Left Ventricular Hypertrophy in Children with CKD
AU - CKD Biomarkers Consortium
AU - Jiang, Kuan
AU - Greenberg, Jason H.
AU - Abraham, Alison
AU - Xu, Yunwen
AU - Schelling, Jeffrey R.
AU - Feldman, Harold I.
AU - Schrauben, Sarah J.
AU - Waikar, Sushrut S.
AU - Shlipak, Michael G.
AU - Wettersten, Nicholas
AU - Coca, Steven G.
AU - Vasan, Ramachandran S.
AU - Gutierrez, Orlando M.
AU - Ix, Joachim H.
AU - Warady, Bradley A.
AU - Kimmel, Paul L.
AU - Bonventre, Joseph V.
AU - Parikh, Chirag R.
AU - Mitsnefes, Mark M.
AU - Denburg, Michelle R.
AU - Furth, Susan
AU - Ramachandran, Vasan S.
AU - Denburg, Michelle
AU - Furth, Susan
AU - Warady, Bradley
AU - Waikar, Sushrut
AU - Sabbisetti, Venkata
AU - Coresh, Josef
AU - Grams, Morgan
AU - Rebholz, Casey
AU - Abraham, Alison
AU - Parikh, Chirag
AU - Coca, Steven
AU - Rhee, Eugene
AU - Kimmel, Paul L.
AU - Kusek, John W.
AU - Rovin, Brad
AU - Shlipak, Michael G.
AU - Sarnak, Mark
AU - Gutiérrez, Orlando M.
AU - Ix, Joachim
AU - Dubin, Ruth
AU - Hostetter, Tom
AU - Deo, Rajat
AU - Feldman, Harold I.
AU - Xie, Dawei
AU - Shou, Haochang
AU - Ballard, Shawn
AU - Whitehead, Krista
AU - Collins, Heather
N1 - Publisher Copyright:
Copyright © 2023 The Author(s).
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Background Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. We have shown that several plasma and urine biomarkers are associated with increased risk of CKD progression. As CKD is associated with LVH, we sought to investigate the association between the biomarkers and LVH.MethodsIn the CKD in Children Cohort Study, children aged 6 months to 16 years with an eGFR of 30-90 ml/min per 1.73 m2 were enrolled at 54 centers in the United States and Canada. We measured plasma biomarkers kidney injury molecule-1 (KIM-1), tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase-type plasminogen activator receptor and urine KIM-1, monocyte chemoattractant protein-1 (MCP-1), YKL-40, alpha-1-microglobulin (alpha-1m), and epidermal growth factor in stored plasma and urine collected 5 months after enrollment. Echocardiograms were performed 1 year after enrollment. We assessed the cross-sectional association between the log2 biomarker levels and LVH (left ventricular mass index greater than or equal to the 95th percentile) using a Poisson regression model, adjusted for age, sex, race, body mass index, hypertension, glomerular diagnosis, urine protein-to-creatinine ratio, and eGFR at study entry.ResultsAmong the 504 children, LVH prevalence was 12% (n=59) 1 year after enrollment. In a multivariable-adjusted model, higher plasma and urine KIM-1 and urine MCP-1 concentrations were associated with a higher prevalence of LVH (plasma KIM-1 prevalence ratio [PR] per log2: 1.27, 95% confidence interval [CI], 1.02 to 1.58; urine KIM-1 PR: 1.21, 95% CI, 1.11 to 1.48; and urine MCP-1 PR: 1.18, 95% CI, 1.04 to 1.34). After multivariable adjustment for covariates, lower urine alpha-1m was also associated with a higher prevalence of LVH (PR: 0.90, 95% CI, 0.82 to 0.99).ConclusionsHigher plasma and urine KIM-1, urine MCP-1, and lower urine alpha-1m were each associated with LVH prevalence in children with CKD. These biomarkers may better inform risk and help elucidate the pathophysiology of LVH in pediatric CKD.
AB - Background Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. We have shown that several plasma and urine biomarkers are associated with increased risk of CKD progression. As CKD is associated with LVH, we sought to investigate the association between the biomarkers and LVH.MethodsIn the CKD in Children Cohort Study, children aged 6 months to 16 years with an eGFR of 30-90 ml/min per 1.73 m2 were enrolled at 54 centers in the United States and Canada. We measured plasma biomarkers kidney injury molecule-1 (KIM-1), tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase-type plasminogen activator receptor and urine KIM-1, monocyte chemoattractant protein-1 (MCP-1), YKL-40, alpha-1-microglobulin (alpha-1m), and epidermal growth factor in stored plasma and urine collected 5 months after enrollment. Echocardiograms were performed 1 year after enrollment. We assessed the cross-sectional association between the log2 biomarker levels and LVH (left ventricular mass index greater than or equal to the 95th percentile) using a Poisson regression model, adjusted for age, sex, race, body mass index, hypertension, glomerular diagnosis, urine protein-to-creatinine ratio, and eGFR at study entry.ResultsAmong the 504 children, LVH prevalence was 12% (n=59) 1 year after enrollment. In a multivariable-adjusted model, higher plasma and urine KIM-1 and urine MCP-1 concentrations were associated with a higher prevalence of LVH (plasma KIM-1 prevalence ratio [PR] per log2: 1.27, 95% confidence interval [CI], 1.02 to 1.58; urine KIM-1 PR: 1.21, 95% CI, 1.11 to 1.48; and urine MCP-1 PR: 1.18, 95% CI, 1.04 to 1.34). After multivariable adjustment for covariates, lower urine alpha-1m was also associated with a higher prevalence of LVH (PR: 0.90, 95% CI, 0.82 to 0.99).ConclusionsHigher plasma and urine KIM-1, urine MCP-1, and lower urine alpha-1m were each associated with LVH prevalence in children with CKD. These biomarkers may better inform risk and help elucidate the pathophysiology of LVH in pediatric CKD.
KW - CKD
KW - children
KW - chronic inflammation
KW - echocardiography
KW - glomerular disease
KW - kidney tubule
KW - left ventricular hypertrophy
KW - pediatric nephrology
KW - pediatrics
KW - renal injury
UR - http://www.scopus.com/inward/record.url?scp=85169504213&partnerID=8YFLogxK
U2 - 10.34067/KID.0000000000000183
DO - 10.34067/KID.0000000000000183
M3 - Article
C2 - 37303083
AN - SCOPUS:85169504213
SN - 2641-7650
VL - 4
SP - 1039
EP - 1047
JO - Kidney360
JF - Kidney360
IS - 8
ER -