Declining Kidney Function Is Associated with Altered Erythrocyte Membrane Fatty Acid Profiles and Estimated Enzymatic Indices

Patients with chronic kidney disease (CKD) face a substantial cardiovascular burden, with altered erythrocyte membrane fatty acids (FAs) representing potential markers of adverse outcomes. However, comprehensive evaluations according to varying levels of kidney function remain limited. This retrospective pooled analysis evaluated the association between kidney function decline, erythrocyte FA profiles, and estimated enzymatic indices (surrogate product-to-precursor ratios) across eight distinct cohorts (N = 282: 33 healthy controls, 131 non-dialysis CKD, 118 end-stage kidney disease). Generalized linear mixed models accounted for inter-cohort heterogeneity with study source as a random intercept, adjusting for age, sex, diabetes, and serum albumin. With declining kidney function, erythrocyte membrane oleic acid exhibited a stepwise increase alongside an elevated elongation of very long-chain fatty acids protein 6 index, whereas linoleic acid and the stearoyl-CoA desaturase 18 index progressively decreased. Multivariable models confirmed that estimated glomerular filtration rate was an independent predictor of oleic (β = −0.012, 95% CI: −0.024 to −0.0003, p = 0.044) and linoleic (β = 0.016, 95% CI: 0.004 to 0.028, p = 0.012) acid levels. In conclusion, kidney dysfunction is independently associated with an altered membrane FA composition, characterized by an increase in monounsaturated FAs and a decline in essential polyunsaturated FAs. These findings suggest a potential link between declining kidney function and altered lipid metabolism, providing a basis for further studies exploring targeted nutritional interventions in CKD.