Features of the development and course of otolaryngological diseases in patients with chronic renal insufficiency

Anastasia A. Savchenko, Sharifa Y. Avkaeva, Shuanet Y. Avkaeva, Elizaveta V. Velmatova, Lada V. Lyaskanova, Esmer M. Geidarova. Features of the Development and Course of Otolaryngological Diseases in Patients with Chronic Renal Insufficiency. Cardiometry; Issue No. 26; February 2023; p. 133-138; DOI: 10.18137/cardiometry.2023.26.133138; Available from:

The development of kidney diseases today, taking into account the environmental situation in the world, as well as under the influence of other factors (stress, reduced nutritional quality, negative influence of heredity, etc.) has a positive trend. At the same time, it must be said that chronic kidney disease (CKD) is a common condition characterized by a decrease in renal function, an indicator of which is the glomerular filtration rate (GFR) of less than 60 ml/min/ 1.73 m2 or the presence of markers of kidney damage that persist for at least 3 months, regardless of the underlying disease [1].

According to the researchers, the prevalence of CKD in Europe reaches, on average, 13-13.5 percent among the adult population [2].

When the condition of patients worsens, when the GFR is already less than 15 ml/ min / 1.73 m2, they are diagnosed with “ End Stage Renal Disease” (ESRD). This stage of the development of the disease requires the use of measures of renal replacement therapy: dialysis, kidney transplantation. The last manipulation provides for the organization of lifelong immunosuppressive treatment, since in its absence the transplanted organ can be rejected by the body [3].

The increase in the number of patients diagnosed with CKD is steadily increasing from year to year, the presence of the disease in question entails the gradual

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development of systemic dysfunctions in the body as a whole and of an otolaryngological nature in particular. The reason for the above is the following: due to the fact that the kidneys do not fully perform the functions assigned to them by nature, nitrogenous waste – “uremic toxins” gradually accumulate in the tissues of the patient’s body. The electrolyte balance is also disrupted, local chemical reactions fail, at the same time immunological, vascular and coagulation changes are noted. In addition, systemic complications in the body of patients with CKD occur due to the long-term use of immunosuppressive drugs by the latter, which are used in specialized therapy. Researchers note that taking immunosuppressive drugs leads to the development of various infectious diseases, as well as to the development of oncological ailments.

The negative impact of CKD on various organ systems is widely described in the specialized literature, but the purpose of this study is to consider the features of the development and course of otolaryngological diseases in patients with CKD.

Materials and methods

When writing this study, studies of specialists were studied, in whose works the development of various otolaryngological diseases in patients with CKD was studied. The results of practical research in the field under consideration were also studied and information on ways to reduce the risk of developing the diseases in question was summarized. When writing the paper, comparative and analytical research methods were used.

Results

In the works of individual researchers, considerable attention is paid to the development of otolaryngological diseases in patients suffering from CKD. At the same time, some of the ENT dysfunctions have been studied in more detail by specialists, since, as we believe, their manifestation is quite common. Thus, such dysfunctional changes as sensorineural hearing loss, nosebleeds, candidiasis, rhinosinusitis, rhinocerebral mucormycosis, sudden sensorineural hearing loss, tinnitus, dizziness, loss of sense of smell, tympanosclerosis, voice disturbance, etc. attracted the attention of researchers most of all. Let’s consider the main risk factors for the development of certain otolaryngological diseases presented above in patients with CKD.

Sensorineural hearing loss (SHL) It acts as a fairly common otorhinolaryngological ailment in patients

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who have been diagnosed with CKD [4]. At the same time, CKD is called as an important independent risk factor for this disease.

This otolaryngological dysfunction is most often bilateral and is diagnosed in patients who have been suffering from CKD for a long time. The prevalence of this disease is quite high and is more than 50%. There is an opinion that the degree of development of this ailment is influenced by the calculated GFR: persons in whom this indicator was higher than 45 ml/min / 1.73 m2 showed the most intensive development of sensorineural hearing loss [5].

Along with sensorineural hearing loss, experts note tinnitus in patients with CKD, which is the perception of sound in the absence of an auditory stimulus from the outside and is a consequence of auditory pathology and may be a concomitant symptom of the previously considered disease.

In addition, experts note that patients with CKD have vestibular dysfunction. It was determined that GFR, a parameter expressing kidney function, negatively correlates with vestibular function. Although the exact cause of dizziness in patients with CKD remains unclear, suspected potential etiological factors were the retention of toxic products followed by vasculopathy, vestibulocochlear neuropathy and vascular calcification in the labyrinth. Also, tests of oculomotor and combined vestibular-induced myogenic potential (VVMP) showed abnormal reactions in patients with CKD, confirming the observation of a decrease in vestibular function in these people [6].

Also, patients with CKD suffer from various lesions of the oropharynx, which represent a potential and preventable cause of adverse health outcomes in such patients.

Most often, patients with CKD are diagnosed with xerostomia. Xerostomia, a subjective sensation of dry mouth, usually accompanied by difficulties in chewing, swallowing and tasting, is very often observed in patients with CKD [7]. This condition determines the development of oral infections and lesions of the oral cavity.

In addition to xerotomy, patients with CKD may suffer from dysgeusia – an abnormal development of taste. This pathology is usually accompanied by a metallic taste in the mouth and is associated with an increased content of urea, dimethyl- and trimethylamine in saliva, a decrease in saliva production, a change in its composition, a decrease in the number of taste receptors, metabolic disorders and medications used for treatment [8]. It is believed that the influence of uremic toxins on both the central nervous system and testicular receptors located in the peripheral nervous system can lead to abnormal taste perception in patients with CKD [9].

Also, patients with CKD often have halitosis – bad breath. This is mainly due to chronic diseases of the oropharynx, sinonasis or teeth, poor oral hygiene, gastrointestinal or systemic diseases. Often in patients with CKD, bad breath is a very common condition, which is mainly associated with high levels of urea.

Patients with CKD are often diagnosed with ulceration of the mucous membrane and gum hyperplasia. The occurrence of hyperplasia is often a consequence of prescribing cyclosporine to patients, which causes changes in gum fibroblasts and its own plate, as a result, deposits of the intercellular matrix are formed and vascularization increases. At the same time, this anomaly is more characteristic of children’s patients.

In addition, lichenoid changes and hairy oral leukoplakia are often diagnosed in patients with CKD after kidney transplantation [10]. The prevalence of lichenoid changes and hairy oral leukoplakia in patients with CKD ranges from 8 to 11% [11]. Manifestations of this pathology in the considered group of patients usually occur in the form of painless irregular white spots that cannot be scraped off; they are located most often on the lateral or dorsolateral surface of the tongue and the mucous membrane of the cheeks and, according to researchers, are also a consequence of patients receiving cyclosporine [12].

Patients with CKD also have pale gums and spontaneous, non-induced bleeding from them. This is most often the result of anemia, platelet dysfunction caused by bacterial toxins, which is enhanced by anticoagulant therapy and improper functioning of vascular wall cells.

Pharyngeal candidiasis is also often diagnosed in patients with CKD. This disease is a fungal infection and occurs as a result of an alkaline pH, which leads to a change in the flora of commensal bacteria. Most often, this condition is expressed in the form of white plaques located on the mucous membrane of the cheeks, palate, tongue, gums and throat, sensations of pain and burning in the mouth and throat, or changes in taste

There is also an opinion that CKD contributes to the calcification of soft tissues and parotid glands, as well as to the development of brown tumors, which act as a kind of focal fibrocystic ostitis caused by secondary hyperparathyroidism.

Patients with CKD quite often also have sinona-sal dysfunctions. Thus, nosebleeds (nosebleeds) are a common symptom of CKD [13].

It should also be noted that as a result of immunosuppression, which occurs in patients with CKD who have undergone kidney transplantation, a number of other sinonasal manifestations may occur: namely, chronic and acute rhinosinusitis, invasive fungal rhinosinusitis, etc. [14]. Experts point out that the introduction of cytostatics and steroids, prolonged antibiotic therapy, drug-induced granulocytopenia, as well as metabolic disorders (uremia, hyperglycemia and poor nutritional status) should be considered as the cause of the development of opportunistic infection in patients after kidney transplantation [15].

Patients with CKD may also suffer from impaired sense of smell. The decrease in this function was noted by a significant part of the specialists who studied this issue. Thus, the literature indicated that the prevalence of loss of sense of smell reached 56% of patients with end-stage renal failure [16].

In patients with ESRD, specialists also observed voice changes. The cause of this condition was excessive accumulation of fluid and toxins, as well as acid-base imbalance [17].

Patients in this group are usually diagnosed with swelling of the vocal cords, decreased lung function or abnormal coordination occurs between the central nervous system and peripheral vocal structures, which is why the voice of such patients changes. In particular, a number of patients with ESRD had temporary postdialysis hoarseness after a hemodialysis session, as there was hemodialysis-induced dehydration, a decrease in the size of the vocal cords and an increase in sublingual pressure [18].

In addition, experts have noted individual cases of hypocalcemic laryngospasms caused by CKD, which arose as a result of increased reflex excitability of recurrent laryngeal nerves in the area of neuromuscular synapses [19]. However, all these observations were of a single nature, and further studies are required to confirm these conclusions.

Discussion

It is also necessary to consider the causes and mechanisms of individual ENT pathologies in pa- tients with CKD. Thus, the cause of the development of sensorineural hearing loss, as noted in the literature, is the presence of structural and functional similarities between the kidneys and the inner ear [20]. The most important similarity is the active transport of electrolytes and fluids carried out in the basement membrane of the glomeruli and in the vascular strips of the cochlea. This is the result of the presence of the Na + K + ATPase pump and the carbonic anhydrase enzyme [21]. It was also pointed out the similarity of the antigenicity of the cochlea and the kidney, which, according to the proponents of this approach, can be confirmed by the peculiarities of individual diseases: in particular, with Alport syndrome, both the inner ear and the kidneys are affected.

Ototoxic drugs were named by specialists as one of the important factors influencing the development of the above-mentioned disease, a similar role is also assigned by specialists to hemodialysis and the duration of continued treatment. Also among the reasons the researchers call electrolyte disorders, elevated levels of urea and creatinine in serum. In some studies, arterial hypertension is also called as a factor contributing to the development of sensorineural hearing loss against the background of CKD.

Researchers indicate that endolymphatic edema, as well as uremic neuropathy, which can lead to changes in the auditory nerve and auditory pathways, are the predestining condition of sensorineural hearing loss [22]. Regular hemodialysis also often causes the formation of amyloid clusters in the cochlea, which leads to hearing impairment.

Confirmation of sensorineural hearing loss is carried out through the use of audiological tests. The most common audiometric anomaly observed in patients with CKD was a loss of high frequencies and a notch at a frequency of 6 kHz. Speech discrimination in these patients is often not impaired. Auditory brainstem response (ABR) is an objective non-invasive electrophysiological test that measures the retrocochlear part of the auditory pathway to the level of the brainstem in response to sounds [23].

One of the alleged causes of tinnitus is the suppression of intracortical suppression associated with damage to the cochlea, but the exact mechanisms of this disease are not fully understood. However, research results demonstrate that patients with CKD are 3.02 times more likely to develop tinnitus than patients with and without other diseases [24].

Most oropharyngeal abnormalities in patients with CKD occur as a result of an increase in the level of urea in saliva. Urea is broken down by urease into ammonium ions and carbon dioxide, which leads to a high alkaline pH of saliva. Immunosuppression, side effects of medications used in therapy, electrolyte imbalance, restricted diet and malnutrition are other causes of oropharyngeal lesions in CKD [25].

It was noted that quite often various lesions of the pharynx occur in patients who have undergone kidney transplantation, and less often in those who are on hemodialysis. Patients with CKD suffer from xerostomia, periodontitis, candidiasis, burning sensation in the mouth, ulceration of the oral mucosa, etc. [26].

A number of assumptions have been made in the literature regarding the causes of the development of xerostomia. The main ones were dehydration, decreased salivation and changes in the morphology of the salivary glands. Therapy that includes certain drugs in the treatment protocol, namely immunosuppressants, opioids, corticosteroids and antimicrobials, can also act as the primary basis for the development of this disease.

The results of separate studies have shown that if salivation reaches about 0.3–0.5 ml/min in healthy people, then salivation decreases by 20-55% in patients with CKD on hemodialysis [27]. However, experts have found that after kidney transplantation, salivation in patients increases, and the symptoms of xerotomy decrease. Separate studies also indicated that salivation returned to normal in some patients after the transplantation procedure. In this regard, it has been suggested that the decrease in the rate of salivation at the pretransplantation stage of CKD is the result of the above-mentioned urea-induced disorders of the salivary glands, taking a number of medications and limiting fluid intake [28].

In patients with CKD who are on dialysis, the morphology of the salivary glands is represented by fibrosis or atrophy, and developing xerostomia can predispose to candidiasis and purulent sialoadenitis. According to various estimates, the average prevalence of this disease among patients with CKD is more than 50%, while it has been suggested that in patients with CKD with a history of diabetes mellitus, the percentage of xerotomy may be 60% or more [29].

The occurrence of halitosis is possible when the level of urea in the blood exceeds 55 mg / dl. The alkaline nature of urea and ammonia maintains an elevated pH level of saliva and bacterial biofilm, contribut- ing to the formation of tartar and reducing the risk of caries in patients with CKD [30].

The cause of nosebleeds in patients with CKD nosebleeds are often associated with the accumulation of toxic elements that should be excreted in the urine through the kidneys, however, due to their dysfunction, this process is not fully realized in this group of patients. Other factors contributing to the occurrence of nosebleeds include anemia and blood clotting disorders.

One of the causes of nosebleeds, according to researchers, is urea. Thus, according to the results of one of the studies, the level of urea in the blood of patients with nosebleeds was 320 mg / 100 ml. which was eliminated by nasal discharge. The aggravation of nosebleeds also occurs due to the decomposition of urea to ammonia by bacteria whose colonies are located in the nasal cavity. The consequence of this process is chemical rhinitis, the manifestations of which are hyperemia, ulceration of the mucous membrane, submucosal hemorrhages [31].

The researchers note that the normalization of urea levels causes the cessation of nosebleeds, which leads to the conclusion that it plays a leading role in the initiation of these bleeds.

In one of the studies, it was indicated that changes in both the peripheral and central nervous systems led to a violation of the sense of smell of the studied group of patients. It was also reported that odor identification was significantly reduced in the majority of patients with CKD (approximately 70%) and terminal renal insufficiency (approximately 90%) [32]. It has also been suggested that olfaction correlates with severe renal insufficiency, since olfactory thresholds, which express the minimum intensity of odor detectable by humans, were significant in patients with endstage renal failure. However, after the dialysis session, as well as after kidney transplantation, olfactory dysfunction in patients decreased.

It has been suggested that olfactory function may be a marker of neurological dysfunction associated with uremia. In particular, experts have indicated that urea may be responsible for olfactory disorders due to its negative effect on both peripheral nerve conduction and cognitive functions [33].

Conclusions

Various ENT diseases quite often act as complications of the course of CKD, as well as measures related to its treatment. Quite frequent complications in pa- tients with CKD are the development of sensorineural hearing loss, tinnitus, vestibular dysfunction, recurrent nosebleeds, opportunistic infections, changes in taste and smell, vocal dysfunction, mucosal abnormalities, xerostomia, etc.

The otorhinolaryngological dysfunctions discussed above that have arisen in patients with CKD are usually permanent and difficult to control, have a negative impact on the quality of life of patients with CKD. For this reason, patients suffering from CKD should be regularly monitored by an otolaryngologist, undergoing regular examinations. The importance of these procedures is determined by the fact that individual otolaryngological disorders, in case of their early detection, may be reversible. In addition, correctly and timely prescribed treatment can limit the development of individual ENT pathologies.

Also, the complex of primary preventive measures for the development of ENT diseases in patients with CKD should include genetic counseling aimed at families in which it is known that they are carriers of diseased genes in order to assess the possibility of developing various otolaryngological pathologies.

In clinical settings, ototoxic drugs such as furosemide and aminoglycosides should be used cautiously and reasonably, avoiding, if possible, a combination of these two groups. It is necessary to inform about the risks of self-medication, the use of herbal products, which can be both ototoxic and nephrotoxic.

It is necessary to raise awareness of patients receiving dialysis sessions about the possible occurrence of symptoms of ENT diseases and introduce screening programs to assess the health status of such patients.