Home Ahead of print Instructions Contacts
About us Current issue Submit article Advertise  
Editorial board Archives Subscribe Login   


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 24  |  Issue : 4  |  Page : 237-241

Effect of N-acetylcysteine on cochlear function in patients with chronic kidney disease undergoing hemodialysis


1 Department of Otolaryngology, Isfahan University of Medical Sciences, Isfahan, Iran
2 Communication Disorders Research Center, Rehabilitation Sciences Institute, Isfahan University of Medical Sciences, Hezar Jarib St, Isfahan University, Isfahan, Iran

Date of Web Publication15-Mar-2019

Correspondence Address:
Dr. Mohammad Shafieyan Sararoodi
No. 64, Bagh Ziar Street, Sohrevardi Street, Isfahan
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/indianjotol.INDIANJOTOL_6_18

Rights and Permissions
  Abstract 


Objective: This study aimed to investigate the effect of N-acetylcysteine (NAC) on cochlear function in patients with chronic kidney disease (CKD). Methodology: The statistical population of this controlled clinical trial included all CKD patients. In total, 64 samples, selected from patients visiting the Dialysis Center of Al-Zahra Hospital from February 2017 to May 2017, were equally randomized into the intervention and control groups. At the baseline, the pure-tone audiometry (PTA) and Distortion Product Oto Acoustic Emissions (DP-OAE) tests were conducted. Then, NAC was administered in the intervention group for 8 weeks. Aforementioned hearing tests were repeated at the end of the interventions and results were compared. Finally, data analysis was carried out in SPSS. Results: Based on the mean scores of hearing threshold, there was no significant between-group difference in the speech discrimination score (SDS) speech reception threshold (SRT) of the left and right sides following NAC administration (P > 0.05). Comparison of the mean OAE following NAC administration showed a significant between-group difference, based on the mean signal/noise ratios (S/N 1000, 2000, and 4000) of the both right and left ears (P < 0.05). To compare the mean DP-OAE changes before and after the intervention between the two groups, the difference between pre- and post-intervention DP-OAE variables was first computed. Then, these changes were compared. A significant between-group difference was observed in S/N ratios of 1000, 2000, and 4000 Hz of the both right and left sides before and after the intervention (P < 0.05). In contrast, changes in other variables did not imply a significant between-group difference (P > 0.05). Conclusion: This study showed the effectiveness of NAC in improving cochlear function in 1, 2, and 4 KHz; whereas, it did not significantly affect the hearing threshold.

Keywords: Antioxidant, chronic kidney disease, N-acetylcysteine, oxidative stress


How to cite this article:
Abtahi H, Mortazavi M, Sararoodi MS, Rogha M, Sepehrnejad M, Nilforoush MH. Effect of N-acetylcysteine on cochlear function in patients with chronic kidney disease undergoing hemodialysis. Indian J Otol 2018;24:237-41

How to cite this URL:
Abtahi H, Mortazavi M, Sararoodi MS, Rogha M, Sepehrnejad M, Nilforoush MH. Effect of N-acetylcysteine on cochlear function in patients with chronic kidney disease undergoing hemodialysis. Indian J Otol [serial online] 2018 [cited 2019 Apr 23];24:237-41. Available from: http://www.indianjotol.org/text.asp?2018/24/4/237/254234




  Introduction Top


Due to the increased prevalence of diabetes and hypertension, as the major risk factors of chronic kidney disease (CKD), the number of CKD patients has been increased in recent years.[1],[2] The prevalence of sensorineural hearing loss in such patients is very higher than the normal population. According to studies, this prevalence varies with 77% mild cases and 46% moderate-to-severe cases.[3],[4],[5],[6]

Regarding the increased longevity of these patients, owing to new dialysis techniques, hearing loss is associated with significant effects on their life and social relations.[7] The relationship between CKD and sensorineural hearing loss has been established by previous studies; however, the main reason behind this connection continues to remain uncertain.[1]

Active water and electrolyte transfer through stria vascularis in the inner ear and renal glomeruli indicates a similar physiological mechanism in glomeruli and cochlea. Glomerular injury because of water electrolyte and hormonal imbalance damages hair cells of cochlea, resulting in sensorineural hearing loss commonly at high frequencies.[8],[9],[10],[11]

Except from these disorders, other plausible reasons of hearing impairment in CKD patients mentioned in the literature are antigenic similarity between the cochlea and the glomeruli suggesting the origin of autoimmunity, uremic toxins, hypotension periods, hypoxia, pharmacodynamic changes of ototoxic drugs, cochlear hair cells dysfunction or loss, collapse of endolymphatic space, auditory cells atrophy and edema, and neuropathy, as well as severe fluctuations in blood pressure during dialysis and the accumulation of toxic substances in dialysis solution in some patients undergoing dialysis.[12],[13]

On the other hand, CKD patients undergoing hemodialysis are prone to exacerbated oxidative stress, which can be attributed to increased production of free radicals of oxygen in the body (because of uremic syndrome, chronic inflammatory state, and bioincompatibility of dialysis solutions and membranes) and reduced antioxidant ability (because of Vitamin C and E deficiencies and reduced activity of glutathione system).[14],[15]

In the process of hearing impairment examination, adoption of a suitable test to examine the organ of hearing is an important and sensitive stage. Otoacoustic emissions (OAEs) are sound waves generated by the cochlea in the process of receiving a sound and transforming it into cellular and neural stimulation. Recording of an OAE implies a functional cochlea and healthy middle ear mechanism.[12] The basic hearing tests, such as the pure-tone audiometry (PTA), may not have the same sensitivity as OAE in detecting initial ototoxic changes. Among other advantages of OAE tests are cost-effectiveness, quickness, and no need for behavioral responses of patients. These advantages make it applicable in a coma state.[16],[17] Studies into ototoxic effects on hearing have reported oxidative stress as the main cause in the pathophysiology of ototoxicity.

To cope with undesirable effects of oxidative stress, different antioxidants, specifically N-acetylcysteine (NAC), are used. It is an antioxidant, which has been originally used and continues to be used as a mucolytic drug in pulmonary patients. Recent studies have investigated and proved the effectiveness of NAC in improving ischemic and toxic damages to the heart, kidney, liver, and lung. The long-lasting protective effects of this drug on the cochlea and its outer hair cells have been shown by some studies.[18],[19],[20],[21],[22]

Among these effects is the protection of hearing cells of inner ear against ototoxic drugs, including cisplatin or aminoglycosides, which may be attributed to its antioxidative property of NAC.[23],[24],[25],[26]

According to these and other advantages of NAC mentioned above (i.e., simplicity, cost-effectiveness, and safety), it seems that administration of this medicine in CKD patients can be an effective and rational measure for preventing from incidence or exacerbation of hearing loss. Despite the conduction of several studies into the effectiveness of NAC in preventing ototoxic effects of drugs and other factors, there are scant studies on the effect of this medicine on hearing of renal patients, apart from drug consumption and ototoxic factors. Therefore, we decided to investigate the effect of NAC on cochlear function in patients with kidney disorder, aiming to take a step toward improving the hearing and quality of life of such patients who account for a large portion of chronic patients.


  Methodology Top


The statistical population of this controlled clinical trial included all CKD patients undergoing hemodialysis. Samples were selected from patients in the Hemodialysis Unit of Al-Zahra Hospital from February 2017 to May 2017. The inclusion criteria were patients with CKD undergoing hemodialysis. Exclusion criteria were CKD patients with a history of ear surgery, congenital hearing loss, acoustic trauma, medicine withdrawal because of NAC complications (anaphylaxis reaction and severe bronchospasm), any disorder in initial hearing tests except sensorineural hearing loss, and giving NAC to control patients for any reason. In addition, patients who requested withdrawal from the study were excluded.

Patients visiting the Hemodialysis Unit of Al-Zahra Hospital were alternately randomized into the intervention and control groups, using the random number table, until achieving 32 samples in each group. Written informed consent of the patients was obtained after explaining the research process by the researcher at enrollment.

First, patients were referred to the audiology center for taking PTA and OAE tests. Tests were administered and interpreted by a specialist with a master's degree in audiology. In the next stage, intervention patients were treated with NAC tablets (Oslyt) 600 mg (Osveh Co.) twice a day for 8 weeks.[24] The control patients received placebo. After the interventions, the audiometric tests were repeated. Other demographic data of patients including age, sex, weight, height, medicines taken, duration of having disease, duration and number of hemodialysis sessions, and biochemical information (BUN-to-creatinine, sodium-potassium, and glomerular filtration rate) was collected from the interview and medical records.

Then, the collected data were analyzed in SPSS version 22 by a specialist with a master's degree in statistics. The independent t-test was used to compare the mean hearing threshold and DP-OAE values before and after the intervention between the two groups. To make within-group comparison of pre- and post-intervention means of hearing threshold and DP-OAE, the paired t-test was used.


  Results Top


The samples were divided into the control and intervention groups, each containing 32 patients.

The mean and standard deviation of demographic and underlying variables were compared between the two groups. The groups were matched in terms of demographic, underlying, and confounding variables and no statistically significant difference was observed between them (P > 0.05).

The mean scores of hearing threshold variables before the administration of NAC were compared between the two groups, using the independent t-test. Results showed no significant between-group difference in the mean hearing threshold, SDS, and SRT of the right and left sides before the administration of NAC (P > 0.05).

The mean scores of hearing threshold variables after the administration of NAC were compared between the two groups, using the independent t-test. Results showed no significant between-group difference in the mean hearing threshold, SDS, and SRT of the right and left sides after the administration of NAC (P > 0.05).

Results from comparison of hearing threshold variables before and after the administration of NAC are presented in [Table 1]. According to them, there was no significant within-groups difference in the mean hearing threshold, SDS, and SRT of the right and left sides before and after the administration of NAC in the intervention group (P > 0.05). However, there was a significant difference in SDS of the left side before and after the administration of NAC in the intervention group (P < 0.05).
Table 1: Comparison of mean hearing threshold, SDS, and SRT before and after administration of N-acetylcysteine in the intervention group

Click here to view


The mean scores of hearing threshold variables before and after the administration of NAC were compared in the control group, using the paired t-test. Results showed no significant within-group difference in the mean hearing threshold, SDS, and SRT of the right and left sides before and after the administration of NAC in the control group (P > 0.05).

To compare the mean hearing threshold changes before and after the intervention between the two groups, the difference between pre- and post-intervention hearing threshold variables was first computed. Then, these changes were compared between the two groups using the independent t-test.

According to [Table 2], there was no significant difference between the mean changes of variables (P > 0.05).
Table 2: Between-group comparison of mean hearing threshold, SDS, and SRT changes before and after administration of N-acetylcysteine

Click here to view


To determine and compare the mean OAE before the administration of NAC between the two groups, the mean DP-OAE variables before the administration of NAC were compared, using the independent t-test. Results showed no significant between-group difference in the mean signal/noise (S/N) ratios of the right and left sides before the administration of NAC (P > 0.05).

Comparison of the mean OAE following the administration of NAC showed a significant between-group difference in the mean S/N ratios (1000, 2000, and 4000 Hz) in the right and left side (P < 0.05) [Table 3].
Table 3: Between-group comparison of otoacoustic emissions results after administration of N-acetylcysteine

Click here to view


The mean scores of OAE variables before and after the administration of NAC were compared in the intervention group using the paired t-test. According to the results, the mean S/N ratios (1000, 2000, and 4000 Hz) of the left and right sides were significantly different before and after the administration of NAC in the intervention group (P < 0.05). However, there was no significant difference in the intervention group before and after the administration of NAC (P > 0.05) [Table 4].
Table 4: Comparison of mean otoacoustic emissions results before and after administration of N-acetylcysteine in the intervention group

Click here to view


Comparison of the mean DP-OAE in the right and left sides before and after the administration of NAC in the control group showed no significant difference (P > 0.05).

To compare the mean DP-OAE changes before and after the intervention between the two groups, the difference between pre- and post-intervention DP-OAE variables was first computed. Then, these changes were compared using the independent t-test. A significant between-group difference was observed in S/N ratios of 1000, 2000, and 4000 Hz in the right and left sides before and after the intervention (P < 0.05). In contrast, changes in other variables did not imply a significant between-group difference (P > 0.05) [Table 5].
Table 5: Between-group comparison of mean otoacoustic emission results changes before and after administration of N-acetylcysteine

Click here to view



  Discussion Top


Results of this study showed no significant between-group difference in the mean hearing threshold, SDS, and SRT of the left and right sides after the administration of NAC (P > 0.05). In this regard, Coleman et al. investigated the effect of three different doses of sodium salicylate (SAL) in combination with one dose of NAC to prevent noise-induced hearing loss in a kind of little rodent. This study was conducted on a group of animals. Findings showed the effectiveness of SAL in combination with NAC in reducing noise-induced injury to the cochlea. In other words, NAC alone did not significantly affect the cochlear function, as compared to other groups.[19] Kocyigit et al. investigated the effect of NAC dose on cochlear function and oxidant situation. Their study was conducted on 46 patients with peritoneal dialysis (PD)-related peritonitis attacks receiving empirical amikacin treatment. According to the results, the mean hearing thresholds in the NAC and control groups were not significantly different.

According to the results, the mean hearing thresholds in the NAC and control groups were not significantly different. Moreover, no significant difference was observed in hearing threshold binaurally after NAC administration in the intervention group (P>0.05). However, OAE results were significantly different between the two groups.

As a result, NAC was found to be safe and effective in amikacin-related ototoxicity in patients with peritoneal dialysis-related peritonitis.[18]

Comparison of the mean OAE following the administration of NAC showed a significant between-group difference in the mean S/N ratios (1000, 2000, and 4000 Hz) in the right and left sides (P < 0.05). In this regard, Bendo et al. investigated 53 individuals (43 dialysis patients and 10 control). According to their findings, the sensorineural hearing loss was observed in 67% of audiometry results of the hemodialysis patients. They also observed DP-OAE reduction in 77% of these patients. They concluded that DP-OAE value was lower than the impedance audiometry value, and thus it can be used for early diagnosis of cochlear injury.[14]

Darrat et al. investigated the role of antioxidants in the management of hearing loss. Results showed the effectiveness of treatment with antioxidants in reducing, curing, or preventing the relapse of different types of acquired hearing loss. According to them, the majority of recent studies have reported the significant effectiveness of antioxidants in treating hearing loss.[15]

In a study conducted by Jafari et al., they showed the effectiveness of N-acetylcysteine (NAC) in treating noise-induced hearing loss in high frequencies. This study can be taken as a foundation for further studies for reducing noise-induced injuries.[27]

Feldman et al. investigated the effectiveness of NAC in improving the provocative autocysts of aminoglycosides in dialysis patients. According to them, aminoglycosides are correlated with high level of autocysts, specifically in patients with kidney failure or poor renal function. In addition, NAC has been shown as an effective and safe antioxidant for dialysis patients.[23]


  Conclusion Top


This study showed the effectiveness of NAC in improving cochlear function. NAC might be useful to add in prescription for CKD patient in order to prevent more hearing loss during their treatment.

Furthermore, hearing evaluations like DP-OAE would be helpful to monitor probable ototoxicity during medical management.

Financial support and sponsorship

This study was financially supported by Isfahan University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gatland D, Tucker B, Chalstrey S, Keene M, Baker L. Hearing loss in chronic renal failure-hearing threshold changes following haemodialysis. J R Soc Med 1991;84:587-9.  Back to cited text no. 1
    
2.
Bendo E, Resuli M, Metaxas S. Hearing evaluation in patients with chronic renal failure. J Acute Dis 2015;4:51-3.  Back to cited text no. 2
    
3.
Sam SK, Subramaniam V, Pai S, Kallikkadan H. Hearing impairment in patients with chronic renal failure. J Med Sci Clin Res 2014;2:406-16.  Back to cited text no. 3
    
4.
Meena RS, Aseri Y, Singh BK, Verma PC. Hearing loss in patients of chronic renal failure: A study of 100 cases. Indian J Otolaryngol Head Neck Surg 2012;64:356-9.  Back to cited text no. 4
    
5.
Jamaldeen J, Basheer A, Sarma AC, Kandasamy R. Prevalence and patterns of hearing loss among chronic kidney disease patients undergoing haemodialysis. Australas Med J 2015;8:41-6.  Back to cited text no. 5
    
6.
Jakić M, Mihaljević D, Zibar L, Jakić M, Kotromanović Z, Roguljić H, et al. Sensorineural hearing loss in hemodialysis patients. Coll Antropol 2010;34 Suppl 1:165-71.  Back to cited text no. 6
    
7.
Bains KS, Chopra H, Sandhu JS, Aulakh BS. Cochlear function in chronic kidney disease and renal transplantation: A longitudinal study. Transplant Proc 2007;39:1465-8.  Back to cited text no. 7
    
8.
Feldman L, Efrati S, Eviatar E, Abramsohn R, Yarovoy I, Gersch E, et al. Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-acetylcysteine. Kidney Int 2007;72:359-63.  Back to cited text no. 8
    
9.
Sazgar AA, Ahmadi F, Akrami K, Akrami S, Abbasi MR, Rasool F, et al. Vestibular evoked myogenic potentials of haemodialysed patients with end stage renal disease. Eur Arch Otorhinolaryngol 2008;265:393-6.  Back to cited text no. 9
    
10.
Stamper GC, Johnson TA. Auditory function in normal-hearing, noise-exposed human ears. Ear Hear 2015;36:172-84.  Back to cited text no. 10
    
11.
Vilayur E, Gopinath B, Harris DC, Burlutsky G, McMahon CM, Mitchell P, et al. The association between reduced GFR and hearing loss: A cross-sectional population-based study. Am J Kidney Dis 2010;56:661-9.  Back to cited text no. 11
    
12.
Naderpour M, Mortazavi F, Jabbari-Moghaddam Y, Sharifi-Movaghar MH. Auditory brain stem response and otoacoustic emission results in children with end-stage renal disease. Int J Pediatr Otorhinolaryngol 2011;75:704-7.  Back to cited text no. 12
    
13.
Sharma R, Gaur S, Gautam P, Tiwari R, Narain A, Lalchandani T. A study on hearing evaluation in patients of chronic renal failure. Indian J Otol 2011;17:109-12.  Back to cited text no. 13
  [Full text]  
14.
Bendo E, Resuli M, Metaxas S. DPOAE measurements in comparison to audiometric measurements in hemodialyzed patients. J Acute Dis 2015;4:226-9.  Back to cited text no. 14
    
15.
Darrat I, Ahmad N, Seidman K, Seidman MD. Auditory research involving antioxidants. Curr Opin Otolaryngol Head Neck Surg 2007;15:358-63.  Back to cited text no. 15
    
16.
Thorson MJ, Kopun JG, Neely ST, Tan H, Gorga MP. Reliability of distortion-product otoacoustic emissions and their relation to loudness. J Acoust Soc Am 2012;131:1282-95.  Back to cited text no. 16
    
17.
Reavis KM, McMillan G, Austin D, Gallun F, Fausti SA, Gordon JS, et al. Distortion-product otoacoustic emission test performance for ototoxicity monitoring. Ear Hear 2011;32:61-74.  Back to cited text no. 17
    
18.
Kocyigit I, Vural A, Unal A, Sipahioglu MH, Yucel HE, Aydemir S, et al. Preventing amikacin related ototoxicity with N-acetylcysteine in patients undergoing peritoneal dialysis. Eur Arch Otorhinolaryngol 2015;272:2611-20.  Back to cited text no. 18
    
19.
Coleman J, Huang X, Liu J, Kopke R, Jackson R. Dosing study on the effectiveness of salicylate/N-acetylcysteine for prevention of noise-induced hearing loss. Noise Health 2010;12:159-65.  Back to cited text no. 19
[PUBMED]  [Full text]  
20.
Maniu A, Perde-Schrepler M, Cosgarea M. Protective effect of L-N-acetylcysteine against gentamycin ototoxicity in the organ cultures of the rat cochlea. Rom J Morphol Embryol 2011;52:159-64.  Back to cited text no. 20
    
21.
Tokgoz B, Ucar C, Kocyigit I. Protective effect of nacetylcysteine from drug-induced ototoxicity in uraemic patients with CAPD peritonitis. Nephrol Dial Transpl 2011;26:4073-8.  Back to cited text no. 21
    
22.
Yoo J, Hamilton SJ, Angel D, Fung K, Franklin J, Parnes LS, et al. Cisplatin otoprotection using transtympanic L-N-acetylcysteine: A pilot randomized study in head and neck cancer patients. Laryngoscope 2014;124:E87-94.  Back to cited text no. 22
    
23.
Feldman L, Sherman RA, Weissgarten J. N-acetylcysteine use for amelioration of aminoglycoside-induced ototoxicity in dialysis patients. Semin Dial 2012;25:491-4.  Back to cited text no. 23
    
24.
Kranzer K, Elamin WF, Cox H, Seddon JA, Ford N, Drobniewski F, et al. A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: Implications for the treatment of multidrug-resistant TB. Thorax 2015;70:1070-7.  Back to cited text no. 24
    
25.
Riga MG, Chelis L, Kakolyris S, Papadopoulos S, Stathakidou S, Chamalidou E, et al. Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: A feasible method with promising efficacy. Am J Clin Oncol 2013;36:1-6.  Back to cited text no. 25
    
26.
Ewert DL, Lu J, Li W, Du X, Floyd R, Kopke R, et al. Antioxidant treatment reduces blast-induced cochlear damage and hearing loss. Hear Res 2012;285:29-39.  Back to cited text no. 26
    
27.
Jafari A, Badiei R, Tooski MY, Kohansal B. The effect of N-acetylcysteine on the reduction of permanent noise-induced hearing loss in workers at HEPCO Company. Arak Med Univ J 2011;14:11.  Back to cited text no. 27
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Methodology
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed138    
    Printed1    
    Emailed0    
    PDF Downloaded19    
    Comments [Add]    

Recommend this journal