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Post-angioplasty Far Infrared Radiation Therapy Improves 1-Year Angioplasty-Free Hemodialysis Access Patency of Recurrent Obstructive Lesions

  • C.-C. Lai
    Affiliations
    Cardiovascular Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    School of Medicine, National Yang-Ming University, Taipei, Taiwan
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  • H.-C. Fang
    Affiliations
    School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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  • G.-Y. Mar
    Affiliations
    Cardiovascular Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    College of Health and Nursing, Meiho University, Pingtung, Taiwan
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  • J.-C. Liou
    Affiliations
    Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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  • C.-J. Tseng
    Affiliations
    Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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  • C.-P. Liu
    Correspondence
    Corresponding author. C.-P. Liu, No. 386 Ta-Chung 1st Rd., Kaohsiung 813-62, Taiwan.
    Affiliations
    School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Open ArchivePublished:October 11, 2013DOI:https://doi.org/10.1016/j.ejvs.2013.09.018

      Objective

      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).

      Conclusions

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

      Keywords

      The study provides data regarding far infrared (FIR) radiation therapy on recurrent hemodialysis (HD) access stenosis that has been treated with balloon angioplasty. The positive results obtained show that FIR radiation therapy following balloon angioplasty is beneficial in the case of recurrent HD access stenosis, especially arteriovenous graft stenosis, in terms of improving the angioplasty-free patency at 1 year. The data may be clinically valid for management of recurrent HD access stenosis and guidance of FIR radiation therapy.

      Introduction

      Vascular access plays an important role in hemodialysis (HD) treatment through two commonly used forms, an autogenous arteriovenous fistula (AVF) and a prosthetic arteriovenous graft (AVG). Vascular access stenosis, which probably emerges over time, is one of the major causes of HD access failure. Percutaneous transluminal angioplasty (PTA) has become a first-line modality for treating stenosis-related access dysfunctions.
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      Effect of secondary interventions on patency of vascular access sites for hemodialysis.
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      • et al.
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      A few studies have been published that propose materials, devices, and techniques with the intention to retard the process of neointimal hyperplasia and improve HD access survival.
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      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      Among these, the novel therapy of far infrared (FIR) radiation has been documented to improve the unassisted patency at 1 year in the AVF population, possibly through thermal and non-thermal effects.
      • Lin C.C.
      • Chang C.C.
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      • Lee P.C.
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      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      Reported beneficial effects of FIR radiation therapy include increased production of endothelial nitric oxide (eNO), inhibition of endothelial inflammation, improvement of impaired endothelial function, and increased skin microcirculation.
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      • et al.
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      To the best of our knowledge, no literature has been published regarding the impact of post-PTA FIR radiation therapy on patency outcome. This study was therefore designed to investigate the effect of post-PTA FIR radiation therapy on unassisted patency outcome in HD patients who had undergone repeated PTA.

      Materials and Methods

      Patient selection

      The study was primarily designed as a single-center, prospective, and randomized study. Eligible recruited patients were those who had received two or more PTA on the target lesions at upper extremities, with the last PTA successfully performed within the week before patient enrollment. After successful completion of at least 1 week of HD treatment, the patients with AVF or AVG were consecutively enrolled and randomly assigned to either a post-PTA FIR radiation group or a control group receiving the usual form radiation therapy at a 1:1 ratio. Excluded patients were those who received HD treatments other than three times a week, who had previously received FIR radiation therapy, who received implantation of an endovascular stent, who had multiple lesions that a single radiation field did not cover or the central lesion was considered too deep to be irradiated, who missed FIR radiation treatments exceeding 10%, who underwent renal transplantation or switched to peritoneal dialysis treatments, or who had any severe disease with an estimated life expectancy of less than 1 year. Data relevant to baseline characteristics and patency outcomes were accumulated between groups. The study was conducted in accordance with the Declaration of Helsinki and the local regulatory guidelines. The medical ethics committee of the hospital approved the study protocol (VGHKS098-CT4-12). Informed consent was obtained from all participants before beginning the study.

      PTA before FIR radiation therapy

      The participants were referred to our center for angiography and PTA as appropriate when the access developed any of the following referral criteria: (a) dysfunctional access signs including abnormal symptoms or physical examination findings suggesting anatomic lesions; (b) presence of decreased flow signs when the inflow rate was set at 300 mL/min; (c) increased dynamic intra-access pressure by 25% from initial baseline; or (d) acutely thrombosed access. A significant lesion was defined as a lumen loss of 50% or more compared with adjacent normal vessel. In the study, the stenotic lesions were treated with balloon PTA using normal-pressure balloon catheters (Fox plus PTA catheter; Abbott, IL, USA) and/or high-pressure balloon catheters (Conquest PTA balloon dilatation catheter; Bard, Tempe, AZ, USA) on an outpatient basis. Patients who received vascular stents were excluded from the study. In general, high-pressure balloon PTA was reserved for lesions refractory to normal-pressure balloon PTA at the rated burst pressure. The inflated pressure was gradually increased until the lesion was totally dilated or the pressure reached the level of rated burst pressure. The double balloon occlusion technique, previously documented to be safe and effective for thrombectomy,
      • Lai C.C.
      • Kang P.L.
      • Tsai H.L.
      • Mar G.Y.
      • Liu C.P.
      Percutaneous management of acutely thrombosed hemodialysis grafts: the double balloon occlusion technique.
      was implemented for salvaging acutely thrombosed AVGs despite the other techniques for thrombectomy reported.
      • Kakkos S.K.
      • Haddad G.K.
      • Haddad J.A.
      • Scully M.M.
      Secondary patency of thrombosed prosthetic vascular access grafts with aggressive surveillance, monitoring and endovascular management.
      In addition, thromboaspiration and pharmacologic thrombolysis (urokinase) were permitted for rescuing acutely thrombosed accesses. Board-certified vascular interventionists with 2 to 7 years' experience performed all study-related procedures. Two independent and experienced physicians interpreted angiographic findings and determined procedural ends for minimization of interobserver bias.

      Post-PTA FIR radiation therapy

      The therapy was administered in three 40-minute sessions per week before, during, or after each HD treatment, either at the HD unit or at our center. The WS TY-101N emitters (WS Far Infrared Medical Technology Co., Ltd, Taipei, Taiwan) used for the FIR radiation therapy were positioned approximately 20 to 25 cm above the skin surface at the site of the major stenotic lesion or at the venous anastomosed site for the occluded type in which the major lesion was undetermined. Irradiating power densities are about 10 and 20 μWatt/cm2 when a radiator is set at a distance of 30 and 20 cm above the skin surface, respectively. Radiation therapy was continued every week until an end-point was reached.

      Follow-up and endpoints

      The target accesses were weekly assessed using the same criteria mentioned above during the 1-year follow-up. Once dysfunctional signs and any of referral criteria recurred in participants with the target accesses, angiography was done to confirm the need for repeat PTA. When a re-PTA was performed, the study ended and radiation therapy was discontinued. Unassisted access patency was defined as the period between the first re-intervention and the initial PTA. Participants who missed over 10% of radiation treatments, switched to peritoneal dialysis, received renal transplantation, or were lost to follow-up were excluded from analysis.

      Statistical analysis

      All variables were analyzed with SPSS software for Windows (Version 12.0; SPSS Inc., Chicago, IL, USA). All categorical data and rates are displayed as percentages and numbers, and the continuous data are shown as means ± standard deviation. Baseline characteristics and outcome data were compared between groups using chi-square test or Fisher exact test for categorical variables, independent Student t tests for continuous variables, and Mann–Whitney U test for non-normally distributed continuous variables. Kaplan–Meier survival analysis with log-rank test was used to detect differences in unassisted patency between groups. A p value <.05 with two-sided 95% confidence interval was considered statistically significant for all tests.

      Results

      Baseline characteristics

      From March 2008 to March 2010, a total of 216 enrolled participants, 97 with AVG and 119 with AVF, were randomly assigned to post-PTA FIR radiation therapy or usual form of radiation therapy at a 1:1 ratio, to create four groups: (1) 49 with AVG receiving post-PTA FIR radiation therapy; (2) 48 with AVG receiving post-PTA usual therapy as control participants; (3) 60 with AVF receiving post-PTA FIR radiation therapy; and (4) 59 with AVF receiving post-PTA usual therapy as control participants. Unpredictably, nine AVF control participants asked to cross over to the FIR-radiated group after the assignments had been made (Fig. 1). During the follow-up period, one participant died from lung cancer and another died suddenly in the AVF population. Finally, 68 AVF participants in the FIR-radiated group (Group 3) and 49 AVF controls (Group 4) were analyzed. No patients missed FIR radiation treatments exceeding 10%, none underwent renal transplantation, and none switched to peritoneal dialysis treatment in the course of the study. As shown in Table 1, baseline characteristics were identical between groups in the AVF or AVG population.
      Table 1Characteristics of the FIR-radiated group and control group in the AVF and AVG populations.
      AVF population (n = 119)AVG population (n = 97)
      FIR-radiated group (n = 69)Control group (n = 50)p
      Comparison between the FIR-radiated group and control group by chi-square test for categorical variables and by independent Student t test for continuous variables.
      FIR-radiated group (n = 49)Control group (n = 48)p
      Comparison between the FIR-radiated group and control group by chi-square test for categorical variables and by independent Student t test for continuous variables.
      Age (years)62.7 ± 10.963.1 ± 12.5.8667.8 ± 15.766.9 ± 9.7.35
      Male/female32/3724/261.0018/3112/36.27
      Hypertension (n)4838.543430.53
      Diabetes (n)4228.712016.53
      Hemodialysis time (years)4.2 ± 3.54.9 ± 4.7.375.7 ± 5.65.7 ± 5.1.83
      Duration of access (months)21.8 ± 23.023.5 ± 22.6.6920.2 ± 19.121.1 ± 22.0.56
      No. of angioplasties at target access before study of.46.80
       11415911
       230201916
       3 or more25152121
      Presentation:
       Stenosis type.39.19
       Elevated pressure ratio15657.14
       Low flow rate36293027.11
       Mixed or uncertain181516.98
       Acute occlusion88.591815
      Lesion site:.79
       Vein-side lesions32263035.44
       Artery-side lesions171222.43
       Multiple lesions20121711.26
      Maximal balloon size.14
       NP: 4–10 mm (n)4(5)/5(27)/6(17)/7(11)/8(8)/9(1)5(23)/6(14)/7(5)/8(5)/9(0)/10(3)5(3)/6(7)/7(21)/8(15)/9(0)/10(3)6(3)/7(25)/8(16)/9(1)/10(3).41
       HP: 5–8 mm (n)5(8)/6(6)/7(4)/8(3)5(6)/6(4)/7(2)/8(2)6(3)/7(10)/8(8)6(2)/7(13)/8(7).58
      Angioplasty-related complication211.00111.00
      FIR radiation-related complication0000
      Death111.0000
      Loss to follow-up0000
      AVF = arteriovenous fistula; AVG = arteriovenous graft; FIR = far infrared radiation; HP = high pressure; NP = normal pressure.
      a Comparison between the FIR-radiated group and control group by chi-square test for categorical variables and by independent Student t test for continuous variables.

      Unassisted patency outcomes

      The results are summarized in Table 2. The 118 participants in Groups 1 and 3, receiving post-PTA FIR radiation therapy, had significantly enhanced unassisted patency rates at 1 year (21.4%, 25/117 vs. 10.3%, 10/97, respectively; p = .04) compared with the 98 participants in Groups 2 and 4 receiving post-PTA usual therapy. The benefit of post-PTA FIR radiation therapy was also demonstrated by Kaplan–Meier survival analysis (p = .02) (Fig. 2).
      Table 2PTA-unassisted patency rates in overall, AVF, and AVG populations during 1-year follow-up.
      Overall (N = 216)AVF population (n = 119)AVG population (n = 97)
      FIR-treated (n = 118)Control (n = 98)p
      Comparison between the FIR-radiated group and the control group by chi-square test.
      FIR-treated (n = 69)Control (n = 50)p
      Comparison between the FIR-radiated group and the control group by chi-square test.
      FIR-treated (n = 49)Control (n = 48)p
      Comparison between the FIR-radiated group and the control group by chi-square test.
      Unassisted patency
       at 3 months71.2% (84)56.1% (55).0278.3% (54)64.0% (32).1061.2% (30)47.9% (23).22
       at 6 months39.0% (46)31.6% (31).3242.0% (29)38.0% (19).7134.7% (17)25.0% (12).38
       at 9 months29.9% (35)18.6% (18).0630.1% (21)28.6% (14).8428.6% (14)8.3% (4).01
       at 12 months21.4% (25)10.3% (10).0425.0% (17)18.4% (9).5016.3% (8)2.1% (1).02
      AVF = arteriovenous fistula; AVG = arteriovenous graft; FIR = far infrared radiation; PTA = percutaneous transluminal angioplasty.
      a Comparison between the FIR-radiated group and the control group by chi-square test.
      Figure thumbnail gr2
      Figure 2One-year cumulative incidence of PTA-unassisted patency is shown overall. The Kaplan–Meier plot denotes a significant increase in 1-year cumulative incidence of PTA-unassisted patency in the group receiving FIR-radiated therapy (FIRT) compared with receiving free-radiation usual therapy after index PTA.
      The impact on patency outcome obviously varied between the AVG and AVF subgroups. In the AVG population, post-PTA FIR radiation therapy (Group 1) significantly augmented the unassisted patency rates at 9 months (28.6%, 14/49 vs. 8.3%, 4/48, respectively; p = .01) and at 1 year (16.3%, 8/49 vs. 2.1%, 1/48, respectively; p = .02) compared with the usual therapy (Group 2). Kaplan–Meier survival analysis also confirmed the benefit of post-PTA FIR radiation therapy in terms of improved cumulative incidence of unassisted patency at 1 year (p = .01) (Fig. 3). In addition, Table 3 shows the results of subgroup analysis of the AVG population. In the AVF population, post-PTA FIR radiation therapy (Group 3) did not produce a statistical difference in unassisted patency rate at 1 year compared with the usual therapy (Group 4) (25.0%, 17/68 vs. 18.4%, 9/49, respectively; p = .50). The similarity of patency outcome was also demonstrated by Kaplan–Meier analysis (p = .45) (Fig. 4).
      Figure thumbnail gr3
      Figure 3One-year cumulative incidence of PTA-unassisted patency is demonstrated using Kaplan–Meier analysis in participants with AVG. The cumulative 1-year incidence of PTA-unassisted patency is significantly higher in the FIRT group compared with the free-radiation control group after index PTA.
      Table 3Subgroup analysis of AVG population in PTA-unassisted patency durations between FIR-radiated group and control group.
      SubgroupsFIR-radiated group (n = 49)Control group (n = 48)p
      Comparison between the FIR-radiated group and the control group by chi-square test.
      Male135.6 (n = 18)106.3 (n = 12).53
      Age > 70 years163.0 (n = 27)70.6 (n = 18)<.01
      Age > 65 years165.9 (n = 35)70.6 (n = 23).07
      Diabetes mellitus133.9 (n = 20)129.6 (n = 16).92
      Non-diabetes mellitus172.8 (n = 29)93.0 (n = 32).01
      Hypertension167.6 (n = 34)113.5 (n = 30).09
      Non-hypertension132.7 (n = 15)91.3 (n = 18).23
      1 previous PTA244.7 (n = 9)96.3 (n = 11)<.01
      2 previous PTA159.4 (n = 19)138.4 (n = 16).66
      3 previous PTA117.0 (n = 21)84.6 (n = 21).23
      Presentation with elevated VP154.8 (n = 30)108.6 (n = 27).10
      Presentation with mixture of elevated VP and low flow145.8 (n = 18)111.9 (n = 15).48
      Vein-side lesion158.1 (n = 30)110.1 (n = 35).10
      Multiple lesions137.9 (n = 17)107.6 (n = 11).51
      Occlusion type176.8 (n = 5)115.7 (n = 7).56
      Non-occlusion (stenosis) type154.6 (n = 44)103.4 (n = 41).03
      Presented as the mean of patency days and number of subgroups. AVG = arteriovenous graft; FIR = far infrared radiation; PTA = percutaneous transluminal angioplasty; VP: venous pressure.
      a Comparison between the FIR-radiated group and the control group by chi-square test.
      Figure thumbnail gr4
      Figure 4One-year cumulative incidence of PTA-unassisted patency is expressed using Kaplan–Meier analysis in participants with AVF. The cumulative 1-year incidences of PTA-unassisted patency are equal between the FIRT group and the free-radiation control group (p = .45).
      Unassisted patency rates significantly differed between the AVG control participants (Group 2) and AVF control participants (Group 4). The AVF control participants were associated with a significantly higher rate of unassisted patency at 1 year compared with the AVG control participants (18.4%, 9/49 vs. 2.1%, 1/48, respectively; p = .01) despite a potential difference in baseline characteristics. In contrast with the control groups, no difference in unassisted patency rate at 1 year was observed between the AVG FIR-radiated group (Group 1) and the AVF FIR-radiated group (Group 3) (16.3%, 8/49, vs. 25.0%, 17/68, respectively; p = .36 by Fisher exact test).

      Complications

      No patients suffered from radiation-related complications such as skin burn injuries or allergies.

      Discussion

      FIR radiation therapy has been reported to improve access blood flow and unassisted patency in patients with functioning AVFs.
      • Lin C.C.
      • Chang C.C.
      • Lai M.Y.
      • Chen T.W.
      • Lee P.C.
      • Yang W.C.
      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      To the best of our knowledge, this is the first study to investigate the impact of post-PTA FIR radiation therapy on unassisted patency in HD patients who had received repeat PTA on recurrent lesions. The study generates four major findings: (a) AVF and AVG that have required more than two PTAs have very poor unassisted 1-year patency rates; (b) post-PTA FIR radiation therapy significantly improves the unassisted patency at 1 year compared with the usual form of radiation therapy; (c) the use of FIR radiation improves the unassisted patency rate in patients with AVG but not in patients with AVF who have previously undergone more than two PTA; (d) post-PTA FIR radiation therapy particularly benefits AVG patients with age exceeding 70 years, no diabetes, fewer previous PTA, and non-occlusion type.
      The proposed thermal and non-thermal effects of FIR radiation therapy may delay the progression of vascular restenosis and prolong the intervention-free survival time.
      • Lin C.C.
      • Chang C.C.
      • Lai M.Y.
      • Chen T.W.
      • Lee P.C.
      • Yang W.C.
      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      FIR radiation emitters generate electromagnetic waves with wavelengths in the spectral range of 3 to 25 μm (most of 5 to 12 μm and peak at 8.2 μm), which are sufficient for producing both thermal and non-thermal effects.
      • Imamura Masakazu
      • Biro Sadatoshi
      • Kihara Takashi
      • Yoshifuku S.
      • Takasaki K.
      • Otsuji Y.
      • et al.
      Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors.
      The thermal effects of FIR radiation therapy are generated by the transfer of heat energy to a depth of 1 to 3 cm in subcutaneous tissue and by an increase in skin temperature of up to 4 °C.
      • Hartel M.
      • Hoffmann G.
      • Wentc M.N.
      • Martignoni M.E.
      • Büchler M.W.
      • Friess H.
      Randomized clinical trial of the influence of local water-filtered infrared A irradiation on wound healing after abdominal surgery.
      Data from animal models have shown that FIR radiation therapy improves vascular endothelial function through thermal effects which lead to up-regulation of endothelial NO synthase (eNOS).
      • Ikeda Y.
      • Biro S.
      • Kamogawa Y.
      • Yoshifuku S.
      • Eto H.
      • Orihara K.
      • et al.
      Repeated thermal therapy upregulates arterial endothelial nitric oxide synthase expression in Syrian golden hamsters.
      • Akasaki Y.
      • Miyata M.
      • Eto H.
      • Shirasawa T.
      • Hamada N.
      • Ikeda Y.
      • et al.
      Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia.
      Furthermore, non-thermal effects considered unique to FIR radiation therapy have been proven to inhibit vascular inflammation by inducing heme oxygenase-1,
      • Lin C.C.
      • Liu X.M.
      • Peyton K.
      • Wang H.
      • Yang W.C.
      • Lin S.J.
      • et al.
      Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1.
      to increase arterial eNOS and NO production in cardiomyopathic hamsters,
      • Ikeda Y.
      • Biro S.
      • Kamogawa Y.
      • Yoshifuku S.
      • Eto H.
      • Orihara K.
      • et al.
      Repeated sauna therapy increases arterial endothelial nitric oxide synthase expression and nitric oxide production in cardiomyopathic hamsters.
      to promote microvascular angiogenesis via extracellular signal-regulated kinase,
      • Rau C.S.
      • Yang Johnson C.S.
      • Jeng S.F.
      • Chen Y.C.
      • Lin C.J.
      • Wu C.J.
      • et al.
      Far-Infrared radiation promotes angiogenesis in human microvascular endothelial cells via extracellular signal-regulated kinase activation.
      to increase skin microcirculation,
      • Lin C.C.
      • Liu X.M.
      • Peyton K.
      • Wang H.
      • Yang W.C.
      • Lin S.J.
      • et al.
      Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1.
      and to improve skin wound healing.
      • Yu S.Y.
      • Chiu J.H.
      • Yang S.D.
      • Hsu Y.C.
      • Lui W.Y.
      • Wu C.W.
      Biological effect of far-infrared therapy on increasing skin microcirculation in rats.
      These beneficial effects may partially account for the superiority of FIR radiation therapy over the usual therapy with regard to patency outcome, particularly in the AVG population. Subgroup analysis also provides us with clues to undergo further investigation.
      The prior study by Lin et al. included 145 participants with functioning AVF who had not received PTA exceeding 3 months before recruitment.
      • Lin C.C.
      • Chang C.C.
      • Lai M.Y.
      • Chen T.W.
      • Lee P.C.
      • Yang W.C.
      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      Most of them (72.4%, 105/145) had not received a PTA previously. The difference in study populations may explain the inconsistent results in unassisted patency at 1 year. It is not surprising that the recurrent AVF lesions treated with repeat PTAs responded poorly to the FIR radiation therapy. The beneficial effects on vascular access provided by this therapy may have been partially attenuated or neutralized in the current series. The findings imply that the impact of FIR radiation therapy on unassisted patency varies among groups with functioning AVF and recurrently PTA-treated AVF. We consider that the PTA-treated lesions are more likely to accelerate neointimal hyperplasia and develop access vascular restenosis requiring re-intervention.
      K/DOQI clinical practice guidelines and clinical practice recommendations 2006 updates hemodialysis adequacy peritoneal dialysis adequacy vascular access.
      • Karakayali F.
      • Basaran O.
      • Ekici Y.
      • Budakoglu I.
      • Aytekin C.
      • Boyvat F.
      • et al.
      Effect of secondary interventions on patency of vascular access sites for hemodialysis.
      • Haage P.
      • Günther R.W.
      Radiological intervention to maintain vascular access.
      • Haskal Z.J.
      • Trerotola S.
      • Dolmatch B.
      • Schuman E.
      • Altman S.
      • Mietling S.
      • et al.
      Stent graft versus balloon angioplasty for failing dialysis-access grafts.
      • Trerotola S.O.
      • Stavropoulos S.W.
      • Shlansky-Goldberg R.
      • Tuite C.M.
      • Kobrin S.
      • Rudnick M.R.
      Hemodialysis-related venous stenosis: treatment with ultrahigh-pressure angioplasty balloons.
      • Bittl J.A.
      • Feldman R.L.
      Cutting balloon angioplasty for undilatable venous stenoses causing dialysis graft failure.
      • Wang Jiann-Jong
      • Huang Wen-Pin
      • Yin Wei-Hsian
      • Young Mason-Shing
      • Wei Jeng
      Application of cutting balloon angioplasty for undilatable venous stenoses causing dialysis access dysfunction.
      For the AVF population, the data, compared with those from the landmark study, demonstrated the apparently lower rate of unassisted patency at 1 year for both the FIR-radiated group (25%, 17/68 vs. 85.9%, 55/64; p < .01) and the control group (14.3%, 7/49 vs. 67.6%, 46/68; p < .01), although the baseline characteristics were potentially different.
      • Lin C.C.
      • Chang C.C.
      • Lai M.Y.
      • Chen T.W.
      • Lee P.C.
      • Yang W.C.
      Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.
      These findings indicate that FIR radiation therapy may be applied earlier to AVF which function well or have not received repeat PTA yet, with the consideration of improving unassisted patency.
      On the other hand, the unassisted patency rate at 1 year unsurprisingly appeared higher in the AVF control participants than in the AVG control participants who received PTA alone.
      • Maya I.D.
      • Oser R.
      • Saddekni S.
      • Barker J.
      • Allon M.
      Vascular access stenosis: comparison of arteriovenous grafts and fistulas.
      K/DOQI clinical practice guidelines and clinical practice recommendations 2006 updates hemodialysis adequacy peritoneal dialysis adequacy vascular access.
      • Karakayali F.
      • Basaran O.
      • Ekici Y.
      • Budakoglu I.
      • Aytekin C.
      • Boyvat F.
      • et al.
      Effect of secondary interventions on patency of vascular access sites for hemodialysis.
      • Haage P.
      • Günther R.W.
      Radiological intervention to maintain vascular access.
      Nevertheless, our data show that the patency rates were the same for the AVF and AVG groups receiving post-PTA FIR radiation therapy. The findings reveal that post-PTA FIR radiation therapy may narrow the gap in patency outcomes between the AVF and AVG groups. The mechanism of the findings is not clear. We infer that variations in vessel size, capacity for producing NO, or susceptibility to NO may potentially have contributed to the results. At the least, we can conclude that the application of non-invasive FIR radiation therapy to HD patients with functioning AVF and even with recurrently PTA-treated AVG is safe and clinically beneficial. Although it should be noted that the low mortality rate in the study may be caused by patient selection excluding severe diseases.

      Limitations

      A few limitations should be emphasized in the study. (a) Dysfunction-driven referral is not the ideal or even the most accurate model for selecting patients with target access restenosis. For example, a non-radiated lesion may occur. (b) It is very difficult to quantify, standardize, and formalize the FIR radiation therapy. This may lead to inequality of the therapy among groups. (c) Detailed lesion properties, HD parameters, and PTA procedures were not considered in the study. They potentially affected the patency outcomes. (d) The study is limited to a small number of participants undergoing repeat PTA at a single center. The results are not generalized to all kinds of HD patients.

      Conclusion

      The data show that post-PTA FIR radiation therapy is safe and effective, and improves PTA-free HD access patency, especially in the AVG series. This study suggests that this form of radiation therapy may be regarded as a helpful tool after PTA in terms of prolonged unassisted patency.

      Acknowledgements

      We appreciate the assistance of Ms. Ya-Ting Wu, Yu Shin, Lu, and Hsiu-Chieh Chang for their statistical, secretarial, and illustration work.

      Conflict of Interest

      None.

      Funding

      This study was supported by a grant from Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. (VGHKS 098-016, 099-013, 099-016).

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