Abstract
Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function between baseline and follow-up of about five years apart. Network analysis was conducted to identify differential lipid classes associated with risk of CKD. In the discovery cohort, we found that higher baseline level of multiple lipid species, including glycerophospholipids, glycerolipids and sphingolipids, was significantly associated with increased risk of CKD, independent of age, sex, body mass index, diabetes and hypertension. Many lipid species were replicated in at least one external cohort at the individual lipid species and/or the class level. Longitudinal change in the plasma lipidome was significantly associated with change in the estimated glomerular filtration rate after adjusting for covariates, baseline lipids and the baseline rate. Network analysis identified distinct lipidomic signatures differentiating high from low-risk groups. Thus, our results demonstrated that disturbed lipid metabolism precedes the onset of CKD. These findings shed light on the mechanisms linking dyslipidemia to CKD and provide potential novel biomarkers for identifying individuals with early impaired kidney function at preclinical stages.
Original language | English |
---|---|
Pages (from-to) | 1154-1166 |
Number of pages | 13 |
Journal | Kidney International |
Volume | 102 |
Issue number | 5 |
DOIs | |
Publication status | Published - Nov 2022 |
Externally published | Yes |
Keywords
- American Indians
- AusDiab
- chronic kidney disease
- lipidomics
- Mexican Americans
- San Antonio Family Heart Study
- Strong Heart Study
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In: Kidney International, Vol. 102, No. 5, 11.2022, p. 1154-1166.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease
AU - Zeng, Wenjie
AU - Beyene, Habtamu B.
AU - Kuokkanen, Mikko
AU - Miao, Guanhong
AU - Magliano, Dianna J.
AU - Umans, Jason G.
AU - Franceschini, Nora
AU - Cole, Shelley A.
AU - Michailidis, George
AU - Lee, Elisa T.
AU - Howard, Barbara V.
AU - Fiehn, Oliver
AU - Curran, Joanne E.
AU - Blangero, John
AU - Meikle, Peter J.
AU - Zhao, Jinying
N1 - Funding Information: The AusDiab Study was supported by the National Health and Medical Research Council of Australia (project grant APP1101320). This work was also supported in part by the Victorian Government’s Operational Infrastructure Support Program. DJM is supported by a Senior Research Fellowship and PJM is supported by an L3 Investigator grant (2009965) from the National Health and Medical Research Council of Australia. HBB was supported by Baker Institute and Monash University Scholarships. Funding Information: This study was supported by the NIH grant R01DK107532. The SHS has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, NIH, Department of Health and Human Services, under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029, and 75N92019D00030. The study was previously supported by research grants R01HL109315, R01HL109301, R01HL109284, R01HL109282, and R01HL109319 and by cooperative agreements U01HL41642, U01HL41652, U01HL41654, U01HL65520, and U01HL65521. Funding Information: Data collection for the SAFHS was funded in part by P01 HL045522. Lipidomic profiling of SAFHS individuals was funded by R01 HL140681. SAFHS analytical methods and software used was supported by R37 MH059490 and R01 EB015611. This work was conducted in part in facilities constructed under the support of NIH grant C06 RR020547. Funding Information: The authors thank participants in the Strong Heart Study (SHS), the San Antonio Family Heart Study (SAFHS), and the Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study. We also thank the Indian Health Service facilities and the participating American Indian tribes for their extraordinary cooperation and involvement, which has contributed to the success of the SHS. The content expressed in this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH) or the Indian Health Service. The AusDiab Study, initiated and coordinated by the International Diabetes Institute, and subsequently coordinated by the Baker Heart and Diabetes Institute, gratefully acknowledges the support and assistance given by A. Allman, B. Atkins, S. Bennett, A. Bonney, S. Chadban, M. de Courten, M. Dalton, D. Dunstan, T. Dwyer, H. Jahangir, D. Jolley, D. McCarty, A. Meehan, N. Meinig, S. Murray, K. O'Dea, K. Polkinghorne, P. Phillips, C. Reid, A. Stewart, R. Tapp, H. Taylor, T. Welborn, T. Whalen, F. Wilson, P. Zimmet, and all the study participants. Also, for funding or logistical support, we are grateful to the National Health and Medical Research Council (grant 233200), Australian Government Department of Health and Ageing, Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, AstraZeneca, Bristol-Myers Squibb, City Health Centre-Diabetes Service-Canberra, Department of Health and Community Services–Northern Territory, Department of Health and Human Services–Tasmania, Department of Health–New South Wales, Department of Health–Western Australia, Department of Health–South Australia, Department of Human Services–Victoria, Diabetes Australia, Diabetes Australia Northern Territory, Eli Lilly Australia, Estate of the Late Edward Wilson, GlaxoSmithKline, Jack Brockhoff Foundation, Janssen-Cilag, Kidney Health Australia, Marian & FH Flack Trust, Menzies Research Institute, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer Pty Ltd, Pratt Foundation, Queensland Health, Roche Diagnostics Australia, Royal Prince Alfred Hospital, Sydney, Sanofi Aventis, and sanofi-synthelabo. This study was supported by the NIH grant R01DK107532. The SHS has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, NIH, Department of Health and Human Services, under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029, and 75N92019D00030. The study was previously supported by research grants R01HL109315, R01HL109301, R01HL109284, R01HL109282, and R01HL109319 and by cooperative agreements U01HL41642, U01HL41652, U01HL41654, U01HL65520, and U01HL65521. Data collection for the SAFHS was funded in part by P01 HL045522. Lipidomic profiling of SAFHS individuals was funded by R01 HL140681. SAFHS analytical methods and software used was supported by R37 MH059490 and R01 EB015611. This work was conducted in part in facilities constructed under the support of NIH grant C06 RR020547. The AusDiab Study was supported by the National Health and Medical Research Council of Australia (project grant APP1101320). This work was also supported in part by the Victorian Government's Operational Infrastructure Support Program. DJM is supported by a Senior Research Fellowship and PJM is supported by an L3 Investigator grant (2009965) from the National Health and Medical Research Council of Australia. HBB was supported by Baker Institute and Monash University Scholarships. Publisher Copyright: © 2022 International Society of Nephrology
PY - 2022/11
Y1 - 2022/11
N2 - Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function between baseline and follow-up of about five years apart. Network analysis was conducted to identify differential lipid classes associated with risk of CKD. In the discovery cohort, we found that higher baseline level of multiple lipid species, including glycerophospholipids, glycerolipids and sphingolipids, was significantly associated with increased risk of CKD, independent of age, sex, body mass index, diabetes and hypertension. Many lipid species were replicated in at least one external cohort at the individual lipid species and/or the class level. Longitudinal change in the plasma lipidome was significantly associated with change in the estimated glomerular filtration rate after adjusting for covariates, baseline lipids and the baseline rate. Network analysis identified distinct lipidomic signatures differentiating high from low-risk groups. Thus, our results demonstrated that disturbed lipid metabolism precedes the onset of CKD. These findings shed light on the mechanisms linking dyslipidemia to CKD and provide potential novel biomarkers for identifying individuals with early impaired kidney function at preclinical stages.
AB - Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-dwelling of individuals, followed by replication in Mexican Americans from the San Antonio Family Heart Study and Caucasians from the Australian Diabetes, Obesity and Lifestyle Study. We also performed repeated measurement analysis to examine the temporal relationship between the change in the lipidome and change in kidney function between baseline and follow-up of about five years apart. Network analysis was conducted to identify differential lipid classes associated with risk of CKD. In the discovery cohort, we found that higher baseline level of multiple lipid species, including glycerophospholipids, glycerolipids and sphingolipids, was significantly associated with increased risk of CKD, independent of age, sex, body mass index, diabetes and hypertension. Many lipid species were replicated in at least one external cohort at the individual lipid species and/or the class level. Longitudinal change in the plasma lipidome was significantly associated with change in the estimated glomerular filtration rate after adjusting for covariates, baseline lipids and the baseline rate. Network analysis identified distinct lipidomic signatures differentiating high from low-risk groups. Thus, our results demonstrated that disturbed lipid metabolism precedes the onset of CKD. These findings shed light on the mechanisms linking dyslipidemia to CKD and provide potential novel biomarkers for identifying individuals with early impaired kidney function at preclinical stages.
KW - American Indians
KW - AusDiab
KW - chronic kidney disease
KW - lipidomics
KW - Mexican Americans
KW - San Antonio Family Heart Study
KW - Strong Heart Study
UR - http://www.scopus.com/inward/record.url?scp=85136577800&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2022.06.023
DO - 10.1016/j.kint.2022.06.023
M3 - Article
C2 - 35853479
AN - SCOPUS:85136577800
SN - 0085-2538
VL - 102
SP - 1154
EP - 1166
JO - Kidney International
JF - Kidney International
IS - 5
ER -