The Use of Complementary and Alternative Medicine among Peritoneal Dialysis Patients at a Second-Level Hospital in Yucatán Mexico

Background: Complementary and alternative medicine (CAM) is widely used for multiple reasons such as treatment of diseases and their symptoms, empowerment, self-care, disease prevention, dissatisfaction, adverse effects or cost of conventional medicine, perception of compatibility with beliefs, and idiosyncrasy. This study investigated CAM use in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD). Methods: A cross-sectional survey study was conducted with 240 eligible patients with CKD in the PD program. By applying the I-CAM-Q-questionnaire, the frequency, level of satisfaction, and reasons for CAM use were explored, and the demographic and clinical data of users and non-users were analyzed. Data analysis included descriptive analysis, Student’s t-test, Mann-Whitney U, chi-square, and Fisher tests. Results: The main types of CAM used were herbal medicine, and chamomile was the most commonly used. To improve the state of well-being was the main reason for use, the attributable benefit of CAM was high, and only a low percentage of users reported side effects. Only 31.8% of the users informed their physicians. Conclusion: The use of CAM is popular among renal patients, and physicians are not adequately informed; in particular, the CAM type ingested represents a risk for drug interactions and toxicity.


Introduction
Chronic kidney disease (CKD) is a condition that leads to disability, decreased quality of life, and substantial social and financial costs. It is now recognized as a global public health priority that has reached epidemic proportions worldwide, with a consequent impact on morbidity and mortality and cost to the health system. In 2017, the global prevalence of CKD was 9.1%, and in 2019, the Pan American Health Organization estimated that it is a leading cause of disease burden, categorized as the 8th cause of mortality and the 10th cause of years of life lost in both sexes [1,2].
CKD is more prevalent in people with obesity, hypertension, and/or diabetes mellitus as well as elderly people, women, and racial minorities and is expected to increase, including the stage with the requirement of a renal replacement therapy, namely peritoneal dialysis (PD) [3,4].
Approximately 80% of the world's population uses complementary and alternative medicine (CAM) to maintain their health [5,6]. The use of CAM by the population has experienced significant growth in the last 15 years, with consequent medical, economic, and sociological impacts; this increase is especially evident in individuals with chronic diseases. Patients mention using it for multiple reasons, such as for the treatment of diseases and appointment follow-up, the patients were interviewed face-to-face by two researchers. The study was conducted at the Dialysis Clinic in the Regional pital "Ignacio García Téllez" of the Instituto Mexicano del Seguro Social (IM level hospital located in Mérida Yucatán, Mexico, from November to Decem

Study Population
A total of 319 patients from the PD program of the Ignacio García T were invited to participate in this study (n = 319). The inclusion criteria wer than 18 years, with at least one clinical evaluation by a nephrologist of the within the last two months, and who agreed to participate with verbal a questionnaire by interview. The exclusion criteria were as follows: renal tr <18 years old, refusal to participate, undergoing hemodialysis, deceased du period, and did not attend the appointment.

Sample Size
The sample size for survey was estimated using an 18% anticipated pre of CAM for dialysis patients [24], and with a 95% level of confidence and a error, the estimated sample size was 227 (Epi Info v. 7.2 CDC, Atlanta, G final sample was comprised of 240 PD patients from our hospital ( Figure 1)

Research Instrument
The data were collected by a questionnaire previously reported and known as I-CAM-Q (the International Complementary and Alternat The total of patients of the program of PD n = 319 Participants n = 240 sample calculated= 227 Patients excluded: Did not attend the appointment (44) Death (22) Hemodialysis user (6) Under-age (3) Refused to participate (3) Renal Transplant (1) Figure 1. The study population selection. PD, peritoneal dialysis.

Research Instrument
The data were collected by a questionnaire previously reported and validated and known as I-CAM-Q (the International Complementary and Alternative Medicine Questionnaire), which includes four parts: (a) examination by health provider, (b) complementary treatments, (c) use of herbal medicine and dietary supplements, and (d) self-help practices [25,26] (Supplementary Materials).

Clinical Characteristics and Biochemical Parameters of Patients
The clinical characteristics of patients were obtained during the medical appointment by clinical exploration. The biochemical parameters of the patients were obtained from their clinical appointment and corresponded to previous bimonthly medical appointments. After at least 12 h fasting, venous blood samples were collected to measure the complete blood count and various biochemical components (glucose, creatinine, urea, uric acid, albumin, calcium, phosphorus, and potassium).

Ethics
The project was approved by the local committee of Investigation and Ethic 3201 of Regional General Hospital Ignacio García Tellez IMSS (registered number R-2018-3201-26). The participants were given information about the aim of the study and the content of the questionnaire. Informed consent was obtained from all patients before confirming their participation in this investigation.

Data Analysis
Continuous variables are expressed as arithmetic mean ±1 standard deviation (±1SD), and categorical variables are presented as frequencies and percentages. For comparison and analysis, the study population was divided into two groups: CAM users and non-CAM users. Continuous variables were analyzed using the Student's t-test or Mann-Whitney's U test depending on the normality distribution of the data, while the categorical variables of the two groups were analyzed using the chi-square test or Fisher's exact test. Differences were considered statistically significant at p-value < 0.05.

Use of CAM
The sociodemographic characteristics of patients are shown in Table 1. The frequency of CAM use in the study population was 55.0% (132/240), of which 50.8% (67/132) were male and 49.2% (65/132) women. No statistically significant differences were observed between the sociodemographic characteristics of the CAM users and non-users (Table 1).
Most of our study population (65.1%; 86/132) referred to using only one type of CAM, while 34.8% (46/132) of patients used more than one CAM in combination; the majority of them used two types of CAM (67.4%; 31/46), followed by three (28.3%; 13/46). The most frequent combination of CAM was herbal medicine and music therapy, followed by herbal medicine and spiritual healing. The distribution of the combinations of CAM types used by the study population is shown in Figure 2.

Perception of Benefit of Using CAM
Regarding the question the benefits attributed to the use of CAM, of the responses, the majority indicated its use was very beneficial (73.3%; 135/184). This

Adverse Effects and Starting Time of CAM Use
Overall, 97.0% (128/132) of CAM users stated that their use did not cause side effe while the remaining 3% (4/132) reported secondary effects on gastrointestinal tract (2 and nervous system (2/4). Regarding the start time of their utilization of CAM, 54 (72/132) of patients noted prior use, and 45.5% (60/132) began use after starting treatm with peritoneal dialysis.

Clinical Characteristics and Biochemical Parameters of Patients
The duration of PD therapy in the participating patients ranged from 1 to 168 mon with a mean of 27.4 months (±27.6), and no statistically significant difference was obser between the months of PD and CAM use or not (p = 0.412). The average volume of resid uresis in our study population ranged from 0 to 3000 mL, with a mean of 649 mL (±5 and no statistically significant difference was observed between the volume of resid uresis and the CAM users or non-users of CAM (p = 0.447).

Adverse Effects and Starting Time of CAM Use
Overall, 97.0% (128/132) of CAM users stated that their use did not cause side effects, while the remaining 3% (4/132) reported secondary effects on gastrointestinal tract (2/4) and nervous system (2/4). Regarding the start time of their utilization of CAM, 54.5% (72/132) of patients noted prior use, and 45.5% (60/132) began use after starting treatment with peritoneal dialysis.

Inform the Use of CAM to Medical Doctor
Only 31.8% (42/132) of CAM users reported to their doctors about use of CAM. The remaining 68.2% (90/132) of the users did not report it for the following reasons: (a) the doctor did not ask (72.2%, 65/90), (b) the patients did not consider it necessary (20.0%; 18/90), (c) the patients did not provide information for fear of disapproval (6.7%; 6/90), and (d) the patients did not have medical assistance at the time they used CAM (1.1%; 1/90).

Clinical Characteristics and Biochemical Parameters of Patients
The duration of PD therapy in the participating patients ranged from 1 to 168 months, with a mean of 27.4 months (±27.6), and no statistically significant difference was observed between the months of PD and CAM use or not (p = 0.412). The average volume of residual uresis in our study population ranged from 0 to 3000 mL, with a mean of 649 mL (±564), and no statistically significant difference was observed between the volume of residual uresis and the CAM users or non-users of CAM (p = 0.447).
Tables 4 and 5 display the clinical characteristics and biochemical parameters of CAM users and non-users, respectively. We did not find significant differences in clinical and biochemical characteristics between the two groups; only the diastolic pressure was significant significantly higher in CAM users (Table 5). On the other hand, most of the patients were overweight (44.2%; 106/240) or obese (26.3%; 63/240). According to levels of albumin and BMI, 72.9% (175/240) had adequate nutritional status. Further, 60% of patients (144/240) had a Karnosfsky index higher than 80 points, which suggests that they were able to independently carry out daily activities. The main etiology of CKD reported was diabetic nephropathy (62.5%; 150/240), and the patients had between two and seven comorbidities.

Discussion
The use of CAM has increased in recent decades, mainly for the prevention and management of chronic diseases and the well-being needs of the older population.
In recent years, the WHO has implemented a strategy for integration, validation, and safety to harness the potential contribution of CAM to health, wellness, and people-centered health care [27]. In Mexico, native peoples have a wide tradition of CAM use. However, studies on CAM use in chronic diseases are scarce. Our study explored the prevalence of CAM use in patients with CKD treated with PD, the types and reasons for its usage, the perception of its benefit, and its adverse effects.
Fifty-five percent of our study population was identified to be using CAM therapy; this finding was similar to the reports of a study in a German population, where 57% of dialysis patients reported to be regular CAM consumers [28]. Studies in a Turkish (72.5%) [29] population showed high frequencies of CAM use; on the other hand, studies in American (18.0%) [24] patients reported lower frequencies. The use of CAM can vary by diverse demographic factors such as age, sex, educational status, socioeconomic status, and occupational status [30]; however, in our study, none of the demographic factors analyzed had a significant influence on CAM. Women are more likely to use CAM than men [31], but we did not find a sex effect on CAM use for CKD in our study. However, studies in patients with kidney disease showed that both men and women are likely to use CAM; in studies in Egyptian [32] and Indian [33] patients, men were more likely to use CAM, whereas studies in Saudi patients showed that women are more likely [34]. Regarding the activity of our patients that identified as CAM users, 24% were housewives, followed by retirees (17.5%), patients with only primary education, and patients with medium-low (21.3%) and medium (22.1%) socioeconomic levels.
Medicinal plants are part of the therapeutic resources of traditional pre-Hispanic medicine in Mexico, and these are culturally and historically popular [35], so it is not unusual for herbal medicine (50.0%) to be the most common type of CAM used by patients. Similar findings were reported in American (67.8%) [24] and Turkish (76.9%) [29] patients; however, it differs from that reported in German patients, whose most common type of CAM was mineral supplements [28]. Occasionally, factors such as culture, history, idiosyncrasies, and beliefs influence the use of different CAM types [36]. On the other hand, 34.8% (46/132) of our patients employed more than one type of CAM-even up to six CAM; in German patients, 27.0% employed more than one CAM, and patients reported using up to five CAM.
Herbal medicines can include a variety of potentially hepatotoxic compounds: (a) natural products such as volatile compounds, glycosides, terpenoids, alkaloids, anthraquinones, phenolics compounds, and other toxins; (b) contaminants or adulterants such as metals, mycotoxins, and pesticides; and herbicidal residues, and their mechanism to induce hepatotoxicity remains mostly imprecise in many cases [37]. In addition, herbal medicines can carry a variety of nephrotoxic compounds such as organic acids, alkaloids, terpenes, lactones, saponins, indeed minerals, and toxic proteins [38]. The use of herbal medicines by CKD patients is especially detrimental because of hepatotoxicity and nephrotoxicity, hemodynamic changes, electrolyte abnormalities, and effects on blood pressure, blood glucose, and coagulation parameters [29,30]. With the increasing of use of herbal medicines, there is a need to monitor and study their safety, especially in patients with CKD. In fact, the WHO recommends including the herbal medicine pharmacovigilance systems [39]. Chamomile (25.8%, 25/97) and moringa leaves (16.0%, 15/97) were the most common herbs used by patients, and various studies have shown the beneficial effects and low side effects of both plants [40,41].
Improving well-being (71.7%; 132/184) was the most frequent reason for using CAM in this study, unlike American patients, who use CAM to improve their energy and concentration [24], and German and Turkish patients, who use it to strengthen their immune system [28,29]. The majority of CAM (73.3%; 135/184) referred to by patients was considered as beneficial, which is similar to the report by Duncan et al. in American patients (77.8%) [24] but less so in Turkish patients (95.5%) [29]. With respect to side effects, 95.4% (126/132) of CAM users did not present adverse effects; however, in a Turkish study, a smaller number of patients (77.3%) did not experience side effects of CAM, probably due to the fact that Turkish patients used more herbal plants, or the plants employed by the patients had undesirable effects [29].
In our study, similar to that reported by Uzdil and Kılıç, the majority of people who recommended CAM were family members and friends. In addition, this investigation reported that 81.6% of patients recommended CAM to another person [29].
A low number of patients (31.8%; 42/132) informed their physicians about CAM consumption compared to German (59%) [28] and American (36.8%) [24] patients. Physicians not asking patients about the use of CAM was the main reason for patients not informing physicians, which reflects the poor interest of medical doctors in the use of CAM. This interest needs to be improved because, as shown before, herbal plants are the most common type of CAM referred by patients, and CKD patients use many drugs for different complications at the same time, and interactions between drugs and herbs may mimic, decrease, or increase the action of prescribed drugs [30,42]. Improving patient-physician communication is essential for positive health outcomes. The lack of adequate discussion about CAM use raises the risk of adverse effects, including interactions with conventional treatments, which could be related to social perceptions [22,43].
All patients included in the study had clinical and biochemical characteristics; previous studies in the literature did not consider these parameters; therefore, we considered these as contributions. Most participants were overweight or obese, and increasing evidence suggests that obesity is a risk factor for diabetes and CKD, and high BMI has been reported to be related to diabetic nephropathy [44]. These data are consistent with the findings of our study, for which the main etiology of CKD was diabetic nephropathy (62.5%; 150/240).
According to levels of serum albumin and BMI, 72.9% (175/240) of patients showed good nutritional status; in addition, other biochemical parameters were analyzed, such as hemoglobin, urea, creatinine, glucose, uric acid, calcium, phosphorus, and potassium, and we did not observe significant differences between users and non-users of CAM. These results indicate that CAM use does not have a negative effect on the health of patients with CKD. In addition, no significant differences were observed in either group with respect to edema grade or systolic pressure, suggesting that the use of CAM is not associated with changes in fluid status in patients with CKD on PD. In contrast, the diastolic pressure was significantly higher in CAM users; however, we believe that this is not clinically relevant.
The patients in our study had between two and seven comorbidities such as acute myocardial infarction, heart failure, peripheral vascular disease, dementia, chronic lung disease, connective tissue diseases, peptic ulcer disease, liver diseases, HIV, and diabetes mellitus, and according to the comorbidity scale, no significant differences were observed between users (score = 3) and non-users (score = 3.1) of CAM. Contrary to other studies, CAM users have a greater number of diseases [28,45].
This investigation has limitations: as a cross-sectional design, the conclusions drawn from the study cannot suggest causation and only included patients from the unique dialysis clinic of one hospital; therefore, our results may not reveal CAM use in other provinces considering the wide difference in culture, beliefs, and idiosyncrasies of Mexico. Despite these limitations, our results provide an important new understanding, and to the best of our knowledge, this is the first study on the use of CAM in CKD patients in Mexico.

Conclusions
The use of CAM is popular among renal patients on PD (55%), with the main type of herbal medicine being chamomile, followed by relaxation as part of the practice of mind and body techniques. The main reason for the use of CAM in our patients was to improve their state of well-being, and only 3% of users reported side effects. Just as 31.8% of the users of CAM informed their doctor, we need continued research and education to identify and break down barriers to the communication of CAM-use topics between patient and doctor, as this is mandatory.  Informed Consent Statement: Informed consent was obtained from all the subjects involved in the study.

Data Availability Statement:
The datasets generated and analyzed in the current study are not publicly available because they are the property of the Instituto Mexicano del Seguro Social. Institutional and federal bodies restrict unlimited access to personal data, but they are available from the corresponding authors upon reasonable request with prior authorization from the institution.