https://orcid.org/0000-0002-4718-448X
Abstract
Objective
Patients on hemodialysis commonly present with elevated inflammatory markers. It is noteworthy, however, that higher levels of these markers may deteriorate residual renal function in in these individuals. Further investigation is essential to clarify the potential link between systemic chronic inflammatory parameters and residual diuresis volume in this population, particularly when accounting for confounding variables such as body composition. This study aimed to explore the possible relationship between inflammatory parameters and residual diuresis volume in patients on hemodialysis.
Methods
Blood samples were collected from patients on hemodialysis for the analysis of soluble receptors: 1) tumor necrosis factor receptor 1 (sTNFR1), 2) tumor necrosis factor receptor 2 (sTNFR2), and 3) leptin. Confounding variables, such as gender, age, duration of hemodialysis, Kt/V (a measure of dialysis adequacy), and body composition assessed using the dual-energy X-ray absorptiometry (DXA), were also evaluated. Data analyses were conducted using both single and multiple regression models, adjusted for the confounding parameters.
Results
Of the total sixty participants, 27 (45%) were classified as anuric, and 33 (55%) as non-anuric. High sTNFR1 plasma levels were associated with a lower residual diuresis volume, irrespective of adjustments for confounding parameters (R² = 25.4%; β = 0.504; p < 0.001).
Conclusion
This study supports the hypothesis that higher systemic levels of sTNFR1 may deteriorate residual renal function, as evidenced by the lower residual diuresis volume observed in patients on hemodialysis. These findings suggest that interventions aimed at reducing systemic inflammation may be beneficial in preserving residual renal function and improving clinical outcomes in these patients.
Chronic Kidney Disease (CKD) is characterized by any persistent alteration or abnormality in kidney structure or function lasting over ninety days [1]. CKD’s subtle onset complicates diagnosis, and once established, it often progresses irreversibly [2]. Recognized globally as a major public health issue [3], CKD affects 10–13% of adults in economically advanced countries [1]. In Brazil, CKD poses significant healthcare challenges, causing over 35,000 deaths annually and incurring substantial treatment costs [4]. Projections indicate around 10 million CKD cases in Brazil, with about 90,000 individuals requiring dialysis [5,6]. This data underscores the urgent need to address CKD as a critical health challenge and develop comprehensive strategies to mitigate its impact on public health and healthcare costs.
Figures
Citation: Gonçalves GT, Santos LMdM, Figueiredo PHS, Freitas JdPC, Santos JM, Santos JNV, et al. (2025) High level of soluble tumor necrosis factor receptors is associated with lower residual diuresis volume in patients on hemodialysis: An exploratory study. PLoS One 20(4): e0320019. https://doi.org/10.1371/journal.pone.0320019
Editor: Te-Ling Lu, China Medical University, TAIWAN
Received: July 5, 2024; Accepted: February 11, 2025; Published: April 29, 2025
Copyright: © 2025 Gonçalves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the article and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Background
According to the 2022 Brazilian Dialysis Census, hemodialysis (HD) is the predominant renal replacement therapy in Brazil, used by 95.3% of patients undergoing treatment [7,8]. In 2018, the number of HD patients was 133,464, marking a threefold increase since 2000 [9].
Residual renal function is crucial for maintaining fluid and electrolyte balance and eliminating toxins in patients undergoing hemodialysis (HD). However, the deterioration of renal function is a significant concern, as it is associated with poorer clinical outcomes [10]. Our previous work found the absence of residual diuresis in patients on hemodialysis is associated with a higher risk of sarcopenia and low functional performance [11]. In addition, physical activity and Parathormone levels are determinant protagonists of functioning in HD [12].
The uremic condition in patients with CKD often leads to protein and energy depletion, resulting in decreased lean body mass and increased fat mass [13]. This can exacerbate systemic chronic inflammation, a key determinant in the progression of renal failure [1,10,14]. CKD promotes tissue damage through redox imbalance, fibrosis, and cellular apoptosis, leading to the release of cytokines such as tumor necrosis factor (TNF), which are processed by renal function [10,15]. Both tumor necrosis factor receptor 1 (sTNFR1) and tumor necrosis factor receptor 2 (sTNFR2), located on cell surfaces, mediate the activity of TNF, a key pro-inflammatory cytokine involved in inflammatory and immune responses in various diseases [16,17]. Elevated levels of TNF and its soluble receptors correlate with increased mortality in patients on HD [18,19].
Evidence indicates that leptin receptors are distributed across various body organs and systems, influencing physiological functions like bone mass quality, systemic chronic inflammation, and stress response. Leptin, a hormone secreted by adipose tissue, interacts with the hypothalamus to regulate body fat, energy expenditure, satiety, and appetite [20]. Notably, leptin may exacerbate low-grade systemic inflammation by inducing the release of cytokines such as TNF, which are processed by renal function [15].
This study was conducted to investigate the hypothesis that elevated systemic chronic inflammation may deteriorate residual renal function, as evidenced by lower residual diuresis volume in patients on hemodialysis. Although previous studies have evaluated the relationship between systemic inflammatory markers and residual diuresis volume in hemodialysis patients, no studies have been found that investigated this relationship considering body composition measured with precise techniques and taking into account confounding factors such as gender, age, hemodialysis duration, Kt/V, and body composition. Therefore, this study aimed to explore the potential association between systemic inflammatory markers and residual diuresis volume in hemodialysis patients, considering these confounding factors.
Materials and methods
The study employed an exploratory cross-sectional design and was conducted from October to December 2019 in HD sector of Santa Casa de Caridade Hospital in Diamantina, Minas Gerais, Brazil. Ethical approval was granted by the Human Research Ethics Committee at Universidade Federal dos Vales do Jequitinhonha e Mucuri under protocol number 3,612,157, in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participating volunteers.
Were included individuals aged 18 years or older diagnosed with CKD who were undergoing HD treatment at least three times per week for more than six months. Patients who were taking non-steroidal anti-inflammatory drugs or corticosteroids were excluded.
Patients underwent HD sessions using low-flux dialysis membranes, which are crucial as they can influence the efficacy of the treatment and the patients’ immune response. Water treatment involved reverse osmosis and ultraviolet light disinfection processes, emphasizing the importance of water quality in preventing infectious complications and ensuring patient safety during dialysis. Unfractionated heparin was used for anticoagulation during the HD sessions, with adjustments based on activated partial thromboplastin time (aPTT) to carefully manage anticoagulation and avoid thrombotic complications.
The sample size was calculated using GPower Software (version 3.1.9.2). A pilot study was conducted with 15 HD patients to evaluate various predictors, including age, duration of HD treatment, Kt/V ratio, body weight, body composition metrics, bone mineral density, and inflammatory markers. With an effect size of 0.78 for residual diuresis volume, a 5% alpha error, and a statistical power of 98%, the required sample size was determined to be 60 patients.
Procedures
Experimental design.
The study incorporated two sessions conducted on dialysis days, collecting data before and after HD sessions.
Initial session.
The patient assessment included anamnesis focusing on personal and disease-related factors such as gender, age, comorbidities, HD duration, and residual diuresis volume [12].
Residual diuresis volume measurement.
Participants measured their residual diuresis using a graduated container, collecting urine 24 hours preceding the first weekly HD session [19]. This procedure is standard in the HD sector, with which patients are already familiar. Based on the volume collected, patients were classified as anuric (less than 100 mL/day) or non-anuric (more than 100 mL/day) (20). Dialysis efficacy, indicated by Kt/V indexes, was assessed according to the standards set by the National Kidney Foundation [9].
Blood biomarkers.
The blood sample was collected by the nursing team from the HD sector at Hospital Santa Casa de Caridade de Diamantina during the puncture of the arteriovenous fistula at the beginning of the second weekly HD session. Two 10 mL tubes of blood samples without anticoagulant were collected from each patient. They were subsequently centrifuged at 3000 rpm for 10 minutes and serum, plasma, and hemolysate samples were separated and stored at −80°C until analysis. To analyze the plasma levels of sTNFR1, sTNFR2, and Leptin, thawed samples were promptly tested using an enzyme-linked immunosorbent assay (ELISA) kit (Quantikine, R&D Systems, Minneapolis, MN) following the manufacturer’s instructions. The ELISA method was employed and reactions were read at 490 nm using a microplate reader (SoftMax Pro, version 2.2.1, Softmax, Sunny Valley, CA). The detection limits for these assays were 5 pg/mL for leptin, sTNFR1, and sTNFR2.
Dual energy x-ray absorptiometry (DEXA).
Utilizing equipment from Lunar Radiation Corporation (Madison, Wisconsin, USA, model DPX), this tool determined body weight, body fat, android/gynoid ratio, visceral fat, fat mass, fat mass index (FMI), lean mass, lean mass index (LMI), height, and bone mineral density at the total hip and lumbar spine (L2-L4). FMI and LMI were calculated by dividing the fat mass and lean mass, respectively, by the square of the height. Assessments were carried out immediately after the second weekly HD session to minimize any impact from excess tissue fluid [20].
Statistical analysis.
Data were analyzed using SPSS version 22.0 (SPSS Inc., Chicago, IL, USA). The Shapiro-Wilk and Levene tests assessed the sample distribution and homoscedasticity, respectively. Descriptive statistics characterized the sample [19]. Continuous data were presented as means with a 95% confidence interval, while categorical variables were presented as absolute numbers and percentages [19]. Group comparisons between anuric and non-anuric patients were made using t-tests or Mann-Whitney tests [19]. Simple linear regression was applied to independent variables with p < 0.20 in correlation tests (Pearson or Spearman), and stepwise multiple linear regression models were developed for outcomes with p < 0.10 in simple regressions [19]. Adjustments were made for age, fractional urea clearance, and hemodialysis vintage, with a significance level set at 5% [12].
Multiple regression analysis.
Four assumptions were verified: linearity, even distribution of residuals, homoscedasticity, and absence of multicollinearity [12]. Linearity and residual distribution were checked using scatter plots and histograms, respectively. Homoscedasticity was confirmed through scatter plots showing an even distribution along the regression line, and absence of multicollinearity was verified with VIF values below 10.0 [21]. The Durbin-Watson test checked for autocorrelation, with acceptable values ranging from 1.5 to 2.5 [12].
Results
Patient selection and characteristics
Of the 128 patients undergoing HD, 109 met the inclusion and 49 were excluded criteria, with 60 subjects ultimately evaluated (62% men; mean age 54.00 years [95% CI: 50.15–57.85]) (Fig 1). All eligible patients underwent hemodialysis through an arteriovenous fistula. Additionally, the study characterized HD patients’ body composition—including lean mass, fat mass, and bone mineral density—and systemic biomarkers (Table 1).The raw dataset containing these data is available in the Supporting Information (S1 Dataset).
Patient classification and biochemical analysis
Out of the evaluated patients, 27 (45%) were classified as anuric, and 33 (55%) as non-anuric. Although anuric patients underwent HD treatment for a longer duration, no significant differences were observed in other clinical variables, such as body composition and bone mineral density. Plasma leptin concentrations were consistent across groups. However, higher concentrations of soluble receptors, specifically sTNFR1 and sTNFR2, were detected in the anuric group (Table 2).
Correlation and association analysis
The analysis revealed a moderately negative correlation between daily residual diuresis volume and hemodialysis vintage, as indicated in Table 3. A weak positive association was found between daily residual diuresis volume and the android/gynoid (a/g) ratio, visceral fat, fat mass, and fat mass index, according to DXA measurements. Notably, there was a weak association with sTNFR2 and a moderately negative correlation with sTNFR1. No statistically significant associations were observed with other anthropometric, clinical, or personal characteristics
Regression analysis
Regression analysis indicated that daily residual diuresis volume had a weak negative association with HD duration, a weak positive association with the a/g ratio, a moderate negative association with sTNFR1, and a weak negative association with sTNFR2. Notably, a high plasma level of sTNFR1 was central catheterd with a lower residual diuresis volume, accounting for 25.4% of the variability in residual diuresis volume, even after adjusting for confounding factors such as gender, age, HD duration, Kt/V, and body composition (Table 4).
Discussion
The primary outcome of this study, which included patients on HD, indicated that elevated levels of soluble tumor necrosis factor receptors (sTNFR), especially sTNFR1, accounted for 25.4% of the variance in lower residual diuresis volume. Remarkably, this association persisted even after adjusting for confounding variables such as gender, age, HD duration, Kt/V, and body composition. These findings suggest that sTNFR1, a biomarker of tubular damage, may significantly influence residual diuresis volume in patients on HD.
Based on our results and given the innovative approach of assessing body composition using more precise equipment, we have identified a research gap concerning the potential association between inflammatory markers and residual diuresis volume in patients on HD. Individuals with higher levels of circulating plasma markers, such as leptin, sTNFR1, and sTNFR2, might exhibit increased systemic chronic inflammation and reduced residual diuresis. Notably, despite the prevalent systemic inflammatory process associated with CKD and HD, there is still a lack of understanding regarding inflammatory biomarkers that influence the reduction of residual diuresis volume.
Consistent with our findings, previous studies have demonstrated that elevated levels of soluble sTNFR, particularly sTNFR1, are associated with the deterioration of renal function, tubular damage, and an increased risk of all-cause mortality in patients on HD, regardless of age [10,18]. Additionally, higher levels of pro-inflammatory cytokines have been observed in patients with diminished residual renal function and advanced renal disease [22]. In contrast, patients on HD with preserved residual diuresis volume tend to have a better quality of life, reduced levels of inflammation, and higher survival rates [18,23]. Notably, sTNFR1 levels were higher in patients on HD without residual renal function [18]. This aligns with our study’s findings, which identified elevated levels of sTNFR1 in the blood of anuric patients. Moreover, previous research indicated that maintaining residual diuresis volume in this population may sustain lower serum concentrations of inflammatory cytokines compared to anuric patients, potentially indicating a less severe inflammatory state [10,24]. Furthermore, preventing or delaying the total loss of GFR can improve survival in these individuals [25].
Localized on cell membranes, sTNFR1 is activated by binding to TNF-alpha, which is produced by various cells of the immune system, initiating inflammatory and stress response pathways [1]. Oxidative stress, driven by the production of reactive oxygen species, plays a crucial role in the development of comorbidities [21]. Experimental studies have shown that TNF-alpha contributes to the pathophysiology of CKD by inducing renal vasoconstriction, which leads to increased superoxide production and a simultaneous decrease in nitric oxide (NO) availability.
In essence, soluble sTNFRs are emerging as promising biomarkers for kidney damage. However, further research is essential to determine the clinical relevance of sTNFR measurements for identifying renal impairments and predicting reduced residual diuresis volume. Preliminary findings from a study involving two independent cohorts highlight the importance of circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in the elderly, even in the absence of diabetes [26].
While this study did not find significant associations between leptin and residual diuresis volume, previous research has shown that leptin acts as a uremic toxin that contributes to the progression of CKD and its deleterious effects [15,27]. Produced by adipose tissue, leptin is affected by variables such as gender, hormones, and medications. Its elimination, facilitated by renal function, decreases as GFR declines, resulting in elevated serum levels in the presence of inflammation-induced hyperinsulinemia. Hyperleptinemia in patients with kidney failure is associated with pathological changes in the kidneys, including glomerular and tubular damage, leading to significant proteinuria and renal parenchymal fibrosis. Additionally, leptin shows a negative correlation with GFR and a positive correlation with Body Mass Index [27,28].
However, the variability in leptin levels and its impact on CKD have been associated with both a lower risk of all-cause mortality and a higher risk of cardiovascular mortality [27]. Consequently, the precise role of leptin in CKD remains unclear, underscoring the need for further research.
Moreover, body composition—including lean mass, bone mass, and fat mass—can influence or be influenced by systemic inflammation in patients on HD. Including a representative measure of body composition in the analysis is crucial to reduce the risk of biased interpretations. The absence of significant correlations in our analysis was contrary to our expectations, given the assumed link between the inflammatory process observed in this population and aspects of body composition and residual renal function [26].
Previous studies have suggested that patients with residual renal function exhibit better nutritional status, a higher percentage of body fat, and a higher lean mass index. The uremic state that develops in conjunction with the decline in glomerular filtration rate stimulates catabolism, increases protein breakdown, and decreases protein anabolism [29,30].
Patients on HD suffer from poorer muscle function, anabolic resistance, and worse protein and caloric balance compared to patients undergoing other treatments for CKD [31]. Despite the non-significant results, the clinical implications of our findings may be useful. Beyond anuria, other factors such as overall health status, the adequacy of the dialysis procedure, and the management of comorbidities may play important roles.
Additionally, we must consider limitations that may have affected the results, such as sample characteristics. Although the mean age is within the age range of the Brazilian population on dialysis, the sample was younger than that studied by other authors. Therefore, further research is essential to explore other factors influencing body composition in the CKD spectrum, especially in older people. These studies should focus on larger sample sizes and the exploration of other factors that may influence body composition in these individuals longitudinally,
Once residual renal function is recognized as a predictor of survival for patients with CKD, being associated with a substantial reduction in mortality risk, greater vitality, fewer dietary restrictions, and less exacerbation of the inflammatory state and oxidative stress and their consequences, monitoring the residual diuresis volume through a simple and reliable measure, as in our study, can be beneficial for this population. This approach can contribute to reducing costs and preventing additional disease-related damage [10,26,32].
In conclusion, our study supports the hypothesis that lower residual diuresis volume in patients on HD may be associated with elevated systemic levels of sTNFR1. However, this association should not be interpreted as indicative of a causal relationship, and the direction of the association is also uncertain. High levels of inflammatory markers can be a consequence (at least partly) of low residual kidney function rather than the etiology of low residual kidney function, or both. Additional research is necessary to clarify the potential mechanisms that link sTNFR1 to residual diuresis volume in HD patients and examine the implications for patient management and treatment strategies.
Strengths and limitations
Our investigation stands out for its meticulous characterization of study participants. It offers detailed insights into kidney phenotypes through comprehensive analyses of the duration of HD, Kt/V values, and other relevant confounding factors. We employed gold standard methods for measuring body composition variables such as body fat, lean mass, and bone mineral density rather than relying on less accurate indirect estimates. Despite these strengths, it is essential to acknowledge certain limitations. The generalizability of our findings to different age and ethnic groups is not assured, which may restrict the external applicability of the study results. Additionally, the cross-sectional observational nature of our study limits our ability to establish causality. Furthermore, although we have detailed data on the glomerular filtration rate, the absence of glomerular ultrafiltration rate data may limit a complete understanding of the renal filtration process during hemodialysis sessions and their clinical implications. Nonetheless, our research contributes significantly to the sparse literature in Latin America on the correlation between inflammatory markers and residual diuresis volume. It enriches the existing body of knowledge and lays crucial groundwork for future longitudinal studies that are needed to clarify the cause-and-effect relationships involving the biomarkers studied.
Conclusion
In conclusion, this study supported the benefits of monitoring residual diuresis volume in hemodialysis patients. Our findings contribute to a limited but growing body of research suggesting that inflammatory biomarkers, such as sTNFR1, can play a role in the progression of end-stage renal disease by triggering inflammatory cascades, which can be associated with residual diuresis volume. Additionally, there is a continuing need for longitudinal studies aimed at developing effective methods for monitoring and preserving residual diuresis volume.
Supporting information
S1 Dataset. Raw dataset containing data from 60 participants used for analysis in this study.
The dataset includes the following variables: Height, Lean Mass (kg), LMI (kg/m²), Fat Mass (kg), FMI (kg/m²), Duration of HD (years), Diuresis Volume (mL), Kt/V, Body Fat (%), A/G Ratio, Visceral Fat (g), BMD Total (g/cm³), BMD Spine (g/cm³), BMD Hip (g/cm³), Leptin (ng/mL), sTNF-R1 (pg/mL), and sTNF-R2 (pg/mL).
https://doi.org/10.1371/journal.pone.0320019.s001
(PDF)
Acknowledgments
We would like to express our gratitude to the Universidade Federal dos Vales do Jequitinhonha e Mucuri, National Council for Scientific and Technological Development, Foundation for Research Support of the State of Minas Gerais, and Coordination for the Improvement of Higher Education Personnel for their support and for providing scholarships. Additionally, our sincere thanks go to the Hemodialysis Unit of Hospital Santa Casa de Caridade de Diamantina, along with its collaborators and volunteers who contributed to this research.
References
- 1. Lim YJ, Sidor NA, Tonial NC, Che A, Urquhart BL. Uremic toxins in the progression of chronic kidney disease and cardiovascular disease: mechanisms and therapeutic targets. Toxins (Basel). 2021;13(2):142. pmid:33668632
- 2. Mihai S, Codrici E, Popescu ID, Enciu A-M, Albulescu L, Necula LG, et al. Inflammation-related mechanisms in chronic kidney disease: prediction, progression, and outcome. J Immunol Res. 2018;2018:2180373. pmid:30271792
- 3. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22. pmid:33069326
- 4. Figueiredo PHS, da Silva ACR, Costa HS, Nominato GA, Lopes PH, Campos P, et al. The Glittre activities of daily living as a potential test for functional evaluation of patients on hemodialysis: a validation study. Disabil Rehabil. 2022;44(10):2083–90. pmid:32870711
- 5. Roshanravan B, Patel KV. Assessment of physical functioning in the clinical care of the patient with advanced kidney disease. Semin Dial. 2019;32(4):351–60. pmid:31044471
- 6. Llanos MA, Sbaraglini ML, Villalba ML, Ruiz MD, Carrillo C, Alba Soto C, et al. A structure-based approach towards the identification of novel antichagasic compounds: Trypanosoma cruzi carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem. 2020;35(1):21–30. pmid:31619095
- 7. Nerbass FB, Lima HN, Moura-Neto JA, Lugon JR, Sesso R. Brazilian dialysis survey 2022. Braz J Nephrol. 2024;46(2):e20230062. pmid:38078834
- 8. Neves PDM, Sesso RCC, Thomé FS, Lugon JR, Nascimento MM. Brazilian Dialysis Census: analysis of data from the 2009-2018 decade. J Bras Nefrol. 2020;42(2):191–200. pmid:32459279
- 9. Daugirdas JT, Depner TA, Inrig J, Mehrotra R, Rocco MV, Suri RS, et al. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930. doi: https://doi.org/https://doi.org/10.1053/j.ajkd.2015.07.015.
- 10. You AS, Kalantar-Zadeh K, Obi Y, Novoa A, Peralta RA, Streja E, et al. Residual urine output and mortality in a prospective hemodialysis cohort. Kidney Int Rep. 2020;5(5):643–53. pmid:32405586
- 11. Rodrigues VGB, Silva WT, Silva ACR, Campos PC, Santos LCM, et al. Relationship between residual diuresis and sarcopenia in patients on hemodialysis. J Ren Nutr. 2024;1:51–6. pmid:38914380
- 12. Santos LMM, Figueiredo PHS, Silva ACR, Campos PC, Gonçalves GT, de Paula C Freitas J, da Silva Junior FA, et al. Determining factors of functioning in patients on hemodialysis using the international classification of functioning, disability and health. BMC Nephrol. 2022;23(1):119. pmid:35331148
- 13. Xu L, Guo J, Moledina DG, Cantley LG. Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition. Nat Commun. 2022;13(1):4892.
- 14. Nowak KL, Rossman MJ, Chonchol M, Seals DR. Strategies for achieving healthy vascular aging. Hypertension. 2018;71(3):389–402. pmid:29311256
- 15. Pedone C, Roshanravan B, Scarlata S, Patel KV, Ferrucci L, Incalzi RA. Longitudinal association between serum leptin concentration and glomerular filtration rate in humans. PLoS One. 2015;10(2):e0117828. pmid:25710704
- 16. Zazzeroni L, Pasquinelli G, Nanni E, Cremonini V, Rubbi I. Comparison of quality of life in patients undergoing hemodialysis and peritoneal dialysis: a systematic review and meta-analysis. Kidney Blood Press Res. 2017;42(4):717–27. pmid:29049991
- 17. Mikami R, Mizutani K, Gohda T, Gotoh H, Matsuyama Y, Aoyama N, Matsuura T, et al. Association between circulating tumor necrosis factor receptors and oral bacterium in patients receiving hemodialysis: a cross-sectional study. Clin Exp Nephrol. 2021;25(1):58–65. pmid:32816134
- 18. Gohda T, Maruyama S, Kamei N, Yamaguchi S, Shibata T, Murakoshi M, Horikoshi S, et al. Circulating TNF receptors 1 and 2 predict mortality in patients with end-stage renal disease undergoing dialysis. Sci Rep. 2017;7:43520.
- 19. Almeida LLS d, Sette LHBC, Fonseca FLA, Bezerra LSVdS S, Oliveira FH, Bérgamo RR. Metabolic and volume status evaluation of patients on hemodialysis with and without residual renal function in the long interdialytic interval. J Bras Nefrol. 2019;41:481–91.
- 20. Carrero JJ, Johansen KL, Lindholm B, Stenvinkel P, Cuppari L, Avesani CM. Screening for muscle wasting and dysfunction in patients with chronic kidney disease. Kidney Int. 2016;90(1):53-66.
- 21. Korczynska J, Czumaj A, Chmielewski M, Swierczynski J, Sledzinski T. The causes and potential injurious effects of elevated serum leptin levels in chronic kidney disease patients. Int J Mol Sci. 2021;22(9):4685. pmid:33925217
- 22. de Sequera P, Corchete E, Bohorquez L, Albalate M, Perez-Garcia R, Alique M, Marques M, et al. Residual renal function in hemodialysis and inflammation. Ther Apher Dial. 2017;21(6):592–8. pmid:28971592
- 23. Obi Y, Streja E, Rhee CM, Ravel V, Amin AN, Cupisti A, et al. Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study. Am J Kidney Dis. 2016;68(2):256–65. pmid:26867814
- 24. Carlsson AC, Larsson TE, Helmersson-Karlqvist J, Larsson A, Lind L, Ärnlöv J. Soluble TNF receptors and kidney dysfunction in the elderly. J Am Soc Nephrol. 2014;25(6):1313–20. pmid:24511129
- 25. van der Wal WM, Noordzij M, Dekker FW, Boeschoten EW, Krediet RT, Korevaar JC, et al. Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant. 2011;26(9):2978–83. pmid:21317411
- 26. Shafi T, Jaar BG, Plantinga LC, Fink NE, Sadler JH, Parekh RS, Powe NR, Coresh J. Association of residual urine output with mortality, quality of life, and inflammation in incident patients on hemodialysis: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010;56(2):348–58. pmid:20605303
- 27. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharmacol Sin. 2018;39(7):1176–88. pmid:29877321
- 28. Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT, NECOSAD Study Group, et al. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol. 2004;15(4):1061–70. pmid:15034110
- 29. Suda T, Hiroshige K, Ohta T, Watanabe Y, Iwamoto M, Kanegae K, Ohtani , Nakashima , et al. The contribution of residual renal function to overall nutritional status in chronic haemodialysis patients. Nephrol Dial Transplant. 2000;15(3):396–401. pmid:10692527
- 30. Kang SH, Cho KH, Park JW, Yoon KW, Do JY. Change in body composition in accordance with residual renal function in patients on peritoneal dialysis. J Ren Nutr. 2013;23(6):438–44.
- 31. Bellafronte NT, Barril G, de Oliveira EP. Editorial: Improving body composition and functional capacity in chronic kidney disease patients. Front Nutr. 2023;10:1223975. pmid:37575328
- 32. Pecoits-Filho R, Heimbürger O, Bárány P, Suliman M, Fehrman-Ekholm I, Lindholm B, Stenvinkel P. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis. 2003;41(6):1212–8.
