Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

Ann A. Wang; Xuan Cai; Anand Srivastava; Pottumarthi V. Prasad; Stuart M. Sprague; James Carr; Myles Wolf; Joachim H. Ix; Geoffrey A. Block; Michel Chonchol; Kalani L. Raphael; Alfred K. Cheung; Dominic S. Raj; Jennifer J. Gassman; Amir Ali Rahsepar; John P. Middleton; Linda F. Fried; Roberto Sarnari; Tamara Isakova; Rupal Mehta

doi:10.34067/KID.0005022021

Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

Ann A. Wang, Xuan Cai, Anand Srivastava, Pottumarthi V. Prasad, Stuart M. Sprague, James Carr, Myles Wolf, Joachim H. Ix, Geoffrey A. Block, Michel Chonchol, Kalani L. Raphael, Alfred K. Cheung, Dominic S. Raj, Jennifer J. Gassman, Amir Ali Rahsepar, John P. Middleton, Linda F. Fried, Roberto Sarnari, Tamara Isakova^*, Rupal Mehta

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m 2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, β estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter.

Original language	English (US)
Pages (from-to)	258-268
Number of pages	11
Journal	Kidney360
Volume	3
Issue number	2
DOIs	https://doi.org/10.34067/KID.0005022021
State	Published - Feb 1 2022

Funding

The COMBINE trial was supported by NIDDK grants U01DK099877, U01DK097093, U01DK099930, U01DK099933, and U01DK099924. This work was also supported by NIDDK grants R01DK102438 (T. Isakova), R01DK081374 (M. Wolf), K23DK120811 (A. Srivastava), P30DK114857, and R01DK093793; and NHLBI grants K24HL150235 (T. Isakova) and K23HL150236 (R. Mehta). Research reported in this publication was also supported, in part, by the NIH National Center for Advancing Translational Sciences grants KL2TR001424 and UL1TR001422 and by an NIDDK Kidney Precision Medicine Project Opportunity Pool grant under U2CDK114886 (A. Srivastava). Acknowledgments

Keywords

albuminuria
cardiac MRI
chronic kidney disease
diastolic dysfunction
mineral metabolism

ASJC Scopus subject areas

Nephrology
Medicine (miscellaneous)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.34067/KID.0005022021

Cite this

Wang, A. A., Cai, X., Srivastava, A., Prasad, P. V., Sprague, S. M., Carr, J., Wolf, M., Ix, J. H., Block, G. A., Chonchol, M., Raphael, K. L., Cheung, A. K., Raj, D. S., Gassman, J. J., Rahsepar, A. A., Middleton, J. P., Fried, L. F., Sarnari, R., Isakova, T., & Mehta, R. (2022). Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial. Kidney360, 3(2), 258-268. https://doi.org/10.34067/KID.0005022021

@article{bb508c04752146d6aa094b96dcfa22e7,

title = "Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial",

abstract = "Background Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m 2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, β estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter.",

keywords = "albuminuria, cardiac MRI, chronic kidney disease, diastolic dysfunction, mineral metabolism",

author = "Wang, {Ann A.} and Xuan Cai and Anand Srivastava and Prasad, {Pottumarthi V.} and Sprague, {Stuart M.} and James Carr and Myles Wolf and Ix, {Joachim H.} and Block, {Geoffrey A.} and Michel Chonchol and Raphael, {Kalani L.} and Cheung, {Alfred K.} and Raj, {Dominic S.} and Gassman, {Jennifer J.} and Rahsepar, {Amir Ali} and Middleton, {John P.} and Fried, {Linda F.} and Roberto Sarnari and Tamara Isakova and Rupal Mehta",

note = "Funding Information: The COMBINE trial was supported by NIDDK grants U01DK099877, U01DK097093, U01DK099930, U01DK099933, and U01DK099924. This work was also supported by NIDDK grants R01DK102438 (T. Isakova), R01DK081374 (M. Wolf), K23DK120811 (A. Srivastava), P30DK114857, and R01DK093793; and NHLBI grants K24HL150235 (T. Isakova) and K23HL150236 (R. Mehta). Research reported in this publication was also supported, in part, by the NIH National Center for Advancing Translational Sciences grants KL2TR001424 and UL1TR001422 and by an NIDDK Kidney Precision Medicine Project Opportunity Pool grant under U2CDK114886 (A. Srivastava). Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2022 by the American Society of Nephrology.",

year = "2022",

month = feb,

day = "1",

doi = "10.34067/KID.0005022021",

language = "English (US)",

volume = "3",

pages = "258--268",

journal = "Kidney360",

issn = "2641-7650",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

Wang, AA, Cai, X, Srivastava, A, Prasad, PV, Sprague, SM, Carr, J, Wolf, M, Ix, JH, Block, GA, Chonchol, M, Raphael, KL, Cheung, AK, Raj, DS, Gassman, JJ, Rahsepar, AA, Middleton, JP, Fried, LF, Sarnari, R, Isakova, T & Mehta, R 2022, 'Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial', Kidney360, vol. 3, no. 2, pp. 258-268. https://doi.org/10.34067/KID.0005022021

TY - JOUR

T1 - Abnormalities in Cardiac Structure and Function among Individuals with CKD

T2 - The COMBINE Trial

AU - Wang, Ann A.

AU - Cai, Xuan

AU - Srivastava, Anand

AU - Prasad, Pottumarthi V.

AU - Sprague, Stuart M.

AU - Carr, James

AU - Wolf, Myles

AU - Ix, Joachim H.

AU - Block, Geoffrey A.

AU - Chonchol, Michel

AU - Raphael, Kalani L.

AU - Cheung, Alfred K.

AU - Raj, Dominic S.

AU - Gassman, Jennifer J.

AU - Rahsepar, Amir Ali

AU - Middleton, John P.

AU - Fried, Linda F.

AU - Sarnari, Roberto

AU - Isakova, Tamara

AU - Mehta, Rupal

N1 - Funding Information: The COMBINE trial was supported by NIDDK grants U01DK099877, U01DK097093, U01DK099930, U01DK099933, and U01DK099924. This work was also supported by NIDDK grants R01DK102438 (T. Isakova), R01DK081374 (M. Wolf), K23DK120811 (A. Srivastava), P30DK114857, and R01DK093793; and NHLBI grants K24HL150235 (T. Isakova) and K23HL150236 (R. Mehta). Research reported in this publication was also supported, in part, by the NIH National Center for Advancing Translational Sciences grants KL2TR001424 and UL1TR001422 and by an NIDDK Kidney Precision Medicine Project Opportunity Pool grant under U2CDK114886 (A. Srivastava). Acknowledgments Publisher Copyright: Copyright © 2022 by the American Society of Nephrology.

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Background Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m 2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, β estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter.

AB - Background Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m 2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, β estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (β estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter.

KW - albuminuria

KW - cardiac MRI

KW - chronic kidney disease

KW - diastolic dysfunction

KW - mineral metabolism

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DO - 10.34067/KID.0005022021

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C2 - 35373122

AN - SCOPUS:85162753729

SN - 2641-7650

VL - 3

SP - 258

EP - 268

JO - Kidney360

JF - Kidney360

IS - 2

ER -

Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial

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UN SDGs

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