Skip to main content
Download PDF
Download ePub

Diaphragmatic dysfunction in hemodialysis patients: risk factors and effect of incentive spirometry training

Renal Replacement Therapy volume 9, Article number: 60 (2023) Cite this article

Abstract

Background

Diaphragmatic dysfunction (DD) in hemodialysis patients is a scarcely studied issue. Incentive spirometry (IS) is a commonly prescribed maneuver used to prevent or manage pulmonary complications. The present study aimed to identify the prevalence and risk factors of DD in 100 HD patients. Moreover, we assessed the role of IS in management of DD in those patients.

Methods

The present study followed a hybrid design with two phases. In the first cross-sectional phase, 100 consecutive maintenance HD patients for at least 3 years were evaluated for the presence of DD using ultrasound. In the second interventional phase, patients with DD (n = 43) were randomly assigned to receive IS (n = 22) or standard care (n = 21) for management of DD.

Results

Comparison between patients with DD and patients without regarding clinical and laboratory data revealed that the former group had significantly higher frequency of males [29 (67.4%)/14 (32.6%) vs. 26 (45.6%)/31 (54.4%), p = 0.03] with lower BMI [23.8 ± 3.8 vs. 26.3 ± 3.5 kg/m2, p < 0.001] and longer HD duration (82.2 ± 42.1 vs. 64.8 ± 36.9 months, p = 0.031). Moreover, it was noted that DD group had significantly higher frequency of patients with moderate/severe malnutrition (81.4% vs. 45.6%, p = 0.005), lower Hb levels (9.6 ± 1.5 vs. 10.3 ± 1.4 gm/dL, p = 0.011), lower albumin levels (3.4 ± 0.4 vs. 4.1 ± 0.5 gm/dL, p < 0.001) and higher hsCRP levels [median (IQR) 113.6 (90.9–130.4) vs. 91.1 (50.9–105.6) mg/dL, p < 0.001] as compared to patients without DD. While no significant differences were found between patients receiving study interventions at baseline, patients submitted to IS training showed significant improvement of diaphragmatic excursion measurements as compared to the standard care group.

Conclusions

In conclusion, DD is commonly encountered in HD patients. Probable risk factors include longer HD duration and low albumin levels. Use of IS can improve diaphragmatic excursion in affected patients.

Background

Through decades, hemodialysis (HD) had steadied its role as the primary treatment option for end stage renal disease (ESRD). Since invention eight decades ago, the procedure had witnessed massive developments in terms of technological innovations and clinical protocols. Unfortunately, use of HD is not without significant drawbacks and one of these is the associated malnutrition-inflammation complex [1]. The consequences of malnutrition in HD patients encompass, among others, muscle wasting, weakness and sarcopenia which are linked to poor clinical outcomes [2].

The diaphragm is the principal breathing muscle and any local or systemic condition that interferes with its appropriate contractility can lead to diaphragmatic dysfunction (DD) and related clinical consequences including dyspnea, easy fatiguability and sleep disturbances [3]. Notably, HD patients were reported to have poor respiratory muscle strength parameters and pulmonary function tests in comparison to healthy counterparts [4]. In spite of the fact that DD in HD patients is a scarcely investigated issue. It was found to be related to troublesome symptoms including dyspnea, fatigue, and hiccup [5] and serious clinical outcomes including non-fatal cardiovascular events and all-cause mortality [6].

Diagnosis of DD is challenging. While application of volitional tests is restricted by the patient effort, other non-volitional tests e.g. neuromuscular stimulation are technically sophisticated [7]. Recently, ultrasound is increasingly used for assessment of diaphragmatic integrity, excursion and thickness [8]. Management options of DD entails training of respiratory muscles, noninvasive ventilation and surgical intervention in advanced cases [9].

Incentive spirometry (IS) is a commonly prescribed maneuver used to prevent or manage pulmonary complications postoperatively [10,11,12,13], after stroke [14]. The present study aimed to identify the prevalence and risk factors of DD in HD patients. Moreover, we assessed the role of IS in management of DD in those patients.

Methods

The present study was conducted et al.-Azhar University Hospitals, Cairo, Egypt. The study protocol was approved by the ethical committee of Al-Azhar University Faculty of Medicine and all patients provided informed written consent before enrollment.

Study design and selection criteria

The present study followed a hybrid design with two phases. In the first cross-sectional phase, 100 consecutive maintenance HD patients for at least 3 years were evaluated for the presence of DD using ultrasound. In the second interventional phase, patients with DD (n = 43) were randomly assigned to receive IS (n = 22) or standard care (n = 21) for management of DD. Patients were excluded if they had history of cardiovascular or cerebrovascular events, cognitive impairment, associated lung disease, malignant conditions or advanced liver disease.

Baseline assessment

Upon recruitment, all patients were submitted to careful history taking, thorough clinical examination and standard laboratory work up. Nutritional status was assessed using the malnutrition inflammation score (MIS) [15]. Patients with MIS < 6 were identified to have mild malnutrition while those with MIS ≥ 6 were identified to have moderate/severe malnutrition.

Ultrasound diagnosis of DD

The diaphragm was assessed during tidal, deep and sniff breathing using ultrasound scanner equipped with 3.5 MHz curvilinear and 8 MHz linear probes (SSI6000, Sonoscape, Nanshan, China) for diaphragmatic excursion (M-mode) and thickness (B-mode). Only the right diaphragm was assessed. It was found to sufficient and more precise for diagnosis of DD in comparison to the left side for technical considerations [16]. All sonographic measurements were made at baseline and after the IS protocol by the same sonographer. Patients were diagnosed with DD if they had diaphragmatic excursion of < 10 mm or the presence of paradoxical movement [17, 18] and/or if they had diaphragm thickening fractions < 20% [8].

Randomization and blinding

Patients were randomized to receive IS or standard care using computer-generated random tables and sealed envelope technique. Sonographers weren’t aware of the type of intervention received by the patients.

Incentive spirometry protocol

IS training was achieved using UNA01 flow-oriented incentive spirometer (UniCare, China). Patients were adequately trained to use the device. The respiratory training protocol consisted of hourly 5–10 episodes during wake time for 8 weeks.

Statistical analysis

Data obtained from the present study were presented as number and percent, mean and standard deviation (SD) or median and interquartile range (IQR) and compared using chi-square test, t test or Mann–Whitney U test. Binary logistic regression analysis was used to identify predictors of DD in the studied patients. All statistical computations were processed using SPSS, 27 (IBM, IL, USA) with p value < 0.05 was considered statistically significant.

Results

The present study included 100 HD patients comprising 55 men and 45 women with an age of 60.7 ± 8.7 year. DD was diagnosed in 43 patients. Comparison between patients with DD and patients without regarding clinical and laboratory data revealed that the former group had significantly higher frequency of males [29 (67.4%)/14 (32.6%) vs. 26 (45.6%)/31 (54.4%), p = 0.03] with lower BMI (23.8 ± 3.8 vs. 26.3 ± 3.5 kg/m2, p < 0.001) and longer HD duration (82.2 ± 42.1 vs. 64.8 ± 36.9 months, p = 0.031) (Table 1).

Table 1 Clinical and laboratory findings in the studied patients (n = 100)
Full size table

Moreover, it was noted that DD group had significantly higher frequency of patients with moderate/severe malnutrition (81.4% vs. 45.6%, p = 0.005), lower Hb levels (9.6 ± 1.5 vs. 10.3 ± 1.4 gm/dL, p = 0.011), lower albumin levels (3.4 ± 0.4 vs. 4.1 ± 0.5 gm/dL, p < 0.001) and higher hsCRP levels [median (IQR) 113.6 (90.9–130.4) vs. 91.1 (50.9–105.6) mg/dL, p < 0.001] as compared to patients without DD (Table 1).

Binary logistic regression analysis identified HD duration [OR (95% CI) 0.98 (0.97–0.99)], moderate/severe malnutrition [OR (95% CI) 3.67 (1.45–9.28)], Hb levels [OR (95% CI) 1.44 (1.08–1.91)] and albumin levels [OR (95% CI) 31.3 (7.98–123.0)] as significant predictors of DD in univariate analysis. However, in multivariate analysis, only albumin levels [OR (95% CI) 43.2 (6.91–270.7)] remained significant (Table 2).

Table 2 Predictors of diaphragmatic dysfunction in the studied patients
Full size table

While no significant differences were found between patients receiving study interventions at baseline, patients submitted to IS training showed significant improvement of diaphragmatic excursion measurements as compared to the standard care group (Table 3).

Table 3 Effect of incentive spirometry exercise on diaphragmatic functions in the studied patients
Full size table

Discussion

The present study found that DD as assessed by ultrasound imaging is highly prevalent in maintenance HD patients. Also, we found an association between DD, and male sex, HD duration, moderate-to-severe malnutrition, lower hemoglobin and albumin levels and high hsCRP levels. Our conclusions are supported by the few studies that assessed DD in HD patients through different designs and protocols.

In their case control study, Wang et al. [5] found that HD patients had lower diaphragmatic thickness, thickening fraction and excursion as compared to healthy controls. However, they didn’t report the prevalence of DD in the studied patients nor assessed the relation between DD and other HD parameters. In another work, Zheng et al. [6] documented DD in 44.9% of the studied HD patients, a figure that is close to that found by the present study. However, patients included in their work included—among others—patients with previous cardiovascular events and congestive heart failure. These conditions may affect the performance of diaphragmatic tests irrespective of the hemodialysis parameters (Fig. 1).

Fig. 1
figure 1

a Baseline right tidal diaphragmatic excursion in one patient of the study. b Right tidal diaphragmatic excursion 8 weeks after incentive spirometry training in same patient of the study

Full size image

Also, the study of Yuenyongchaiwat et al. [4] noted that HD patients exhibited significantly impaired respiratory muscles strength parameters in comparison to healthy controls. They added that this impairment is related to HD duration in harmony with our conclusions.

DD is HD patients may be explained by multiple factors. As shown by the present study and other studies [19], malnutrition is quite prevalent in HD patients. Malnutrition was also linked to reduced diaphragmatic thickness and function in many populations [19,20,21] probably due to increased proteolysis and reduced protein synthesis [22, 23] mediated by autocrine/paracrine [24] or inflammatory [25] pathways.

The persistent proinflammatory state related to HD is another suggested contributor to DD. Multiple reports identified impaired diaphragmatic functions in patients with proinflammatory conditions [26,27,28].

Patients with DD in the present study were subsequently advanced to a clinical experiment where they were randomized to receive IS of standard care for DD. Patients in the IS arm showed significant improvement of diaphragmatic excursion after 8-week training protocol.

Interestingly, no corresponding improvement was noted regarding diaphragmatic thickness. This is probably attributed to the muscle wasting commonly seen in this population. In fact, some studies reported that HD patients failed to gain muscle mass after exercise while others identified improved muscle mass in response to exercise protocols as shown by one systematic review [29].

The positive impact of IS in HD patients is probably attributed to improved pulmonary functions and blood gases as suggested by previous studies. In one study, IS proved to be effective in improving arterial blood gases, pulmonary functions tests and diaphragmatic excursion in chronic obstructive pulmonary disease patients [30]. In diabetic patients, it was reported that IS improved all cardiopulmonary functions, functional capacity and event glycemic control [31]. Similar findings were recognized in stroke patients where flow-oriented IS outperformed volume oriented IS and diaphragmatic breathing [14]. Also, the study of Ribeiro et al. [32] concluded that use of IS in Parkinson’s disease was associated with markedly improved pulmonary functions. In conclusion, DD is commonly encountered in HD patients. Probable risk factors include longer HD duration and low albumin levels. Use of IS can improve diaphragmatic excursion in affected patients. However, these conclusions are limited by the fact that this is a single-center study. Moreover, the long-term effects of IS training on HD patients’ health outcomes and quality of life wasn’t studied. It’s also recommended to assess the relation between sarcopenia and frailty commonly seen in HD patients and DD.

Availability of data and materials

Data of this research will be available upon reasonable request.

References

  1. Sahathevan S, Khor BH, Ng HM, et al. Understanding development of malnutrition in hemodialysis patients: a narrative review. Nutrients. 2020;12(10):3147. https://doi.org/10.3390/nu12103147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Slee A, McKeaveney C, Adamson G, et al. Estimating the prevalence of muscle wasting, weakness, and sarcopenia in hemodialysis patients. J Ren Nutr. 2020;30(4):313–21. https://doi.org/10.1053/j.jrn.2019.09.004.

    Article  PubMed  Google Scholar 

  3. Ricoy J, Rodríguez-Núñez N, Álvarez-Dobaño JM, et al. Diaphragmatic dysfunction. Pulmonology. 2019;25(4):223–35. https://doi.org/10.1016/j.pulmoe.2018.10.008.

    Article  CAS  PubMed  Google Scholar 

  4. Yuenyongchaiwat K, Vasinsarunkul P, Phongsukree P, et al. Duration of hemodialysis associated with cardio-respiratory dysfunction and breathlessness: a multicenter study. PeerJ. 2020;4(8):e10333. https://doi.org/10.7717/peerj.10333.

    Article  Google Scholar 

  5. Wang B, Yin Q, Wang YY, et al. Diaphragmatic dysfunction associates with dyspnoea, fatigue, and hiccup in haemodialysis patients: a cross-sectional study. Sci Rep. 2019;9(1):19382. https://doi.org/10.1038/s41598-019-56035-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zheng J, Yin Q, Wang SY, et al. Ultrasound-assessed diaphragm dysfunction predicts clinical outcomes in hemodialysis patients. Sci Rep. 2022;12(1):16550. https://doi.org/10.1038/s41598-022-20450-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Laghi FA Jr, Saad M, Shaikh H. Ultrasound and non-ultrasound imaging techniques in the assessment of diaphragmatic dysfunction. BMC Pulm Med. 2021;21(1):85. https://doi.org/10.1186/s12890-021-01441-6.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dass C, Dako F, Simpson S, et al. Sonographic evaluation of diaphragmatic dysfunction: technique, interpretation, and clinical applications. J Thorac Imaging. 2019;34:W131–40.

    Article  PubMed  Google Scholar 

  9. Windisch W, Schönhofer B, Magnet FS, et al. Diagnosis and treatment of diaphragmatic dysfunction. Pneumologie. 2016;70(7):454–61. https://doi.org/10.1055/s-0042-106694.

    Article  CAS  PubMed  Google Scholar 

  10. Eltorai AEM, Szabo AL, Antoci V Jr, et al. Clinical effectiveness of incentive spirometry for the prevention of postoperative pulmonary complications. Respir Care. 2018;63(3):347–52.

    Article  PubMed  Google Scholar 

  11. Kotta PA, Ali JM. Incentive spirometry for prevention of postoperative pulmonary complications after thoracic surgery. Respir Care. 2021;66(2):327–33.

    Article  PubMed  Google Scholar 

  12. Sullivan KA, Churchill IF, Hylton DA, et al. Use of incentive spirometry in adults following cardiac, thoracic, and upper abdominal surgery to prevent post-operative pulmonary complications: a systematic review and meta-analysis. Respiration. 2021;100(11):1114–27.

    Article  PubMed  Google Scholar 

  13. Chang PC, Chen PH, Chang TH, et al. Incentive spirometry is an effective strategy to improve the quality of postoperative care in the patients undergoing pulmonary resection: a systematic review and meta-analysis. Asian J Surg. 2022;S1015–9584(22):01588–93. https://doi.org/10.1016/j.asjsur.2022.11.030.

    Article  Google Scholar 

  14. Shetty N, Samuel SR, Alaparthi GK, et al. Comparison of diaphragmatic breathing exercises, volume, and flow-oriented incentive spirometry on respiratory function in stroke subjects: a non-randomized study. Ann Neurosci. 2020;27(3–4):232–41. https://doi.org/10.1177/0972753121990193.

    Article  PubMed  Google Scholar 

  15. Kalantar-Zadeh K, Kopple JD, Block G, et al. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis. 2001;38(6):1251–63. https://doi.org/10.1053/ajkd.2001.29222.

    Article  CAS  PubMed  Google Scholar 

  16. Bobbia X, Clément A, Claret PG, et al. Diaphragmatic excursion measurement in emergency patients with acute dyspnea: toward a new diagnostic tool? Am J Emerg Med. 2016;34(8):1653–7. https://doi.org/10.1016/j.ajem.2016.05.055.

    Article  PubMed  Google Scholar 

  17. Boussuges A, Gole Y, Blanc P. Diaphragmatic motion studied by m-mode ultrasonography: methods, reproducibility, and normal values. Chest. 2009;135:391–400.

    Article  PubMed  Google Scholar 

  18. Kim WY, Suh HJ, Hong SB, et al. Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. Crit Care Med. 2011;39:2627–30.

    Article  PubMed  Google Scholar 

  19. Güngör Ş, Doğan A. Diaphragm thickness by ultrasound in pediatric patients with primary malnutrition. Eur J Pediatr. 2023;182(7):3347–54.

    Article  PubMed  Google Scholar 

  20. Hart N, Tounian P, Clément A, et al. Nutritional status is an important predictor of diaphragm strength in young patients with cystic fibrosis. Am J Clin Nutr. 2004;80(5):1201–6.

    Article  CAS  PubMed  Google Scholar 

  21. You Y, Chen M, Chen X, Yu W. Diaphragm thickness on computed tomography for nutritional assessment and hospital stay prediction in critical COVID-19. Asia Pac J Clin Nutr. 2022;31(1):33–40.

    CAS  PubMed  Google Scholar 

  22. Lewis MI, Bodine SC, Kamangar N, et al. Effect of severe short-term malnutrition on diaphragm muscle signal transduction pathways influencing protein turnover. J Appl Physiol 1985. 2006;100(6):1799–806.

    CAS  PubMed  Google Scholar 

  23. Bando JM, Fournier M, Da X, et al. Effects of malnutrition with or without eicosapentaenoic acid on proteolytic pathways in diaphragm. Respir Physiol Neurobiol. 2012;180(1):14–24.

    Article  CAS  PubMed  Google Scholar 

  24. Lewis MI, Li H, Huang ZS, et al. Influence of varying degrees of malnutrition on IGF-I expression in the rat diaphragm. J Appl Physiol 1985. 2003;95(2):555–62.

    CAS  PubMed  Google Scholar 

  25. Lewis MI, Da X, Li H, et al. Tumor necrosis factor-alpha and malnutrition-induced inhibition of diaphragm fiber growth in young rats. J Appl Physiol 1985. 2005;99(5):1649–57.

    CAS  PubMed  Google Scholar 

  26. Soilemezi E, Savvidou S, Sotiriou P, et al. Tissue doppler imaging of the diaphragm in healthy subjects and critically Ill patients. Am J Respir Crit Care Med. 2020;202(7):1005–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Spiesshoefer J, Orwat S, Henke C, et al. Inspiratory muscle dysfunction and restrictive lung function impairment in congenital heart disease: association with immune inflammatory response and exercise intolerance. Int J Cardiol. 2020;1(318):45–51.

    Article  Google Scholar 

  28. Chen Y, Liu Y, Han M, et al. Quantification of diaphragmatic dynamic dysfunction in septic patients by bedside ultrasound. Sci Rep. 2022;12(1):17336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bakaloudi DR, Siargkas A, Poulia KA, et al. The effect of exercise on nutritional status and body composition in hemodialysis: a systematic review. Nutrients. 2020;12(10):3071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. El-Koa AA, Eid HA, Abd Elrahman SR, et al. Value of incentive spirometry in routine management of COPD patients and its effect on diaphragmatic function. Egypt J Bronchol. 2023;17:8.

    Article  Google Scholar 

  31. Aweto HA, Obikeh EO, Tella BA. Effects of incentive spirometry on cardiopulmonary parameters, functional capacity and glycemic control in patients with type 2 diabetes. Hong Kong Physiother J. 2020;40(2):121–32. https://doi.org/10.1142/S1013702520500110.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ribeiro R, Brandão D, Noronha J, et al. Breath-stacking and incentive spirometry in Parkinson’s disease: randomized crossover clinical trial. Respir Physiol Neurobiol. 2018;255:11–6. https://doi.org/10.1016/j.resp.2018.04.011.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We heartfully thank all patients participating in the study.

Funding

The research is self-funded from the authors.

Author information

Authors and Affiliations

  1. Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

    Laila Abdel Naby Ahmed, Wagenat E. Ali & Hanaa Elsayed Abozeid

  2. Chest Diseases Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

    Heba H. Eltrawy, Amira Mohamed Elsadek, Sanaa Fathy Qutb & Fatma Gamal Elsayed

  3. Radiodiagnosis Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

    Alshimaa A. Ezzat M. Enayet

  4. Department of Physical Therapy for Cardiovascular, Respiratory and Geriatric Disorders, Faculty of Physical Therapy, Cairo University, Giza, Egypt

    Ahmed A. Elshehawy

Authors
  1. Laila Abdel Naby Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heba H. Eltrawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amira Mohamed Elsadek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wagenat E. Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanaa Elsayed Abozeid
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sanaa Fathy Qutb
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fatma Gamal Elsayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alshimaa A. Ezzat M. Enayet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ahmed A. Elshehawy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Laila Abdel Naby Ahmed.

Ethics declarations

Ethics approval and consent to participate

The study protocol was approved by the ethical committee of Al-Azhar University Faculty of Medicine (Approval No. 202008330).

Consent for publication

Informed consent was obtained from all individuals included in this study.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmed, L.A.N., Eltrawy, H.H., Elsadek, A.M. et al. Diaphragmatic dysfunction in hemodialysis patients: risk factors and effect of incentive spirometry training. Ren Replace Ther 9, 60 (2023). https://doi.org/10.1186/s41100-023-00516-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s41100-023-00516-w

Keywords

Renal Replacement Therapy

ISSN: 2059-1381

Contact us