Introduction
Aim of the study
Methods
Otorhinolaryngological changes in patients with CKD (Fig. 1, Table 1)
Hearing dysfunctions
Sensorineural hearing loss (SNHL)
Group of disorders | Disorder | Prevalence | Pathophysiology | Additional information | |
---|---|---|---|---|---|
Hearing dysfunction | SNHL | It might result from several structural and functional similarities in kidney and in inner ear, as well as similar antigenicity [8] Potential mechanisms leading to SNHL in CKD Electrolyte disturbances [6] Elevated serum urea and creatinine levels [6] Treatment (ototoxic drugs: aminoglycosides and furosemide, HD itself and prolonged treatment duration) [6, 8] Coexisting hypertension or DM [6] Vitamin D deficiency and reduction of Na+ K+ activated ATPase [8] Endolymphatic edema [8] Uremia-induced dysfunctions in nervous system, called “uremic neuropathy” leading to auditory nerve and hearing pathway alterations [8] Formation of amyloid collections in the cochlea induced by permanent HD [8] Toxic influence of aluminum on inner ear [8] | SNHL in CKD is usually bilateral and mainly affects high frequencies [8] Speech discrimination seems not to be affected in these patients [8] DPOAE are reduced or absent, and might detect subclinical cochlear dysfunction in CKD [10] ABR tests might reveal lower neural auditory conduction defined by prolongation of ABR waves [11] ABR test might be improved after HD sessions (potentially because of Ca++ ions and urea changes after HD), nevertheless hearing never return to normal [11] | ||
SSNHL | 1.57-times higher than in GP [12] | Mechanism is unknown | Worse prognosis of recovery than in non-CKD patients while undergoing systemic steroid therapy for SSNHL [12] Promising treatment results after intratympanic steroid injections in these patients [12] | ||
Tinnitus | 3.02-times higher in CKD than in GP [9] 4.586-higher in CKD on HD than in GP [9] | Mechanism is unclear Might be an effect of downregulation of intracortical suppression that is linked to the cochlear damage [9] | Commonly coexisting with SNHL | ||
Oropharyngeal changes | Xerostomia | Results from dehydration, reduced saliva flow and urea-induced changes in salivary gland morphology (fibrosis and atrophy) [21] | In patients with CKD saliva flow is 20–55% reduced [20] Cases with no measurable saliva flow are also present in these patients [20] | ||
Dysgeusia | Exact mechanism is unknown It might emerge from the influence of uremic toxins on both, the central nervous system and on the teste receptors located in the peripheral nervous system [17]. High levels of urea, dimethyl and trimethylamine in saliva, reduced saliva production, altered saliva composition, reduced number of taste buds, metabolic disorders, and drugs used in treatment (mainly antihypertensive agents) play a role [17] | Commonly accompanied with “metallic taste”; sour and sweet tastes might be more significantly affected than salty and bitter tastes [17] | |||
Halitosis | 91% of patients with CKD not on HD; 90% of patients with CKD on HD are affected [25] | Results from high urea levels (above 55 mg/dl) Alkaline nature of urea and ammonia maintain increased pH levels of saliva promoting bacteria development and unpleasant odor from oral cavity [23] | Increased risk of dental calculus formation and reduced risk of caries because of alkaline saliva pH [23] | ||
Sore throat | Higher than in GP *[17] | Might be a consequence of reduced saliva production, dehydration and urea decomposing commensal bacteria [17] | |||
Mucosal ulceration | 8.6% of patients with ESKD 1.3% of RTRs [16] | Might be a consequence of reduced saliva production, dehydration and urea decomposing commensal bacteria [17] | |||
Gingival overgrowth | 85% of RTRs are affected [23] | It mainly results from drug-induced changes in gingival fibroblasts and lamina propria that lead to formation of deposits of the intercellular matrix and increase in vascularity [26] | In patients in pre-dialysis or HD stage of CKD it is mainly induced by calcium channel blockers, while in RTRs by cyclosporine [26] | ||
Lichenoid changes/leukoplakia | 8–11% of RTRs are affected [27] | Mechanism is unknown Might be a result of drug-induced reactivation of EBV in the oral epithelium [28] Negative EBV cases were also presented [23] | Usually present as painless, irregular white patches that could not be scraped of, mainly located on lateral or dorsolateral tongue and buccal mucosa [26] Frequently observed in those on cyclosporine therapy [26] No potential to malignant transformation revealed [26] | ||
Candidiasis | 37% of patients with CKD are affects [28] | Occur because of alkaline pH that leads to modification in commensal bacteria flora [28] | Typical presentation [28] White plaques located on buccal mucosa, palate, tongue, gingivae and throat Painful and burning sensation in the oral cavity and throat Altered taste | ||
“Uremic frost” | Higher than in GP* [17] | Results from urea crystals depositions on oral mucosa due to saliva evaporation [17] | |||
Gingival bleeding/ pallor | Higher than in GP* [26] | Occur because of anemia, platelet dysfunction induced by bacterial toxins, and anticoagulant therapy [26] | |||
Oropharyngeal changes in general | 97% of patients with CKD [17] according to Oyetola et al. (n = 90) 100% of patients with CKD [19] according to Patil et al. (n = 100) | ||||
Head and neck malignancy | Lip cancer | Prevalence | Total no of studied patients | Smoking and solar UV radiation promote oncogenesis in these patients [31] | Potentially not related to viral infection [36] Risk of LC is higher in RTRs than in patients with CKD on HD [37] |
15-times higher in RTRs Laprise et al [33] 46- times higher in RTRs than in GP Krynitz et al. [40] 9.4-times increased risk in RTRs Piselli et al. [38] 47.08- times increased risk in RTRs Vajdic et al. [42] | n = 261,500 n = 10,476 n = 7217 n = 28,855 | ||||
Thyroid cancer | Prevalence | Total no of studied patients | Might result from [41] Metabolic changes induced by chronic kidney failure, mainly hypocalcaemia-induced secondary hyperparathyroidism Decreased serum levels of selenium | Potentially not related to viral infection [36] | |
6.77-times increased risk in RTRs van Leeuwen et al. [39] 1.85-times increased risk in organ recipients Mowery et al. [5] 6.9-times increased risk in RTRs Vajdic et al. [42] | n = 8173 n = 19 173 n = 28,855 | ||||
Salivary gland cancer | Prevalence | Total no of studied patients | Mechanism is unknown | Potentially not related to viral infection [36] Studies on the risk in pre-transplantation CKD are lacking | |
2.91-times increased risk after organ transplantation Mowery et al. [5] 5.8- times increased risk in RTRs Piselli et al. [38] | n = 19,173 n = 7217 | ||||
Oral cancer | Prevalence | Total no of studied patients | Lack of immunosurveillance in RTRs because of drug-induced immunosuppression. Immunosuppression affects tumor immunosurveillance and reduces immunologic control of oncogenic viral infection subsequently leading to cancer development [30] Smoking and alcohol consumption as coexisting promoting factors [34] | RTRs are at higher risk of carcinogenesis than those at pre-transplant stage of CKD [30] | |
3.2-times increased in organ recipients Grulich et al. [36] 4-times increased in RTRs Makitie et al. [34] 2.42-times increased risk in CKD patients on HD Taborelli et al. [37] | n = 31,977 n = 2890 n = 3407 | ||||
Pharyngeal cancer | Prevalence | Total no of studied patients | Lack of immunosurveillance in RTRs because of drug-induced immunosuppression Immunosuppression affects tumor immunosurveillance and reduces immunologic control of oncogenic viral infection subsequently leading to cancer development [30] Oncogenesis induced by oncogenic viruses, especially HPV (oro- and hypopharyngeal cancers), and EBV (nasopharyngeal cancer) [32, 34‐36] Smoking and alcohol consumption as coexisting promoting factors [34] | RTRs are at higher risk of carcinogenesis than those at pre-transplant stage of CKD [30] | |
3.2-times increased in organ recipients Grulich et al. [36] 4-times increased in RTRs Makitie et al. [34] | n = 3977 n = 2890 | ||||
Laryngeal cancer | Prevalence | Total no of studied patients | Lack of immunosurveillance in RTRs because of drug-induced immunosuppression. Immunosuppression affects tumor immunosurveillance and reduces immunologic control of oncogenic viral infection subsequently leading to cancer development [30] -Smoking and alcohol consumption as coexisting promoting factors [34] | RTRs are at higher risk of carcinogenesis than those at pre-transplant stage of CKD [30] | |
4-times increased in RTRs Makitie et al. [34] 2.03-times increased risk in CKD patients on HD Taborelli et al. [37] | n = 2890 n = 3407 | ||||
HNC in general | 80% (n = 2284) of all HNC in RTRs are of cutaneous type [34] Makitie et al 93% (n = 359) of post-transplantation HNC are of cutaneous type [43] Rabinovisc et al | ||||
Sinonasal disorders | Epistaxis | Higher than in GP* [3] | Predisposing mechanism Collection of toxins (mainly high blood urea levels) not properly removed by kidneys [3] Anemia and coagulation dysfunctions [3] Bacteria colonizing nasal cavity that decompose urea to ammonia [3] | One of the most common sites of bleeding in patients with uremia [3] Nasal bleeding could be resolved/reduced after blood urea level is normalized [3] | |
Mucormycosis (rhino-cerebral) | 52–56.25% of RTRs are affected [4] | Might result from [4] Cytotoxic drugs and steroids incorporation Prolonged antibiotic therapy Drug-induced granulocytopenia Uremia Hyperglycemia Poor nutritional status | Sinonasal/rhino-cerebral mucormycosis mainly presents as headache, facial swelling and pain (especially over affected areas), nasal discharge, and necrotic lesions on the face, nasal cavities, or palates [4, 45] Rhino-cerebral form is most common form of mucormycosis in RTRs [4] Maxillary and ethmoid sinuses are mainly affected [45] | ||
Olfactory loss/dysfunction | 56% of patients with ESKD are affected [48] | Exact mechanism is unknown It might result from uremia-induced negative effect on peripheral nerve conduction and central cognitive functions [47] | Might be reversible- improvement of proper olfaction observed after renal transplantation and after dialysis session [47] Olfactory identification and discrimination are mainly affected; thresholds seem to remain unchanged [47] | ||
Rhinosinusitis | Consensus is lacking No increase in RTRs [44] according to Ryu et al. | Sinonasal examination is not recommended in asymptomatic individuals because of no exacerbations observed in RTRs [44] CT of paranasal sinuses before organ transplant not recommended in asymptomatic individuals because of the high rate of false positive results [44] Relatively low incidence of rhinosinusitis in RTRs might result from persistent low-dose prednisone therapy withholding the inflammatory responses that frequently promote CRS [44] | |||
Voice dysfunction | Hoarseness | 24–60% of patients with ESKD are affected [50] | Potential mechanism [15] Excessive fluid and toxins accumulation, and acid–base imbalance Vocal cord edema Decreased pulmonary function Abnormal coordination between central nervous system and peripheral phonatory structures Laryngeal muscles fatigue | Patients with ESKD on HD might suffer from temporary post-dialysis hoarseness as a result of HD-induced dehydration, reduction of the vocal cord size and increase in subglottic pressure [50] | |
Bony changes | Renal osteodystrophy in H&N area | Higher than in GP* [16] | May present as demineralization of the mandible and maxilla, loss of the lamina dura, and metastatic calcification in hard tissues [26] The most common abnormalities are temporomandibular joint deformation, maxillofacial fractures and malocclusion [26] | ||
Brown tumor | 1.5–1.7% of patients with CKD-induced secondary parathyroidism are affected [29] | Occurs secondary to CKD-induced hyperparathyroidism [29] | Mainly observed in mandible, palate or facial bones; less frequently in skull bones and paranasal sinuses [29] | ||
Middle ear dysfunction | Tympano-sclerosis/myringo-sclerosis | Consensus is lacking Potentially higher in CKD on HD than in GP [13] | The accumulation of serum phosphate binding to free calcium may lead to calcification in middle ear structures [13] | Increased risk of myringosclerosis was found in CKD patients on HD lasting longer than 3 years [13] No similar association was found between HD duration and myringosclerosis formation [14] | |
Vestibular dysfunction | Vertigo | Higher than in GP* [15] | Mechanism is unclear Might be an effect of toxic products retention with subsequent vasculopathy, vestibulocochlear neuropathy and vascular calcification in the labyrinth [10] | Abnormal responses in oculomotor and combined vestibular-evoked myogenic potential (VEMP) tests in patients with CKD [10] Negative correlation between eGFR and labyrinth function [15] | |
Neck disorder | Deep neck infections | 3-times higher risk of serious infection in CKD on HD than in GP [54] Need for hospitalization because of serious DNI is almost 10-times higher in CKD on HD than in GP [54] | Predisposing mechanisms Uremia (interfering with primary host defense mechanisms subsequently elevating the risk of bacterial infections) [51, 54] Neutrophil dysfunction induced by impaired glucose metabolism, secondary hyperparathyroidism, iron accumulation, malnutrition and HD [54] Constant immunosuppression and immunity alterations that favor the growth of opportunistic organisms in RTRs [56] | Dysfunctional neutrophils present malfunctioning chemotaxis, degranulation and phagocytosis, subsequently failing to prevent CKD host from developing infection [54] CKD constituted 3rd most common condition predisposing to DNIs following DM and nasopharyngeal cancer after radiotherapy [58] |