Acute Effect of Photobiomodulation Therapy in Quadriceps Strength, Fatigue and Pain of Patients With Chronic Kidney Failure: A Randomized, Double-blind, Placebo Controlled Crossover Clinical Trial

Acute Effect of Photobiomodulation Therapy in Quadriceps Strength, Fatigue and Pain of Patients With Chronic Kidney Failure: A Randomized, Double-blind, Placebo Controlled Crossover Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Acute Effect of Photobiomodulation Therapy in Quadriceps Strength, Fatigue and Pain of Patients With Chronic Kidney Failure: A Randomized, Double-blind, Placebo Controlled Crossover Clinical Trial Ana Paula Oliveira Barbosa, Lidiane Martins Santos, Amanda Marques Catelli, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8149683/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background Patients with chronic kidney failure (CKF) present changes in physical capacity and low exercise tolerance. Photobiomodulation therapy (PBMT) has shown an ergogenic effect on exercise in studies with different populations and may be an adjuvant treatment in rehabilitation programs for CKF patients. This study aimed to evaluate the acute effects of different doses of PBMT on quadriceps strength, fatigue and muscle pain in CKF patients. Methods This study is a randomized, placebo-controlled, double-blind, crossover clinical trial. Adult patients with CKF received four PBMT applications with different energy doses (30J, 60J, 90J, or placebo), administered in a random order. A one-week interval was maintained between each dose, and an 830 nm laser was applied to six points of the quadriceps muscle. Immediately after PBMT, maximum isometric quadriceps muscle strength was assessed by dynamometry. Before the intervention and after the assessment of muscle strength, muscle fatigue (Borg rating of perceived exertion scale and blood lactate) and pain perception in the lower limbs (visual analogue scale) were measured. Results Fifteen patients were randomized and 14 completed the study. There was no significant difference between the doses tested for maximum isometric muscle strength in the right (p = 0.053) and left (p = 0.509) quadriceps. The perception of fatigue assessed by the modified Borg scale was not altered (p = 0.703) nor were blood lactate levels, regardless of the PBMT dose and measurement time (t0: p = 0.126; t3: p = 0.667; t6: p = 0.700). There was no change in pain perception after quadriceps irradiation for any of the PBMT doses tested (p = 0.566). Conclusion A single application of PBMT with a dose of 30J, 60J, or 90J did not alter maximum isometric quadriceps muscle strength, fatigue, or muscle pain perception in the lower limbs of CKF patients on HD. Kidney failure chronic Renal dialysis Low-level light therapy Phototherapy Randomized controlled trial Figures Figure 1 Figure 2 Figure 3 INTRODUTION Chronic kidney disease (CKD) is a condition that affects the health of millions of people around the world, with an estimated 9.5% average prevalence of the population [ 1 ]. CKD is defined by parenchymal damage and/or decreased renal function for a period of more than three months [ 2 ]. In the most severe phase of disease known as chronic kidney failure (CKF), patients are candidates for kidney transplantation and/or life-sustaining renal replacement therapy, such as hemodialysis (HD) [ 3 – 4 ]. Organic dysfunction resulting from kidney failure and accumulation of uremic toxins is associated with cardiovascular, musculoskeletal, inflammatory, endocrine, neurological and respiratory disorders, among others [ 5 ]. Patients with CKD have a protein synthesis imbalance caused by metabolic acidosis, resistance to insulin and insulin-like growth factor type 1 (IGF1), hormonal changes, cytokines, mitochondrial respiratory chain dysfunction, inflammatory processes, diminished appetite and increased malnutrition [ 6 – 9 ]. Thus, they have low total lean body mass density and loss of muscle fibers, mainly type II [ 7 ]. Sarcopenia is characterized by reduced muscle strength associated with decreased mass and/or reduced muscle function, and affects approximately 20% of kidney patients undergoing HD [ 10 ]. Sarcopenia and chronic fatigue due to exertion are related to reduced exercise capacity and tolerance, decreased quality of life and increased mortality in CDK patients [ 11 ]. Therefore, lifestyle changes such as the adoption of physical exercise, are an excellent non-drug intervention to mitigate the effects of uremic syndrome [ 11 – 13 ], thus reducing the risk of disease progression and severity [ 14 ]. Studies have explored photobiomodulation therapy (PBMT) due to analgesic, anti-inflammatory and regenerative effects [ 15 – 17 ], as well as ergogenic resource for exercise [ 18 ]. PBMT refers to the use of photons as non-thermal, non-ionizing radiation to alter biological activity for therapeutic purposes. Increased expression of cytochrome c-oxidase (CCO) photoreceptors in the mitochondrial respiratory chain, stimulated by PBMT, leads to an increase in adenosine triphosphate (ATP) production, in photodissociation of nitric oxide (NO) [ 19 ], in promoting lactate removal [ 20 ] and reactive oxygen species (ROS) level modulation [ 21 ]. These effects improve mitochondrial activity providing greater cellular energy, reducing oxidative stress and favoring microcirculation [ 19 – 21 ]. Furthermore, PBMT may stimulate the release of calcium (Ca²⁺) from the sarcoplasmic reticulum and enhance Ca²⁺ influx through membrane channels, optimizing muscle contraction and performance [ 22 ]. Patients with CKF and long-term HD have a deregulated and compromised mitochondrial respiratory system, mainly in the expression of proteins of the subunit I e IV of complex IV of the oxidative phosphorylation system; and these findings were associated with increased oxidative stress and the production of ROS [ 19 ]. By the way, these patients have low levels of physical activity and intolerance to overload, therefore, PBMT can be a strategy to improve muscle function, making exercise easier. A previous study on this population observed positive results when evaluating the acute effect of PBMT on handgrip strength [ 19 ]. To date, to the best of our knowledge, no study has evaluated the acute effect of PBMT on the muscle strength of the lower limbs of patients with CKF undergoing HD. Furthermore, the optimal dose of PBMT for this muscle group is unknown. We hypothesized that a single application of PBMT would increase quadriceps muscle strength during exercise and reduce or prevent worsening muscle fatigue and pain in these patients after effort. Thus, this study aimed to evaluate the acute effect of different doses of PBMT on isometric quadriceps muscle strength, fatigue and muscle pain in patients with CKF on HD. PATIENTS AND METHODS Design This study is a randomized, double-blind, placebo controlled crossover clinical trial, conducted in accordance with the Consolidated Standards of Reporting Trials (CONSORT) recommendations [ 23 – 24 ]. Isometric quadriceps muscle strength was considered the primary outcome of the study. Fatigue and muscle pain perception were considered secondary outcomes. Human Ethics and Consent to Participate declarations The project was reviewed and approved by the Human Research Ethics Committees of Santa Casa de Porto Alegre (SCPA) hospital, register CAAE: 59705722.1.0000.5335, report number: 5.531.413; and registered in the ClinicalTrials.gov system in May 21, 2023, number ID NCT05881772. The evaluations and procedures were performed at the HD outpatient center at Policlinica Santa Clara of SCPA hospital, between June and August 2023, in accordance with the ethical standards of the Declaration of Helsinki , revised in 2013 in Brazil. The volunteers that fulfilled the eligibility criteria signed the free and informed consent form to participate prior to any procedure. Eligibility criteria Patients with CKF on HD for a period equal to or greater than three months, both sexes, aged between 18 and 80 years old, adequate urea clearance [urea reduction ratio (URR) ≥ 65%] and weekly dialysis frequency of three times/week were included in the study. Exclusion criteria were: inability to understand commands to perform the evaluations; epidermal lesions at the site of the PBMT application; stroke sequelae; recent acute myocardial infarction (two months); uncontrolled hypertension (systolic pressure > 230 mmHg and diastolic pressure > 120 mmHg); IV grade heart failure according to the New York Heart Association or decompensated; unstable angina; deep venous thrombosis in the lower limbs; incapacitating osteoarticular or musculoskeletal disease; uncontrolled diabetes (glycemia > 300mg/dL); febrile state and/or infectious disease, systemic lupus erythematosus; and cancer. Procedures All the patients from HD outpatient center were invited to participate in the study. Those who showed interest had their electronic medical records consulted to verify the eligibility criteria. Identification, demographic and anthropometric data, risk factors and cause that led to CKF were collected from patients included in the study. After enrollment, patients were randomized to the order in which they would receive the four doses of PBMT. The assessment and intervention procedures were carried out in a multidisciplinary office, at the HD outpatient center, free from noise and external interruptions. Randomization and blindness The patients received four doses of PBMT (30 J, 60 J, 90 J or placebo), with a one-week interval between them, and according to the individual randomization order. Randomization was performed by a researcher external to the study, using the www.random.orgwebsite . The dose was revealed to the intervention therapist only before the application of the PBMT to ensure concealment of the allocation. Participants and the outcome evaluator were blinded to the therapeutic dose. Participants used protective glasses and headphones with music during the application of PBMT, and the evaluator was instructed to leave the room during the interventions. Still, the cluster was maintained at each application point for one minute, regardless of the dose. Evaluations All assessment procedures were performed prior to the second weekly hemodialysis session over four weeks. The PBMT doses were administered at one-week intervals to avoid the residual effect of the previous dose. Patients were instructed to not perform any effort or physical exercises prior to the assessment and to wear comfortable clothing on the day of the tests. The assessments were performed before irradiation of the quadriceps with PBMT in the following order: 1) Perceived exertion; 2) Measurement of blood lactate; 3) Assessment of muscle pain in the lower limbs. After the PBMT application and the subsequent performance of the maximum isometric quadriceps strength test, the following assessments were repeated: 4) Perceived exertion; 5) Measurement of blood lactate (times 0, 3 and 6 minutes); 6) Assessment of muscle pain in the lower limbs (Fig. 1 ). All assessments were conducted by trained researchers who were blinded to the doses of PBMT applied. a) Maximum Isometric Quadriceps Strength Evaluation The maximum isometric quadriceps strength was measured by dynamometry using a load cell (SDS 1000, traction mode, nominal capacity of 200 kg, 0.1 kg resolution). It was calibrated and connected to a data acquisition system (Miotool, model 400 USB, Miotec, Porto Alegre/RS, Brazil). The patient was positioned in sitting position on a litter with an adapted back support. The initial position was an angle of 90º degrees of hip and knee flexion. The participant was asked to perform and maintain knee extension at a 60º angle (Fig. 2 ). As a previous study, the load cell position was fixed using a velcro ankle strap to guarantee a perpendicular alignment of the sensor [ 25 ]. For the patient's angle position, an acrylic goniometer (ProFisiomed, Porto Alegre, RS, Brazil) with a one-degree resolution was used. The patient was instructed to perform and sustain the maximum isometric force generated by the quadriceps for five seconds and receiving verbal stimulation through standardized phrases [ 25 – 26 ]. A minimum number of three and a maximum of five measurements were taken, with a two-minute rest interval between them. Only standardized measurements were considered valid, excluding those with a value greater or less than 10%. The force peak generated was considered for analysis. Measurements were recorded using the MiotecSuite 1.0 software and analyzed using the Miograph program and expressed in kgF units. The maximum isometric strength of the quadriceps evaluation was executed immediately after irradiation of the PBMT dose in the patient's right lower limb. After measurements of the right limb, the left lower limb was irradiated, and the assessment of maximum isometric quadriceps strength was performed. b) Muscle Fatigue Evaluation Muscle fatigue was measured using the Borg Rating of Perceived Exertion Scale and blood lactate levels. The patient was asked about the “tiredness of his legs” and instructed to quantify it, where 0 indicates no effort or fatigue and 10 indicates maximum effort [ 27 ]. Lactate levels (mmol/L) were measured through a drop of blood on a BM-Lactate reagent strip (Roche Diagnostics GmbH, Mannheim, Germany), which was then introduced into the Accutrend® Lactate meter (Roche Diagnostics GmbH, Mannheim, Germany). To collect capillary blood, automatic self-lancets (G-Tech® − 28G needle) were used at the end of the index finger. Lactate was measured before PBMT application (basal), immediately after the maximum isometric quadriceps strength evaluation of both legs (time 0 - t0), three (t3) and six (t6) minutes later [ 28 ]. c) Muscle Pain Evaluation Lower limb muscle pain was measured using the visual analogue scale (VAS), where point 0 (zero) represents no pain and point 10 (ten) the worst possible pain. The patient will be asked about the “muscle pain in their legs” and instructed to quantify it using the scale [ 29 ]. Intervention PBMT were applied using a low-intensity infrared cluster laser with four diodes, 830 nm wavelength (HTM®, model Fluence MAXX, São Paulo, Brazil). Detailed parameters can be seen in chart 1 . All patients received four doses of laser radiation with a one-week intervals: 30J (180J per leg), 60J (360J per leg), 90J (540J per leg) or placebo. The doses were determined based on clinical and scientific recommendations for the use of PBMT for muscle performance [ 30 ], a meta-analysis [ 18 ], and previous studies [19, 31–33), considering the therapeutic window of 60 to 300 J for large muscle groups. Similarly, the PBMT application was performed immediately before the activity (strength test) for the expected acute effects. The order of each dose application was determined by randomization. The placebo treatment was carried out with the equipment turned off. For application, the patient was positioned in the same sitting position of the evaluations and the treatment was executed with the probe fixed in direct contact with the skin at a 90º angle, using the continuous emission mode. The therapy was applied to the quadriceps muscle, bilaterally. Two points were irradiated in the distal region of the vastus medialis, two points in the distal region of the vastus lateralis and two points in the central region of the rectus femoris, like a previous study [ 34 ]. A map of the application points was drawn after the first application with PBMT to ensure that the same locations were irradiated in the subsequent applications. The intervention with PBMT was conducted always by the same therapist. Statistical analyses The sample size calculation estimated 10 patients, and it was based on a previous study [ 34 ] which evaluated the acute effect of PBMT on maximum quadriceps isometric strength in patients with chronic obstructive pulmonary disease (COPD). Sample calculation considered a difference of 17.49 N.m for maximum voluntary isometric contraction, standard deviation of 11.02, power of 80% and alpha error of 5%. Anticipating losses and taking the sample calculation as a basis, the sample was estimated at 15 patients for this study. The categorical variables were presented as absolute and relative frequencies and quantitative variables as mean and standard deviation. When appropriate, the delta of change (∆) was reported according to the following equation: ∆ = (POST average - basal average). Normality was verified by the Shapiro-Wilk test. A repeated measures ANOVA was applied to compare the outcomes according to the doses. It was considering the peak value of strength to analyze maximum isometric quadriceps strength and delta was used for fatigue (Borg scale and lactate measure) and muscle pain (VAS). A repeated measures ANOVA, followed by the Tukey post hoc test, was employed to assess a possible learning effect. The significance level adopted was 0.05, and the per-protocol analyses were performed using SPSS statistical software (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY: IBM Corp.) RESULTS The flowchart for patient selection and inclusion in the study is shown in Fig. 3. Seventeen CKF patients on HD were evaluated for eligibility, fifteen were randomized and fourteen analyzed. Demographic, anthropometric and clinical characteristics of the patients at the baseline of the study are summarized in Table 1. TABLE 1 Characteristics of patients admitted to the study n=14 Age (years) a 57.4 ± 15.2 Sex (male) c 9 (64.3) Dry weight (kg) a 66.2 ± 16.9 Wet weight (kg) a 69.6 ± 18 High (m) a 1.7 ± 0.1 BMI (kg/m 2 ) a 23.6 ± 3.7 HD time (months) b 25.7 (17.7 – 59.4) URR (%) a 72.6 ± 5.0 Primary disease c - Diabetes mellitus 4 (28.6) - Polycystic kidney disease 2 (14.3) - COVID-19 1 (7.1) - NSAIDs induced nephrotoxicity 1 (7.1) - Solitary kidney 1 (7.1) - Hemolytic-Uremic Syndrome 1 (7.1) - Unknown 4 (28.6) Risk factors c - Ex-smoker 5 (35.7) - Hypertension 11 (78.6) - Sedentary lifestyle 11 (78.6) - Diabetes mellitus 3 (21.4) - Heart disease 4 (28.6) - Peripheral vascular disease 1 (7.1) Legend: M: male; BMI: body mass index; HD: hemodialysis; URR: urea reduction rate; NSAIDs: non-steroidal anti-inflammatory drugs; FH: family history. Data are expressed as: a: mean ± standard deviation; b: median and interquartile range (P25P75); or c: frequency and (percentage prevalence). No learning effect was observed by patients to assess muscle strength. This can be seen in Table 2, when the averages of maximum isometric muscle strength of the quadriceps generated after the application of PBMT are compared throughout the four radiation applications, regardless of the dose used. Table 2 Maximum isometric quadriceps strength in the first, second, third and fourth PBMT session, regardless of dose 1st session 2nd session 3rd session 4th session p-value Right limb strength (kgF) 26.5 ± 7.9 26.9 ± 6.7 28.4 ± 8.7 27.6 ± 7.1 0.531 Left limb strength (kgF) 26.3 ± 8.3 26.3 ± 9.3 28.0 ± 8.3 27.2 ± 10.0 0.400 Legend: Data are expressed as mean ± standard deviation. The maximum isometric muscle strength of the quadriceps of the right and left legs did not show significant changes after the application of PBMT, regardless of the dose applied, nor when compared to placebo PBMT. There was a tendency for an increase in muscle strength when the 90J dose was used; however, this was without statistical significance (Table 3). Table 3 Values for maximum isometric quadriceps strength, fatigue and pain after PBMT Variables Placebo (n = 14) 30J (n = 14) 60J (n = 14) 90J (n = 14) p-value Quadriceps strength Right limb (kg/F) 27.7 ± 7.52 27.91 ± 7.88 25.68 ± 7.81 28.24 ± 8.68 0.053 Left limb (kg/F) 25.8 ± 8.83 26.89 ± 8.05 26.69 ± 9.09 27.39 ± 10.09 0.509 Muscle fatigue (lactate - mmol/L) Δt0-basal 0.14 ± 1.01 0.15 ± 1.68 0.06 ± 1.20 -0.91 ± 1.79 0.126 Δt3-basal -0.34 ± 0.87 -0.18 ± 0.85 -0.34 ± 0.7 -0.70 ± 2.15 0.667 Δt6-basal -0.43 ± 0.99 -0.66 ± 0.96 -0.29 ± 0.82 -0.39 ± 1.91 0.700 Muscle fatigue (Borg scale) Pre 1.72 ± 2.55 2.36 ± 2.98 2.07 ± 2.89 2.00 ± 2.35 - Post 1.29 ± 1.98 2.57 ± 2.79 1.5 ± 1.83 1.57 ± 2.82 - Δ post-pre -0.43 ± 1.45 0.21 ± 1.97 -0.57 ± 2.32 -0.43 ± 2.28 0.703 Pain Pre 0.72 ± 1.49 1.07 ± 2.43 1.36 ± 2.44 1.71 ± 2.10 - Post 0.79 ± 1.67 1.07 ± 2.37 0.79 ± 1.67 1.64 ± 3.27 - Δ post-pre 0.07 ± 0.83 0.00 ± 0.39 -0.57 ± 1.5 -0.07 ± 2.62 0.566 Legend: Data are expressed as: a: mean ± standard deviation. Δ delta. Muscle fatigue induced by the muscle strength test and assessed by serum blood lactate levels did not change significantly after the application of any of the doses of PBMT at any of the measured times (immediately after the test, 3 and 6 minutes later). Likewise, the perception of leg fatigue assessed by the modified Borg scale was not altered after the application of PBMT, regardless of the dose used (Table 3). Muscle pain was not influenced by the application of any dose of PBMT performed prior to the assessment of quadriceps muscle strength (Table 3). DISCUSSION This was the first randomized, double-blind, placebo controlled crossover clinical trial to evaluate the acute effect of different doses of PBMT energy (30, 60 and 90J) on muscle strength, fatigue and pain in the lower limbs in CKF patients. Our results demonstrate a tendency for an increase in maximum isometric muscle strength when the quadriceps was irradiated with 90J/point (180J/leg), however, without statistical difference when compared to other doses. In previous studies with chronic patients, a single application of PBMT was able to increase lower limb muscle strength in patients with chronic obstructive pulmonary disease (COPD) (905nm, 510J/leg) [ 34 ]. On the other hand, such effects were not observed in patients with heart failure (808nm, 28J/leg) [ 28 ] or those undergoing coronary artery bypass grafting (CABG) (850nm, 240J/leg) [ 35 ]. However, a limited number of studies have explored the PBMT effects on muscle strength in CKF patients on HD and there are gaps in the literature regarding its influence on exercise capacity of this group of patients. Macagnan et al. [ 19 ] demonstrated for the first time the acute effect of PBMT during HD. The crossover study with fifteen participants compared different doses of infrared laser irradiation (850 nm) on the finger flexor muscles. The findings suggested that a single session with doses of 60J and 90J increased the handgrip strength of these patients, with a superior response at 60J. Although our parameters align with those defined in the literature [ 36 ], the specificity of the target muscles used by Macagnan et al [ 19 ] may have contributed to the positive results. The therapeutic effects of PBMT are associated with the use of appropriate wavelength and energy dose parameters, within a specific therapeutic window [ 18 , 37 – 39 ], as well as the suitability of the target tissue or muscle group to be irradiated [ 32 , 39 ]. Smaller muscles with less adjacent adipose tissue may enhance light penetration into the muscle fibers, optimizing the effects of photobiomodulation [ 18 ]. In other randomized clinical trial, Schardong et al [ 31 ] evaluated the chronic effect of PBMT on the quadriceps muscle. CKF patients received 24 treatment sessions (810 nm, 30 J/application site) over 8 weeks, three times/week, during HD. They findings indicated an increase in the distance covered in the six-minute walk test as well as in the muscle strength of the lower limbs, assessed by the 10-repetition sit-to-stand test for the treated group when compared to the control. Even though we irradiated the same muscle group in our study, the effect of a single application did not yield similar results. The biphasic response relating to the applied dose, described by the Arndt-Schulz Law, can be enhanced by the cumulative effect of the results found in chronic treatment from regular and continuous application of light therapy over time [ 20 , 38 ]. PBMT has been observed as a potential ergogenic resource for exercise, with the aim of improving performance and recovery after activity [ 36 – 37 , 40 ]. The mechanism of PBMT action provides a reduction in oxidative stress and inflammation in muscles and stimulates the synthesis of muscle proteins [ 18 ], as well as promoting the formation of new blood vessels by increasing the supply of oxygen and the total volume of blood around the irradiated area [ 31 ]. This may act on processes causing fatigue, such as the accumulation of metabolites and electrolyte imbalance (loss of sodium, potassium, and magnesium through sweat), as well on pain receptors, reducing sensitivity and the transmission of pain signals to the central nervous system [ 15 , 33 ]. It was hypothesized that PBMT prior to the strength protocol would stimulate muscle metabolism and, consequently, reducing fatigue and pain levels in patients with CKF. However, no effects were found on muscle fatigue measured by Borg scale and blood lactate levels. These findings corroborate those found in a randomized crossover clinical trial that evaluated the acute effect of PBMT (850 nm, 240J) on the quadriceps muscle in patients after CABG. Stein et al [ 35 ] did not show any change for functional capacity, fatigue, tissue damage markers and oxidative stress after applying a session of PBMT. On the other hand, the study by Bublitz et al [ 28 ] evaluated the acute effect of PBMT (808nm, 28J) on the quadriceps of patients with heart failure and demonstrated a significant reduction in the perception of effort (Borg scale) for the treated group compared to placebo. Furthermore, the blood lactate level increased for the placebo group, suggesting that PBMT accelerates the removal of peripheral lactate. In this study, the total dose irradiated on the quadriceps femoris was lower when compared to our study, only 4J/per point. This finding may be related to the effect of the amount of energy absorbed by the cell, generating inhibition or stimulation of intracellular processes [ 20 , 38 ]. Miranda et al [ 34 ] evaluated the effect of PBMT (superpulsed laser 905 nm; LEDs 875 nm; LEDs 640 nm; 180 J) in patients with chronic obstructive pulmonary disease and found that one application on the quadriceps muscle increased the force of maximal voluntary isometric contraction of the quadriceps and reduced the sensation of dyspnea and fatigue (assessed by the Borg scale). It is important to highlight that, unlike our study, the study by Miranda et al [ 34 ] uses three different wavelengths for irradiation of the lower limb. Our findings also did not demonstrate any change in pain levels in the lower limbs after the application of PBMT compared to placebo PBMT. This result corroborates that found by Schardong et al [ 31 ] where PBMT, even when applied chronically, had no effect on reducing lower limb pain in patients with CKD undergoing HD. We emphasize that the baseline pain level of the patients evaluated was low, therefore, the lack of results, regardless of the therapeutic dose used, is justified. Although pain is a common symptom reported by 58–84% of patients with CKF [ 12 , 41 ], this was not a symptom observed in the sample of our study. This study has limitations that should be considered when interpreting its results. The subjectivity and fragility of the scales used for pain and perceived exertion assessment, despite being validated, may also have influenced the results. The instrument used for strength assessment (dynamometer by load cell) is a less robust method compared to the gold standard, isokinetic dynamometry. While the load cell is widely used due to its practicality and confiability, it lacks the ability to assess muscle strength at variable speeds and provides less detailed information about muscle performance, such as peak torque and range of motion, which are better captured by isokinetic dynamometry. For future studies that aim to evaluate the acute effect of PBMT in patients with CKF, it is suggested that higher doses of irradiation be tested prior to the maximum voluntary isometric strength test in the lower limb in this population. In addition, randomized clinical trials that evaluate the chronic effect of the application of PBMT prior to a resistance exercise program are necessary to validate whether patients with CKF can benefit from this therapeutic resource as an adjuvant treatment to improve muscle performance. Finally, it is important to highlight that the PBMT did not result in any adverse effects and was well tolerated by the participants. CONCLUSION A single application of PBMT did not increase isometric quadriceps muscle strength and did not alter fatigue and pain in the lower limbs in patients with CKF on HD, regardless of the therapeutic dose used. However, there was a trend towards increased muscle strength when the therapeutic dose of 90 J/point was used. This may guide future studies, aiming to find the ideal therapeutic window. Further clinical trials are needed to understand the therapeutic potential of PBMT in patients with CKF on HD. Declarations Conflicts of interest: The authors declare no conflict of interest. Financial support: This study was funded in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). References Bello AK, Levin A, Lunney M, Osman MA, Ye F, Ashuntantang GE et al (2019) Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey. bmj. ;367. 10.1136/bmj.l5873 . 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Photomed Laser Surg. ;36(3):122-9. 10.1089/pho.2017.4270 PMID: 29466116 Dellagrana RA, Rossato M, Sakugawa RL, Lazzari CD, Baroni BM, Diefenthaeler F (2018) Dose-response effect of photobiomodulation therapy on neuromuscular economy during submaximal running. Lasers Med Sci. ;33(2):329 – 36. 10.1007/s10103-017-2378-4 PMID: 29101708 Leal-Junior EC, Vanin AA, Miranda EF, de Carvalho Pde T, Dal Corso S, Bjordal JM (2015) Effect of phototherapy (low-level laser therapy and light-emitting diode therapy) on exercise performance and markers of exercise recovery: a systematic review with meta-analysis. Lasers Med Sci. ;30(2):925 – 39. 10.1007/s10103-013-1465-4 PMID: 24249354 Hauck M, Schardong J, Donini G, Normann TC, Plentz RDM (2023) Effects of photobiomodulation therapy (PBMT) over endothelial function in healthy individuals: a preliminary crossover clinical trial. Lasers Med Sci. ;38(1):104. 10.1007/s10103-023-03762-w PMID: 37072603 Felician MCP, Belotto R, Tardivo JP, Baptista MS, Martins WK (2023) Photobiomodulation: Cellular, molecular, and clinical aspects. Journal of Photochemistry and Photobiology. :100197. https://doi.org/10.1016/j.jpap.2023.100197 Borsa PA, Larkin KA, True JM (2013) Does phototherapy enhance skeletal muscle contractile function and postexercise recovery? A systematic review. J Athl Train. ;48(1):57–67. 10.4085/1062-6050-48.1.12 PMID: 23672326 Lambert K, Mooyman A, Burns P, Mullan J (2021) Prevalence of pain and analgesic use in people with chronic kidney disease. Ren Soc Australasia J 17(2):46–53. 10.33235/rsaj.17.2.46-53 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 Feb, 2026 Reviews received at journal 27 Jan, 2026 Reviews received at journal 25 Jan, 2026 Reviews received at journal 23 Jan, 2026 Reviewers agreed at journal 18 Jan, 2026 Reviewers agreed at journal 17 Jan, 2026 Reviewers agreed at journal 16 Jan, 2026 Reviews received at journal 16 Jan, 2026 Reviewers agreed at journal 16 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers invited by journal 14 Jan, 2026 Editor assigned by journal 14 Jan, 2026 Submission checks completed at journal 02 Dec, 2025 First submitted to journal 18 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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1","display":"","copyAsset":false,"role":"figure","size":88200,"visible":true,"origin":"","legend":"\u003cp\u003eProcedure of data collection\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8149683/v1/b8bec1c76323edd939618d35.png"},{"id":100665574,"identity":"93ca991b-3475-46cc-9771-aaa75448b2d0","added_by":"auto","created_at":"2026-01-20 09:28:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27395,"visible":true,"origin":"","legend":"\u003cp\u003eAssessment of isometric quadriceps muscle strength by load cell.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8149683/v1/13c0260cb2ded37babb4c7e5.png"},{"id":100665589,"identity":"352ba7c5-f55d-4471-8470-d8158d5f1346","added_by":"auto","created_at":"2026-01-20 09:28:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1001402,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT Flow diagram of participants\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8149683/v1/8d0a8edac15337dbde4cb9d2.png"},{"id":100669798,"identity":"bcdb2ddb-d06b-4220-9b52-5e11bf5f1786","added_by":"auto","created_at":"2026-01-20 10:08:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1797228,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8149683/v1/c0f25e15-eefe-4884-9961-d6dddb375257.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAcute Effect of Photobiomodulation Therapy in Quadriceps Strength, Fatigue and Pain of Patients With Chronic Kidney Failure: A Randomized, Double-blind, Placebo Controlled Crossover Clinical Trial\u003c/p\u003e","fulltext":[{"header":"INTRODUTION","content":"\u003cp\u003eChronic kidney disease (CKD) is a condition that affects the health of millions of people around the world, with an estimated 9.5% average prevalence of the population [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. CKD is defined by parenchymal damage and/or decreased renal function for a period of more than three months [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the most severe phase of disease known as chronic kidney failure (CKF), patients are candidates for kidney transplantation and/or life-sustaining renal replacement therapy, such as hemodialysis (HD) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOrganic dysfunction resulting from kidney failure and accumulation of uremic toxins is associated with cardiovascular, musculoskeletal, inflammatory, endocrine, neurological and respiratory disorders, among others [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients with CKD have a protein synthesis imbalance caused by metabolic acidosis, resistance to insulin and insulin-like growth factor type 1 (IGF1), hormonal changes, cytokines, mitochondrial respiratory chain dysfunction, inflammatory processes, diminished appetite and increased malnutrition [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Thus, they have low total lean body mass density and loss of muscle fibers, mainly type II [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSarcopenia is characterized by reduced muscle strength associated with decreased mass and/or reduced muscle function, and affects approximately 20% of kidney patients undergoing HD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Sarcopenia and chronic fatigue due to exertion are related to reduced exercise capacity and tolerance, decreased quality of life and increased mortality in CDK patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, lifestyle changes such as the adoption of physical exercise, are an excellent non-drug intervention to mitigate the effects of uremic syndrome [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], thus reducing the risk of disease progression and severity [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies have explored photobiomodulation therapy (PBMT) due to analgesic, anti-inflammatory and regenerative effects [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], as well as ergogenic resource for exercise [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. PBMT refers to the use of photons as non-thermal, non-ionizing radiation to alter biological activity for therapeutic purposes. Increased expression of cytochrome c-oxidase (CCO) photoreceptors in the mitochondrial respiratory chain, stimulated by PBMT, leads to an increase in adenosine triphosphate (ATP) production, in photodissociation of nitric oxide (NO) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], in promoting lactate removal [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and reactive oxygen species (ROS) level modulation [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These effects improve mitochondrial activity providing greater cellular energy, reducing oxidative stress and favoring microcirculation [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Furthermore, PBMT may stimulate the release of calcium (Ca\u0026sup2;⁺) from the sarcoplasmic reticulum and enhance Ca\u0026sup2;⁺ influx through membrane channels, optimizing muscle contraction and performance [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients with CKF and long-term HD have a deregulated and compromised mitochondrial respiratory system, mainly in the expression of proteins of the subunit I e IV of complex IV of the oxidative phosphorylation system; and these findings were associated with increased oxidative stress and the production of ROS [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. By the way, these patients have low levels of physical activity and intolerance to overload, therefore, PBMT can be a strategy to improve muscle function, making exercise easier. A previous study on this population observed positive results when evaluating the acute effect of PBMT on handgrip strength [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo date, to the best of our knowledge, no study has evaluated the acute effect of PBMT on the muscle strength of the lower limbs of patients with CKF undergoing HD. Furthermore, the optimal dose of PBMT for this muscle group is unknown. We hypothesized that a single application of PBMT would increase quadriceps muscle strength during exercise and reduce or prevent worsening muscle fatigue and pain in these patients after effort. Thus, this study aimed to evaluate the acute effect of different doses of PBMT on isometric quadriceps muscle strength, fatigue and muscle pain in patients with CKF on HD.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDesign\u003c/h2\u003e \u003cp\u003eThis study is a randomized, double-blind, placebo controlled crossover clinical trial, conducted in accordance with the Consolidated Standards of Reporting Trials (CONSORT) recommendations [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Isometric quadriceps muscle strength was considered the primary outcome of the study. Fatigue and muscle pain perception were considered secondary outcomes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHuman Ethics and Consent to Participate declarations\u003c/h3\u003e\n\u003cp\u003e The project was reviewed and approved by the Human Research Ethics Committees of Santa Casa de Porto Alegre (SCPA) hospital, register CAAE: 59705722.1.0000.5335, report number: 5.531.413; and registered in the ClinicalTrials.gov system in May 21, 2023, number ID NCT05881772. The evaluations and procedures were performed at the HD outpatient center at Policlinica Santa Clara of SCPA hospital, between June and August 2023, in accordance with the ethical standards of the Declaration of \u003cem\u003eHelsinki\u003c/em\u003e, revised in 2013 in Brazil. The volunteers that fulfilled the eligibility criteria signed the free and informed consent form to participate prior to any procedure.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003ePatients with CKF on HD for a period equal to or greater than three months, both sexes, aged between 18 and 80 years old, adequate urea clearance [urea reduction ratio (URR)\u0026thinsp;\u0026ge;\u0026thinsp;65%] and weekly dialysis frequency of three times/week were included in the study. Exclusion criteria were: inability to understand commands to perform the evaluations; epidermal lesions at the site of the PBMT application; stroke sequelae; recent acute myocardial infarction (two months); uncontrolled hypertension (systolic pressure\u0026thinsp;\u0026gt;\u0026thinsp;230 mmHg and diastolic pressure\u0026thinsp;\u0026gt;\u0026thinsp;120 mmHg); IV grade heart failure according to the New York Heart Association or decompensated; unstable angina; deep venous thrombosis in the lower limbs; incapacitating osteoarticular or musculoskeletal disease; uncontrolled diabetes (glycemia\u0026thinsp;\u0026gt;\u0026thinsp;300mg/dL); febrile state and/or infectious disease, systemic lupus erythematosus; and cancer.\u003c/p\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eAll the patients from HD outpatient center were invited to participate in the study. Those who showed interest had their electronic medical records consulted to verify the eligibility criteria. Identification, demographic and anthropometric data, risk factors and cause that led to CKF were collected from patients included in the study. After enrollment, patients were randomized to the order in which they would receive the four doses of PBMT. The assessment and intervention procedures were carried out in a multidisciplinary office, at the HD outpatient center, free from noise and external interruptions.\u003c/p\u003e\n\u003ch3\u003eRandomization and blindness\u003c/h3\u003e\n\u003cp\u003eThe patients received four doses of PBMT (30 J, 60 J, 90 J or placebo), with a one-week interval between them, and according to the individual randomization order. Randomization was performed by a researcher external to the study, using the \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.random.orgwebsite\u003c/span\u003e\u003c/span\u003e. The dose was revealed to the intervention therapist only before the application of the PBMT to ensure concealment of the allocation. Participants and the outcome evaluator were blinded to the therapeutic dose. Participants used protective glasses and headphones with music during the application of PBMT, and the evaluator was instructed to leave the room during the interventions. Still, the cluster was maintained at each application point for one minute, regardless of the dose.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEvaluations\u003c/h2\u003e \u003cp\u003eAll assessment procedures were performed prior to the second weekly hemodialysis session over four weeks. The PBMT doses were administered at one-week intervals to avoid the residual effect of the previous dose. Patients were instructed to not perform any effort or physical exercises prior to the assessment and to wear comfortable clothing on the day of the tests. The assessments were performed before irradiation of the quadriceps with PBMT in the following order: 1) Perceived exertion; 2) Measurement of blood lactate; 3) Assessment of muscle pain in the lower limbs. After the PBMT application and the subsequent performance of the maximum isometric quadriceps strength test, the following assessments were repeated: 4) Perceived exertion; 5) Measurement of blood lactate (times 0, 3 and 6 minutes); 6) Assessment of muscle pain in the lower limbs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All assessments were conducted by trained researchers who were blinded to the doses of PBMT applied.\u003c/p\u003e \u003cp\u003ea) Maximum Isometric Quadriceps Strength Evaluation\u003c/p\u003e \u003cp\u003eThe maximum isometric quadriceps strength was measured by dynamometry using a load cell (SDS 1000, traction mode, nominal capacity of 200 kg, 0.1 kg resolution). It was calibrated and connected to a data acquisition system (Miotool, model 400 USB, Miotec, Porto Alegre/RS, Brazil). The patient was positioned in sitting position on a litter with an adapted back support. The initial position was an angle of 90\u0026ordm; degrees of hip and knee flexion. The participant was asked to perform and maintain knee extension at a 60\u0026ordm; angle (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As a previous study, the load cell position was fixed using a velcro ankle strap to guarantee a perpendicular alignment of the sensor [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For the patient's angle position, an acrylic goniometer (ProFisiomed, Porto Alegre, RS, Brazil) with a one-degree resolution was used.\u003c/p\u003e \u003cp\u003eThe patient was instructed to perform and sustain the maximum isometric force generated by the quadriceps for five seconds and receiving verbal stimulation through standardized phrases [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. A minimum number of three and a maximum of five measurements were taken, with a two-minute rest interval between them. Only standardized measurements were considered valid, excluding those with a value greater or less than 10%. The force peak generated was considered for analysis. Measurements were recorded using the MiotecSuite 1.0 software and analyzed using the Miograph program and expressed in kgF units.\u003c/p\u003e \u003cp\u003eThe maximum isometric strength of the quadriceps evaluation was executed immediately after irradiation of the PBMT dose in the patient's right lower limb. After measurements of the right limb, the left lower limb was irradiated, and the assessment of maximum isometric quadriceps strength was performed.\u003c/p\u003e \u003cp\u003eb) Muscle Fatigue Evaluation\u003c/p\u003e \u003cp\u003eMuscle fatigue was measured using the Borg Rating of Perceived Exertion Scale and blood lactate levels. The patient was asked about the \u0026ldquo;tiredness of his legs\u0026rdquo; and instructed to quantify it, where 0 indicates no effort or fatigue and 10 indicates maximum effort [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLactate levels (mmol/L) were measured through a drop of blood on a BM-Lactate reagent strip (Roche Diagnostics GmbH, Mannheim, Germany), which was then introduced into the Accutrend\u0026reg; Lactate meter (Roche Diagnostics GmbH, Mannheim, Germany). To collect capillary blood, automatic self-lancets (G-Tech\u0026reg; \u0026minus;\u0026thinsp;28G needle) were used at the end of the index finger. Lactate was measured before PBMT application (basal), immediately after the maximum isometric quadriceps strength evaluation of both legs (time 0 - t0), three (t3) and six (t6) minutes later [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ec) Muscle Pain Evaluation\u003c/p\u003e \u003cp\u003eLower limb muscle pain was measured using the visual analogue scale (VAS), where point 0 (zero) represents no pain and point 10 (ten) the worst possible pain. The patient will be asked about the \u0026ldquo;muscle pain in their legs\u0026rdquo; and instructed to quantify it using the scale [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003ePBMT were applied using a low-intensity infrared cluster laser with four diodes, 830 nm wavelength (HTM\u0026reg;, model Fluence MAXX, S\u0026atilde;o Paulo, Brazil). Detailed parameters can be seen in chart \u003cspan refid=\"Str1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All patients received four doses of laser radiation with a one-week intervals: 30J (180J per leg), 60J (360J per leg), 90J (540J per leg) or placebo. The doses were determined based on clinical and scientific recommendations for the use of PBMT for muscle performance [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], a meta-analysis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and previous studies [19, 31\u0026ndash;33), considering the therapeutic window of 60 to 300 J for large muscle groups. Similarly, the PBMT application was performed immediately before the activity (strength test) for the expected acute effects. The order of each dose application was determined by randomization. The placebo treatment was carried out with the equipment turned off.\u003c/p\u003e \u003cp\u003eFor application, the patient was positioned in the same sitting position of the evaluations and the treatment was executed with the probe fixed in direct contact with the skin at a 90\u0026ordm; angle, using the continuous emission mode. The therapy was applied to the quadriceps muscle, bilaterally. Two points were irradiated in the distal region of the vastus medialis, two points in the distal region of the vastus lateralis and two points in the central region of the rectus femoris, like a previous study [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. A map of the application points was drawn after the first application with PBMT to ensure that the same locations were irradiated in the subsequent applications. The intervention with PBMT was conducted always by the same therapist.\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eThe sample size calculation estimated 10 patients, and it was based on a previous study [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] which evaluated the acute effect of PBMT on maximum quadriceps isometric strength in patients with chronic obstructive pulmonary disease (COPD). Sample calculation considered a difference of 17.49 N.m for maximum voluntary isometric contraction, standard deviation of 11.02, power of 80% and alpha error of 5%. Anticipating losses and taking the sample calculation as a basis, the sample was estimated at 15 patients for this study.\u003c/p\u003e \u003cp\u003eThe categorical variables were presented as absolute and relative frequencies and quantitative variables as mean and standard deviation. When appropriate, the delta of change (∆) was reported according to the following equation: ∆ = (POST average - basal average). Normality was verified by the Shapiro-Wilk test. A repeated measures ANOVA was applied to compare the outcomes according to the doses. It was considering the peak value of strength to analyze maximum isometric quadriceps strength and delta was used for fatigue (Borg scale and lactate measure) and muscle pain (VAS). A repeated measures ANOVA, followed by the Tukey post hoc test, was employed to assess a possible learning effect. The significance level adopted was 0.05, and the per-protocol analyses were performed using SPSS statistical software (IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY: IBM Corp.)\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe flowchart for patient selection and inclusion in the study is shown in Fig.\u0026nbsp;3. Seventeen CKF patients on HD were evaluated for eligibility, fifteen were randomized and fourteen analyzed. Demographic, anthropometric and clinical characteristics of the patients at the baseline of the study are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTABLE 1\u0026nbsp;\u003c/strong\u003eCharacteristics of patients admitted to the study\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"397\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003en=14\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57.4 ± 15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSex (male)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9 (64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDry weight (kg)\u003csup\u003ea\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66.2 ± 16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWet weight (kg)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e69.6 ± 18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHigh (m)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.7 ± 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.6 ± 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHD time (months)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.7 (17.7 – 59.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eURR (%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72.6 ± 5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePrimary disease\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Diabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Polycystic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- COVID-19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- NSAIDs induced nephrotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Solitary kidney\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Hemolytic-Uremic Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRisk factors\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Ex-smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11 (78.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Sedentary lifestyle\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11 (78.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Diabetes mellitus\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Heart disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e- Peripheral vascular disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n \u003cdiv align=\"left\"\u003eLegend: M: male; BMI: body mass index; HD: hemodialysis; URR: urea reduction rate; NSAIDs: non-steroidal anti-inflammatory drugs; FH: family history. Data are expressed as: a: mean ± standard deviation; b: median and interquartile range (P25P75); or c: frequency and (percentage prevalence).\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003c/div\u003e\n\u003cp\u003eNo learning effect was observed by patients to assess muscle strength. This can be seen in Table 2, when the averages of maximum isometric muscle strength of the quadriceps generated after the application of PBMT are compared throughout the four radiation applications, regardless of the dose used.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eMaximum isometric quadriceps strength in the first, second, third and fourth PBMT session, regardless of dose\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e1st session\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2nd session\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e3rd session\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e4th session\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRight limb strength (kgF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.5 ± 7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.9 ± 6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.4 ± 8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.6 ± 7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.531\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeft limb strength (kgF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.3 ± 8.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.3 ± 9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.0 ± 8.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.2 ± 10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eLegend: Data are expressed as mean ± standard deviation.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe maximum isometric muscle strength of the quadriceps of the right and left legs did not show significant changes after the application of PBMT, regardless of the dose applied, nor when compared to placebo PBMT. There was a tendency for an increase in muscle strength when the 90J dose was used; however, this was without statistical significance (Table\u0026nbsp;3).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eValues for maximum isometric quadriceps strength, fatigue and pain after PBMT\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo (n = 14)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e30J (n = 14)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e60J (n = 14)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e90J (n = 14)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuadriceps strength\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRight limb (kg/F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.7 ± 7.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.91 ± 7.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.68 ± 7.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.24 ± 8.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeft limb (kg/F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.8 ± 8.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.89 ± 8.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.69 ± 9.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.39 ± 10.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle fatigue (lactate \u003cem\u003e- mmol/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eΔt0-basal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.14 ± 1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.15 ± 1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06 ± 1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.91 ± 1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eΔt3-basal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.34 ± 0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.18 ± 0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.34 ± 0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.70 ± 2.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.667\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eΔt6-basal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.43 ± 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.66 ± 0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.29 ± 0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.39 ± 1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.700\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle fatigue (Borg scale)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.72 ± 2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.36 ± 2.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.07 ± 2.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.00 ± 2.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.29 ± 1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.57 ± 2.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.5 ± 1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.57 ± 2.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eΔ post-pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.43 ± 1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21 ± 1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.57 ± 2.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.43 ± 2.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.703\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72 ± 1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.07 ± 2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.36 ± 2.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.71 ± 2.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79 ± 1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.07 ± 2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79 ± 1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.64 ± 3.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eΔ post-pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.07 ± 0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.00 ± 0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.57 ± 1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.07 ± 2.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.566\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eLegend: Data are expressed as: a: mean ± standard deviation. Δ delta.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eMuscle fatigue induced by the muscle strength test and assessed by serum blood lactate levels did not change significantly after the application of any of the doses of PBMT at any of the measured times (immediately after the test, 3 and 6 minutes later). Likewise, the perception of leg fatigue assessed by the modified Borg scale was not altered after the application of PBMT, regardless of the dose used (Table 3).\u003c/p\u003e\n\u003cp\u003eMuscle pain was not influenced by the application of any dose of PBMT performed prior to the assessment of quadriceps muscle strength (Table 3).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis was the first randomized, double-blind, placebo controlled crossover clinical trial to evaluate the acute effect of different doses of PBMT energy (30, 60 and 90J) on muscle strength, fatigue and pain in the lower limbs in CKF patients.\u003c/p\u003e \u003cp\u003eOur results demonstrate a tendency for an increase in maximum isometric muscle strength when the quadriceps was irradiated with 90J/point (180J/leg), however, without statistical difference when compared to other doses. In previous studies with chronic patients, a single application of PBMT was able to increase lower limb muscle strength in patients with chronic obstructive pulmonary disease (COPD) (905nm, 510J/leg) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. On the other hand, such effects were not observed in patients with heart failure (808nm, 28J/leg) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] or those undergoing coronary artery bypass grafting (CABG) (850nm, 240J/leg) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. However, a limited number of studies have explored the PBMT effects on muscle strength in CKF patients on HD and there are gaps in the literature regarding its influence on exercise capacity of this group of patients.\u003c/p\u003e \u003cp\u003eMacagnan et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] demonstrated for the first time the acute effect of PBMT during HD. The crossover study with fifteen participants compared different doses of infrared laser irradiation (850 nm) on the finger flexor muscles. The findings suggested that a single session with doses of 60J and 90J increased the handgrip strength of these patients, with a superior response at 60J. Although our parameters align with those defined in the literature [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], the specificity of the target muscles used by Macagnan et al [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] may have contributed to the positive results. The therapeutic effects of PBMT are associated with the use of appropriate wavelength and energy dose parameters, within a specific therapeutic window [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], as well as the suitability of the target tissue or muscle group to be irradiated [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Smaller muscles with less adjacent adipose tissue may enhance light penetration into the muscle fibers, optimizing the effects of photobiomodulation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn other randomized clinical trial, Schardong et al [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] evaluated the chronic effect of PBMT on the quadriceps muscle. CKF patients received 24 treatment sessions (810 nm, 30 J/application site) over 8 weeks, three times/week, during HD. They findings indicated an increase in the distance covered in the six-minute walk test as well as in the muscle strength of the lower limbs, assessed by the 10-repetition sit-to-stand test for the treated group when compared to the control. Even though we irradiated the same muscle group in our study, the effect of a single application did not yield similar results. The biphasic response relating to the applied dose, described by the Arndt-Schulz Law, can be enhanced by the cumulative effect of the results found in chronic treatment from regular and continuous application of light therapy over time [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePBMT has been observed as a potential ergogenic resource for exercise, with the aim of improving performance and recovery after activity [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The mechanism of PBMT action provides a reduction in oxidative stress and inflammation in muscles and stimulates the synthesis of muscle proteins [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], as well as promoting the formation of new blood vessels by increasing the supply of oxygen and the total volume of blood around the irradiated area [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. This may act on processes causing fatigue, such as the accumulation of metabolites and electrolyte imbalance (loss of sodium, potassium, and magnesium through sweat), as well on pain receptors, reducing sensitivity and the transmission of pain signals to the central nervous system [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt was hypothesized that PBMT prior to the strength protocol would stimulate muscle metabolism and, consequently, reducing fatigue and pain levels in patients with CKF. However, no effects were found on muscle fatigue measured by Borg scale and blood lactate levels. These findings corroborate those found in a randomized crossover clinical trial that evaluated the acute effect of PBMT (850 nm, 240J) on the quadriceps muscle in patients after CABG. Stein et al [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] did not show any change for functional capacity, fatigue, tissue damage markers and oxidative stress after applying a session of PBMT.\u003c/p\u003e \u003cp\u003eOn the other hand, the study by Bublitz et al [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] evaluated the acute effect of PBMT (808nm, 28J) on the quadriceps of patients with heart failure and demonstrated a significant reduction in the perception of effort (Borg scale) for the treated group compared to placebo. Furthermore, the blood lactate level increased for the placebo group, suggesting that PBMT accelerates the removal of peripheral lactate. In this study, the total dose irradiated on the quadriceps femoris was lower when compared to our study, only 4J/per point. This finding may be related to the effect of the amount of energy absorbed by the cell, generating inhibition or stimulation of intracellular processes [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMiranda et al [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] evaluated the effect of PBMT (superpulsed laser 905 nm; LEDs 875 nm; LEDs 640 nm; 180 J) in patients with chronic obstructive pulmonary disease and found that one application on the quadriceps muscle increased the force of maximal voluntary isometric contraction of the quadriceps and reduced the sensation of dyspnea and fatigue (assessed by the Borg scale). It is important to highlight that, unlike our study, the study by Miranda et al [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] uses three different wavelengths for irradiation of the lower limb.\u003c/p\u003e \u003cp\u003eOur findings also did not demonstrate any change in pain levels in the lower limbs after the application of PBMT compared to placebo PBMT. This result corroborates that found by Schardong et al [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] where PBMT, even when applied chronically, had no effect on reducing lower limb pain in patients with CKD undergoing HD. We emphasize that the baseline pain level of the patients evaluated was low, therefore, the lack of results, regardless of the therapeutic dose used, is justified. Although pain is a common symptom reported by 58\u0026ndash;84% of patients with CKF [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], this was not a symptom observed in the sample of our study.\u003c/p\u003e \u003cp\u003eThis study has limitations that should be considered when interpreting its results. The subjectivity and fragility of the scales used for pain and perceived exertion assessment, despite being validated, may also have influenced the results. The instrument used for strength assessment (dynamometer by load cell) is a less robust method compared to the gold standard, isokinetic dynamometry. While the load cell is widely used due to its practicality and confiability, it lacks the ability to assess muscle strength at variable speeds and provides less detailed information about muscle performance, such as peak torque and range of motion, which are better captured by isokinetic dynamometry.\u003c/p\u003e \u003cp\u003eFor future studies that aim to evaluate the acute effect of PBMT in patients with CKF, it is suggested that higher doses of irradiation be tested prior to the maximum voluntary isometric strength test in the lower limb in this population. In addition, randomized clinical trials that evaluate the chronic effect of the application of PBMT prior to a resistance exercise program are necessary to validate whether patients with CKF can benefit from this therapeutic resource as an adjuvant treatment to improve muscle performance. Finally, it is important to highlight that the PBMT did not result in any adverse effects and was well tolerated by the participants.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eA single application of PBMT did not increase isometric quadriceps muscle strength and did not alter fatigue and pain in the lower limbs in patients with CKF on HD, regardless of the therapeutic dose used. However, there was a trend towards increased muscle strength when the therapeutic dose of 90 J/point was used. This may guide future studies, aiming to find the ideal therapeutic window. Further clinical trials are needed to understand the therapeutic potential of PBMT in patients with CKF on HD.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFinancial support:\u003c/strong\u003e This study was funded in part by Coordena\u0026ccedil;\u0026atilde;o de Aperfei\u0026ccedil;oamento\u003c/p\u003e\n\u003cp\u003ede Pessoal de N\u0026iacute;vel Superior (CAPES).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBello AK, Levin A, Lunney M, Osman MA, Ye F, Ashuntantang GE et al (2019) Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey. bmj. ;367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.l5873\u003c/span\u003e\u003cspan address=\"10.1136/bmj.l5873\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 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A systematic review. J Athl Train. ;48(1):57\u0026ndash;67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4085/1062-6050-48.1.12\u003c/span\u003e\u003cspan address=\"10.4085/1062-6050-48.1.12\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e PMID: 23672326\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLambert K, Mooyman A, Burns P, Mullan J (2021) Prevalence of pain and analgesic use in people with chronic kidney disease. Ren Soc Australasia J 17(2):46\u0026ndash;53. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.33235/rsaj.17.2.46-53\u003c/span\u003e\u003cspan address=\"10.33235/rsaj.17.2.46-53\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Kidney failure, chronic, Renal dialysis, Low-level light therapy, Phototherapy, Randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-8149683/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8149683/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePatients with chronic kidney failure (CKF) present changes in physical capacity and low exercise tolerance. Photobiomodulation therapy (PBMT) has shown an ergogenic effect on exercise in studies with different populations and may be an adjuvant treatment in rehabilitation programs for CKF patients. This study aimed to evaluate the acute effects of different doses of PBMT on quadriceps strength, fatigue and muscle pain in CKF patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study is a randomized, placebo-controlled, double-blind, crossover clinical trial. Adult patients with CKF received four PBMT applications with different energy doses (30J, 60J, 90J, or placebo), administered in a random order. A one-week interval was maintained between each dose, and an 830 nm laser was applied to six points of the quadriceps muscle. Immediately after PBMT, maximum isometric quadriceps muscle strength was assessed by dynamometry. Before the intervention and after the assessment of muscle strength, muscle fatigue (Borg rating of perceived exertion scale and blood lactate) and pain perception in the lower limbs (visual analogue scale) were measured.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFifteen patients were randomized and 14 completed the study. There was no significant difference between the doses tested for maximum isometric muscle strength in the right (p\u0026thinsp;=\u0026thinsp;0.053) and left (p\u0026thinsp;=\u0026thinsp;0.509) quadriceps. The perception of fatigue assessed by the modified Borg scale was not altered (p\u0026thinsp;=\u0026thinsp;0.703) nor were blood lactate levels, regardless of the PBMT dose and measurement time (t0: p\u0026thinsp;=\u0026thinsp;0.126; t3: p\u0026thinsp;=\u0026thinsp;0.667; t6: p\u0026thinsp;=\u0026thinsp;0.700). There was no change in pain perception after quadriceps irradiation for any of the PBMT doses tested (p\u0026thinsp;=\u0026thinsp;0.566).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eA single application of PBMT with a dose of 30J, 60J, or 90J did not alter maximum isometric quadriceps muscle strength, fatigue, or muscle pain perception in the lower limbs of CKF patients on HD.\u003c/p\u003e","manuscriptTitle":"Acute Effect of Photobiomodulation Therapy in Quadriceps Strength, Fatigue and Pain of Patients With Chronic Kidney Failure: A Randomized, Double-blind, Placebo Controlled Crossover Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 08:32:28","doi":"10.21203/rs.3.rs-8149683/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-01T19:27:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-27T10:22:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-25T16:06:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-23T06:11:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96154412677381263680801786951588093344","date":"2026-01-18T08:05:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"81752306041151694809312170717256204869","date":"2026-01-17T19:58:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"115184806456151314174575108070252555891","date":"2026-01-17T02:20:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T20:51:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62316184535872995535412888265059057404","date":"2026-01-16T19:00:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20954499187900691174996989117927492419","date":"2026-01-15T02:38:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-15T02:07:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-15T02:06:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-03T04:04:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2025-11-19T01:26:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bdb3fc1e-f82b-41a8-8476-4d93fdea5321","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-05T00:54:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 08:32:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8149683","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8149683","identity":"rs-8149683","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}