The Hearing of the Patients Treated with Hemodialysis: A Long Term Follow-Up Study

Auris·Nasus·Larynx (Tokyo) 19, 105-113 (1992)

THE HEARING OF THE PATIENTS TREATED WITH HEMODIALYSIS: A LONG TERM FOLLOW-UP STUDY Jun KusAKARI, M.D., Akira HARA, M.D., Minoru TAKEYAMA, M.D., Shigeru SUZUKI, M.D.,* and Tairiku IGARI, M.D.** Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan *Department of Otolaryngology and **Department of Urology, Kesennuma Municipal Hospital, Kesennuma, Japan

Sensorineural hearing loss is frequently found in the patients under the treatment with hemodialysis, but the responsible etiological factor(s) still remains controversial. The purpose of the present study was to determine by a long term follow-up study whether hemodialysis per se or other factors induce sensorineural hearing loss. Thirty-seven patients with the observation periods of 4 years or longer were selected for the analysis. Hearing tests were performed soon after the initiation of hemodialysis and every 3 to 12 months thereafter. Significant hearing loss was found in 16 cases ( 31 ears) at the first test. Although 3 cases ( 5 ears) of the initially normal group and one case (2 ears) of the group with already existing hearing loss exhibited significant hearing loss, the change in the hearing level was quite minimal in remaining 67 ears during the observation period. Although the cochlea in patients under the treatment with hemodialysis is susceptible to various insults, we conclude that hemodialysis per se does no harm to the cochlea and the hearing can be maintained at the pre-hemodialysis level in the majority of the cases. The patients under the treatment of hemodialysis (HD) frequently exhibit the sensorineural hearing loss (SNHL). Although several causes of this SNHL had been proposed, the true etiology is still controversial. Many investigators attribute the SNHL to metabolic disturbances secondary to renal failure or ototoxic drugs given during the course of the treatment (Y ASSIN, BADRY, and FATTHI, 1970; BERGSTROM, JENKINS, SANDO, and ENGLISH, 1973; QUICK, 1976; THOMSEN, BECH, and SZPIRT, 1979; MIRAHMADI and VAZIRI, 1980; KUSAKARI, Received for publication October 3, 1991 This paper was presented at the 20th International Congress of Audiology, Puerto de Ia Crus, Spain, in October 1990. 105

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KOBAYASHI, ROKUGO, ARAKAWA, 0HYAMA, KAWAMOTO, and SEKINO, 1981; ZAKOSCHIELNA, UKLEJA, NARTOWICZ, and RAJEWSKI, 1982) but several reports ascribe it to HD per se (RANSOME, BALLANTYNE, SHALDON, BOSHER, and HALLPIKE, 1966). Consequently, it is worthwhile examining the course of hearing during the period of HD treatment. However, studies along this line are quite limited (HENRICH, THOMPSON, BERGSTROM, and LUM, 1977; KLINGERMAN, SOLANGI, VENTRY, GOODMAN, and WESLEY, 1981) and the long term follow-up study has not been reported in review of the available literature. The purpose of the present study is to determine by a long term follow-up study whether the hearing deteriorates or not. MATERIALS AND METHODS The test subjects were patients treated with HD at Kesennuma Municipal Hospital under the diagnosis of chronic renal failure. Pure tone audiometry was performed soon after the initiation of HD treatment and every 3 to 12 months thereafter. This study was started with 24 patients in November 1977 and 31 new patients were added thereafter. Among these patients, 37 cases (27 males and 10 females) in which the duration of follow-up studies were 4 years or longer were selected for analysis in the present study. Their ages at the time of the first hearing test were 40.4± 10.5 in male and 42.3± 16.5 in female (mean±SD), respectively, and the duration of follow-up study was 8 years and 9 months in average (the longest was 11 years and 8 months) (Fig. 1). The general conditions of these patients were well controlled by HD. In the present study, significant hearing loss was defined when the hearing level was lower than the normal mean of the same age group by 20 dB or more. RESULTS The results of hearing test at the time of HD initiation are shown in Table 1. 10

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The hearing corresponding to age was found in 43 ears, whereas a significant hearing loss was observed in 31 ears. The shape of the audiogram was a high tone loss in the majority of these cases and was bilaterally symmetric in all cases except for one in which one ear was normal but the other exhibited a hearing loss at 8kHz. The results of the long term observation are shown in Table 2. In group A in which the hearing was normal at the first test, the hearing significantly deteriorated in only 3 cases ( 5 ears) during the period of the observation and follow-up studies on these ears revealed that the hearing had completely recovered in 2 ears, partially recovered in one and not recovered in the remaining two. In group B where the hearing was already reduced at the first test, the hearing level was unchanged in all ears except for one case in which both ears exhibited further deterioration. Consequently, other 67 showed neither deterioration nor improvement during the observation period, although minor fluctuation in hearing (within lOdB) was occasionally observed. The difference in averages of 7 frequencies between the first and the last tests was only 2.3±5.9dB in these 67 ears. There was no difference in the amount of hearing loss between the groups with the observation periods of 4 to 7 years (2.2±6.4dB, n =37) and 8 to 12 years (2.4±5.6dB, n =30). The histories and clinical courses of the 4 cases which exhibited a significant hearing loss were as follows. Case 1. A 26-year-o/d male The first hearing test was performed in November 25, 1977, and his hearing had been confirmed to be normal until January 7, 1981. He was involved by a traffic accident on January 18 of the same year and developed the fracture of his right tibia. He was admitted to a local orthopedic hospital and treated by a cast and

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medication, the details of which are unknown. During the treatment, he noticed tinnitus in the bilateral ears and the hearing test performed in March 11, 1981, revealed significant hearing loss at 8kHz (Fig. 2). His audiogram remained unchanged during the following 6 and a half years. Case 2. A 24-year-old female Her hearing had been within normal limits until at least May 15, 1983, since the first examination (November 25, 1977). She noticed some fullness and obstructive feeling in her bilateral ears around the end of September 1983. Hearing test performed in October 24 revealed bilaterally symmetric low tone loss of 20 dB or so in air and bone conductions. Her complaints gradually progressed and the hearing loss at the low tone area had increased to 30 to 35 dB 3 months later. The patient was treated with oral administration of pentoxifylline and a minor tranquilizer. Her complaints gradually improved with medication and her hearing returned to the normal level by February 2, 1984 (Fig. 3). Case 3. A 43-year-old male His hearing had been normal since the first examination (January 22, 1978) until October 10, 1983, when his left ear suddenly developed total deafness. He was treated with steroid and his hearing was gradually improved at low frequencies but there was no remarkable recovery at mid and high frequencies (Fig. 4). Case 4. A 64-year-old female The first hearing test (March 16, 1978) revealed a significant hearing loss at 8

HEARING LOSS AND HEMODIALYSIS 125

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kHz but the hearing levels at other frequencies were within normal limits for her age. During the observation of 9 years, her hearing gradually worsened (Fig. 5). DISCUSSION AND CONCLUSION Renal insufficiency has been known to induce SNHL since GRAHE's report ( 1924) and there are several animal experiments suggesting that the renal failure induces SNHL (ADLER, FIEHN, and RITZ, 1980; IKEDA, KUSAKARI, ARAKAWA,

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Audiogram of case 4. (I) March 16, 1978; (2) June 28, 1983; (3) August 4, 1987. Table 3.

Percentage of the patients with SNHL. Patients with SNHL/Total No.

Authors YASSIN eta/. BERGSTROM et a/. OoA et al. QUICK THOMSEN et a/. MIRAHMADI and VAZIRI KUSAKARI et a/. ZAKOSCIELNA et a[.

Table 4. 1. 2. 3. 4. 5. 6. 7.

53/71 91/224 43/290 107/602 26/262 9/23 137/229 27/35

(1970) (1973) (1974) (1976) (1976) (1980) (1981) ( 1982)

(74.6%) (40.6%) (14.6%) (17.8%) (9.9%) (39.1%) (59.8%) (77.1%)

Possible etiological factors.

Ototoxic drugs Uremic toxin Anemia Vascular problems Electrolyte imbalance Disturbances in metabolism Immunodeficiency

and KAWAMOTO, 1987). HD has prolonged the life span of the patients with chronic renal failure, so that the number of the such patients has been increasing annually. Many investigators have reported the high incidence of SNHL in HD patients (Table 3) and the possible candidates for etiological factors proposed so far are summarized in Table 4. Then, the question arises as to whether

0HYAMA, INAMURA,

HEARING LOSS AND HEMODIALYSIS

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this high incidence of SNHL is due to the renal failure before the induction of HD treatment or the direct harm to the cochlea by HD treatment. In 37 cases in the present study, significant hearing loss was observed in 24 cases ( 4 7 ears) at the first hearing test, although the causes of SNHL in these patients were not determined in all cases except for two, one was caused by acoustic trauma and another by Streptomycin ototoxicity. These results indicate that SNHL had already existed before the induction of HD treatment in most cases and it is highly likely that SNHL was induced by metabolic disturbances secondary to renal failure or insult to the cochlea possibly potentiated by the status of renal insufficiency. It is the main purpose of the present study to know what happens in these already existing SNHL after the induction of HD treatment and whether new SNHL is induced during the period of HD treatment. In the present study, 4 cases exhibited significant hearing loss during the observation period. Case I developed bilateral hearing loss at 8 kHz during the treatment for the bone fracture. Although it was impossible to obtain detailed information on medication used, it is highly possible that aminoglycoside antibiotic was given to prevent infection. It is well known that the ototoxicity of aminoglycoside antibiotics is potentiated in case of renal failure and its initial symptom is a high tone hearing loss (BALLANTYNE, 1976; BROGARD, CONRAUX, COLLADO, and LAVILLAUREIX, 1982; JOHNSON, 1988). Although we have no clear evidence, it is highly possible that the hearing loss in this case is due to the ototoxic antibiotics. Case 2 exhibited a low tone hearing loss. This type of hearing loss is known to occur at the early stage of Meniere's disease in which the endolymphatic hydrops is a characteristic feature. The stria vascularis plays an important role in the production of endolymph and maintenance of its characteristic ionic composition. Several temporal bone studies on HD patients had shown the edema and/or atrophy of the stria vascularis suggesting its dysfunction (BERGSTROM eta/., 1973; 0DA, PRECIADO, QUICK, and PAPARELLA, 1974; RIZVI and HOLMES, 1980). Furthermore, BERGSTROM eta/. ( 1973) clearly demonstrated a case with endolymphatic hydrops. It is also reported that a rapid reduction in serum osmolarity by HD produces migration of the fluid from the serum into intracellular and interstitial spaces (reverse urea phenomenon) which may facilitate the induction of the endolymphatic hydrops (PETERSON and SWANSON, 1964). Accordingly, it is highly possible that the low tone deafness in this case is due to the transient endolymphatic hydrops. The third case developed sudden deafness. Several investigators reported higher incidence of sudden deafness in HD patients (RANSOME et a/., 1966; BERGSTROM et a/., 1973; QUICK, 1976). Although the etiology of this disease is not fully understood, the most probable candidates are viral infection and vascular disorders, both of which are frequently seen in HD patients. Namely, they are easily infected because of a depressed immunodefence mechanism and frequently have vascular disorders especially in the brain due to the disturbances in lipid metabolism or long term heparinization (MAHER, 1981). In case 4, hearing level progressively deteriorated

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with age. It is likely that the age factor was enhanced by metabolic disturbances secondary to renal insufficiency. RANSOME et al. (1966) considered Polybrene (hexadimethrine bromide, Abbott) used during the HD treatment induces SNHL by obstructing small blood vessels in the cochlea. THOMSEN et al. (1976) and ODA et al. (1973) reported the number of SNHL cases increased as the period of HD was prolonged. In contrast to these reports, several investigators have described that the hearing threshold is not significantly changed during the course of HD treatment. KLINGERMAN, SOLANGI, VENTRY, GOODMAN, and WESELEY (1981) examined the hearing before and 1 year after the initiation of HD treatment, and found no significant change. HENRICH et al. (1977) reported the results of follow-up study of 20 patients (average of the observation period was 18.4 months), which exhibited no change, decrease, and improvement in hearing level in 15, 2, and 3 cases, respectively. Their observation periods, however, do not seem to be long enough to evaluate sufficiently the effect of HD upon the hearing and the present work is the first report to study for this purpose as far as we reviewed the available literature. In the present 37 cases in which the period of follow-up study was 4 years or longer, all cases except for 4 described above exhibited neither the improvement nor the deterioration in hearing during the observation period. This result strongly suggests that the high incidence of SNHL in HD patients is mainly due to renal failure before the induction of HD treatment and HD per se does not harm the cochlea, although the cochlea of the HD patient is always susceptible to development of SNHL. In other words, the hearing can be maintained to the level before the induction of HD in majority of the cases, unless additional insult is given to the cochlea. The authors are indebted to Mr. T. Onodera and Mrs. M. Kumagai of Kesennuma Municipal Hospital for their technical assistance. REFERENCES ADLER, D., FIEHN, W., and RITZ, E.: Inhibition of Na+,K+ -stimulated ATPase in the cochlea of the guinea pig. Acta Otolaryngol. (Stockh.) 90: 55-60, 1980. BALLANTYNE, J. C.: Ototoxic drugs. In Scientific Foundations of Otolaryngology (Hinchcliff, R., and Harrison, D., eds.), pp. 849-8!i2, William Heinemann Medical Books, London, 1976. BERGSTROM, L., JENKINS, P., SANDO, I., and ENGLISH, G. M.: Hearing loss in renal disease: Clinical and pathological studies. Ann. Otol-Rhinol-Laryngol. 82: 555-576, 1973. BROGARD, J. M., CONRAUX, C., COLLADO, M., and LAVILLAUREIX, J.: Ototoxicity oftoburamycin in humans-Influence of renal impairment. Int. J. Clin. Pharmacal. Ther. Toxicol. 20:408-416, 1982. GRAHE, K.: Hor- und Gleichgewichtsstorungen bei Nephritis. Z. Hals-Nasen-Ohrenheilkd. 8: 375-389, 1924.

HENRICH, W. L., THOMPSON, P., BERGSTROM, L., and LUM, G. M.: Effect of dialysis on hearing acuity. Nephron 18: 348-351, 1977. IKEDA, K., KUSAKARI, J., ARAKAWA, E., 0HYAMA, K., INAMURA, N., and KAWAMOTO, K.: Cochlear potentials of guinea pigs with experimentally induced renal failure. Acta Otolaryngol.

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(Stockh.) Suppl. 435: 40-45, 1987. JoHNSON, C. A.: Hearing loss following the application of topical neomycin. J. Burn Care Rehabil. 9: 162-164, 1988. KLINGERMAN, A. B., SOLANGI, K. B., VENTRY, I. M., GOODMAN, A. 1., and WESELEY, S. A.: Hearing impairment associated with chronic renal failure. Laryngoscope 91: 583-592, 1981. KUSAKARI, J., KOBAYASHI, T., ROKUGO, M., ARAKAWA, E., 0HYAMA, K., KAWAMOTO, K., and SEKINO, H.: The inner ear dysfunction in hemodialysis patients. Tohoku J. Exp. Med. 135: 359369, 1981. MAHER, J. E.: Dialysis. In Contemporary Nephrology, Vol. 1 (Klahr, S., and Massery, S. G., eds.), pp. 579-629, Plenum Medical Book Co., New York and London, 1981. MIRAHMADI, M. K., and VAZIRI, N. D.: Hearing loss in end-stage renal disease--Effect of dialysis. J. Dialysis 4: 159-165, 1980. 0DA, M., PRECIADO, M. C., QUICK, C. A., and PAPARELLA, M. M.: Labyrinthine pathology of chronic renal failure patients treated with hemodialysis and kidney transplantation. Laryngoscope 84: 1489-1506, 1974. PETERSON, H., and SWANSON, A. G.: Acute encephalopathy occuring during hemodialysis. Arch. Intern. Med. 113: 877-880, 1964. QUICK, C. A.: Hearing loss in patients with dialysis and renal transplants. Ann. Otol-Rhinol-Laryngol. 85: 776-790, 1976. RANSOME, J., BALLANTYNE, J. C., SHALDON, S., BOSHER, S. K., and HALLPIKE, C. S.: Perceptive deafness in subjects with renal failure treated with hemodialysis and polybrene. J. Laryngol. 80: 651-677, 1966. RIZVI, S. S., and HOLMES, R. A.: Hearing loss from hemodialysis. Arch. Otolaryngol. 106: 751-756, 1980. THOMSEN, J., BECH, P., and SzPIRT, W.: Otologic symptoms in chronic renal failure. The possible role of aminoglycoside-furosemide interaction. Arch. Otol-Rhinol-Laryngol. 214: 71-79, 1976. YASSIN, A., BADRY, A., and FATT-HI, A.: The relationship between electrolyte balance and cochlear disturbances in cases of renal failure. J. Laryngol. 84: 429-435, 1970. ZAKOSCIELNA, L., UKLEJA, Z., NARTOWICZ, E., and RAJEWSKI, W.: Hearing acuity evaluation in patients dialysed for chronic renal failure. Otolaryngol. Pol. 36: 147-153, 1982.

Request reprints to: Dr. J. Kusakari, Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305, Japan