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Length polymorphisms of heme oxygenase-1 determine the effect of far-infrared therapy on the function of arteriovenous fistula in hemodialysis patients: a novel physicogenomic study. Nephrol Dial Transplant. 2013 May;28(5):1284-93.


    • The objective of this study was to evaluate the interaction between the length polymorphism of the guanosine thymidine repeat [(GT)n] in the heme oxygenase-1 (HO-1) gene and far-infrared (FIR) therapy on access flow (Qa) and arteriovenous fistula (AVF) patency in hemodialysis (HD) patients.


    • METHODS:
    • A total of 280 HD patients were randomized into a control group (n = 141) and the FIR group (n = 139) who received 40 min of FIR therapy three times weekly for a year during the study period from May 2005 to December 2007. Access flow was measured during HD. The [(GT)n] was determined with the definition of long (L) allele as [(GT)n] ≥ 30 and short (S) allele as [(GT)n] < 30.


    • RESULTS:
    • The Qa decreased from S/S to S/L and further to the L/L group but increased by FIR therapy with the highest Qa increase in the S/S group. The incidence of AVF malfunction decreased both from the L/L, S/L to S/S group (32.4 versus 17.2 versus 10.9%, P = 0.007) and from the control group to FIR group (27.5 versus 12.6%, P = 0.004). Significant associations were found between AVF malfunction and the following factors (hazard ratio, P-value): a past history of AVF malfunction (2.45, P = 0.044), FIR therapy (0.369, P = 0.03) and L/L genotypes of HO-1 (2.531 versus S/S + S/L genotypes). The 1-year unassisted patency decreased from 91.9 and 77.6% in S/S and S/L subgroups with and without FIR therapy to 75.8 and 60% for L/L subgroup with and without FIR therapy, respectively (P < 0.001).


  • FIR therapy improves Qa and patency of AVF in HD patients, with the best protective effect in those with S/S genotype of HO-1.

Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients. J Am Soc Nephrol. 2007 Mar;18(3):985-92.

  • Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) – Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) – Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) – Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) – Qa(2)) – Delta(Qa(3) – Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.

Far-infrared irradiation can improve blood flow and patency of arteriovenous fistulas in hemodialysis patients. Nat Clin Pract Nephrol. 2007 Aug;3(8):422-3.

Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):739-45.

    • Survival of arteriovenous fistulas (AVFs) in hemodialysis patients is associated with both far infrared (FIR)therapy and length polymorphisms of the heme oxygenase-1 (HO-1) promoter. In this study, we evaluated whether there is an interaction between FIR radiation and HO-1 in regulating vascular inflammation.


    • Treatment of cultured human umbilical vein endothelial cells (ECs) with FIR radiation stimulated HO-1 protein, mRNA, and promoter activity. HO-1 induction was dependent on the activation of the antioxidant responsive element/NF-E2-related factor-2 complex, and was likely a consequence of heat stress. FIR radiation also inhibited tumor necrosis factor (TNF)-alpha-mediated expression of E-selectin, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-8, and the cytokine-mediated adhesion of monocytes to ECs. The antiinflammatory action of FIR was mimicked by bilirubin, and was reversed by the HO inhibitor, tin protoporphyrin-IX, or by the selective knockdown of HO-1. Finally, the antiinflammatory effect of FIR was also observed in patients undergoing hemodialysis.


  • These results demonstrate that FIR therapy exerts a potent antiinflammatory effect via the induction of HO-1. The ability of FIR therapy to inhibit inflammation may play a critical role in preserving blood flow and patency of AVFs in hemodialysis patients.

Prognostic factors influencing the patency of hemodialysis vascular access: literature review and novel therapeutic modality by far infrared therapy. J Chin Med Assoc. 2009 Mar;72(3):109-16.

    • In Taiwan, more than 85% of patients with end-stage renal disease undergo maintenance hemodialysis (HD). The native arteriovenous fistula (AVF) accounts for a prevalence of more than 80% of the vascular access in our patients. Some mechanical factors may affect the patency of hemodialysis vascular access, such as surgical skill, puncture technique and shear stress on the vascular endothelium. Several medical factors have also been identified to be associated with vascularaccess prognosis in HD patients, including stasis, hypercoagulability, endothelial cell injury, medications, red cell mass and genotype polymorphisms of transforming growth factor-beta1 and methylene tetrahydrofolate reductase. According to our previous study, AVF failure was associated with a longer dinucleotide (GT)n repeat (n > or = 30) in the promoter of the heme oxygenase-1 (HO-1) gene. Our recent study also demonstrated that far-infrared therapy, a noninvasive and convenient therapeutic modality, can improve access flow, inflammatory status and survival of the AVF in HD patients through both its thermal and non-thermal (endothelial-improving, anti-inflammatory, antiproliferative, antioxidative) effects by upregulating NF-E2-related factor-2-dependent HO-1 expression, leading to the inhibition of expression of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1.

Effect of far infrared therapy on arteriovenous fistula maturation: an open-label randomized controlled trial. Am J Kidney Dis. 2013 Aug;62(2):304-11.

      Malfunction of the arteriovenous fistula (AVF) is an important cause of morbidity and hospitalization in hemodialysis (HD) patients. The aim of this study is to evaluate the effect of far infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5.
      Randomized controlled study.
      Patients with estimated glomerular filtration rate of 5-20 mL/min/1.73 m².
      40 minutes of far infrared therapy 3 times weekly for a year.
      The primary outcome is the rate of AVF malfunction within 12 months, with malfunction defined as either: (1) thrombosis without thrill for AVFs not undergoing HD or (2) receiving any type of interventional procedure due to a lower Kt/V (<1.2) for patients undergoing HD. Secondary outcomes include: (1) cumulative primary unassisted AVF patency, defined as time from creation of the AVF to the first episode of AVF malfunction; (2) physiologic maturation of the AVF by the definition of AVF access blood flow (Qa) ≥500 mL/min and AVF diameter ≥4 mm at 3 months; and (3) clinical maturation of the AVF suitable for HD at 1 year.
      AVF Qa was measured by Doppler ultrasonography at 2 days and 1, 2, 3, and 12 months.
      We enrolled 122 patients who were randomly allocated to the intervention (n = 60) and control (n = 62) groups. In comparison to controls, patients in the intervention group had higher Qa values at 1, 2, 3, and 12 months; a higher rate of physiologic maturation (90% vs 76%; P = 0.04) at 3 months; and a lower rate of AVF malfunction (12% vs 29%; P = 0.02) but higher rates of AVF cumulative unassisted patency (87% vs 70%; P = 0.01) and clinical maturation (82% vs 60%; P = 0.008) within 12 months.
      This is a single-center nonblinded study.
      Far infrared therapy improves the access flow, maturation, and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5.

Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free hemodialysis access patency of recurrent obstructive lesions. Eur J Vasc Endovasc Surg. 2013 Dec;46(6):726-32.

    • To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA).


    • METHODS:
    • This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached.


    • RESULTS:
    • Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02).


  • This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA.

Role of far infra-red therapy in dialysis arterio-venous fistula maturation and survival:systematic review and meta-analysis. PLoS One. 2014 Aug 12;9(8):e104931.

    • A well-functioning arteriovenous fistula (AVF) is the best modality for vascular access in patients with end-stage renal disease (ESRD) requiring haemodialysis (HD). However, AVFs’ main disadvantage is the high rate of maturation failure, with approximately one third (20%-50%) not maturing into useful access. This review examine the use of Far-Infra Red therapy in an attempt to enhance both primary (unassisted) and secondary (assisted) patency rates for AVF in dialysis and pre-dialysis patients.


    • METHOD:
    • We performed an online search for observational studies and randomised controlled trials (RCTs) that evaluated FIR in patients with AVF. Eligible studies compared FIR with control treatment and reported at least one outcome measure relating to access survival. Primary patency and secondary patency rates were the main outcomes of interest.


    • RESULTS:
    • Four RCTs (666 patients) were included. Unassisted patency assessed in 610 patients, and was significantly better among those who received FIR (228/311) compared to (185/299) controls (pooled risk ratio of 1.23 [1.12-1.35], p = 0.00001). In addition, the two studies which reported secondary patency rates showed significant difference in favour of FIR therapy–160/168 patients–compared to 140/163 controls (pooled risk ratio of 1.11 [1.04-1.19], p = 0.003).


  • FIR therapy may positively influence the complex process of AVF maturation improving both primary and secondary patency rates. However blinded RCTs performed by investigators with no commercial ties to FIR therapy technologies are needed.

Far Infrared Therapy as a Novel Treatment for Hand Ischemia Following Arteriovenous Graft for Hemodialysis. EJVES Short Reports 2015. Vol.28 p.30-33.

    • •Hemodialysis access-induced distal ischemia (HAIDI) is a critical problem which often requires surgical intervention.
    • •The present case report demonstrates the relief of HAIDI after far-infrared therapy (FIR)
    • •FIR is a promising therapeutic modality to treat HAIDI by decreasing arterial vascular resistance distal to the anastomosis.


    • Hand ischemia following vascular access surgery is an uncommon complication. A clinical dilemma exists between prioritizing the preservation of vascular access and the need for surgical intervention to rescue the ischemic hand.


    • REPORT:
    • An 80 year old man who had hand ischemia following creation of a polytetrafluoroethylene arteriovenous graft with clinical evidence of ischemic pain of the left hand and Doppler ultrasound evidence of diastolic flow reversal is described. Far infrared therapy (FIR) was applied over the distal part of the affected limb, and the symptoms and signs of ischemia improved remarkably. Follow up ultrasonography also revealed the disappearance of diastolic flow reversal.


  • FIR therapy is a promising and non-invasive therapeutic modality to treat vascular access related hand ischemia by decreasing vascular resistance and improving hand perfusion.

Clinical utility of far-infrared therapy for improvement of vascular access blood flow and pain control in hemodialysis patients. Kidney Res Clin Pract. 2016 Mar;35(1):35-41.

    • Maintenance of a well-functioning vascular access and minimal needling pain are important goals for achieving adequate dialysis and improving the quality of life in hemodialysis (HD) patients. Far-infrared (FIR) therapy may improve endothelial function and increase access blood flow (Qa) and patency in HD patients. The aim of this study was to evaluate effects of FIR therapy on Qa and patency, and needling pain in HD patients.


    • METHODS:
    • This prospective clinical trial enrolled 25 outpatients who maintained HD with arteriovenous fistula. The other 25 patients were matched as control with age, sex, and diabetes. FIR therapy was administered for 40 minutes during HD 3 times/wk and continued for 12 months. The Qa was measured by the ultrasound dilution method, whereas pain was measured by a numeric rating scale at baseline, then once per month.


    • RESULTS:
    • One patient was transferred to another facility, and 7 patients stopped FIR therapy because of an increased body temperature and discomfort. FIR therapy improved the needling pain score from 4 to 2 after 1 year. FIR therapy increased the Qa by 3 months and maintained this change until 1 year, whereas control patients showed the decrease in Qa. The 1-year unassisted patency with FIR therapy was not significantly different from control.


  • FIR therapy improved needling pain. Although FIR therapy improved Qa, the unassisted patency was not different compared with the control. A larger and multicenter study is needed to evaluate the effect of FIR therapy.

An update of the effect of far infrared therapy on arteriovenous access in end-stage renal disease patients. J Vasc Access. 2016 Jul 12;17(4):293-8.

  • The life qualities of end-stage renal disease (ESRD) patients rely largely on adequate dialysis, and a well-functioning vascular access is indispensable for high quality hemodialysis. Despite the advancement of surgical skills and the optimal maintenance of arteriovenous fistula (AVF), malfunction of AVF is still frequently encountered and has great impact on the life of ESRD patients. Several medical, mechanical and genetic prognostic factors are documented to affect the patency of AVF and arteriovenous graft (AVG). Heme oxygenase-1 (HO-1) is one of the genetic factors reported to play a role in cardiovascular disease and the patency of vascular access. Far infrared (FIR), a novel therapeutic modality, can not only conduct heat energy to AVF but also stimulate the non-thermal reactions mediated by HO-1. The use of FIR therapy significantly enhances the primary patency rate and maturation of AVF with fewer unfavorable adverse effects, and also achieves higher post-angioplasty patency rate for AVG. The only limitation in proving the effectiveness of FIR therapy in enhancing patency of AVF is that all the studies were conducted in Chinese people in Taiwan and thus, there is a lack of evidence and experience in people of other ethnicities.

Effects of far infrared therapy on arteriovenous fistulas in hemodialysis patients: a meta-analysis. Ren Fail. 2017 Nov;39(1):613-622.

Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

A single treatment, using Far Infrared light improves blood flow conditions in arteriovenous fistula. Clin Hemorheol Microcirc. 2017;66(3):211-217.

    • Far infrared (FIR) therapy may have a beneficial effect on maturity and function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this pooled analysis to assess the protective effects of FIR therapy in HD patients.


    • METHODS:
    • The randomized controlled trials (RCTs) and quasi-RCTs of FIR therapy for HD patients were searched from multiple databases. Relevant studies were screened according to the predefined inclusion criteria. The meta-analyses were performed using RevMan 5.2 software (The Cochrane Collaboration, Oxford, UK).


    • RESULTS:
    • Meta-analysis showed that FIR therapy could significantly increase the vascular access blood flow level (MD, 81.69 ml/min; 95% CI, 46.17-117.21; p < .001), AVFs diameter level (MD, 0.36 mm; 95% CI, 0.22-0.51; p < .001), and the primary AVFs patency (pooled risk ratio = 1.24; 95% CI, 1.12-1.37, p < .001). In addition, therapy with FIR ray radiation could decrease AVFs occlusion rates (pooled risk ratio = 0.20; 95% CI, 0.08-0.46; p < .001) and the level of needling pain (pooled risk ratio = 0.08; 95% CI, 0.06-0.10, p < .001).


  • FIR therapy can reduce AVFs occlusion rates and needling pain level, while significantly improve the level of vascular access blood flow, AVFs diameter and the primary AVFs patency.