Inflammation and Fish Oil (PISCES) in Hemodialysis

Bottom line

PISCES is the first large positive cardiovascular prevention trial in hemodialysis. It is a single trial, and it says nothing about nutrition.

• Inflammation predicts cardiovascular death. In observational cohorts, cardiovascular mortality was 23% versus 5% with a CRP above versus below 8 mg/L ¹, and each 1-log rise in IL-6 carried an HR of 1.43 for cardiovascular death ². Remove the sources first, starting with catheters ³.
• IL-6 blockade is not ready for dialysis. Ziltivekimab failed in ZEUS, a non-dialysis CKD outcome trial (MACE HR 0.99) ⁴. The dialysis outcome trial of clazakizumab is still recruiting, with primary completion estimated in 2029 ⁵.
• PISCES (RCT; NEJM 2026, online November 2025): 1,228 hemodialysis patients took four 1-g capsules a day — 2.4 g EPA+DHA — or corn oil. Serious cardiovascular events, counting recurrences, fell with fish oil: HR 0.57 (95% CI 0.47–0.70) ⁶.
• Patient-level result: 20.8% versus 33.7% had at least one serious cardiovascular event — ARR 12.9 percentage points, NNT 8 over a mean of approximately 2.3 years. All-cause death did not differ significantly (HR 0.89). Serious bleeding was not increased (4.8% versus 7.6%) ⁶.
• Fish oil does not meaningfully raise albumin in hemodialysis. Pooled estimates run from 0.00 g/dL ⁷ to +0.14 g/dL (95% CI 0.01–0.28; I² 87.5%) ⁸, and PISCES measured albumin only at baseline ⁶. CRP falls modestly in some pools but not in KDOQI’s ^9,10. Prescribe it for the cardiovascular result, not for nutrition.
• Guidelines lag the trial. KDOQI 2020 predates PISCES and suggests against routine use (2B) ⁹; UpToDate (updated November 2025) suggests fish oil for maintenance dialysis patients (Grade 2B). Dose by EPA+DHA content. Prescription omega-3 products are off-label for this use ^11,12.

1. What inflammation predicts

• CRP (observational). In a 1999 cohort, CRP above 8 mg/L was present in 46% of hemodialysis patients without apparent infection. Overall mortality was 31% versus 16%, and cardiovascular mortality 23% versus 5%, with elevated versus normal CRP ¹. In a multinational DOPPS analysis, CRP’s association with 1-year mortality had no safe threshold, and CRP added more predictive information than albumin, ferritin, or white-cell count ¹³.
• IL-6 (observational). In patients starting dialysis, IL-6 quartile stratified survival in both hemodialysis and peritoneal dialysis ¹⁴. In prevalent hemodialysis, each 1-log rise in plasma IL-6 carried an adjusted HR of 1.19 for death and 1.43 for cardiovascular death ².
• Consequences. Inflammation is linked to cardiovascular death ^1,2,15, wasting and hypoalbuminemia ^16,17,18, and ESA hyporesponsiveness through hepcidin (see Anemia: targets, ESAs, and hyporesponsiveness).

Albumin is partly an inflammation marker: inflammation lowers it by speeding its breakdown, while diet mainly affects its synthesis ^17,18.

CRP is not a routine monthly test in most US units; it is worth ordering when albumin falls without a dietary cause, ESA needs climb, or hidden infection is suspected.

2. Sources of inflammation you can remove

3. Ultrapure dialysate

Dialysate is not sterile. Bacterial fragments and endotoxin cross high-flux membranes and stimulate cytokines.

• Before–after cohort (Schiffl 2001): switching to ultrapure fluid lowered IL-6 and CRP and raised dry weight, albumin, and nPCR over 12 months ²⁶.
• Meta-analysis (Susantitaphong 2013; 31 studies, 23 pooled arms, 2,221 patients): ultrapure dialysate lowered CRP by 3.2 mg/L, raised albumin by 0.11 g/dL and hemoglobin by 0.40 g/dL, and reduced weekly epoetin by 273 units; the results held in controlled trials ²⁴.
• National cohort (Hasegawa 2015; 130,781 patients): facility dialysate endotoxin of 0.1 EU/mL or more was associated with 28% higher 1-year mortality than endotoxin below 0.001 EU/mL ²⁷.
• Randomized outcome trial (Asci 2013; 704 patients): ultrapure versus standard dialysate did not reduce cardiovascular events (HR 0.90; 95% CI 0.61–1.32); a post hoc benefit after more than 3 years on dialysis is hypothesis-generating ²⁸.

US facilities must meet the AAMI RD52:2004 water and dialysate standard incorporated in the federal Conditions for Coverage ²⁹. Ultrapure fluid consistently improves surrogate inflammation markers. It has not been shown to prevent cardiovascular events.

4. IL-6 inhibition (status September 2026)

IL-6 sits upstream of CRP, fibrinogen, serum amyloid A, hepcidin, and the albumin catabolic rate. It is the obvious target. It has not yet delivered.

Appraisal. Every dialysis IL-6 result so far is a surrogate. ZEUS is the warning: suppressing the biomarker in non-dialysis CKD did not move MACE, and serious infections increased ⁴. Infection is the second leading cause of death on hemodialysis ³⁵, and the 10-mg clazakizumab arm quadrupled serious infections in 12 weeks ³³. Until the phase 3 dialysis trial reports, anti-cytokine therapy has no place outside a trial.

5. Omega-3 fatty acids before PISCES

The biology was always plausible. Hemodialysis patients have low circulating long-chain omega-3 levels ⁶. In incident US hemodialysis patients (observational), the highest quartile of omega-3 levels carried one-fifth the odds of first-year sudden cardiac death of the lowest (OR 0.20) ³⁶. Reported fish intake was associated with about 50% lower mortality in a small cohort ³⁷.

Earlier randomized trials in dialysis were small or aimed at access. OPACH (206 patients with prior cardiovascular disease; EPA 0.77 g + DHA 0.64 g/day) found no difference in cardiovascular events plus death (62 versus 59 events), with fewer MIs as a secondary finding (4 versus 13) ^9,38. FISH (201 new AV grafts; 1.6 g EPA + 0.8 g DHA versus corn oil) missed its graft-patency endpoint (48% versus 62% loss of patency; RR 0.78, 0.60–1.03) but showed better cardiovascular event-free survival as a secondary outcome (HR 0.43; 0.19–0.96) ³⁹. FAVOURED (567 new fistulas) was null for fistula failure ⁴⁰, and a 24-patient graft trial with a striking patency result was never replicated ⁴¹.

A 2020 meta-analysis of 60 trials (4,129 participants, median follow-up 6 months) found low-certainty evidence that omega-3 supplementation reduced cardiovascular death in hemodialysis (RR 0.45; 95% CI 0.23–0.89), based on only 39 events, with no effect on all-cause mortality (RR 1.05) ⁴². That is where KDOQI 2020 stood: plausible biology, one suggestive secondary endpoint, and no adequately powered trial. It suggested against routine use (2B) and named PISCES as the pending answer ⁹.

6. PISCES: the trial

Lok CE et al. N Engl J Med 2026;394:128–137, published online November 7, 2025 ⁶. The protocol was published in January 2024 ⁴³.

7. PISCES: results

From Table 2 of the paper; follow-up 1,394 and 1,382 patient-years. Confidence intervals for secondary endpoints were not adjusted for multiplicity ⁶.

In absolute terms

Patient-level proportions over a mean of about 2.3 years, with HRs where the paper reports them. ARR and NNT are crude values derived from the published proportions; the paper cautions that its binary analyses do not account for differential follow-up ⁶.

Event rates were 11.3 versus 22.4 per 100 patient-years, about 11 events prevented per 100 patient-years of treatment. That figure describes events, not people; quoting it as an “11% per year” absolute risk reduction mislabels an event rate as a patient-level risk ⁶.

Safety. Serious bleeding (not adjudicated) was 4.8% versus 7.6%, gastrointestinal 2.6% versus 4.2%. Serious infections (20.3% versus 17.8%) and respiratory events (5.1% versus 3.7%) showed numerical imbalances that the editorialists flagged ^6,35. Atrial fibrillation was not reported as a safety outcome ⁶.

8. PISCES: critical appraisal

1. The effect is larger than the trial was designed to find. The investigators powered for HR 0.825 and observed 0.57 ⁶. Large effects in moderate-sized trials often shrink on replication. The NEJM editorial and a 2026 review both asked for a larger confirmatory trial before fish oil becomes standard care ^35,44.
2. The primary endpoint counts repeat events. That captures total burden where events cluster ⁴⁵, but it weights patients with many events, and correspondents argued that it may amplify benefit while survival barely moves ⁴⁶. The first-event and component analyses point the same way: first cardiovascular event or death HR 0.73; cardiac death HR 0.55 ^6,47.
3. Nobody lived longer. There were 175 versus 195 deaths (HR 0.89) ⁶. Subtracting primary events from the “primary events plus noncardiac death” composite leaves 108 noncardiac deaths with fish oil versus 72 with placebo (derived) ⁶. The authors proposed competing risk: fewer cardiovascular deaths left more patients alive to die of infection or withdrawal from dialysis ⁴⁷. That is plausible, but the net survival effect is what patients experience. The authors’ reply reports all-cause HR 0.90 (0.72–1.13) from a different model ⁴⁷. Either way, no survival benefit was shown.
4. The placebo was corn oil, not mineral oil. The mineral-oil comparator in REDUCE-IT raised IL-6 16%, hs-CRP 22%, and oxidized LDL 11% over 12 months ⁴⁸. PISCES used corn oil, as STRENGTH did ⁴⁹. The placebo event rate (0.61) was below the design assumption (0.74), so if corn oil did anything, it probably biased the result toward the null ^6,47,50.
5. Who was studied. Patients in Canada and Australia with low lipid levels, 35% with prior cardiovascular disease; effect estimates were similar with and without it ^6,47. Baseline omega-3 status was measured in only about 20% of participants, so whether patients who already eat a lot of fish benefit is unanswered ^47,51. PISCES did not recruit in the United States, despite the editorial’s statement that it did ^6,35.
6. Adherence and prespecification. EPA was measured only once, at 3 months in a random sample; placebo patients showed no rise, which argues against drop-in use of over-the-counter fish oil ⁶. The trial was registered (ISRCTN00691795), but the full protocol with the recurrent-event plan was published in January 2024, after the last follow-up visit ^6,43.
7. Arrhythmia was not reported. PISCES reported neither atrial fibrillation nor sudden cardiac death separately, and its mechanism of benefit is unknown ^6,44. In general-population trials, omega-3 supplementation increases atrial fibrillation ⁵².
8. Secondary sources already garble it. One 2026 review puts heart-failure hospitalization and arrhythmia in the primary endpoint, which the NEJM paper did not ⁴⁵. Cite the primary paper.

Post-PISCES synthesis. A 2026 meta-analysis of 13 hemodialysis RCTs (2,755 patients), dominated by PISCES, found lower cardiovascular mortality (RR 0.55; 95% CI 0.42–0.71) and unchanged all-cause mortality (RR 0.93; 0.80–1.08) ⁵³.

9. How PISCES fits the other omega-3 trials

Three explanations are offered for why PISCES stands apart, and none is proven ^6,35,44,45:

• Baseline risk. A third of the placebo group had an event in about 2.3 years, and absolute benefit scales with absolute risk ⁶.
• Low baseline omega-3 levels in dialysis patients ⁶.
• Not the comparator. STRENGTH used the same corn-oil placebo with a DHA-containing product at a similar dose and was null in non-dialysis patients ⁴⁹, so the mineral-oil critique of REDUCE-IT does not explain the gap. That makes replication more pressing.

The atrial fibrillation signal. Across 7 outcome trials, marine omega-3 supplementation was associated with atrial fibrillation (HR 1.25; 95% CI 1.07–1.46), and HR 1.49 at doses above 1 g/day ⁵²; VITAL Rhythm, at 840 mg/day, found no significant increase ⁵⁶. Both prescription labels carry atrial fibrillation warnings ^11,12.

10. Products and doses

The PISCES regimen was 2.4 g/day of EPA+DHA as ethyl esters, in a 2:1 EPA:DHA ratio ⁶. Dose by the EPA+DHA total, not by capsule weight or the words “fish oil.”

• A capsule labeled “1,000 mg fish oil” is not 1,000 mg of EPA plus DHA ⁵⁷.
• Four capsules a day, not necessarily at separate times, adds to a heavy pill burden ⁶.
• Cost determines uptake: in an Austrian survey of 525 hemodialysis patients, 79.4% would take fish oil if reimbursed but only 38.1% at €40 per month ⁵⁹.
• Over-the-counter products cannot be assumed equivalent to the trial product; that is a limitation to explain, not a reason to withhold the regimen ^57,58.
• Fish or shellfish allergy excluded patients from PISCES, and both prescription labels carry allergy cautions as well as bleeding and atrial fibrillation warnings ^6,11,12.

11. What guidelines and references say (September 2026)

• KDOQI 2020 suggests not routinely prescribing long-chain omega-3 fatty acids to lower mortality (2C) or cardiovascular events (2B) in maintenance hemodialysis, and named PISCES as the ongoing trial that would address the question ⁹. It was written before PISCES.
• KDIGO has no statement as of September 2026, and KDOQI has not updated its guidance.
• UpToDate (Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis), updated November 21, 2025) suggests fish oil supplements for patients on maintenance dialysis (Grade 2B) to prevent new and recurrent cardiovascular events, and states that confirmatory trials are warranted.
• Commentaries favor confirmation before universal adoption while acknowledging that some physicians will recommend fish oil now ^35,44,45.

12. Fish oil, albumin, and inflammatory markers

PISCES did not measure albumin as an outcome

PISCES measured albumin only at baseline: 38 g/L (IQR 35–40), that is, 3.8 g/dL in both arms (Supplementary Appendix, Table S3) ⁶. No follow-up albumin, nutrition, inflammation, or lipid value appears in the paper or its appendix, and the protocol never mentions albumin ^6,43. The only follow-up laboratory measure was plasma phospholipid EPA + DHA at 3 months in 232 patients: +1.92 percentage points versus placebo (95% CI 1.46–2.38) ⁶. This was a well-nourished (mean BMI about 27 kg/m²), normotriglyceridemic population, and the trial cannot say whether its benefit ran through nutrition or inflammation.

The meta-analysis that reported an albumin rise

Bagheri 2023 (Nutrition Reviews) pooled 50 RCTs framed as studies of “hospitalized patients.” Its dialysis estimate was +0.14 g/dL (95% CI 0.01–0.28; P = 0.042; I² 87.5%) across 15 trials: borderline and highly heterogeneous ⁸. It does not survive a close read:

• No dose–response. The effect was significant only below 1,000 mg/day, and the linear estimate was +0.03 g/dL per 1,000 mg/day (−0.03 to 0.09; P = 0.304). The PISCES dose of 2.4 g/day sits outside the only significant dose subgroup ^6,8.
• Risk of bias: 11 of the 15 dialysis trials were rated high risk and 1 low ⁸. That one low-risk trial (Asemi 2016) ⁶¹ comes from a trial whose companion report carries a 2023 expression of concern ⁶².
• Design mix: four comparisons had no placebo, and one “hemodialysis” trial enrolled peritoneal dialysis patients ^8,63.
• Size: IL-6 blockade raised albumin 0.21–0.28 g/dL in 12 weeks ³³; a supplement achieving more than half of that would be surprising.

The other pooled analyses

The largest dialysis-specific pool, Liu 2022 (14 trials), found a mean difference of 0.00 g/dL (−0.05 to 0.04) ⁷. Three smaller pools agree that there is no reliable effect: He 2016, 0.12 (−0.56 to 0.80) across 5 trials ⁶⁴; Dezfouli 2020, a standardized mean difference of 0.91 (−0.78 to 2.59) that its text reports as g/dL, although the four trials’ raw between-group changes were +0.2, 0.0, +0.4, and −0.1 g/dL ⁶⁵; and Xu 2016, −0.33 (−0.83 to 0.17), the wrong direction ⁶⁶. KDOQI 2020 did not analyze albumin ⁹.

The randomized trials in maintenance hemodialysis

Twelve placebo- or oil-controlled RCTs have reported albumin, nutritional, or inflammatory outcomes in hemodialysis. None ran longer than 6 months, the largest with an albumin result enrolled 120 patients, and albumin was the primary outcome in none ^{60,61,62,67,68,69,70,71,72,73,74,75,76,77}.

• Daud 2012 (63 randomized, albumin ≤3.9 g/dL; 2.4 g EPA+DHA three times weekly after dialysis, directly observed, plus protein in both arms; 6 months) is the only trial sized for albumin: +0.1 ± 0.3 versus 0.0 ± 0.3 g/dL (P = 0.295). MIS, nPNA, BMI, and CRP did not change ⁶⁰.
• Null for albumin or nutritional indices: Gharekhani 2014, Moeinzadeh 2016, Valle Flores 2020, Zakaria 2021, and Abbas Torki 2024 ^{69,72,73,75,76}.
• Albumin reported only incidentally: Saifullah 2007 and Hung 2015, with between-group changes of −0.1 and +0.4 g/dL as extracted by Dezfouli ^65,67,70.
• The two positive trials are the weakest. Asemi 2016 reported better MIS with omega-3, but its companion report carries an expression of concern ^61,62. Zhang 2020 compared end-of-study PEW prevalence (38% versus 68%), not change, at 0.53 g/day EPA+DHA ⁷⁴.

The large outcome trials (FISH, OPACH, FAVOURED) did not report albumin ^38,39,40. The belief that fish oil raises albumin traces largely to uncontrolled before–after and non-randomized studies, which cannot exclude regression to the mean ^78,79.

CRP, IL-6, TNF-α, and triglycerides

CRP falls by roughly 1–3 mg/L, mostly in patients who start above 5 mg/L ¹⁰. The guideline’s own pool was not significant ⁹, and the ethyl-ester formulation PISCES used did not significantly lower CRP in Blair’s subgroup ⁸¹. Liu’s CRP interval is implausibly narrow for 20 heterogeneous trials ⁷. The triglyceride effect is the most reproducible metabolic finding, and KDOQI suggests 1.3–4 g/day to lower triglycerides and LDL (2C) ⁹. Flaxseed oil lowered CRP in small trials ^82,83,84, but its alpha-linolenic acid is not EPA or DHA, and PISCES does not apply to it.

What to do with it

• Do not prescribe fish oil to raise albumin. If albumin is the concern, look for the inflammation and fix intake; see Nutrition and protein-energy wasting on hemodialysis.
• Expect no change on the monthly lab. A patient’s albumin moving on fish oil reflects inflammation and intake, not the capsules. Clazakizumab cut hs-CRP 86–92% and moved albumin only 0.21–0.28 g/dL ³³; omega-3 lowers CRP by 1–3 mg/L at best ^10,80.
• When fish oil is prescribed, prescribe it for the PISCES cardiovascular result ⁶.

13. Who might be offered fish oil

PISCES is a well-conducted, academically funded, double-blind trial with a large effect on cardiovascular events and no survival benefit. It is one trial. The known harms are small; the unmeasured one, atrial fibrillation, is real in other populations ^6,52.

A reasonable approach is to offer it through shared decision-making to stable hemodialysis patients resembling the PISCES population, with or without prior cardiovascular disease ⁶, who:

• have no fish or shellfish allergy;
• can manage four more capsules a day; and
• are not in hospice or a comfort-focused plan in which a two-year cardiovascular benefit is not the goal.

Discuss first — these were not exclusions in PISCES, but the risks are unstudied or labeled:

• paroxysmal or persistent atrial fibrillation, given the label warnings and the absence of atrial fibrillation data from PISCES ^11,12,52;
• anticoagulation or dual antiplatelet therapy: 23% of PISCES participants took an anticoagulant or a non-aspirin antiplatelet agent, which is not evidence for triple therapy ⁶;
• LDL cholesterol concerns with DHA-containing products ¹¹.

What to monitor

Evidence gaps

1. PISCES needs replication, ideally in the United States, with atrial fibrillation and sudden cardiac death reported, baseline omega-3 status measured in everyone, and a prespecified first-event analysis alongside total events ^6,35,44.
2. Formulation equivalence. Whether prescription omega-3-acid ethyl esters (EPA:DHA about 1.2:1) or a well-made over-the-counter concentrate reproduces the 2:1 PISCES product is unknown ^11,57.
3. Competing risk. Why noncardiac deaths rose while cardiac deaths fell in PISCES is unexplained ^6,47.
4. Omega-3 and nutrition. No long, adequately powered trial has tested fish oil against albumin or PEW ^8,60.
5. IL-6 inhibition in dialysis. Outcome data are not expected before 2029, after a negative non-dialysis outcome trial ^4,5.
6. Ultrapure dialysate improves surrogates without proven event reduction ^24,28.
7. Periodontal treatment has only uncontrolled evidence ²³.

At the chair

References

Numbered for this page. Every reference is drawn from the canonical evidence review for this module and was verified against its PubMed record or primary document (guideline, federal regulation, FDA label, trial registry, or company announcement) in September 2026.

1. Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int. 1999;55(2):648-58. PMID: 9987089
2. Rao M, Guo D, Perianayagam MC, et al. Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis. 2005;45(2):324-33. PMID: 15685511
3. Goldstein SL, Ikizler TA, Zappitelli M, Silverstein DM, Ayus JC. Non-infected hemodialysis catheters are associated with increased inflammation compared to arteriovenous fistulas. Kidney Int. 2009;76(10):1063-9. PMID: 19675528
4. Novo Nordisk. Novo Nordisk provides update on the ZEUS phase 3 trial in people with ASCVD, CKD and inflammation. Company announcement (GlobeNewswire), July 31, 2026. Top-line result, not peer reviewed.
5. CSL Behring. Combined dose-finding and CV outcomes study with CSL300 (clazakizumab) in adult subjects with ESKD undergoing dialysis (POSIBIL6ESKD). ClinicalTrials.gov NCT05485961; record last updated September 21, 2026.
6. Lok CE, Farkouh M, Hemmelgarn BR, et al. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. N Engl J Med. 2026;394(2):128-137. PMID: 41201837
7. Liu R, Jiang J, Fu Z, Liu C, Yao L, Quan H. Effects of Omega-3 Fatty Acid Intake in Patients Undergoing Dialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Nutr Assoc. 2022;41(7):697-712. PMID: 34635026
8. Bagheri A, Soltani S, Asoudeh F, Esmaillzadeh A. Effects of omega-3 supplementation on serum albumin, pre-albumin and the CRP/albumin ratio in hospitalized patients: a systematic review and meta-analysis. Nutr Rev. 2023;81(3):237-251. PMID: 35939371
9. Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1-S107. PMID: 32829751
10. Zhou J, Tang G, Tang S, Yuan W. The effect of fish oil on inflammation markers in adult patients undergoing hemodialysis: A meta-analysis. Semin Dial. 2022;35(1):6-14. PMID: 34459522
11. LOVAZA (omega-3-acid ethyl esters) capsules. US prescribing information, DailyMed set ID 21cfa4ce-0b05-47ed-b268-339eb1b83b75, published March 11, 2026.
12. VASCEPA (icosapent ethyl) capsules. US prescribing information, Amarin Pharma; DailyMed set ID 9c1a2828-1583-4414-ab22-a60480e8e508, published March 30, 2026.
13. Bazeley J, Bieber B, Li Y, et al. C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(10):2452-61. PMID: 21868617
14. Pecoits-Filho R, Bárány P, Lindholm B, Heimbürger O, Stenvinkel P. Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment. Nephrol Dial Transplant. 2002;17(9):1684-8. PMID: 12198224
15. Stenvinkel P, Heimbürger O, Paultre F, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999;55(5):1899-911. PMID: 10231453
16. Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis. 2003;42(5):864-81. PMID: 14582032
17. Kaysen GA, Dubin JA, Müller HG, Mitch WE, Rosales LM, Levin NW. Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients. Kidney Int. 2002;61(6):2240-9. PMID: 12028466
18. Kaysen GA, Chertow GM, Adhikarla R, Young B, Ronco C, Levin NW. Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. Kidney Int. 2001;60(1):333-40. PMID: 11422769
19. Banerjee T, Kim SJ, Astor B, Shafi T, Coresh J, Powe NR. Vascular access type, inflammatory markers, and mortality in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2014;64(6):954-61. PMID: 25266479
20. Nassar GM, Fishbane S, Ayus JC. Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of erythropoietin resistance and chronic inflammation in hemodialysis patients. Kidney Int Suppl. 2002(80):49-54. PMID: 11982813
21. Kshirsagar AV, Craig RG, Beck JD, et al. Severe periodontitis is associated with low serum albumin among patients on maintenance hemodialysis therapy. Clin J Am Soc Nephrol. 2007;2(2):239-44. PMID: 17699419
22. Kshirsagar AV, Craig RG, Moss KL, et al. Periodontal disease adversely affects the survival of patients with end-stage renal disease. Kidney Int. 2009;75(7):746-51. PMID: 19165177
23. Siribamrungwong M, Puangpanngam K. Treatment of periodontal diseases reduces chronic systemic inflammation in maintenance hemodialysis patients. Ren Fail. 2012;34(2):171-5. PMID: 22229644
24. Susantitaphong P, Riella C, Jaber BL. Effect of ultrapure dialysate on markers of inflammation, oxidative stress, nutrition and anemia parameters: a meta-analysis. Nephrol Dial Transplant. 2013;28(2):438-46. PMID: 23291370
25. Blankestijn PJ, Vernooij RWM, Hockham C, et al. Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure. N Engl J Med. 2023;389(8):700-709. PMID: 37326323
26. Schiffl H, Lang SM, Stratakis D, Fischer R. Effects of ultrapure dialysis fluid on nutritional status and inflammatory parameters. Nephrol Dial Transplant. 2001;16(9):1863-9. PMID: 11522871
27. Hasegawa T, Nakai S, Masakane I, et al. Dialysis fluid endotoxin level and mortality in maintenance hemodialysis: a nationwide cohort study. Am J Kidney Dis. 2015;65(6):899-904. PMID: 25641063
28. Asci G, Töz H, Ozkahya M, et al. The impact of membrane permeability and dialysate purity on cardiovascular outcomes. J Am Soc Nephrol. 2013;24(6):1014-23. PMID: 23620396
29. Centers for Medicare & Medicaid Services. Conditions for Coverage for End-Stage Renal Disease Facilities. 42 CFR Part 494 (§494.40, §494.80, §494.90, §494.110, §494.140), current as of September 2026. eCFR.
30. Pergola PE, Devalaraja M, Fishbane S, et al. Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. J Am Soc Nephrol. 2021;32(1):211-222. PMID: 33272965
31. Ridker PM, Devalaraja M, Baeres FMM, et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021;397(10289):2060-2069. PMID: 34015342
32. Ridker PM, Baeres FMM, Hveplund A, et al. Rationale, Design, and Baseline Clinical Characteristics of the Ziltivekimab Cardiovascular Outcomes Trial: Interleukin-6 Inhibition and Atherosclerotic Event Rate Reduction. JAMA Cardiol. 2026;11(1):89-97. PMID: 41369941
33. Chertow GM, Chang AM, Felker GM, et al. IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial. Nat Med. 2024;30(8):2328-2336. PMID: 38796655
34. Neuen BL, Catanese B, Chang A, et al. Effects of Clazakizumab on Anemia and Iron Metabolism in Patients with Kidney Failure. J Am Soc Nephrol. 2025;36(5):923-925. PMID: 39908111
35. Mc Causland FR, Charytan DM. Fish Oil for Patients Receiving Hemodialysis — Red Herring or Great Catch? N Engl J Med. 2026;394(2):193-194. PMID: 41201835
36. Friedman AN, Yu Z, Tabbey R, et al. Inverse relationship between long-chain n-3 fatty acids and risk of sudden cardiac death in patients starting hemodialysis. Kidney Int. 2013;83(6):1130-5. PMID: 23389417
37. Kutner NG, Clow PW, Zhang R, Aviles X. Association of fish intake and survival in a cohort of incident dialysis patients. Am J Kidney Dis. 2002;39(5):1018-24. PMID: 11979345
38. Svensson M, Schmidt EB, Jørgensen KA, Christensen JH. N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin J Am Soc Nephrol. 2006;1(4):780-6. PMID: 17699287
39. Lok CE, Moist L, Hemmelgarn BR, et al. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA. 2012;307(17):1809-16. PMID: 22550196
40. Irish AB, Viecelli AK, Hawley CM, et al. Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(2):184-193. PMID: 28055065
41. Schmitz PG, McCloud LK, Reikes ST, Leonard CL, Gellens ME. Prophylaxis of hemodialysis graft thrombosis with fish oil: double-blind, randomized, prospective trial. J Am Soc Nephrol. 2002;13(1):184-190. PMID: 11752036
42. Saglimbene VM, Wong G, van Zwieten A, et al. Effects of omega-3 polyunsaturated fatty acid intake in patients with chronic kidney disease: Systematic review and meta-analysis of randomized controlled trials. Clin Nutr. 2020;39(2):358-368. PMID: 30905498
43. Lok CE, Hemmelgarn BR, Moist LM, Polkinghorne K, Tomlinson G, Tonelli M. Protection against Incidences of Serious Cardiovascular Events Study with daily fish oil supplementation in dialysis patients (PISCES): protocol for a randomised controlled trial. BMJ Open. 2024;14(1):e072239. PMID: 38199618
44. Ferro CJ, Thomas MR, Khattak S, Chanouzas D, Townend JN. Fish oil supplements in patients with chronic kidney disease. Clin Kidney J. 2026;19(6):sfag168. PMID: 42293365
45. Mazón-Ruiz J, de Cos Gomez M, González Bores P, Corral P. Interpreting the PISCES trial on fish oil in hemodialysis patients: lessons on trial design, biological exposure, and outcome measurement. Clin Kidney J. 2026;19(5):sfag118. PMID: 42100717
46. Marchini M, Trezzi M. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. N Engl J Med. 2026;395(3):311-312. PMID: 42456147
47. Lok CE, Polkinghorne KR, Tomlinson G. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. Reply. N Engl J Med. 2026;395(3):312. PMID: 42456148
48. Ridker PM, Rifai N, MacFadyen J, et al. Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy. Circulation. 2022;146(5):372-379. PMID: 35762321
49. Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268-2280. PMID: 33190147
50. Zhang Z, He S. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. N Engl J Med. 2026;395(3):311. PMID: 42456146
51. Yamanouchi M, Tominaga N, Yonaha T. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. N Engl J Med. 2026;395(3):311. PMID: 42456145
52. Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Circulation. 2021;144(25):1981-1990. PMID: 34612056
53. Ahmed Jilani HB, Baig BM, Rasool A, et al. Impact of OMEGA-3 fatty acid in patients undergoing hemodialysis: a systematic review and meta-analysis. BMC Nephrol. 2026;27(1). PMID: 42321661
54. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. PMID: 30415628
55. Manson JE, Cook NR, Lee IM, et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23-32. PMID: 30415637
56. Albert CM, Cook NR, Pester J, et al. Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial. JAMA. 2021;325(11):1061-1073. PMID: 33724323
57. Hilleman DE, Wiggins BS, Bottorff MB. Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review. Adv Ther. 2020;37(2):656-670. PMID: 31919792
58. Albert BB, Derraik JG, Cameron-Smith D, et al. Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA. Sci Rep. 2015;5:7928. PMID: 25604397
59. Niknam-Saeidi J, Mussnig S, Zabel A, et al. Willingness to take fish-oil supplementation among hemodialysis patients: a multicenter survey following the PISCES trial. Clin Kidney J. 2026;19(9):sfag269. PMID: 42699138
60. Daud ZA, Tubie B, Adams J, et al. Effects of protein and omega-3 supplementation, provided during regular dialysis sessions, on nutritional and inflammatory indices in hemodialysis patients. Vasc Health Risk Manag. 2012;8:187-95. PMID: 22536073
61. Asemi Z, Soleimani A, Shakeri H, Mazroii N, Esmaillzadeh A. Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients. Int Urol Nephrol. 2016;48(11):1887-1895. PMID: 27554670
62. Asemi Z, Soleimani A, Bahmani F, et al. Effect of the omega-3 fatty acid plus vitamin E supplementation on subjective global assessment score, glucose metabolism, and lipid concentrations in chronic hemodialysis patients. Mol Nutr Food Res. 2016;60(2):390-8. PMID: 26518514 Expression of concern: Mol Nutr Food Res. 2023;67(17):e2370200. PMID: 37655944
63. An WS, Lee SM, Son YK, et al. Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients. Prostaglandins Leukot Essent Fatty Acids. 2012;86(1-2):29-34. PMID: 22071008
64. He L, Li MS, Lin M, Zhao TY, Gao P. Effect of fish oil supplement in maintenance hemodialysis patients: a systematic review and meta-analysis of published randomized controlled trials. Eur J Clin Pharmacol. 2016;72(2):129-39. PMID: 26558899
65. Dezfouli M, Moeinzadeh F, Taheri S, Feizi A. The Effect of Omega-3 Supplementation on Serum Levels of Inflammatory Biomarkers and Albumin in Hemodialysis Patients: A Systematic Review and Meta-analysis. J Ren Nutr. 2020;30(3):182-188. PMID: 31420233
66. Xu T, Sun Y, Sun W, et al. Effect of omega-3 fatty acid supplementation on serum lipids and vascular inflammation in patients with end-stage renal disease: a meta-analysis. Sci Rep. 2016;6:39346. PMID: 28008943
67. Saifullah A, Watkins BA, Saha C, Li Y, Moe SM, Friedman AN. Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients--a pilot study. Nephrol Dial Transplant. 2007;22(12):3561-7. PMID: 17623719
68. Kooshki A, Taleban FA, Tabibi H, Hedayati M. Effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients. Ann Nutr Metab. 2011;58(3):197-202. PMID: 21757893
69. Gharekhani A, Khatami MR, Dashti-Khavidaki S, et al. Effects of oral supplementation with omega-3 fatty acids on nutritional state and inflammatory markers in maintenance hemodialysis patients. J Ren Nutr. 2014;24(3):177-85. PMID: 24613294
70. Hung AM, Booker C, Ellis CD, et al. Omega-3 fatty acids inhibit the up-regulation of endothelial chemokines in maintenance hemodialysis patients. Nephrol Dial Transplant. 2015;30(2):266-74. PMID: 25204316
71. Deger SM, Hung AM, Ellis CD, et al. High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients. Clin J Am Soc Nephrol. 2016;11(7):1227-1235. PMID: 27281699
72. Moeinzadeh F, Shahidi S, Mortazavi M, et al. Effects of Omega-3 Fatty Acid Supplementation on Serum Biomarkers, Inflammatory Agents, and Quality of Life of Patients on Hemodialysis. Iran J Kidney Dis. 2016;10(6):381-387. PMID: 27903997
73. Valle Flores JA, Fariño Cortéz JE, Mayner Tresol GA, Perozo Romero J, Blasco Carlos M, Nestares T. Oral supplementation with omega-3 fatty acids and inflammation markers in patients with chronic kidney disease in hemodialysis. Appl Physiol Nutr Metab. 2020;45(8):805-811. PMID: 31935118
74. Zhang C, Ge C, Wang J, Sun D. Effects of fish oil during hemodialysis on nutritional status and quality of life: a randomized double-blinded trial. Food Nutr Res. 2020;64. PMID: 32821255
75. Zakaria H, Mostafa TM, El-Azab GA, Ah Sayed-Ahmed N. Fish oil plus wheat germ oil have no prominent effect on homocysteine levels and nutritional indices in hemodialysis patients. Int J Vitam Nutr Res. 2021;91(1-2):56-62. PMID: 31433269
76. Abbas Torki S, Roumi Z, Tahavorgar A, et al. Effect of omega-3 fatty acids supplementation on muscle mass, fat mass, and visceral fat of hemodialysis patients; A randomized clinical trial. J Basic Clin Physiol Pharmacol. 2024;35(6):347-352. PMID: 39533425
77. Shafaei Kachaei H, Abbasi Mobarakrh K, Azaryan F, et al. Modulation of Inflammatory Indices by Omega-3 Fatty Acids Supplementation in Hemodialysis: A Clinical Trial Approach. Clin Transl Sci. 2026;19(5):e70531. PMID: 42045798
78. Perunicic-Pekovic GB, Rasic ZR, Pljesa SI, et al. Effect of n-3 fatty acids on nutritional status and inflammatory markers in haemodialysis patients. Nephrology (Carlton). 2007;12(4):331-6. PMID: 17635746
79. de Lima K, Mazur CE, Vicente Cavagnari MA, Castilho AJ, Schiessel DL. Omega-3 supplementation effects on cardiovascular risk and inflammatory profile in chronic kidney disease patients in hemodialysis treatment: An intervention study. Clin Nutr ESPEN. 2023;58:144-151. PMID: 38056999
80. Fatima K, Mahmood A, Sayeed FZ, et al. Effectiveness of fish oil in controlling inflammation in adult patients undergoing hemodialysis: A systematic review and meta-analysis. SAGE Open Med. 2024;12:20503121241275467. PMID: 39286404
81. Blair C, Slee A, McKeaveney C, et al. Anti-inflammatory effects and safety of omega-3 fatty acids in haemodialysis: A systematic review and meta-analysis. Clin Nutr ESPEN. 2026;72:102957. PMID: 41692069
82. Lemos JR, Alencastro MG, Konrath AV, Cargnin M, Manfro RC. Flaxseed oil supplementation decreases C-reactive protein levels in chronic hemodialysis patients. Nutr Res. 2012;32(12):921-7. PMID: 23244537
83. Mirfatahi M, Tabibi H, Nasrollahi A, Hedayati M, Taghizadeh M. Effect of flaxseed oil on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients: a randomized controlled trial. Int Urol Nephrol. 2016;48(8):1335-1341. PMID: 27115157
84. Tabrizi R, Azizi Z, Bazmi S, et al. The impact of flaxseed oil on lipid profiles, weight loss, and inflammatory markers in hemodialysis patients: A systematic review and meta-analysis of randomized controlled trials. Ther Apher Dial. 2024;28(4):534-546. PMID: 38726572

Also in the Maintenance Hemodialysis module

Part of the Maintenance Hemodialysis mastery module. Module index.

• M20: Nutrition and protein-energy wasting on hemodialysis
• M12: Cardiometabolic monitoring: lipids and statins, glycemic markers, cardiovascular screening
• M16: Adequacy, nutrition, depression/cognition — and what quality metrics miss
• M17a: Anemia: targets, ESAs, and hyporesponsiveness
• M17b: Anemia: iron, HIF-PH inhibitors, and transfusion
• M19: Catheter care, lock solutions, and bloodstream infection
• M7: Intradialytic hypotension and dialysate cooling
• M22: Atrial fibrillation and anticoagulation in HD