Hearing in renal failure

The incidence of sensorineural hearing loss among patients with chronic renal failure (CRF) is considerably higher than in the general population. Bazzi et al . [ 1 ] found an incidence of 77% including patients with mild and very mild hearing loss. Ozturan and Lam [ 2 ] found a moderate to severe hearing loss in 46% of the tested patients. The general consensus in audiometric findings among patients with CRF claims a high frequency hearing loss [ 3 , 4 ] with a notch at 6 kHz [ 2 ]. Presence of hearing loss and estimation of type and degree constitute one of the most common methods used to investigate the effects of renal disease on the auditory system. Degree of hearing loss may give an indication of the extent of damage to auditory function, whereas the type of hearing loss may distinguish between lesions in the outer and middle ear (conductive hearing loss) or the cochlea and the neural pathways (sensorineural hearing loss). In addition to these indicators, the reports to be reviewed in the following sections have also described auditory function in CRF with methods such as otoacoustic emissions (OAEs) (namely transient evoked OAEs, TEOAEs and distorion product OAEs, DPOAEs), and auditory evoked potentials (AEPs). OAEs are low level sounds emitted by the cochlea in the process of receiving the sound vibrations and transforming them to cellular and neural stimulation. Recording of OAEs implies a functioning cochlea and healthy middle ear mechanism. TEOAEs are produced by the action of the hair cells, and they reflect special characteristics of the stimulus. DPOAEs are produced when the ear is stimulated with a combination of pure tones that are close in frequency (the primary tones). DPOAEs reflect non-linear processes of hair cell motion. Both TEOAEs and DPOAEs are generated by the active cochlear mechanisms responsible for enhancing basilar membrane vibration; this is known as the ‘cochlear amplifier’ [ 5 ]. AEPs represent neural activity related to auditory stimulation. They show summated neural energy at the various synaptic levels of the auditory pathway; this activity is generated by specific stimuli and extracted from the ongoing EEG activity by specialized technical manipulation. AEPs are recorded from the scalp representing activity in the cochlea and brainstem, thalamus and cortical areas. They are distinguished in early, middle and late evoked potentials, respectively. AEPs recorded from the cochlea include the cochlear microphonic (CM), the summating potential (SP) and the auditory nerve action potential (AP). The CM originates in the outer hair cells and mirrors the incoming signal. The SP also reflects hair cell function. The auditory nerve AP represents the sum of synchronous responses of auditory nerve fibers at the level of the cochlea. The largest component of the AP is the N1, a characteristic wave that constitutes also the first identifiable component of the auditory brainstem response (ABR). The ABR is also an ‘early’ evoked response, as it reflects neural function along the ascending auditory pathway, from the cochlea to the inferior colliculus. The five distinct waves of the normal ABR waveform are mainly generated by successive nuclei in the ascending auditory pathway: waves I and II originate from the distal and proximal portions of the auditory nerve, respectively, wave III originates from the cochlear nucleus, wave IV originates from the superior olivary complex and wave V originates from the lateral lemniscus/inferior colliculus. Each higher level order wave receives contributions from lower levels of the pathway [ 6 ]. The AEP reflecting function from auditory cortical areas is the Auditory Late Response (ALR). Major identifiable waves of the ALR are the N1 and P2 waves. ALR measurements reflect higher-level auditory function [ 7 ]. In general, latency of AEP waves indicates speed of neural function, whereas amplitude is a variable indicator of response robustness. The cochlea and kidney have similar physiological mechanisms, namely the active transport of fluid and electrolytes accomplished by the stria vascularis and the glomerulus, respectively [ 2 , 8 ]. They may also have common antigenicity [ 9 , 10 ]. These may account for similar effects of medications (i.e. nephrotoxic and ototoxic effects of aminoglycosides) and immunological factors on the two organs. Inner ear and kidney development are both influenced by similar genetic factors in hereditary conditions such as Alport's syndrome and branchio-oto-renal syndrome. Several aetiological factors have been linked to hearing loss in renal failure [ 11 ] including use of ototoxic medications, electrolyte disturbances, hypertension [ 12 , 13 ] and haemodialysis treatment itself [ 1 , 14–16 ]. Brookes [ 17 ] suggested that vitamin D deficiency might be a contributing factor to hearing loss in renal failure. Adler et al . [ 18 ] found a significant reduction of Na + , K + -activated ATPase in the inner ear of uraemic guinea pigs. They also reported an inverse correlation between serum creatinine levels and Na + , K + -activated ATPase. As Na + , K + -activated ATPase in the cochlea is important for maintaining cationic gradients, they suggested that inhibition of this enzyme system may be a factor in inner ear dysfunction among uraemic patients [ 18 ]. Treatment evolution may have modified the contribution of several factors in causing hearing loss. For example, hyponatraemia, a common occurrence three decades ago [ 13 ], is no longer a concern with newer haemodialysis methods. Other pathologies linked to renal failure may contribute to auditory dysfunction. Albertazzi et al . [ 19 ] documented the presence of alterations in the peripheral and central nervous system of uraemic patients demonstrating the existence of ‘uraemic neuropathy’. Di Paolo et al . [ 20 ] indicated a very high incidence of nerve conduction dysfunction in groups of CRF patients. They found decreased conduction velocity in sensory and motor units, with the sensory units being more affected than the motor. In agreement with these studies, several ABR studies of CRF indicated dysfunction of the auditory nerve and pathways [ 4 , 15 , 21–27 ]. Renal failure is linked to hearing loss irrespective of the treatment method; it has been difficult, however, to separate the effects of disease duration, haemodialysis treatment, possible contributions of medication ototoxicity, age, exposure to noise and possible interactions. As treatments become more efficient and patients’ life span increases, there is a better chance of observing co-existing conditions as well as the added factors of geriatric concerns. This issue is circumvented when children with CRF are observed [ 27–32 ]. Antonelli et al . [ 4 ] present a detailed review of possible causes of hearing loss in patients with CRF; they stipulate that even with strict control for confounding variables, there remains evidence of sensorineural hearing loss among these patients. Published research exploring hearing loss in CRF presents common directions that will be reviewed in the following sections. Study of animal models with induced renal failure offered more specific description of the disease and effects. Although methodologies of inducing renal failure and time of measurements of auditory function vary among studies, the general consensus seems to be that the site of auditory lesion in induced CRF is the cochlea. Ohashi et al . [ 33 ] found that with greater renal damage, amplitudes of the cochlear potentials N1 and CM were smaller and latency of N1 was prolonged, while AP was within normal range. This pattern points to the sensory cells of the cochlea as the site of damage caused by the disease, although light microscopy of the cochlea did not reveal alterations. The authors attributed the hearing loss to metabolic disturbances, electrolyte imbalance and endocrine dysfunction due to the disease. Ikeda et al . [ 34 ] induced renal failure to guinea pigs and measured cochlear potentials at 1, 2 and 3 months post-operatively. They initially found small changes in the compound AP and CM, which were exacerbated with time; they found no change in the endocochlear potentials similar to Ohashi et al . [ 33 ]. They concluded that CRF affects the cochlear hair cells. Furthermore, they observed a synergy between CRF and noise exposure because animals with CRF did not recover from exposure to broadband noise as did controls. This may suggest that patients with CRF, apart from the associated hearing loss, might be susceptible to additional noise-induced hearing loss [ 34 ]. Shvili et al . [ 24 ] reported similar findings by inducing CRF in rats and measuring ABRs after 3 months. They found prolongation of wave I, with normal I–V interpeak latency, suggesting a site of damage either at the cochlea or along the proximal part of the acoustic nerve. Anteunis and Mooy [ 35 ] presented a case of acute renal failure and hearing loss. Hearing loss and neural function of the auditory nerve recovered after therapy indicating that acute renal failure causes reversible cochlear and neural dysfunction. Hearing loss among patients with CRF has been a common finding in studies investigating the effects or renal failure on auditory function. Despite differences in methodologies and indices of auditory function, existence of hearing loss has been a common thread ( Tables 1 and 2 ). The higher incidence of hearing loss among children with CRF has long been established and is constantly being verified by new studies [ 27 ]. Bergstrom et al . [ 36 ] reported hearing loss in 40% of the CRF patients on haemodialysis. Bergstrom and Thompson [ 28 ] reported that 47% of 151 paediatric end-stage renal patients had hearing loss. Hearing loss is a more commonly reported finding than vestibular dysfunction. Kusakari et al . [ 37 ] reported on inner ear function of 229 patients on chronic haemodialysis. They found that 60% had hearing loss, 36% had vestibular dysfunction and 26% had a combination of both. Johnson and Mathog [ 38 ] noted high frequency hearing loss in 61 adults early in the course of haemodialysis. Charachon et al . [ 39 ] reported that 75% of 54 patients with CRF had hearing loss. Zeigelboim et al . [ 40 ] measured thresholds between 9 and 18 kHz in 37 patients with CRF undergoing conservative treatment and a control group with normal hearing function. Age ranges in both groups were 30–59 years. They found a more severe high-frequency hearing loss in the group with Hearing loss among patients with CRF to a after the first research is in 2 . effects of haemodialysis treatment on hearing one haemodialysis treatment effects of haemodialysis treatment on hearing one haemodialysis treatment on effects of CRF on hearing on effects of CRF on hearing Bergstrom et al . [ 36 ] a group of patients with hearing loss of one with and one with They found no between the were not related to disease or be related to the presence of hearing loss. studies of the inner ear in renal failure are and to the disease may the auditory pathway [ , ]. Charachon et al . [ 39 ] the on from this They reported on a case with associated with of the cochlear and a cell loss of in the The high incidence of hearing loss in this group was attributed to the caused by renal failure. and [ ] reported a with hearing loss to of CRF, and haemodialysis. They found changes in the of the and which they attributed to caused by haemodialysis. the finding of hearing loss is not with Antonelli et al . [ 4 ] auditory function in adults pure measurements and They pure ABR wave and interpeak latency differences of patients with CRF undergoing haemodialysis with a control group of and They also ABR findings of the patients with CRF with a control group by degree of hearing loss. They reported that pure hearing loss as well as wave I latency of the CRF group was with and with serum I was with These findings were as effects of and The with and might of the changes observed in studies of patients with CRF including in the stria vascularis and loss of outer hair cells and cells [ ], as well as [ ]. finding was reported by Bergstrom et al . [ 36 ], found no correlation between cochlear and for age, Antonelli et al . [ 4 ] found that the group with CRF had a longer wave interpeak latency this reflects conduction time from the cochlea to the level of the cochlear nucleus, it was as a dysfunction of the nerve caused by uraemic CRF to hearing loss and neural conduction even than although it be to distinguish between the effects of uraemic and because of disease. et al . [ ] also reported differences in ABR latency between 36 patients with CRF on haemodialysis and 10 controls. These findings indicated neural in the auditory dysfunction associated with renal failure and et al . [ ] reported ABR from patients on chronic in with a control They found significant of waves III and et al . [ ] recorded TEOAEs in 34 children with CRF, 27 on haemodialysis and on conservative They found children with hearing loss and five children with severe sensorineural hearing loss. The patients had normal hearing when with pure This finding is in to findings of studies with CRF patients et al . [ 12 ] found incidence of high frequency hearing loss, while et al . [ ] found incidence of high frequency hearing loss). of cochlear children with CRF had lower levels and than controls. of these patients had or no In even among normal hearing children with CRF, OAEs of cochlear not by pure indicating an to hearing loss. be that cochlear dysfunction to the hearing loss measured among adults with CRF, because the incidence of cochlear dysfunction in children was similar to the incidence of hearing loss in The in these findings is that cochlear dysfunction among children was observed in the whereas the consensus among adults with CRF points to a high frequency hearing loss. [ 12 , 40 , ]. et al . [ ] found hearing loss in of the children with CRF, with hearing mainly affected in the high with CRF had hearing in amplitudes were smaller among children with CRF, even in hearing was OAEs were or smaller among the CRF These findings are in with evidence of cochlear dysfunction as reported by et al . [ ] the that children with CRF may have of effects on cochlear function, which is of hearing loss. Furthermore, et al . [ 27 ] reported that of ABR wave I, V and interpeak and I–V were longer than indicating a in addition to cochlear dysfunction. et al . [ ] pure thresholds and ABRs from children on associated with hearing was among CRF patients than in controls. They found no evidence that hearing loss was associated with Furthermore, they concluded that is a better indicator of hearing function than In auditory function is affected by CRF in reported as well as findings are between of renal and hearing function hearing is affected by Several studies have between of the disease, levels and et al . [ ] reported hearing loss in of patients with disease and in of children with renal disease. et al . [ ] found that 75% of the patients no of hearing the time of They concluded that hearing loss is common in renal it not with of et al . [ ] found no correlation between pure findings and with serum electrolyte Kusakari et al . [ 37 ] reported that inner ear dysfunction hearing loss and vestibular dysfunction or a was not with and serum creatinine levels or with of haemodialysis Johnson et al . [ 3 ] found no between of hearing and serum K + , Na + , and In a similar . [ ], found that hearing loss was not related to changes in K + , Na + , , or et al . [ ] recorded ABRs from patients with CRF of treatment and from patients on They found that both groups had of waves III and Furthermore, the group had interpeak latency was no correlation between ABR and serum or of haemodialysis. In agreement with et al . [ ], they suggested that neural conduction along the auditory pathway is irrespective of haemodialysis due to the disease. et al . [ ] found no correlation between ABR wave prolongation and level of vitamin and of disease not to have a significant on auditory function. et al . [ ] sensorineural hearing loss in three groups of children with on conservative treatment, 18 on haemodialysis and 36 with renal They found sensorineural hearing loss in of the children on conservative treatment, of the children on haemodialysis and 47% of the children with renal were no between hearing loss, of and haemodialysis The authors concluded as the incidence of hearing loss was in the conservative treatment and haemodialysis there be an early of the suggesting that the disease is linked to hearing loss, not the et al . [ ] found a higher incidence of cochlear dysfunction among children on haemodialysis with children on conservative treatment, in to [ ] similar of haemodialysis. renal function among patients on is than among patients on conservative treatment, which the between the effects of a more severe renal from effects of the and this finding be with in light of the small of in the conservative treatment et al . [ ] auditory function among children with CRF, with renal disease, 15 on and 9 on They found that a had hearing loss. hearing loss and for whereas was of it be attributed to CRF or haemodialysis. Hearing was in the high with of the affected to a degree in the middle and low of the children in the haemodialysis group had hearing loss, with in the of renal group and in the when for small the between the two methods of was not The finding that children on haemodialysis hearing loss more than on conservative treatment, was with et al . [ ]. et al . [ ] recorded AEPs from two groups of 13 patients and patients on haemodialysis and them with from a control They found differences in brainstem however, the most findings in the In the chronic middle latency wave was and amplitude was smaller than and patients for the whereas both CRF groups had smaller amplitudes the The authors concluded that the group function to normal than the chronic patients [ ]. et al . [ 15 ] recorded ABRs from 17 CRF patients on conservative treatment and 11 on chronic They found responses in of the patients. was normal in most of the with latency prolongation of waves following wave ABRs were more in the conservative treatment The studies that of treatment may the of the disease on a to be and more reports present findings possible contributions of haemodialysis treatment to hearing loss in renal failure. of these reports on the effects of a on hearing function [ 2 , 12 , , , ] and of groups with on the treatment [ 1 , 12 , ]. studies are in 1 . et al . [ ] reported an of 20 in the hearing of patients following haemodialysis. They suggested that changes in serum and fluid may the hearing as changes in the of these hearing may not be as affected from haemodialysis as it was at that are several more reports in the the and [ ] reported that pure thresholds did not change after haemodialysis. They did which they attributed to imbalance in the caused by haemodialysis. et al . [ 12 ] recorded pure thresholds on patients and after a of haemodialysis. They in the and documented a low frequency hearing loss, which on of the patients after As sensorineural hearing loss is related to they that changes in fluid haemodialysis may be for the low frequency hearing there was no correlation between and hearing changes after haemodialysis. Ozturan and Lam [ 2 ] found a notch at 6 kHz among CRF patients not related to haemodialysis the frequency of possible effects remains et al . [ ] tested pure thresholds of 19 patients of to and 1 and 24 following a of haemodialysis. They noted a high frequency hearing loss, no specific effects of haemodialysis. et al . [ 27 ] found no of a haemodialysis on the hearing of et al . [ ] the hearing of patients with CRF, following 12 of them for 1 as they were haemodialysis. group of patients not on haemodialysis were at the of the a group haemodialysis for 3 and 6 was in the Bazzi et al . [ 1 ] reported pure audiometric findings on three groups of patients on haemodialysis for for and for more than 10 years. Both studies found a high-frequency hearing loss in groups related to the disease and They did not a correlation between haemodialysis and of hearing loss. on haemodialysis treatment did not to the degree of hearing loss in the CRF population. Auditory evoked responses and OAEs were used to auditory function in several and ABR a to cochlear and nerve function, a better of the auditory pathway in Ozturan and Lam [ 2 ] the effects of a of haemodialysis on pure thresholds and They tested 15 patients of of to and following a of haemodialysis in a similar with et al . [ ]. were no significant changes in the pure thresholds or the amplitude in either et al . [ ] ABRs from 38 patients and after haemodialysis along with They found ABRs in of the patients at and in of the patients at the These of and interpeak latency differences indicating both a cochlear and a The of haemodialysis on III and V at the and I and V at the were with changes in These findings are with et al . [ 12 ], found a in I–V interpeak latency following haemodialysis. this finding was noted in two which et al . [ ] found that brainstem function was normal in of the 20 patients They reported a of brainstem conduction 24 after the the five patients they three had brainstem function to normal after renal et al . [ ] recorded ABRs from patients with CRF of them with of patients on and they the effects of a of haemodialysis. They found that wave were affected in both to a of wave III This finding was a change with no on neural conduction of patients on et al . [ ] recorded auditory evoked responses from patients on haemodialysis for between 5 and 10 and more than 10 years. They found prolongation of wave and when with a group of no between the groups with In they found evidence of along the auditory pathway in the CRF with no indication that the of treatment or the of the disease may this et al . [ ] the ABR of children between the of 6 and 17 years. They found that of waves I, III and V were after a of haemodialysis. They suggested that this of ABR might a of haemodialysis on even with the of wave the ABR waveform was not in the normal range. was no correlation between uraemic fluid and the observed changes in the on these they concluded that there was no of a haemodialysis on the ABR of the observed et al . [ 27 ] the ABR findings and added that interpeak and I–V were after a of haemodialysis. They also noted of DPOAEs after the haemodialysis in they were the amplitude following haemodialysis. They concluded that of might neural conduction and hair cell function. As haemodialysis treatment has the it is from the most that there is no correlation between a or treatment and changes in the patients’ hearing or auditory function. The to the [ 12 ] did not a correlation between hearing and in order to the observed between haemodialysis and of As there are no reported studies to this it remains to be the that haemodialysis not hearing will be The high incidence of hearing loss among children and adults with CRF is in on haemodialysis treatment not to have a significant although the of treatment may the of the disease on The that the site of lesion is cochlear with findings in auditory brainstem of correlation between hearing function and a detailed description of the mechanisms causing hearing loss in in the treatment have the effects of of on hearing function. on it is that there is no correlation between a or treatment and changes in the patients’ hearing or auditory function. of .