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INTRODUCTION
Chronic kidney disease (CKD) is a global public health condition that affects millions of people and has a significant impact on patients’ quality of life. It is characterized by a progressive and irreversible loss of kidney function and is closely associated with serious complications such as cardiovascular disease, metabolic disorders and a substantial increase in the risk of mortality1.
Globally, hemodialysis is still the most important renal replacement therapy. With the continued development and optimization from the technology of dialysis, the time of survival of patients on maintenance hemodialysis (MHD) is gradually prolonged. However, even in developed countries, the mortality rate of patients with MHD remains high2.
The function renal and evaluated for the filtration glomerular (FG) and the your decrease and observed in CKD, associated with the loss of regulatory, excretory and endocrine functions of the kidney. When GFR reaches very low values, less than 15mL/min/1.73m2, what we call functional renal failure (FFR) is established, that is, the most advanced stage of the continuum of progressive functional loss observed in CKD3.
This loss of kidney function is slow, progressive and irreversible, causing the body to no longer be able to maintain metabolic and hydroelectrolytic balance4,5.
Despite recent advances in dialysis technology, solutes, and membranes6, patients in dialysis run one risk significantly increased of death premature due to the high risk of cardiovascular and infectious complications, often related to wasting7. This increased risk is closely linked to the underlying inflammatory processes that also play a crucial role in the progression of chronic kidney disease8.
The inverse relationship between glomerular filtration rate (GFR) and inflammation levels has recently been established. In the Chronic Renal Insufficiency study Cohort (CRIC), it was observed that inflammatory biomarkers, such as IL-1β , IL-1 receptor antagonist, IL-6, TNF-α, CRP and fibrinogen, showed inverse associations with measures of renal function and positive associations with albuminuria9. Different biomarkers of inflammation appear to have different predictive value in CKD10.
It is known what to the proportions of different components of the cells blood they are new inflammatory markers, which have good predictive value in the outcome of CKD, cardiovascular diseases, rheumatic diseases, among others, including the neutrophil/lymphocyte ratio (NLR)11-14, monocyte/lymphocyte ratio (MLR)15-18 and platelet/lymphocyte ratio (PLR)19-23.
Given the current socioeconomic scenario, it is crucial to seek biological markers that offer an advantageous cost-effectiveness ratio. As we explore the utility of markers extrapolated from other areas, the platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) have been increasingly used in renal patients. Specifically, they are employees as indicators of inflammation, damage endothelial and, more recently, as predictors of mortality24-26.
These markers are promising due to their ease of measurement, low cost and potential predictive value in renal patients. By analyzing the relationship between these parameters and clinical outcomes, healthcare professionals can obtain important information to guide patient management and follow-up, even in challenging socioeconomic contexts24-26.
In view of the above, the objective of this study was to evaluate the profile inflammatory, through the parameters neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte in patients with CKD on hemodialysis.
METHODS
Design of study
Analytical cross-sectional study , with a quantitative approach with hemodialysis patients.
Study location and period
The search he was developed node Hospital of the Kidneys from the city of River White, Acre, northern region of Brazil. The hospital come on consolidating its assistance to its patients in quality and safety with cutting-edge technology, including one of the most modern hemodynamic services on the market. With a complete structure, it serves a dozen specialties, as cardiology, oncology, neurosurgery, between others. The hospital account still with a highly modern ICU.
All the data collected were of month September of 2023.
Population of study and criteria of eligibility
The sample consisted of chronic renal patients on HD at the Hospital who were over 18 years old, of both sexes, who had not undergone transplants, who had been on hemodialysis for more than 6 months and who agreed to have access to their medical records containing biochemical tests. There are a total of 112 patients, divided into two daily shifts, Monday, fourth and Friday and other in the third, fifth and Saturday. THE first turn of each day starts at 7a.m. and ends to the 12:30 p.m. The second turn start to the 12hours and ends to the 6pm each turn with 30 patients.
Collect of data
To the collect of data, they were made collected laboratory monthly for the hospital and the data obtained by the machine of hemodialysis Fresenius Medical Care 4008S V10, always in the first week of each month and on the same days.
All data were collected in the month of September 2023. Sociodemographic data included: age, sex, income monthly, marital status and education. Clinical and hematologic data included neutrophil count (mm/3), lymphocytes (mm/3), monocytes (mm/3), platelets (mm/3). RNL, RML and RPL they were calculated dividing you neutrophil, monocyte and platelet per lymphocyte ratios, respectively.
For the inflammation score, NLR, RPL and RML values were used. According to the study of Liao et al.2, where determined you values of court of RNL, RPL and RML through of receiver operating characteristic (ROC) analyses, found that a NLR cutoff value of 4.56 had a sensitivity of 0.695 and a specificity of 0.602; a cutoff value of RML of 0.38 had sensitivity of 0.780 and specificity of 0.634; one value of RPL cutoff of 202 had a sensitivity of 0.559 and specificity of 0.509 to differentiate mortality put all to the causes, put quite of analysis ROC. From agreement with you values of ideal cutoffs, RNL, RML, and RPL were given 0 or 1 points, respectively. Then, the inflammation score was obtained by adding the scores of RNL, RPL, and RML.
Analysis of the data
All to the analysis they were carried out using the software R, version 4.2.2 (R Core Team, 2023).
The analysis sociodemographic of the patients hemodialysis with and without inflammation, were performed as to the aspects descriptive (frequency absolute and relative), the comparison between groups was performed using the chi-square test. 112 patients were analyzed, however, in function from the lack of information of some patients us aspects sociodemographic (variable), the size sample put variable he was changed, then the patient without information to the respective variable analyzed was excluded from the analysis.
Biomarker data: Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and Monocyte/Lymphocyte Ratio (RML) were analyzed put using boxplot , to check for symmetry and extreme values (outlier). In this analysis, a boxplot was first performed with all the data for each biomarker and then with the data from patients without inflammation and with inflammation separately, for the three biomarkers.
Student ‘s t-test was performed to verify whether patients without and with inflammation differed. For this purpose, for each marker, patients without and with inflammation were separated into independent samples. The data from patients without and with inflammation detected by each biomarker were compared separately using the Student ‘s t-test to the reference value of the biomarker (NLR = 4.56; RPL = 202; RML = 0.38). In this analysis, the sample mean is compared to the reference mean to verify whether there is a statistical difference between them . Before performing the Student ‘s t-test, the data underwent normality analyses using the Shapiro-Wilk test and equality of variances using the Levene test, with the aid of the byf.shapiro () and eveneTest () functions , respectively.
Aspects ethical and legal from the search
The study was approved with opinion number: 6,085,783 by the Research Ethics Committee. of Hospital of the Clinics of ACRE – HCA/FUNDACRE and followed all the recommendations of resolution no. 466/2012 of the National Health Council, which deals with research and testing on human beings. All participants signed the Free and Informed Consent Form.
RESULTS
It was observed what the gender no influence node process inflammatory us 3 biomarkers evaluated, no having difference statistically significant (p>0.05) between you patients with inflammation and without inflammation according to sex (table 1).
Table 1 : Description of sex of patients without inflammation and with inflammation of hospital of the Kidneys of the city of Rio Branco-Acre, for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Sex | Without inflammation | With inflammation | total | p-value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| Feminine | 29 | 42.65 | 7 | 28.00 | 36 | 0.29 |
| Masculine | 39 | 57.35 | 18 | 72.00 | 57 | |
| Relationship platelet/lymphocyte | ||||||
| Feminine | 27 | 40.30 | 9 | 34.62 | 36 | 0.79 |
| Masculine | 40 | 59.70 | 17 | 65.38 | 57 | |
| Relationship monocyte/lymphocyte | ||||||
| Feminine | 18 | 46.15 | 18 | 33.33 | 36 | 0.30 |
| Masculine | 21 | 53.84 | 36 | 66.67 | 57 | |
Source: authors
He was observed what the range age no influenced node process inflammatory of the patients (table 2). Thus, age was not shown to be a determining factor for the inflammatory process of hemodialysis patients (p>0.05).
Table 2 : Description from the range age of patients without inflammation and with inflammation, Hospital dos Rins in the city of Rio Branco-Acre, for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Age range (years) | Without inflammation | With inflammation | Total | p-value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| Until 60 years | 37 | 59.68 | 11 | 50 | 48 | 0.59 |
| Over 60 years | 25 | 40.32 | 11 | 50 | 36 | |
| Relationship platelet/lymphocyte | ||||||
| Until 60 years | 14 | 56 | 34 | 57.63 | 48 | 0.99 |
| Over 60 years | 11 | 44 | 25 | 42.37 | 36 | |
| Relationship monocyte/lymphocyte | ||||||
| Until 60 years | 24 | 51.06 | 24 | 64.86 | 48 | 0.29 |
| Over 60 years | 23 | 48.94 | 13 | 35.14 | 36 | |
Source: authors
In table 3, according to the data, the inflammatory process is independent of purchasing power and was not a fundamental factor for the onset of the clinical condition. When statistical analysis was performed, no difference was observed in this variable (p>0.05).
Table 3 : Description from the income of patients without inflammation and with inflammation, hospital of the Kidneys of the city of Rio Branco-Acre, for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Income | Without inflammation | With inflammation | Total | p-value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| Until 3 wages | 55 | 79,71 | 18 | 78,26 | 73 | 0,99 |
| Above 3 wages | 14 | 20,29 | 5 | 21,74 | 19 | |
| Relationship platelets/lymphocytes | ||||||
| Until 3 wages | 53 | 77,94 | 20 | 83,33 | 73 | 0,99 |
| Above of 3 wages | 15 | 22,06 | 4 | 16,67 | 19 | |
| Relationship monocyte/lymphocyte | ||||||
| Until 3 wages | 31 | 79,49 | 42 | 79,25 | 73 | 0,08 |
| Above of 3 wages | 8 | 20,51 | 11 | 20,76 | 19 | |
Source: authors
You patients with inflammation and without inflammation they were analyzed and separated put shifts, morning and afternoon. Regardless of the circadian cycle and hormonal production, both the morning and afternoon shifts did not influence (p>0.05) the inflammatory process of hemodialysis patients (table 4).
Table 4 : Description of turn of service of patients without inflammation and with inflammation at the Kidney Hospital in the city of Rio Branco-Acre for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Shift of day | Without inflammation | With inflammation | total | p-value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| First | 31 | 58.49 | 10 | 52.63 | 41 | 0.86 |
| Second | 22 | 41.51 | 9 | 47.37 | 31 | |
| Relationship platelet/lymphocyte | ||||||
| First | 28 | 54.90 | 13 | 61.90 | 41 | 0.78 |
| Second | 23 | 45.10 | 8 | 38.10 | 31 | |
| Relationship monocyte/lymphocyte | ||||||
| First | 20 | 55.56 | 21 | 58.33 | 41 | 0.99 |
| Second | 16 | 44.44 | 15 | 41.67 | 31 | |
Source: authors
Table 5 illustrates the relationship between marital status and inflammation. It was observed that regardless of whether the patient had a stable emotional relationship, marital status did not statistically influence the inflammatory process (p>0.05).
Table 5 : Description of state civil of patients without inflammation and with inflammation, at the Kidney Hospital in the city of Rio Branco-Acre, for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Marital status | Without inflammation | With inflammation | total | p-value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| Married | 44 | 62.86 | 18 | 72.00 | 62 | 0.56 |
| Single | 26 | 37.14 | 7 | 28.00 | 33 | |
| Relationship platelet/lymphocyte | ||||||
| Married | 48 | 69.57 | 14 | 53.85 | 62 | 0.23 |
| Single | 21 | 30.43 | 12 | 46.15 | 33 | |
| Relationship monocyte/lymphocyte | ||||||
| Married | 28 | 70.00 | 34 | 61.82 | 62 | 0.54 |
| Single | 12 | 30.00 | 21 | 38.18 | 33 | |
Source: authors
Regarding education (table 6), it was evident that regardless of whether the patient had higher education or not, this was not statistically significant for the inflammatory process (p>0.05).
Table 6 : Description from the education of patients without inflammation and with inflammation, at the Kidney Hospital in the city of Rio Branco-Acre, for the biomarkers neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and monocyte/lymphocyte ratio
| Education | Without inflammation | With inflammation | Total | p- value | ||
|---|---|---|---|---|---|---|
| N | % | N | % | |||
| Relationship neutrophil/lymphocyte | ||||||
| With superior | 58 | 82.86 | 24 | 96.00 | 82 | 0.19 |
| Without superior | 12 | 17.14 | 1 | 4.00 | 13 | |
| Relationship platelet/lymphocyte | ||||||
| With superior | 59 | 85.51 | 23 | 88.46 | 82 | 0.97 |
| Without superior | 10 | 14.49 | 3 | 11.54 | 13 | |
| Relationship monocyte/lymphocyte | ||||||
| With superior | 35 | 87.50 | 47 | 85.45 | 82 | 0.99 |
| Without superior | 5 | 12.50 | 8 | 14.55 | 13 | |
Source: authors.
There was a statistical difference between the groups without inflammation and with inflammation in the biomarkers RNL (p = 2.632-9), RPL (p = 5.855-5) and RML (2.2-16) (Figures 1a, 1b and 1c). The results from RNL and RPL showed that there were, respectively, 1 and 3 patients with a very high degree of inflammation, compared to other patients with inflammation (figures 1a and 1b).
Source: authors.
Figure 1 : Comparison between groups without inflammation and with inflammation, identified regarding Neutrophil/Lymphocyte Ratio (NLR) (a), Platelet/Lymphocyte Ratio (PLR) (b) and Monocyte/Lymphocyte Ratio (MLR) (c) of patients at the Kidney Hospital in the city of Rio Branco- Acre
To verify the consistency of the diagnosis, patients in the inflamed and non-inflamed groups had their parameters compared to the biomarker reference values (table 7). It was observed that the 2 groups differed statistically in the 3 biomarkers (p<0.05). of value of reference, the exception of the patients with inflammation, what node marker RPL did not differ from the reference value.
Table 7 : Averages of patients without and with inflammation compared the values of reference of the biomarkers neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR)
| Group | Biomarkers | |||||
|---|---|---|---|---|---|---|
| RNL | p-value | RPL | p-value | RML | p-value | |
| No inflammation | 2.76 | 2.2 -16* | 181.02 | 1.215 -9* | 0.28 | 8,277 -13* |
| With inflammation | 6.76 | 4.776 -5* | 189.22 | 0.272 | 0.61 | 2.52 -11* |
| Reference value | 4.56 | - | 202 | - | 0.38 | - |
* Indicates difference significant between each group (without inflammation and with inflammation) with the value of reference at 5% probability by Student’s t-test. The lack of asterisk indicates absence of statistical difference between each group (without inflammation and with inflammation) with the value reference, considering an alpha of 5% probability by the Student’s t-test. Source: authors.
DISCUSSION
The results of this study together provide important elements regarding the usefulness of hematologic biomarkers in identifying inflammatory processes in patients undergoing hemodialysis. Although the sociodemographic analysis did not reveal statistically significant differences in the distribution of the biomarkers analyzed, the comparison between patients with and without inflammation, using reference values, highlighted significant nuances. In particular, the platelet/lymphocyte ratio (PLR) in patients with inflammation did not differ from reference values, suggesting that this biomarker, in isolation, he can no to be enough to detect inflammation in that group. Nonetheless, When the biomarkers were evaluated individually, a statistically significant relationship was observed between inflammation and the other markers, reinforcing the need for an integrated and multifactorial approach for a more accurate diagnosis of inflammation in hemodialysis patients.
THE age advanced and one factor of risk to the DRC, the Society Brazilian of Nephrology developed the Census Brazilian of Dialysis in 2012, performing one stratification of those who undergo renal replacement therapy and it was found that the vast majority of patients (63.6%) they were in the range age of 19 the 64 years. In our study, 57.15% of the patients were aged up to 60 years and 42.85% were aged higher than 60 years27. In study by Da Cunha et al., 54.89% of patients were over 60 years old and 45.12% were under 60 years old28.
The realization that no there was statistically significant difference between age groups in relation to the inflammatory process suggests that the impact of age may not be an aggravating factor in this specific pathological process for the population studied.
The socioeconomic situation of hemodialysis patients, as well as their families, is a factor to be considered as it can be decisive in the quality and continuity of treatment. failure renal chronic. There is of if consider what such fact he can come the influence on access to medicines not provided by the Unified Health System, which favors the appearance of complications that aggravate the progression of kidney disease29.
A study carried out with people undergoing hemodialysis found that most of them no work then no present conditions physical to carry out activity labor30,31. In our study, 79.35% of patients receive up to 3 minimum wages per month, and only 20.65% receive more than 3 minimum wages per month. Corroborating our studies, NR de Vargas et al., reported that in their research, hemodialysis patients who received up to 3 minimum wages represented 80.8% of patients, while 15.4% received up to 3 minimum wages and 3.8% did not report their monthly income32.
Those results highlight the complexity of the interactions between factors socioeconomic factors and health. While financial status may influence access to health care resources, it is important to recognize that other factors, such as lifestyle, genetics, and quality of medical treatment, also play significant roles in regulating the inflammatory profile.
So while financial status is a crucial consideration, it is equally important to assess and address these other factors that may impact patients’ inflammatory status. This more comprehensive approach may provide more accurate insights. on to the influences multiple and interconnected in the health and to help the guide more effective intervention and treatment strategies.
Regarding the shift in which hemodialysis is carried out, there appears to be a divergence in the literature regarding the benefits and challenges associated with different hemodialysis shifts. While some studies suggest that hemodialysis in the morning shift is associated with better sleep quality, increased survival and lower prevalence of insomnia, others studies point to one bad quality of sleep subjective and high prevalence of depression between you patients submitted the hemodialysis node turn from the morning, with one potentially better sleep quality in night shift patients33-35.
These discrepancies may be attributed to a variety of factors, including differences in study methodology, patient demographic and clinical characteristics, and of variations us protocols of treatment of hemodialysis in different centers physicians. For example, age, comorbidities, duration of hemodialysis, quality of treatment and individual adaptation to the schedule may influence the results33-35.
Despite the discrepancies found in the literature regarding the different hemodialysis shifts and their potential effects on patients’ quality of life and sleep, it is important to highlight that in relation to the inflammatory process, we did not find statistically significant differences between the different shifts.
When analyzing marital status, positive marital quality is generally associated with lower low-grade chronic inflammation, but not everyone benefits equally from spousal support36.
Factors such as perceived quality of relationship, the effectiveness of the support received and the individual characteristics of the partners can influence the magnitude of the impact of the support conjugal in the health. Put example, in some cases, same in relationships positive, can exist stressors external or internal what mitigate you benefits of support conjugal in reducing chronic inflammation36.
Additionally, individuals in negative or conflictual relationships may experience an increase in chronic inflammation due to stress and lack of emotional support. Therefore, while the quality conjugal positive he can be a factor protector against chronic inflammation for many, it is important to recognize that the effects may vary according to a number of contextual and individual factors36.
Spousal support plays a crucial role in couples’ relationships, but its implications to the health they can to be varied. Second Wilson SJ and al., influenced by prejudice of assignment and by the theories of aging, conclude what both the age as for satisfaction conjugal play papers important in the relations between the support conjugal and biomarkers of healthy aging37.
This suggests that the quality of relationship and the age of partners may interact in complex ways to influence how spousal support affects aging processes. He can be one association more strong between the support conjugal and biomarkers of healthy aging in older couples or in couples with higher levels of marital satisfaction37. However, in our study, it was found that there was no difference in the process inflammatory in relationship to the state civil, those results suggest what, although the marital support may have positive health implications with regard to the inflammatory process evaluated by the biomarkers in our study, the state civil of the patients does not appear to be a determining factor.
Node level of education, Boylan JM et al., examined multiple aspects from the experience and expression from the anger (frequency, expression external, suppression, control) as moderators of the association of social inequality measured by educational status with markers of inflammation, interleukin 6 and protein W reactive (IL-6 and PCR) and coagulation, where found that relationships inverse between education and markers of inflammation they were more strong between individuals with high anger and were attenuated among those with high anger control38.
Results distinct they were found in this study, indicating what others factors beyond the level educational they can perform one paper more significant in the regulation from the inflammatory response. Those factors they can include questions genetics, environmental, of style of life and even the quality of medical treatment received.
Inflammation is one of the central pathophysiological factors in kidney disease. In a review systematic, he was verified that you biomarkers inflammatory more used were TNF- α and IL-6, which they are biomarkers what no do part of blood count and exams of routines and need to be requested39, showing what you parameters evaluated in that work they can be useful in clinical practice and low cost.
Albarrán -Sánchez A, et al., report what you patients who passed away had diagnosed with hypertension for more years and presented significant differences in the blood count and acute phase reactants and an increase in NLR40.
Lu et al., evaluated 86 patients undergoing peritoneal dialysis (PD) for follow-up of 36 months to investigate the association between the RNL and markers of arterial stiffness. The results suggest that elevated NLR is independently associated with arterial stiffness and predicts cardiovascular and all-cause mortality in patients with PD41.
Kato A, et al., evaluated Glasgow Prognostic Score (standard and modified), NLR, PLR, Prognostic Index and Prognostic Nutritional Index, in long-term hemodialysis patients term and reported what all the markers (including RNL and RPL) were associated with higher total mortality rates42.
In a study published by Catabay et al., elevated NLR in incident hemodialysis patients predicted mortality, especially in the short term. NLR, but not PLR, added a modest benefit in predicting mortality along with demographics, comorbidities, and serum albumin, and should be included in prognostic approaches43. In our work, when verifying the diagnostic consistency of the 3 biomarkers, the RPL no differed of value of reference, or it is, with basis in that biomarker, patients might not be diagnosed as inflamed.
In the study by Erhan Tártaro, et al., where they investigated the association of the neutrophil/lymphocyte ratio and of the platelet/lymphocyte ratio with clinical outcomes in geriatric patients with chronic kidney disease (CKD), concluded that the neutrophil/lymphocyte ratio predicts all-cause mortality in geriatric patients with chronic kidney disease, however, the relationship platelets/lymphocytes no he was associated the death and the need of therapy renal replacement therapy independently44.
Liao et al., established an inflammation scoring system including NLR, MLR, and PLR and found that a higher inflammation score was independently associated with all-cause mortality in HD patients2.
Study limitations
Some patients did not provide complete information on sociodemographic variables, which may affect the analysis. Future studies could expand the sample size and explore other inflammatory biomarkers to validate the findings presented. In addition, longitudinal approaches could clarify the progression of inflammation in hemodialysis patients.
CONCLUSION
This study highlights the importance of hematologic biomarkers in detecting inflammation in hemodialysis patients. Although sociodemographic analysis did not show differences significant us biomarkers, the comparison between patients with and without inflammation revealed important points. The relationship platelet/lymphocyte ratio (PLR) in patients with inflammation was similar to reference values, suggesting that this biomarker alone may not be sufficient to detect inflammation. However, other markers showed a significant association with inflammation, reinforcing the importance of an integrated approach for a more accurate diagnosis.
