Kidney Blood Press Res. 2026;51(1):915-922. doi: 10.1159/kbr/adjag008. Epub 2026 Sep 30.
ABSTRACT
In the article "Lipids and Lipid Metabolites in the Diagnosis, Risk Prediction, and Treatment of Chronic Kidney Disease and Acute Kidney Injury: A Narrative Review" [Kidney Blood Press Res. 2026;51:567-588. https://doi.org/10.1159/000552568] by Erfurt et al. Table 1 was incorrectly transferred during the production process. A corrected version of Table 1 is available below.Table 1.Summaries of all studies discussed, including design and outcomesReferenceDesignMethodologyMain findingsConclusionDiagnostic and prognostic role of fatty acids and their metabolites in CKDShearer et al. [36] (2012)Comparison of plasma fatty acid (FA) profiles in patients with stage 3-4 CKD (n = 10), stage 5 CKD near dialysis initiation (n = 20; one excluded for poor FA recovery), and 10 non-CKD controls from Karolinska prospective cohorts (mean follow-up for stage 5 = 2.7±1.7 years)FAs measured by gas chromatography; eGFR (MDRD) and FA relationships assessed using Deming orthogonal regression and Cox models (age-adjusted)Stage 5 CKD patients had lower relative abundances of polyunsaturated Fas - especially arachidonate synthesis intermediates - and lower stearic acid; EPA was lower in stage 5 vs. stage 3-4 and controls. Monounsaturated FAs showed opposing trends with declining eGFR (palmitate decreased, oleic acid increased). Nervonic acid abundance was a strong age-adjusted predictor of mortality in dialysis patientsMetabolic intermediates of arachidonic acid synthesis are reduced in CKDNervonic acid significantly predicts all-cause mortalityAfshinnia et al. [39] (2016)Nested case-control study used fasting serum from a subcohort of the CRIC cohort to identify lipidomic predictors of progression to end-stage kidney disease (ESKD)LC-MS shotgun lipidomics510 lipids detected (382 after filtering); 49 showed nominal differences between progressors and nonprogressors. Statistical selection combined t tests with FDR correction, PLS-DA, and Random Forest, and candidates were tested in logistic regression models adjusted for eGFR, UPCR, demographics, diabetes, hypertension, and heart failure. Two diacylglycerols (DAG 36:0 and DAG 32:0) were lower in progressors and each 1-SD higher level was associated with substantially reduced progression risk; monoacylglycerol MAG 16:0 was higher in progressors and associated with increased risk. Class-level findings showed enrichment and differential regulation of cholesterol esters, DAGs, and phosphatidylethanolamines, with chain length and unsaturation patterns differing between groupsMultimarker lipid panels significantly improve discrimination vs. a base model (eGFR + UPCR)Gollasch et al. [37] (2020)Comparison of fatty acid profiles in 15 healthy volunteers and 15 end-stage kidney disease (ESKD) patients on maintenance hemodialysis (HD)Venous blood collected from controls and pre-/post-HD from patients; RBC and plasma fatty acids measured by HPLC-MSESRD patients showed altered RBC and plasma fatty acid patterns: reduced EPA (C20:5 n-3) and certain n-6 species and increased very-long-chain monounsaturated fatty acids (e.g., C24:1 n-9); most free fatty acids were higher in plasma and RBCs of patients. A single HD session produced only minor changes in several total plasma saturated and n-6 fatty acids and did not meaningfully change RBC fatty acid composition or the RBC omega-3 indexTotal fatty acid levels differed significantly in RBCs from healthy controls and CKD patients, hemodialysis has no effect on plasma or RBC fatty acid levelsSikorska-Wisniewska et al. [38] (2020)Cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (n = 43)Fatty acids (FA) assessed by gas chromatography-mass spectrometry; same FA analysed in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controlsSerum omega-3 and omega-6 PUFA levels were highest in controls and lowest in RTx patients. No associations were found between GFR and FA levels. Fish intake correlated with EPA/DHA levels in some groups, but ALA intake did not correlate with serum ALA; EPA, DHA, LA, and AA generally correlated inversely with triglycerides (some correlations reached significance), while no meaningful links were found with CRP, albumin, BMI, or adipose tissue PUFA compositionRTx patients present significantly lower serum content of all the examined PUFAs, in comparison to the CKD-ND group and controlsLanzon et al. [47] (2021)Comparison of 11 severely obese patients with chronic kidney disease (OD) and 14 obese controls without CKD (O)Serum lipidomics (LC-MS) and polar metabolomics (GC-HRAM-MS)Lipidomics: 71 serum lipids differed (most increased in OD), notably rises in TGs (many unsaturated, short-/medium-chain), diglycerides (DGs), phosphatidylcholines (PCs), lysophosphatidylcholines (LysoPCs) and plasmalogens, while sphingomyelins (SMs) and phosphatidylinositols (PIs) decreased. Short-chain TGs correlated negatively with eGFR in OD; many lipids correlated with glucose in O but not in OD. Metabolomics: several essential and conditionally essential amino acids (e.g., isoleucine, lysine, proline) were higher in OD. After bariatric surgery OD patients showed lipidomic shifts toward profiles closer to O; DGs and medium-chain TGs correlated with uric acid post-surgery. Serum levels of several essential amino acids (isoleucine, lysine, threonine, valine) and some conditional amino acids fell after surgery; urine valine and glutamine decreased while hippuric acid increasedResults justify the use of lipidomics to validate possible early markers of risk of CKD in patients with severe obesityMika et al. [40] (2021)Study of 198 kidney transplant (Tx) patients (age 18-70) and 48 matched controlsAnalysis of fasting plasma fatty acid (FA) profiles by GC-MS after Folch extractionTx patients - treated with standard triple immunosuppression and excluding FA supplement users - showed distinct FA alterations vs. controls: lower long- and very-long-chain saturated and polyunsaturated FAs (many n-3/n-6 PUFA and branched-chain FAs), but higher palmitic (16:0) and certain monounsaturated FAs (16:1, 18:1). Disturbances were greatest within the first month post-transplant (Tx1M) and partially normalized by >12 months, though differences from controls persisted. PCA and hierarchical clustering clearly separated Tx and control groups. Comorbidities and clinical factors affected profilesFA profiles are significantly different between patients and controls, tendency for normalization in long-term kidney recipients, n-3 PUFA strong inverse associated with inflammationPinto et al. [41] (2021)Investigation of relationships between dialysis, sleep and 24 h heart rate variability (HRV) and LC n-3 PUFA status in hemodialysis patients (CKD stage 5) (n = 45)Pre-dialysis blood samples, measurement of erythrocyte and plasma fatty acid compositionCompared with controls, patients had higher heart rates, lower HRV, more inflammation, and lower LC n-3 PUFA levels; erythrocyte omega-3 index was low overall. While no consistent associations were found for erythrocyte O3I, EPA, or DHA with HRV, plasma DHA correlated positively with HRV during dialysis, plasma EPA with 24-h HRV, and EPA:DHA ratio, DPA(n-3), and EPA showed mixed inverse or negative associations with short-term HRV, indicating a complex relationshipImpaired EPA metabolism might contribute to sudden cardiac death (SCD) risk increase in dialysis patientsŚledziński et al. [42] (2022)Study of 35 CKD patients (19 men, 16 women; age 22-70) comparison of serum fatty acid (FA) profiles before and 3 months after deceased-donor kidney transplantationCollection of fasting serum, lipids extracted and converted to FAMEs, subsequently analyzed by GC-EI-MSTotal even-chain saturated FAs, odd- and branched-chain FAs, and total SFAs did not change, but specific FAs shifted: decreases in some 12-, 18-, and 26-carbon FAs, a rise in palmitic acid (16:0), and a significant reduction in ultra-long-chain FAs (≥26C), especially 26:0. Total MUFAs were unchanged though 20:1 increased and the 18:1/18:0 desaturation index rose. Among PUFAs, total n-6 was stable despite decreases in DGLA (20:3n-6), ARA, and AdA (22:4n-6) while 18:2n-6 increased; total n-3 PUFAs declinedSignificant reduction in n-3 PUFAs in renal transplant recipients 3 months after transplantation, which may contribute to increased cardiovascular riskŚledziński et al. [45] (2024)Prospective study of 25 CKD patients (23 deceased-donor, 2 living-donor)Quantification of serum fatty acid (FA) profiles before kidney transplantation (KTx), 3 months after, and 6-12 months after. Samples analyzed by GC-MSTotal saturated FAs were largely unchanged except for an increase in odd-chain SFAs; very-long-chain FAs (>20C) rose by 6-12 months, whereas ultra-long-chain FAs (≥26C) fell progressively. Total MUFAs were stable overall, but C20:1, C22:1, C24:1 increased and C18:1 trended down. Total n-3 PUFAs (including DHA) and some n-6 PUFAs (ARA, DGLA) decreased at 3 months then increased by 6-12 months; linoleic acid rose at 3 monthsFA dynamics following KTx are complex and may indicate a need for supplementationMantovani et al. [46] (2023)Follow-up of 85 post-menopausal women with non-insulin-treated T2DM and preserved kidney function at baselineSerum NEFA concentrations measured using enzymatic colorimetric method, eGFR was estimatedHigher baseline NEFA levels strongly predicted kidney function decline. Patients in the highest NEFA tertile had significantly greater risk by Kaplan-Meier analysisHigher circulating levels of NEFA strongly associated with faster kidney function declineOng et al. [43] (2023)Pooled analysis by the Fatty Acids and Outcomes Research Consortium, combination of de novo data from 19 prospective cohorts (25,570 participants without baseline CKD; median follow-up 11.3 years) to examine circulating/adipose n-3 PUFA biomarkers and risk of incident chronic kidney disease (CKD)Biomarkers (ALA, EPA, DPA, DHA) were measured by gas chromatography in various lipid compartments, and incident CKD was defined as follow-up eGFR <60 mL/min/1.73 m2 among those with baseline eGFR ≥60See "Conclusion"Meta-analyses (adjusted Cox/Poisson and linear models) showed higher seafood-derived n-3 PUFAs (EPA/DPA/DHA) were associated with lower risk of incident CKD (8% lower per interquintile range; highest vs. lowest quintile RR 0.87) and with slower annual eGFR decline; results were consistent across compartments and sensitivity analyses. ALA showed no association with incident CKD or eGFR decline. Associations were not modified by age, race, hypertension, diabetes, coronary disease, or baseline eGFRKoh et al., 2024 [44]Prospective observational cohort study, 73.419 participants without CKD and 6. 735 with CKDAnalysis of systemic PUFA levelsHigher PUFA levels - especially omega-3s like DHA - were linked to lower risk of developing CKD and reduced all-cause mortality; higher PUFA levels also correlated with younger age, female sex, nonwhite race, nonsmoking, and healthier clinical profilesAmong participants without CKD, higher plasma levels of total PUFAs are associated with a lower risk of developing CKDFatty acids, their metabolites and modulators of fatty acid metabolism in CKD managementBarden et al. [55] (2015)Double-blinded, placebo-controlled intervention, CKD patients randomized to n-3 fatty acids, CoQ, both or control, daily for 8 weeksExamination of n-3 fatty acid effects on plasma and urinary 20-HETE, plasma and urinary F2-isoprostanes, changes in blood pressureTreatment raised platelet n-3 and plasma CoQ (confirming compliance) and significantly lowered plasma 20-HETE and F2-isoprostanes (urinary levels unchanged) and reduced systolic and diastolic BP during both awake and asleep periods. Post-intervention 20-HETE was positively associated with 24-h SBP and DBP (driven by daytime BP)Identification of a plausible mechanism underlying the reduction in blood pressure observed in patients with chronic kidney disease after omega-3 fatty acid supplementationHu et al. [56] (2017)Review and meta-analysis: 9 RCT with CKD patients includedEvaluation of the benefits and risks of omega-3 fatty acid supplementationSee "Conclusion"Omega-3 supplementation significantly reduces proteinuria and lowers risk of ESKD but does not significantly affect creatinine clearance rate or eGFR. Subgroup analysis shows location, age, and study quality influences the proteinuria benefitDe Boer et al. [57] (2019)RCT: 1,312 adults with type 2 diabetesRandomization to receive vitamin D3 and omega-3 fatty acids and placebo for 5 years, primary outcome: GFR changeNo significant differences in eGFR, urine ACR, or a composite of kidney failure/death between supplement and placebo groups. Adverse events similar across groupsResults do not support use of vitamin D or omega-3 fatty acid supplementationValle Flores et al. [58] (2020)Prospective, randomized, double-blind study in CKD patients undergoing hemodialysisTwo groups: group A (46 patients) received omega-3 fatty acids during 12-week, control group (group B, 47 patients) received paraffin oil, general characteristics, analysis of nutritional indicators, renal disease markers and CRP, IL-6, IL-10, and TNF-α evaluatedOmega-3 supplementation produced significant reductions in inflammatory markers and significantly raised the IL-10/IL-6 ratio, while IL-10 increased nonsignificantly; no meaningful changes in the control groupOral omega-3 fatty acid supplementation significantly reduces inflammatory marker concentrations in patients with chronic kidney disease undergoing hemodialysisBunout et al. [59] (2021)RCT: 100 CKD patients supplemented for 3 months with docosahexaenoic and eicosapentaenoic acids or a corn oil supplementEvaluation at baseline, 6 weeks, 12 weeks; variables: blood and morning spot urine samples, blood pressure, carotid intima media thickness, and pulse wave velocity, main outcome: reduction of ≥20% in urine albuminThe n-3 PUFA group showed significant rises in EPA/DHA and omega-3 index and a drop in triglycerides, while both groups had reductions in urine albumin excretion (no significant between-group difference). Pulse wave velocity remained stable with n-3 PUFA but increased in controls; HbA1c rose in both groups and inflammatory markers were unchanged. Secondary analysis revealed systolic blood pressure fall in n-3 PUFA usersOmega-3 fatty acid supplement does not modify urine albumin excretion in patients with CKD but improves pulse wave velocity and serum triglyceride levelsLin et al. [60] (2022)Investigation of oral supplementation with omega-3 PUFA on circulating IL-6, cardiometabolic parameters, skin moisturization, and symptoms of pruritus in hemodialysis patientsTwenty-seven subjects consumed fish oil daily for 3 months and were measured at baseline, first, second, and third month post-supplementationFish oil did not change BMI, serum calcium, phosphorus, or iPTH but significantly reduced pruritus and improved skin hydration. Inflammatory markers (CRP, IL-6), plasma creatinine, and several lipid measures (total cholesterol down, HDL up, TG improved; LDL fell then rose slightly by month three) also improvedOmega-3 PUFA beneficial in hemodialysisAo et al. [61] (2024)24,497 patients with diabetes includedCox proportional hazards regression models used to estimate hazard ratios for CKD risk and impact of fish oilAdjusted analyses found lower CKD risk in diabetic patients who used fish oil and an approximate 2.79-year delay in CKD onset, with stronger effects in men, older adults, non-smokers, and those with healthier diets. Fish oil use also associated with lower HbA1c and CRP and higher HDLFish oil might reduce CKD risk in diabeticsFei et al. [62] (2024)Review and meta-analysis: 9 studies, total of 347 proteinuric participants included in the analysisAnalysis of the impact of omega-3 fatty acid supplementation on proteinuriaSee "Conclusion"Pooled results using fixed- and random-effects models showed non-significant standardized mean differences, with substantial heterogeneity. Study quality was moderate (JADAD 2-4); funnel plot showed no clear publication bias but power was limited by few studies. Overall, omega-3s did not demonstrate a significant anti-proteinuric benefit, though heterogeneity limits confidenceLok et al. [63] (2026)Double-blinded randomized trial of 1,228 adults on maintenance hemodialysisDaily fish-oil supplementation (4 g n-3 fatty acids: 1.6 g EPA + 0.8 g DHA) in comparison with corn-oil placebo over 3.5 yearsFish-oil significantly reduced the rate of serious cardiovascular events (primary end point) vs. placebo and lowered risks of cardiac death, myocardial infarction, stroke, and amputations, with similar adherence and adverse events between groupsFish-oil reduces cardiovascular and mortality risk in hemodialysis patientsDiagnostic and prognostic role of fatty acids and their metabolites in AKIWang et al. [50] (2020)Prospective pilot study: pediatric intensive care, 101 sepsis patients, 30 healthy controlsSerum ApoA5 levels were determined by ELISAApoA5 was lower in septic children than healthy controls and significantly lower in nonsurvivors vs. survivors, correlating with MODS and AKI; low ApoA5 was an independent risk factor for PICU mortality. ROC analysis showed ApoA5 had diagnostic and prognostic value, and it correlated positively with serum calciumLower serum ApoA5 level predicts sepsis-associated complications, e.g., AKI, or MODS in childrenSun et al. [51] (2021)Pilot study: 17 patients with new diagnosed AKI and 17 healthy controlsSerum metabolomic profilingFrom thousands of ion features, 51 reliable metabolites were examined; 1-arachidonoyl-lysoPC was prominent on day 1, while creatine, citrulline, and others distinguished survivors from non-survivors at day 8, with higher levels in those who died. Multimetabolite ROC models predicted outcomes: a 4-metabolite (m4) day-1 model performed best for mortality, an 11-metabolite (m11) day-8 model showed high specificity, and a 3-metabolite (m3) model predicted KRT independence with a favorable AUCDistinct metabolite panels enable assessment of mortality risk in acute kidney injury (AKI)Zhang et al. [53] (2022)Retrospective, observational cohort study: 1,028 patients with primary nephrotic syndrome, AKI (n = 81), non-AKI (n = 947)Examination of serum free fatty acids by enzyme endpoint methodsPrematch, AKI patients were older, more often male, and had more infections, higher SBP, BMI, proteinuria, and serum free fatty acids (FFA), plus lower albumin and HDL. After propensity matching (77 pairs), multivariate analysis found infection, higher SBP, greater proteinuria, and higher FFA associated with AKI No FFA differences by stage or pathological type; FSGS had the highest AKI incidenceSerum FFA showed only weak diagnostic value for AKIin primary nephrotic syndromeZhou et al. [54] (2023)Prospective cohort study: 67 patients with sepsis associated AKI and 20 healthy controlsOxidative lipid analysis in plasma samples, liquid chromatography, tandem mass spectrometric detectionPlasma oxidative lipidomics reveals 21 significantly oxidized lipids. Machine learning (Random Forest, LASSO) highlighted five key biomarkers - particularly 9,10-DiHOME and 5,6-DiHETrE. Pathway analysis showed altered lipid metabolism, including downregulation of vascular smooth muscle contraction and involvement of serotonergic synapse pathwaysIdentification of 9,10-DiHOME and 5,6-DiHETrE as potential biomarkers for detecting sepsis associated AKI, 5-isoPGF2VI: a potential biomarker to distinguish AKI stage III from AKI stages I-II.Zhou et al. [48] (2025)Prospective cohort study in 17 patients with cardiac surgery-associated acute kidney injury (CSA-AKI) and 17 controlsLipidomic analysis through liquid chromatography-mass spectrometry (LC-MS)Broad lipidomic profiling found most differentially expressed lipids were upregulated in CSA-AKI, including acylcarnitines, cholesteryl esters, certain ceramides, lysophosphatidic acids, lysosphingomyelins, PG, and PIP species. Multivariate and network analyses implicated altered glycerophospholipid metabolism and flagged PE(14:0/22:2) and PE(39:1) as early-increased candidates, while PI(18:0/18:1) showed broad negative correlationsIdentification of PE(14:0/22:2) and PE(39:1) as early-increased candidates in CSA-AKIFatty acids, their metabolites and modulators of fatty acid metabolism in AKI managementHoogeveen et al. [64] (2014)2,344 patients with myocardial infarctionRandomization to 4 groups, substitution of eicosapentaenoic acid and docosahexaenoic acid, α-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid and α-linolenic acid, or placebo for 40 months, eGFR measuredDaily EPA-DHA slows eGFR decline compared with placebo, with a larger benefit in those with baseline CKD. ALA showed no significant effect. EPA-DHA does not significantly reduce the incidence of CKD or rapid kidney-function decline, so effects were modest and variableLong-term supplementation with eicosapentaenoic acid-docosahexaenoic acid associated with small beneficial effects on kidney functionAlrowaie et al. [65] (2021)RCT: 130 patients undergoing coronary angiographyTwo groups: 67 received N-acetylcysteine (NAC), 63 received omega-3 fatty acid before interventionNAC group older with higher prevalence of hyperlipidemia, omega-3 group uses more ACEi/ARBs. Rates of contrast-induced nephropathy, kidney replacement therapy, in-hospital death, MI/stroke, and length of stay significantly not different between treatmentsOmega-3 fatty acids no beneficial effects on contrast-induced nephropathy.
PMID:42814674 | DOI:10.1159/kbr/adjag008