The FHN Trial

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The FHN Trial Group, et al. "In-center hemodialysis six times per week versus three times per week". New England Journal of Medicine. 2010. 363(24):2287-2300.
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Clinical Question

What will happen if we could do more frequent dialysis? Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain.

Bottom Line

The optimal “dose” of hemodialysis remains uncertain. HEMO Study showed that there was no benefit from more intensive hemodialysis (higher per-session Kt/Vurea) , when patients underwent hemodialysis three times a week.12 However, solute removal can be dramatically augmented by increasing the frequency of hemodialysis sessions.

Major Points

Several uncontrolled studies showed that there were significant improvements in patient-reported outcomes and results of laboratory tests when patients were treated with more frequent in-center or at-home hemodialysis.

Because of ongoing uncertainty regarding the optimal dose of hemodialysis, we tested the hypothesis that frequent (six times per week) in-center hemodialysis, as compared with conventional thrice-weekly hemodialysis, would improve an array of objective and patient-reported outcomes.

In this randomized clinical trial, they aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.


No Guidelines


The Frequent Hemodialysis Network (FHN) Daily Trial was a multicentre, prospective, randomized, parallel-group trial of frequent (six times per week), as compared with conventional (three times per week) in-centre hemodialysis. The study was conducted between January 2006 and March 2010 at 11 university-based and 54 community-based hemodialysis facilities in North America Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. Study type = Interventional (Clinical trial ) Actual Enrollment = 245 Participant Allocation = Randomized Intervention model = Parallel assignment Masking = Non Open Label Primary purpose = Treatment Official Title = Frequent Hemodialysis Network Daily Trail Study start date = January 2006 Actual primary completion date = March 2010 Actual study completion date = March 2010


Inclusion Criteria

  • Patients with end-stage renal disease requiring chronic renal replacement therapy
  • Age≥13 years and weight≥30 kg (Daily Trial)
  • Age≥18 years (Nocturnal Trial)
  • Achieved mean eKt/V≥1.1 on at least two consecutive baseline sessions

Exclusion Criteria

  • Residual renal urea clearance > 3 mL/min per 35 L.
  • Expectation that native kidneys will recover
  • Vascular access being used for HD is a non-tunneled catheter
  • Inability to come for in-center 6 days a week, including inability to arrange adequate transportation
  • History of poor adherence to thrice weekly HD
  • Medical conditions that would prevent the subject from performing the cardiac MRI procedure (e.g., inability to remain still for the procedure, a metallic object in the body, including cardiac pacemaker, inner ear (cochlear) implant, brain aneurysm clips, mechanical heart valves, recently placed artificial joints, and older vascular stents)
  • Unable to verbally communicate in English or Spanish
  • Requires HD > 3 times per week due to medical co-morbidity (such as, but not limited to: systemic oxalosis, or requiring total parenteral nutrition). Occasional ultrafiltration on a fourth day per week is not an exclusion criterion.
  • Currently on daily or nocturnal HD, or less than 3 months since the subject discontinued daily or nocturnal HD
  • Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD, or plans to relocate to another center within the next 14 months
  • Expected geographic unavailability at a participating HD unit for > 2 consecutive weeks or > 4 weeks total during the next 14 months (excluding unavailability due to hospitalizations) (frequent HD subjects who leave for vacation may resort back to conventional HD during these time periods)
  • Less than 3 months since the patient returned to HD after acute rejection resulting in allograft failure
  • Currently in acute or chronic care hospital
  • Life expectancy < 6 months
  • A medical history that might limit the subject's ability to take trial treatments for the 12 month duration of the study, including: currently receiving chemo or radiotherapy for a malignant neoplastic disease other than localized non-melanoma skin cancer, active systemic infection (including tuberculosis, disseminated fungal infection, active AIDS but not HIV, and cirrhosis with encephalopathy)
  • Current pregnancy, or actively planning to become pregnant in the next 12 months
  • Contraindication to heparin, including allergy or heparin induced thrombocytopenia
  • Current use of investigational drugs or participation in another clinical trial that contradicts or interferes with the therapies or measured outcomes in this trial
  • Unable or unwilling to follow the study protocol for any reason (including mental incompetence)
  • Unable or unwilling to provide informed consent or sign IRB-approved consent form


After randomization, prescriptions for dialysis were determined centrally and were transmitted to each clinical centre. Patients who were assigned to thrice-weekly hemodialysis (120 patients) continued their usual dialysis prescriptions, which included a minimum target equilibrated Kt/Vurea of 1.1 and a session length of 2.5 to 4.0 hours. The equilibrated Kt/Vurea is the ratio of the equilibrated urea clearance during each dialysis session (Kt) to the patient's volume of urea distribution (V). The target equilibrated Kt/Vn, where Vn=3.271×V2/3, in the group that underwent hemodialysis six times per week (125 patients) was 0.9 provided that the length of the session was between 1.5 and 2.75 hours.

These prescriptions were factored by V2/3 rather than V (similar to scaling surface area from body mass) to reduce the dependence of dialysis prescriptions on body mass and to avoid unfeasibly long dialysis treatments for patients with large body mass. Simulation studies indicated that these interventions would provide substantial differences in targeted weekly standard Kt/Vurea between the treatment groups.


Primary Outcome Measures : 1.a composite of mortality with the change over 12 months in left ventricular mass [ Time Frame: 12 months ] 2.a composite of mortality with the change over 12 months in the SF-36 RAND physical health composite. [ Time Frame: 12 months ]

Secondary Outcome Measures : 1.cardiovascular structure and function (change in LV mass) [ Time Frame: 12 months ] quality of life/physical function (change in the PHC) [ Time Frame: 12 months ] 3.depression/burden of illness (change in Beck Depression Inventory) [ Time Frame: 12 months ] 4.nutrition (change in serum albumin) [ Time Frame: 12 months ] 5.cognitive function (change in the Trail Making Test B) [ Time Frame: 12 months ] 6.mineral metabolism (change in average predialysis serum phosphorus) [ Time Frame: 12 months ] 7.clinical events (rate of non-access hospitalization or death) [ Time Frame: 12 months ] 8.hypertension [ Time Frame: 12 months ] 9.anemia [ Time Frame: 12 months ]


Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/Vurea (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.


Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Clinical-trials.

Adverse Events

As compared with patients in the conventional-hemodialysis group, patients undergoing frequent hemodialysis were more likely to undergo interventions related to vascular access, both in the analysis of the time to the first intervention (hazard ratio, 1.71; 95% CI, 1.08 to 2.73) ,and in the analysis of multiple interventions (hazard ratio, 1.35; 95% CI, 0.84 to 2.18). There were 95 interventions related to vascular access (19 interventions to correct access failure and 76 other procedures) in the frequent-hemodialysis group and 65 interventions (23 to correct access failure and 42 other procedures) in the conventional-hemodialysis group; 47% of the patients in the frequent-hemodialysis group underwent at least one procedure, as compared with 29% in the conventional-hemodialysis group. The percentages of events affecting fistulas, grafts, and catheters were 51%, 32%, and 17%, respectively, in the frequent-hemodialysis group and 48%, 38%, and 14%, respectively, in the conventional-hemodialysis group.


the Frequent Hemodialysis Network Trial Group, did not bring forth any valuable results, but at least confirmed what was already known . The Frequent Hemodialysis Network Nocturnal Trial, committed a Type II statistical error because of tremendous recruitment problems leading to an inadequate number of subjects.


Supported by the National Institutes of Health (NIH), National Institutes of Diabetes and Digestive and Kidney Diseases, the Center for Medicare and Medical Services, and the NIH Research Foundation. Contributors to the NIH Foundation in support of the FHN trials included Amgen, Baxter, and Dialysis Clinics. Additional support was provided by DaVita, Dialysis Clinics, Fresenius Medical Care, Renal Advantage, Renal Research Institute, and Satellite Healthcare.

Further Reading

Long-term Effects of Frequent Nocturnal Hemodialysis on Mortality: The Frequent Hemodialysis Network (FHN) Nocturnal Trial. Rocco MV, Daugirdas JT, Greene T, Lockridge RS, Chan C, Pierratos A, Lindsay R, Larive B, Chertow GM, Beck GJ, Eggers PW, Kliger AS; FHN Trial Group. Am J Kidney Dis. 2015 Sep;66(3):459-68. doi: 10.1053/j.ajkd.2015.02.331. Epub 2015 Apr 8.

Effects of daily hemodialysis on heart rate variability: results from the Frequent Hemodialysis Network (FHN) Daily Trial. Chan CT, Chertow GM, Daugirdas JT, Greene TH, Kotanko P, Larive B, Pierratos A, Stokes JB; Frequent Hemodialysis Network Daily Trial Group. Nephrol Dial Transplant. 2014 Jan;29(1):168-78. doi: 10.1093/ndt/gft212. Epub 2013 Sep 26.

Commentary for 'effect of frequent hemodialysis on residual kidney function': Frequent Hemodialysis Network (FHN) Trials.