Correlation of Medical Anamnesis with Current Disease in Chronic Kidney Disease Patients Receiving Hemodialysis : A Retrospective Study of Causative and Exacerbating Factors from Homeopathic Point of View

Conclusions: This retrospective study investigates the factors that may play a role in the manifestation of CKD through the knowledge and research of both conventional medicine and homeopathy. Correlation of Medical Anamnesis with Current Disease in Chronic Kidney Disease Patients Receiving Hemodialysis: A Retrospective Study of Causative and Exacerbating Factors from Homeopathic Point of View orIgInal


Background
The causes of chronic diseases seemingly have unsatisfactory explanations for modern medicine.Thus, medical science defines a set of illnesses as diseases of unknown etiology (idiopathic diseases),

Section: toxicology & therapeuticS
Issn: 1755-7682 J in which the disease's cause is not readily apparent.Examples include idiopathic hypertension, idiopathic glomerulonephritis, fever of unknown origin, urticaria of unknown origin, pulmonary fibrosis, and, by extension, chronic autoimmune diseases, malignancies, and focal segmental glomerulosclerosis [1][2].In addition, the "comprehensive" causative relationships between the cause and the progression of a disease do not seem to explain this complexity [3].Chronic diseases are illnesses or other health conditions that are persistent and have long-term effects on the physical status of the human body.They disrupt and undermine the patient's health to such a degree that the energy of the vital force that automatically drives life can defy these diseases only in part and without effect both at their onset and during their progression [4].The manifestation of a chronic disease is a multifactorial affair, especially in chronic kidney disease (CKD) which is a priori the result of the coexistence of multiple chronic diseases.This also constitutes a first approach, according to conventional medicine, as to why not all humans with the same diseases also present the same progression or complications [5].CKD is a representative chronic syndrome, since it is characterized by a gradual progression and multifactorial nature [6][7].
Significant number of diseases can lead to the manifestation of CKD, and, notably, many of them are idiopathic.As evidenced by literature and daily clinical practice, there is an inability to identify and analyze the causes and pathophysiologic mechanisms that are responsible for the manifestation of CKD.This is despite the rapid development in medical science and pharmaceutical technology as well as a plethora of research trials.This study therefore investigates factors that may play a role in the manifestation of CKD through the knowledge and research of both conventional medicine and homeopathy.
Homeopathy approaches the human body holistically, considering it as a whole-a set of interacting mental, emotional, and physiological processes.The fundamental principle of homeopathy is that each symptom the body develops is the expression of its defense and its effort to combat the disorder [8].According to Professor Vithoulkas, the key differences between conventional medicine and homeopathy lie in the principles encompassing them.Specifically, conventional medicine looks for the causes of a disease and targets it directly (e.g., a bacterium or a virus), whereas homeopathy tries to stimulate and strengthen the defense mechanism so that the body can address the underlying cause through its immune system.When adverse factors are more potent than the body's defenses, symptoms manifest and constitute the expression of the disorder on a physical and/or mental level [9][10].A miasm is the body's predisposition for certain categories of diseases and something that hinders the action of the homeopathic remedy.As a result, the body's vital force is unable to fight them.Homeopathic medicine defines a miasm as a "peculiar morbid derangement of the vital force" of the human body [10][11][12][13][14].According to Hahnemann, the initial exposure of the body to miasms causes local symptoms, such as skin or venereal diseases, but if these symptoms are suppressed by chemical medications, the cause-the miasm-goes deeper and begins to manifest itself in the form of diseases of internal organs.Thus, homeopathy maintains that the attempt to treat diseases by directly addressing their symptoms (as usually applied in conventional medicine) is ineffective [15][16][17][18].Notably, according to the homeopathic analysis of miasms, the predisposed weakness of the human body's defense mechanism can be affected by three major factors: 1) the hereditary effect, 2) potent infectious diseases, and 3) previous therapies and vaccinations.In addition, for a deeper disorder, the internal miasm will manifest itself as a serious disease following exposure to stress, poor living conditions, and improper and exhaustive allopathic therapy [15].Consequently, according to the law of disease sup-pression, when a disease is not treated in depth and causally, then it is simply suppressed.A disease manifesting in the body must be cured and, according to the homeopathic view, by treating the symptoms only, one does not truly address the disease because one is applying a mere superficial treatment of deeper health disorders.Suppressing the symptoms of a disease often causes adverse effects on the body.The suppressed disease tends to affect deeper structures and settles in healthier tissues and organs [20][21].The consolidated theory on disease constitutes a valuable source of information and understanding of the natural history of a disease, since it also allows for the analysis of symptoms as well as the pathophysiological behavior of the human body.Thus, it is interesting that through the life of a person, from birth to death, there is a 'continuum' in the pathological conditions a person may experience.The body, as a whole, suffers deeply any time there is an acute or a chronic condition that is either maltreated or neglected.Chronic and acute diseases in the medical history of a person constitute a rigidly related chain of immune responses in the form of a real 'continuum' that at every point in time indicates the end result of this continuum, [4].Suppression of symptoms and diseases, which is often achieved through excess chemical agents, often overwhelms the body's natural defenses and forces the immune system to compromise.This starts a deeper line of defense, which then constitutes the beginning of a new chronic condition [19].

Study Objective
The objectives of this study are: 1) to investigate the correlation between the disease and the patients' demographics, 2) to comparatively evaluate the relationship between the disease and the existence of other infections, and 3) factors regarding the anamnesis and the clinical presentation of the patients.

Methods
This study included 81 patients with CKD and investigated the correlation between the disease and the patients' demographics, anamnesis, and clinical presentation, as well as the potential relationship between the disease and other illnesses.Women accounted for 51.8% of study participants; the remaining 48.2% were men.The median age was 60.7 years with a standard deviation of 11.39 years (range: 38 -85 years).At the start of the study, we recorded the sex and the age of the participants, the age of onset of CKD, disease treatments, clinical presentation, and anamnesis.Specifically, clinical presentation included whether the subject developed fever (and how high) or had had high fever in recent years, infections (and the age of onset and treatment), and relapses.Reporting anamnesis included frequent use of antibiotics or chronic use of chemical medicines, as well as a family history of kidney disease or sexually transmitted diseases.
Questionnaires were completed following interview of the subjects.We studied and analyzed descriptors of the variables.Standard measures of position and dispersion were used for the description of demographics and the recording of the frequency and the relative frequency of the questions included in the main questionnaire.For the potential correlation between personal details, as well as the various factors reported regarding the health status of patients with CKD, we used Pearson X2 (chi-square) heterogeneity test.Where the conditions were not met, we used Fisher's exact test.In addition, Pearson's correlation coefficient was used to check the potential relationships between quantitative variables.Reported p-values were based on two-sided tests, and p < 0.05 was considered statistically significant.The software SPSS (SPSS Inc., 2003, Chicago, USA) was used for the statistical analysis.

Basic Descriptive Data
With regards to the underlying cause of CKD, 45.7% of subjects had chronic glomerulonephritis, 23.2% tubular necrosis, 4.9% obstructive uropathy, and the remaining 26.2% had other diseases.For history of infection, 17.3% of the subjects had urinary tract infection, and 76.5% developed some other type of infection.Only 6.2% did not develop any infection (Table 1).Next, we analyzed etiological factors that were possibly connected to CKD.We found that 92.6% of subjects had concomitant physical illnesses, and 6.2% presented anxiety disorders, while only one subject did not manifest other diseases (Table 2).Regarding chemical medicines, 93.3% of subjects used antibiotics, while 66.7% frequently used them (Table 3).Moreover, 82.7% made chronic use of chemical medicines (Table 4).
In addition, 43.1% of subjects developed infection relapse (Table 5).Notably, 23.5% of the subjects with CKD had a family history of kidney disease (Table 6) and 32.1% had a history of sexually transmitted diseases (Table 7).

Statistically Significant Data
There was a strong correlation (p-value < 0.001) between the disease and recurrent infections.We found that 79.17% of the aggregate sample presented recurrent infections.The correlation between the disease and the development of recurrent urinary tract infections was also statistically significant (Fisher's exact p-value < 0.001) (Table 8).In addition, we found a strong correlation (X 2 = 79.98 and p-value < 0.001) between the disease and the chronic use of chemical medicines.We found that 95.7% of subjects with CKD were using chemical medicines (Table 9).Of the subjects asked about their history of sexually transmitted diseases, 26 of 81 patients with CKD reported a history of sexually transmitted diseases (STD).
Of them, 53% reported urethritis (either gono-coccal or non-gonococcal), 32% reported Human Papillomavirus (HPV) infection, and 15% could not report the type of the sexually transmitted disease.Furthermore, there was a correlation between CKD and the history of STD (X 2 = 19.33 and pvalue < 0.001).Finally, the relationship between the disease and the existence of causative factors (physical and mental stress) showed a strong correlation (X 2 = 93.29 and a p-value < 0.001).Specifically, 92.6% of subjects with CKD presented physical stress, but only 6.2% presented mental stress (Table 10).

Discussion
Chronic, non-communicable diseases are by far a major cause of mortality worldwide [5][6][7].CKD is representative of such chronic conditions.It is characterized by its gradual progression and mainly by its numerous etiological factors.The progression of CKD does not consistently depend on the extent and the severity of the original cause/disease.Patients with CKD, even when the cause of kidney damage is not active, present with a deterioration of the renal function, and it is only in rare cases that they recover to a normal kidney function.These observations indicate that it is not only the original cause that contributes to the progression of CKD but also various other factors, such as the diet, environmental conditions, physical status (defense mechanism), exposure to toxic agents, and age.A characteristic example in kidney failure is the structural and functional impairment of the nephrons, which are unable to maintain the body's homeostasis [22][23][24][25][26].The homeopathic approach considers that, in patients with CKD, miasms can potentially affect the body's structure.This way, in some CKD cases, the behavior of the "sick" system is predefined by its composition.End stage CKD is a chronic syndrome, resulting from one or more chronic diseases and leading to patients having to take longterm medicines for the treatment of the underlying diseases.
The effectiveness of homeopathy has been established in numerous studies for a broad range of acute and chronic diseases [27].A prospective study including 3,981 elderly subjects showed that the course of chronic diseases improved in a marked and sustained way in patients who received homeopathic treatment [28].Its results strengthened the view that homeopathic treatment can play an important role in patients with chronic diseases.According to another meta-analysis, homeopathy is also effective in treating chronic allergies [29].Of particular interest is a pooled study reviewing the 83 most important clinical trials conducted in the last thirty years regarding treatment of acute and chronic diseases.The authors prove that homeopathy is a safe and effective treatment [30].Furthermore, a comparative cohort study comparing homeopathy and conventional medicine for treating acute respiratory tract and ear infections concluded that homeopathy is not inferior [31].In addition, according to a nationwide study conducted in Switzerland, patients receiving homeopathic treatment in primary care were significantly satisfied compared to those receiving conventional medicine.The study also concluded that the risk of side effects in homeopathic treatment is two or three times lower than in conventional medicine [32].Furthermore, a study conducted in Germany observed no medical toxicity or poisoning in children inadvertently taking big quantities of homeopathic remedies [33].
Not only do homeopathic treatments present a low risk of adverse reactions, the low cost of homeopathic preparations is low and they distinction from the concept of placebo [29,34].In contrast, chronic use of chemical medicines can be interpreted from a homeopathic view as a phenomenon of "symptom suppression," given that patients may develop terminal kidney failure [20].In addition, it is well documented that a vast number of antimicrobial medicines administered for the treatment of urinary tract infections also cause nephrotoxicity .For example, the use of nitrofurantoin administered as a long term chemical prophylaxis in recurrent urinary tract infections led to acute granulomatous interstitial nephritis [52].The use of antimicrobial medicines in patients with kidney disorders, as well as their repeated use in recurrent infections, clearly constitutes an aggravating factor, leading to renal impairment.
Often, however, long-term administration of different chemical medicines is necessary for the treatment of CKD, despite adverse reactions.The epidemiology of renal impairment-inducing medicines is complex, and the exact mechanism of drug nephrotoxicity is unknown [51,62].The administration of chemical preparations and vaccines seemingly causes a complex internal process with the participation of various organs, resulting in manifestation of toxicity.Chronic use of chemical substances/medicines can result in a status of health where not only there is no cure, but side effects and other pathologies may also be caused [35,[62][63][64].This may also be the case for the regular vaccination of patients with chronic diseases who develop chronic renal impairment.As proven in daily medical practice, a large number of patients do not know they are in early stages of renal impairment and take nephrotoxic antibiotics for forthcoming infections, thus further deteriorating their renal function.As earlier mentioned, homeopathic remedies are known to have fewer side effects and lower nephrotoxicity.More specifically, in our study, 92.6% of subjects with CKD had other concomitant diseases, given that CKD is a chronic syndrome.Notably, 1% to 5% of patients receiving non-steroidal anti-inflammatory drugs develop nephrotoxic syndrome, and analgesic nephropathy is one of the chronic renal diseases leading to end stage CKD [65].
Thus, the concern arises whether analgesics and other chemical medicines have a substantial therapeutic effect, as well as whether symptoms of chronic diseases are potentially suppressed as a result of their abuse.Many patients with CKD receive immunosuppressive therapy with corticoids making them susceptible to recurrent infections, which in turn are treated with antibiotics.Thus there is a vicious circle of the disease's manifestation and treatment.Since the nephrotoxicity mechanisms of various medicines have not yet been fully elucidated, impairment of renal function is observed in a number of patients receiving chemical medicines for a certain period of time.Further studies should be conducted to elucidate which are the causative factors for renal impairment in certain patients following use of chemical medici-nes.Despite the advancements in pharmacology, there is a potential inability to justify the factors causing nephrotoxicity in a particular group of patients.According to homeopathic theory, the disease outcome pathways and the exact causative factors should be considered during the progression of a disease for which suppressive therapy is administered.Urinary tract infections and especially recurrent febrile urinary tract infections (such as pyelonephritis) can lead to impairment of renal function.For example, recurrent urinary tract infections due to the bacterium P. mirabilis cause permanent renal parenchyma lesions, given that they form infection stones [66].Studies have also shown that recurrent urinary tract infections, infection stones, high blood pressure, and diabetes mellitus appear to be high risk factors for developing chronic renal impairment.The presence of infections and recurrent infections in patients with impaired renal function can lead to CKD.Furthermore, patients with chronic renal impairment have an imbalanced immune system, which is a direct result of renal impairment as well as the primary disease that led to its manifestation [67].
Patients with recurrent infections and CKD often receive chemical medicines and /or immunosuppressants, such as corticosteroids and antibiotics, to treat their underlying conditions.In an effort to interpret the frequent relapses of infections from a homeopathic perspective, a potential miasmatic dimension of the disease arises.According to homeopathy, chronic predispositions are the reason why patients develop relapses despite receiving the correct treatment.Notably, in the phenomenon of symptom/disease "suppression," patients with CKD address these infection relapses by taking chemical medicines, such as antibiotics, antipyretics, and anti-inflammatory agents.Hahnemann states that by treating acute infections with "allopathic" therapies and with high doses of medicines, local symptoms of the diseases are suppressed, and the risk of chronic disease is increased [15][16].Furthermore, by aiming at balancing the body's vital reaction, homeopathic treatment seeks a holistic physiological response of the body.As a result, this approach is indicated for the treatment of both acute infections and chronic diseases [30,[68][69][70][71].
Sexually transmitted diseases are conditions of the urogenital system, often first manifesting themselves as skin conditions, such as in HPV infection, genital herpes, and syphilis .They often manifest with relapses and, as a result with very few exceptions (e.g., genital warts), the use of antibiotics is needed to treat them.Once again, antibiotics have potential nephrotoxic properties.Approaching sexually transmitted diseases with the homeopathic concept of "disease suppression" ("when a disease is not treated in depth and causally, then it is simply suppressed"), any disease presenting itself in the human body must be thoroughly cured [19].By treating the symptoms, one does not treat the disease itself.It is simply a symptomatic treatment of the health disorder, not a complete cure of the disease.By analyzing the health course of patients with CKD and a history of sexually transmitted diseases, it is not a course leading to cure, as stated in Hering's Law, "from a more important organ to a less important one."[72] On the contrary, by holistically analyzing patients with CKD and STD, one observes that they lead to the manifestation of deeper pathologies.Often, the suppressive treatment of a disease has damaging effects on the body.The suppressed disease tends to affect deeper structures and to settle in more important tissues and organs.According to Hahnemann, initial exposure to miasms causes local symptoms, such as skin or venereal diseases; if however these symptoms are suppressed by chemical medication, the cause-the miasm-goes deeper and begins to manifest itself as disease of the internal organs.Therefore, one could argue that there is the potential of manifestation of a miasmatic condition in patients with CKD and a history of sexually transmitted diseases [15,16].Furthermore, the deoxyribonucleic acid (DNA) of viruses, bacteria, and microorganisms leave an "imprint," a traceable frequency in the body fluids, which opens the way for the development of a highly sensitive detection system for chronic bacterial infections in human and animal diseases [73].
Our study shows that a large number of patients with CKD have a history of sexually transmitted diseases.More specifically, by focusing on gonorrhea with regards to the potential development of predisposition/miasmatic disposition in some patients, it is known that the disease may present recurrent manifestations.Gonorrhea tends to relapse with no apparent development of protective immunity arising from previous episodes of infection.Thus, a new hypothesis emerges regarding gonococcal infections [74].Neisseria gonorrhoeae has been associated with humans for several millennia.It has adapted remarkably well to the human immune system and, accordingly, has evolved to evade destruction by the host's immune defenses.Regarding treatment of sexually transmitted diseases, the use of homeopathic remedies is recommended.Each year, the number of CKD patients as well as those with sexually transmitted diseases is increased.A characteristic example in kidney failure is the structural and functional impairment of the nephrons, which are unable to maintain the body's homeostasis.This could be true for patients with CKD, in which miasmatic conditions potentially affect the body's structure.Accordingly, in some CKD cases, the behavior of the "sick" system is predefined by its composition.

Conclusions
In conclusion, the multifactorial nature of CKD and the complexity of the human body should be approached both through the documented research of conventional medicine as well as by homeopathy.Further studies in patients with CKD and other chronic diseases should be conducted using and comparing the abovementioned approaches and treatments.Analysis through the homeopathic theory of disease suppression, as well as that of miasms, provide a new approach, while offering a future prospect for conducting studies aimed at finding new causative factors in patients with renal impairment who later develop end stage CKD.New data and answers may therefore arise regarding the manifestation and course of renal impairment.Homeopathy provides an alternative treatment solution, with lower nephrotoxicity rates and proven effectiveness.Taking into account the polyfarmacy of patients with CKD, as well as their susceptibility to recurrent infections due to immunosuppression, there is a real need for further investigation for the comparative study of chemical medicines used in conventional medicine and homeopathic preparations.
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Table 1 .
Distribution (absolute and relative frequencies) of the health characteristics of patients enrolled in the study.

Table 2 .
Table of correlation between causative factors and CKD.

Table 3 .
Table of correlation between antibiotic use and CKD.

Table 5 .
Table of correlation between recurrent urinary infection and CKD.

Table 6 .
Table of correlation between CKD and family history.

Table 7 .
Table of correlation between CKD and sexually transmitted diseases.

Table 8 .
Table of correlation between the disease (Chronic Kidney Disease) and recurrent acute infections, for patients of the total sample.

Table 9 .
Table of correlation between the disease (CKD) and the use of chemical drugs for patients of the total sample.

Table 10 .
Table of correlation between the disease and the availability of the causative factors, for patients of the total sample.

Table 4 .
Table of correlation between Chronic use of chemical medicines and CKD