Circulating saturated fatty acids and incident chronic kidney disease: A meta-analysis of de-novo prospective cohort investigations

Authors: LIDGARD, BENJAMIN - University Of Washington; FRETTS, AMANDA - University Of Washington; ZELNICK, LEILA - Non ARS Employee; VAN WESTING, ANNIEK - Wageningen University; GELEIJNSE, JOHANNA - Wageningen University; STEUR, MARINKA - Non ARS Employee; SAMIERI, CECILIA - Bordeaux University; HELMER, CATHERINE - Bordeaux University; LE GOFF, MELANIE - Bordeaux University; CHEN, YUN - Taipei Veterans General Hospital; CHIEN, KUO - National Taiwan University; ONG, KWOK - University Of Sydney; MOZAFFARIAN, DARIUSH - Tufts University; SISCOVICK, DAVID - New York Academy Of Medicine; HU, JASON - The George Institute For Global Health; DE BOER, IAN - University Of Washington; IMAMURA, FUMIAKI - University Of Cambridge; FOROUHI, NITA - University Of Cambridge; WAREHAM, NICHOLAS - University Of Cambridge; BIRUKOV, ANNA - German Institute Of Human Nutrition; JÄGER, SUSANNE - German Institute Of Human Nutrition; SCHULZE, MATTHIAS - German Institute Of Human Nutrition; TUOMILEHTO, JAAKKO - Finnish Institute For Health And Welfare; UUSITUPA, MATTI - University Of Eastern Finland; LINDSTRÖM, JAANA - Finnish Institute For Health And Welfare; TINTLE, NATHAN - Fatty Acid Research Institute; HARRIS, WILLIAM - Fatty Acid Research Institute; YAMASAKI, KEISUKE - Kyushu University; HIRAKAWA, YOICHIRO - Kyushu University; NINOMIYA, TOSHIHARU - Kyushu University; VIRTANEN, JYRKI - University Of Eastern Finland; VOUTILAINEN, ARI - University Of Eastern Finland; SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); RICH, STEPHEN - University Of Virginia; TSAI, MICHAEL - University Of Minnesota; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); YANG, XIAOWEI - Chinese Academy Of Sciences; SUN, LIANG - Chinese Academy Of Sciences; LI, HUAIXING - Chinese Academy Of Sciences; LIN, XU - Chinese Academy Of Sciences; LEMAITRE, ROZENN - University Of Washington

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2025
Publication Date: 2/16/2026
Citation: Lidgard, B., Fretts, A.M., Zelnick, L.R., van Westing, A.C., Geleijnse, J.M., Steur, M., Samieri, C., Helmer, C., Le Goff, M., Chen, Y.Y., Chien, K.L., Ong, K.L., Mozaffarian, D., Siscovick, D., Hu, J.H., de Boer, I.H., Imamura, F., Forouhi, N.G., Wareham, N.J., Birukov, A., Jäger, S., Schulze, M.B., Tuomilehto, J., Uusitupa, M., Lindström, J., Tintle, N., Harris, W.S., Yamasaki, K., Hirakawa, Y., Ninomiya, T., Virtanen, J.K., Voutilainen, A., Senn, M.K., Rich, S., Tsai, M.Y., Wood, A.C., Yang, X., Sun, L., Li, H., Lin, X., Lemaitre, R.N. 2026. Circulating saturated fatty acids and incident chronic kidney disease: A meta-analysis of de-novo prospective cohort investigations. The American Journal of Clinical Nutrition. https://doi.org/10.1016/j.ajcnut.2025.101138.
DOI: https://doi.org/10.1016/j.ajcnut.2025.101138

Interpretive Summary: Chronic kidney disease (CKD) affects more than 10% of adults worldwide and is closely linked to diet and metabolic health. Scientists have long suspected that certain dietary fats might influence kidney function, but previous studies mostly focused on unsaturated fats. This international analysis combined data from over 18,000 participants across 13 studies in nine countries to examine whether saturated fats circulating in the blood are linked to kidney disease risk. Researchers found that people with higher levels of one specific fat—stearic acid (18:0)—had about a 13% lower risk of developing CKD, while other saturated fats showed no clear associations. These results suggest that not all saturated fats are harmful and that stearic acid may even help protect the kidneys. Further studies are needed to understand how this fat might support kidney health and whether diet or medication can safely raise its levels. These findings are important for clinicians, researchers, and policymakers working to prevent CKD through improved nutrition and metabolic health.

Technical Abstract: Chronic kidney disease (CKD) is a global health problem which is associated with poor outcomes, and its prevalence is expected to increase. Identifying novel risk factors for CKD may lead to improved outcomes. Circulating saturated fatty acids (SFAs) have been posited as contributors to CKD risk. We aimed to evaluate associations between circulating SFAs (measured in phospholipids in 7 cohorts, serum or plasma total in 5 cohorts, and cholesterol esters in 1 cohort) and incident CKD in 13 cohorts, and to pool results by meta-analysis across the studies. SFAs were measured in 13 cohorts in the Fatty Acids Outcomes Research Consortium, including 18,193 participants with estimated glomerular filtration rate >60 mL/min/1.73 m2 across 9 countries. Associations between each SFA [palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)] and incident CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2and =25% decrease from baseline) were assessed by Cox or Poisson regressions. Results were pooled using inverse variance weighted meta-analysis. In total, 2554 participants developed CKD over a weighted median follow-up of 7.6 y. After adjustment, higher concentrations of 18:0 were associated with a lower risk of CKD with minimal heterogeneity (relative risk per interquintile range: 0.87; 95% confidence interval: 0.80, 0.95, P=0.003, I**2=14.7%). These associations remained consistent in secondary and sensitivity analyses. We did not observe significant associations of other SFAs with CKD. In a meta-analysis of 18,193 participants across 9 countries, we observed no indication that SFA increased CKD risk, whereas higher 18:0 concentrations were associated with a lower risk of CKD. Future research is needed to assess mechanisms by which SFA 18:0 may exert kidney-protective effects, and how circulating SFA 18:0 concentrations may be altered.