Prospective analysis of the impact of Chronic Kidney Disease on patients and caregivers

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INTRODUCTION
Chronic kidney disease (CKD), which consists of progressive and irreversible damage to the kidneys 1 , is currently considered a global public health challenge [2][3][4] due to its high incidence and prevalence 5,6 and the high financial cost of renal replacement therapies (RRTs), especially for public health systems 7 .In addition to costs, there is a human burden, as CKD is associated with high levels of morbidity, mortality and chronic disability 8,9 .
CKD in the predialysis phase, especially when there is a need for RRT, causes significant changes in the lives of patients, for example, changes in eating patterns because of dietary restrictions, especially water restrictions.Physical capacity is limited, and very often, it is impossible for patients to maintain their work activities.Disruptions in relationships and reductions in social bonds are also common 10 .In this context, the impacts on the mental health and quality of life (QoL) [11][12][13][14] of patients who present depressive [15][16][17][18][19][20] , anxiety 21,22 , and stress 23 symptoms and physical and mental manifestations, for example, fatigue 24- 26 , is notable.Clinical complications may also occur during treatment, and these complications are related to worse QoL and mental health conditions 27 .
Patients with CKD, especially those with greater limitations, require assistance in treatment and activities of daily living, and for these patients, there is usually a family member who assumes the role of caregiver 28 , i.e., responsible for providing care and directly involved in the CKD treatment or daily activities of the patient.Caregivers also suffer from various impacts on mental health 29,[30][31][32][33] , and among this group, high levels of anxiety, depression [34][35][36][37] , and stress and reductions in QoL are observed 38 .The overlapping responsibilities of caregivers, who often add the care provided to the patient to their daily life and work routine, can lead to overload and symptoms of fatigue and can have impacts on the ability to perform daily activities.In addition, the various aspects of caregivers' mental health may worsen over time and with the increase in the intensity of care provided 39 .
CKD has a substantial impact on the mental health of patients and their caregivers, leading to the need for social support and comprehensive care for patients and caregivers so that researchers and clinicians can understand these various impacts and design strategies to improve the QoL of these patients 40 .To our knowledge, there has been no evaluation of this complex context with regard to patients with CKD, but there have been studies that separately investigate aspects of mental health [41][42][43][44][45][46][47][48][49] .The objective of evaluating the association between the mental health of caregivers and CKD patients on dialysis.

Variables analysed
The following patient-related variables were analysed: sociodemographic data (age, sex, race (self-declaration), income, education, marital status (according to IBGE) and religion).The following clinical data were analysed: CKD aetiology, comorbidities.These data were obtained from the medical records of the included patients.
The following caregiver-related data were analysed: sociodemographic data (age, sex, race (self-declaration), income, education, marital status (according to IBGE) and religion).
Psychological variables were analysed.The variables associated with the psychological assessment applied to caregivers and patients are presented in Table 1.The surveys were administered to patients on haemodialysis (HD) during dialysis sessions.For patients treated with peritoneal dialysis (PD), the surveys were administered at the PD outpatient clinic when each patient arrived for their medical appointments.For caregivers, interviews took place at the outpatient clinic during patient consultations or when sitting in the waiting room.
Sociodemographic, clinical and psychological variables data were collected at baseline (T0) and four years later (T1) and clinical outcomes, death and loss to follow-up were collected at T1. Psychologist, nonanonymous instrument.Hospital Anxiety and Depression Scale (HADS) 14-item scale (7 for HADS-A and 7 for HADS-D) used to assess the presence of symptoms of anxiety and depression, scored using a Likert scale.Each item is scored from zero to three.The maximum score is 21 points for each scale.The cut-off point for the presence of symptoms is a score ≥9 50 .
Perceived Social Support Scale (PSSS) 29-item instrument that evaluates the social support perceived by the respondent; each item is scored from 1 to 4. The scale evaluates social support in two dimensions: practical and emotional 51 .

Fatigue Pictogram
Illustrated instrument for evaluating fatigue; two sets of figures are used to evaluate the intensity and impact of fatigue in usual activities.Two questions and figures are presented on an ordinal scale with five graduated and captioned illustrations that assess the intensity and impact of fatigue.This evaluation does not have a cut-off point for the diagnosis or classification of fatigue intensity, as it is easier for participants to interpret and provides information that can be interpreted in an ordinal way 52 .

Lipp Stress Symptom Inventory (LSI)
A self-report instrument to identify the presence of stress symptoms, the type of symptoms (somatic or psychological predominance) and the stage (alertness, resistance, near exhaustion and exhaustion) 53 .
Quality of Life Questionnaire (SF-36) Short version of the Medical Outcomes Trust questionnaire that assesses various domains of QoL.
Scores range from 0 to 100, with scores closer to zero indicating poorer quality of life and scores closer to 100 indicating better quality of life 54 .

Statistical analysis
The sociodemographic data and questionnaire data are presented as the mean±standard deviation, median (interquartile range), percentage or frequency on the basis of the characteristics of the data.Subsequently, patients who were still being followed up and those who died were separated into two groups, and depression, quality of life, stress and fatigue and the clinical and laboratory variables of the patients at T0 were compared between the groups using paired Student's t test, the Wilcoxon test or the chi-square test.Sequently, these same variables were compared between T0 and T1 for patients, between T0 and T1 for caregivers and between patients and caregivers at T1.A confidence interval of 95% was considered.The statistical software SPSS 17.0 was used for all analyses.

RESULTS
Convenience sampling was used to recruit patients receiving treatment at the RRT service of UH/UFJF.Over three shifts, patients were approached randomly and individually during treatment or while waiting for RRT and offered the opportunity to participate in the study.Figure 1 shows the study flowchart.As seen in Table 3, when comparing T0 vs. T1 for the patients, there was a decrease in anxiety (p=0.028) and psychological symptoms of stress (0.001), and a tendency towards improvements in social aspects within the QoL score (p=0.08).Regarding caregivers (Table 4), when comparing T0 vs.
T1, there was a decrease in anxiety (p=0.017), a trend towards an increase in emotional social support (p=0.08), a decrease in physical (p=0.051), and psychological stress (p=0.02) and tendency towards an increase in vitality within the QoL score (p=0.093).
In Figures 2 and 3, after four years of follow-up (T1), patients and caregivers presented very similar scores without significant differences.T1: second stage of the study, after a 4-year follow-up, with the second stage of data collection; All other aspects described in the figure (functional capacity, physical aspects, pain, general health status, vitality, social aspects, emotional aspects and mental health) refer to the various aspects of quality of life that were assessed using the SF-36 quality of life questionnaire.There were seven deaths during the follow-up period.
Comparing survivors vs. deaths (Table 5), patients who had higher levels of physical symptoms of stress at T0 had lower mortality (p=0.09).

DISCUSSION
The results of this study indicated that the mental health of caregivers and patients was impacted by CKD and, notably, that the variables evaluated were not different between these two groups at the end of four years, indicating overload resulting from the disease for both groups.The main limitation of our study is the decrease in the sample size; however, in prospective studies of populations with a mortality rate of approximately 20% per year, this decrease was expected 55 .The most relevant aspect of the study is the broad assessment of the mental health of the patientcaregiver dyad.
The age range for patients in this study was similar to that for patients on dialysis in Brazil 56 ; however, the majority of patients in this study were female, a finding that is inconsistent with the literature, with most patients on dialysis being male.Additionally, in agreement to data from the Brazilian Society of Nephrology (SBN), most patients undergo HD as RRT 55 .The socioeconomic profile also reflects the Brazilian reality, i.e., patients with low education levels and most without jobs (retired).The aetiologies of CKD and the most prevalent comorbidities identified herein are consistent with those observed in Brazil [55][56][57][58] .Regarding caregivers, the majority were women, a finding that is consistent with the literature, with close kinship and a significant percentage maintaining their work activities [59][60][61][62] .
While the majority of patients declared themselves black, the majority of caregivers declared themselves white.This data may be due to self-declaration of color and/or miscegenation that means that the caregiver and the patient do not have the same perception of skin color.We emphasize that it is about color and not race or ancestry.
Interestingly, in this study, for patients, there was a decrease in anxiety and psychological symptoms of stress over time as well as a tendency towards improvements in the social aspects of QoL.Regarding improvements in the aforementioned aspects and patients' ability to adapt, there are several factors that impact patient coping, such as patients' perception of their own disease 63 , beliefs, emotions and behaviours 63 , coping style 64 , religious coping 65 , and spirituality 66 .A previous study showed that lower psychological resilience, lower education and greater cognitive distortions are factors associated with depression and anxiety in patients with CKD 67 .Other recent studies have indicated that patients go through several phases of adaptation, that the resilience potential of patients is related to perceived stress 68 and that perceived stress, general QoL and QoL subcomponents are related to the resilience profile of patients with CKD 69 .Thus, interdisciplinary teams should develop specific interventions to build resilience in patients with CKD, aiming to facilitate their adaptation to treatment and positively impact their lives in general.It is essential to fully recognize the emotional demands of patients 70 .A space for listening 71 and psychological reception for each patient should be ensured.
For the caregivers, after four years, there was also a decrease in anxiety, a tendency towards an increase in emotional social support, a decrease in physical and psychological stress and a trend towards an increase in vitality within QoL.
Several factors are associated with the presence of anxiety and depression in caregivers, including close kinship with the patient, increasing age of the caregiver, low education level, being retired, having children and poor financial conditions 72 .Most of these risk factors were present in the profile of the participants in this study.The decrease in the levels of anxiety and stress in the caregivers in this study may reflect a coping strategy for adapting to conditions of care.The increase in emotional social support in caregivers reinforces that the role of caregiver is often assumed by a family member; however, care is not limited to that person.Informal support networks include other family members as well as friends, neighbours and people from the community who are linked to the patient [73][74][75] .The support offered can be objective, practical or instrumental depending on the task, such as helping with medication, monitoring appointments and procedures, and providing financial aid.Support can also be emotional, addressing emotional aspects of the patient in times of crisis.Thus, there are several ways of expressing support that relate to the health of the patient attended 75 .This better social support may foster caregivers' greater adaptation to the care required.
Interestingly, after four years, there were no statistically significant differences between patients and caregivers, with no overall improvement in patients and a worsening of scores for caregivers.Our research shows that caregivers, despite all the impacts suffered, maintain daily activities and their formal employment, beyond patient care, suggesting overload.Caregiver burden in the context of nephrology, especially in dialysis treatment 76 .
The mental health of caregivers impacts patient support 77 , and this support is related to adherence to treatment 78 and patient health outcomes 79 .
Assessing the conditions associated with mortality, only age was a predictor in the bivariate analysis, a finding that is expected in studies evaluating survival.Although the small sample size makes this analysis difficult to interpret.This finding is not corroborated by study that reported that QoL was an independent predictor of mortality in PD patients 80 .
Additionally, a recent review indicated that several studies associate mental health and mortality in patients with CKD on RRT 81 .Despite the difficult prognosis, social and family support offered to patients is essential for maintaining their health and clinical care.Multidisciplinary teams in nephrology must determine and, if needed, intervene in the social and family support network of patients with CKD to improve the care offered to patients and promote positive impacts on their physical and mental health and QoL, with the expectation of positive effects leading to greater survival 50 .This context highlights the need for mental health diagnosis and interventions for patients with CKD and their family caregivers in the prevention of illness and promotion of health, quality of life and well-being 82 , encompassing various health factors such as the provision of adequate social, economic, physical and psychological support for this population 83,84 .Psychological interventions are strongly indicated for this population 85,86 .

CONCLUSION
The evaluation of mental health beyond QOL score, with a broader assessment of this complex context, that is, patients with CKD on dialysis, is necessary, and clinics that provide dialysis treatment to these patients should offer a multiprofessional team with psychologists, social workers and professionals already involved in direct care, such as physicians, nurses and nutritionists, to improve the quality of life of patients and caregivers, and reduce the burden on caregivers of these patients.

Sample
This prospective cohort study was conducted at University Hospital of the Federal University of Juiz de Fora (HU/CAS -UFJF) in the city of Juiz de Fora during the period from 2015 to 2019.The RRT service of HU/UFJF follows the norms of Federal Collegiate Directive Resolution (RDC) number 11 of 2014, providing treatment through a multidisciplinary team of physicians, nurses, social workers, nutritionists and psychologists.As such, patients received psychological interventions, if needed, during the follow-up.The study design was observational, and no interventions other than those considered routine were performed.The inclusion criteria were: aged over 18 years, of both sexes, and patients with CKD with a family caregiver, who had been on RRT for at least six months and who agreed to participate in the study by signing an informed consent form (ICF). Caregivers named by the patients were included.The noninclusion criteria were individuals who demonstrated difficulty in understanding the questionnaires and individuals whose medical records indicated severe cognitive impairment.The study was reviewed by the Research Ethics Committee (CEP) of HU/UFJF and initiated after its approval under number 2,592,113, following the precepts of Resolution 196 of 1996 (MS, CNS 196/96).

Figure 3 .
Figure 3.Comparison of quality of life between patients and caregivers after four years of follow-up (T1).

Table 1 .
Descriptive list of the psychological instruments used in this study.

Table 2 .
Sociodemographic and clinical data of the study population at T0 and T1.

Table 3 .
Comparison of anxiety and depression, fatigue, stress and quality of life between patients at T0 (n=21) vs. T1 (n=14).
T1: second stage of the study, after a 4-year follow-up, with the second stage of data collection; HADS-A: questions used to assess symptoms of anxiety in the Hospital Anxiety and Depression Scale; HADS-D: questions used to assess symptoms of depression in the Hospital Anxiety and Depression Scale; SS Practical: practical social support aspects of the Perceived Social Support Scale; SS Emotional: emotional social support aspects of the Perceived Social Support Scale; Fatigue: fatigue rated using the Fatigue Pictogram; Limitations due to Fatigue: limitations in daily activities caused by fatigue, as rated using the Fatigue Pictogram; Physical stress: physical component of stress assessed using the Lipp Stress Inventory; Psychological Stress: emotional component of stress assessed using the Lipp Stress Inventory.

Table 5 .
Comparison of sociodemographic and clinical data, anxiety and depression, fatigue, stress and quality of life at T0 between patients who lived through the followup period and those who died (T test, chi-square).Hospital Anxiety and Depression Scale corresponding to the evaluation of anxiety symptoms; ** Hospital Anxiety and Depression Scale corresponding to the evaluation of depressive symptoms; *** Perceived Practical Social Support Scale.**** Perceived Social Emotional Support Scale; ***** Lipp Stress Symptom Inventory; ***** Quality of Life Questionnaire.