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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 18  |  Issue : 2  |  Page : 76-81

Evaluation of central neuropathy in patients of chronic renal failure with normal hearing


1 Department of ENT and Head and Neck Surgery, Subharti Medical College, Subhartipuram, Meerut, Uttar Pradesh, India
2 Department of Paediatrics, Subharti Medical College, Subhartipuram, Meerut, Uttar Pradesh, India
3 Department of Medicine, Subharti Medical College, Subhartipuram, Meerut, Uttar Pradesh, India

Date of Web Publication6-Sep-2012

Correspondence Address:
Ravinder Sharma
46 Saketkunj, Saket, Meerut, Uttar Pradesh - 250 003
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-7749.100716

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  Abstract 

Aims and Objective: The aim of the study was to study the involvement of inner ear and eighth nerve in patients of chronic renal failure (CRF) with normal hearing. Further, the mean absolute and inter-peak latencies were correlated with the duration of disease, blood urea level, and the severity of the disease. Materials and Methods: A total of 46 patients of CRF with normal hearing (29 males and 17 females) were included in the study. Majority of the patients were in 21 to 40 year age group. Mean absolute latencies of wave I, III, and V, and inter-peak wave latencies I-III, III-V, and I-V were calculated and compared with the mean wave latencies in 15 normal hearing age- and sex-matched control subjects. Student's t test was applied to evaluate the significance of delay in wave latencies. The patients were divided on the basis of the duration of disease (less than 2 years and more than 2 years), blood urea level (less than 200 mg% and more than 200 mg%), and severity of disease (Patients with glomerular filtration rate [GFR] less than 60 mL/min/1.73 m 2 but more than 10 mL and patients with GFR less than 10 mL/min/1.73 m 2). The significant differences between the hearing thresholds of these two groups were assessed using student's t test for unequal samples. Results: There was a statistically significant delay in absolute latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V. Mean wave latencies with values outside mean ± 2 SD of control were considered as abnormal. Abnormal absolute wave latencies and inter-peak latencies were present in 63.05% and 67.39% of cases, respectively. There was a significant delay in mean absolute latency of wave V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with duration of disease more than 2 years as compared with patients of CRF with duration of disease less than 2 years. There was a significant delay in mean absolute latency of wave III and V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with blood urea level more than 200 mg% as compared to patients of CRF with blood urea level less than 200 mg%. There was a significant delay in mean absolute latency of wave III and V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with GFR less than 10 as compared with patients of CRF with GFR less than 60 but more than 10. Conclusion: The study suggests the involvement of central neural axis and auditory end organ in patients of CRF with normal hearing. It further establishes the role of brainstem evoked response audiometry in earlier detection of central neural axis and auditory end organ. As the duration of disease increases, inferior colliculus and auditory pathway is more prone to damage by uremic neuropathy. An increase in blood urea and decrease in GFR (severity of disease) leads to uremic neuropathy causing damage to superior olivary nucleus and inferior colliculus. Increased blood urea also causes delay in inter-peak latencies, suggesting diffuse axonal neuropathy in patients of CRF.

Keywords: Brainstem evoked response audiometry, Central neuropathy, Chronic renal failure, Hearing


How to cite this article:
Sharma R, Gautam P, Gaur S, Kumar S, Taneja V. Evaluation of central neuropathy in patients of chronic renal failure with normal hearing. Indian J Otol 2012;18:76-81

How to cite this URL:
Sharma R, Gautam P, Gaur S, Kumar S, Taneja V. Evaluation of central neuropathy in patients of chronic renal failure with normal hearing. Indian J Otol [serial online] 2012 [cited 2018 Nov 20];18:76-81. Available from: http://www.indianjotol.org/text.asp?2012/18/2/76/100716


  Introduction Top


Chronic renal failure (CRF) is characterized by gradually progressive loss of renal function. With the progressive destruction of nephrons, there is increase in blood urea and serum creatinine, accumulation of toxins, electrolyte imbalance, and metabolic acidosis. One of the common complications of CRF is uremic neuropathy. Few studies suggest the presence of peripheral and central neuropathy in patients of CRF. [1],[2]

This study was planned to evaluate the involvement of end organ and auditory pathway (central neuropathy) in patients of CRF with normal hearing. A total of 46 patients of CRF with normal hearing attending nephrology unit in a tertiary care center from January 2009 to December 2009 were included in the study and the absolute latencies of wave I, III, and V and inter-peak latencies of wave I-III, III-V, and I-V obtained were compared with age- and sex-matched controls. Further, the mean absolute latencies and inter-peak latencies were correlated with the duration of disease, severity of disease, and blood urea level. The results of the findings are presented, with the review of literature.


  Materials and Methods Top


The patients included in the study were cases of CRF attending nephrology unit at a tertiary care center from January 2009 to December 2009. The patients were diagnosed as CRF on the basis of clinical and lab data. The criterion of diagnosis was decreased kidney glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m 2 for 3 or more months. The aims of the study were as follows:

  1. To calculate the absolute wave latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V in patients of CRF with normal hearing and compare values obtained with age- and sex-matched normal hearing controls.
  2. To correlate the mean absolute latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V wave latencies with the duration of CRF.
  3. To correlate the mean absolute latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V wave latencies with blood urea level in the study group.
  4. To correlate the absolute latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V wave latencies with severity of CRF.
A total of 46 patients were included in the study group (29 males and 17 females). These cases were first evaluated in the nephrology unit. A general medical check-up was performed and patients were enquired about the disease (as per proforma). Cases with past history of noise exposure, ear trauma, conductive hearing loss, sensorineural hearing loss, history of ototoxic medication, ear discharge, diabetes, and hypertension were not included in the study.

Thereafter, all patients were subjected to basic tests of renal function (Hb, Hct, blood urea, serum creatinine, blood urea nitrogen (BUN), sodium, and potassium). On the basis of the findings of biochemical investigations, GFR was calculated. Critically ill patients requiring urgent medical attention were not included in the study.

All these patients were then evaluated in the ENT department. In all cases, history was taken for ear symptoms and examination was done. Otoscopy (Welsh Allyn otoscope, [Welch Allyn, NY USA]), tuning fork tests (512 Hz), tympanometry (impedance audiometer AT235 Interacousticus [A/S, MN, USA] with Probe tone frequency of 226 Hz and probe tone intensity of 85dBSPL) and pure tone audiometry (ALPS advanced digital audiometer AD2000, [ Alps0 India Limited, India] with telephonics TDH 39 P headphone and oticon A 20 bone conduction vibrator) was done in all cases to rule out middle ear disease. Ear with perforation of TM and attico-antral disease were not included in the study. Only cases with normal hearing on pure tone audiogram were included in the study.

Brainstem evoked response audiometry was done in all cases with normal hearing. Mean absolute latencies of wave I, III, and V and inter-peak latencies of wave I-III, III-V, and I-V were calculated, and results were compared with mean wave latencies in the control group. Control group included 15 age- and sex-matched normal hearing subjects. Student's t test was applied to evaluate the significance of the difference in wave latencies. Cases with value of wave latencies more than mean wave latencies in control group ± 2 SD were considered as abnormal wave latencies. Further analysis of data was done to evaluate the frequency of delayed wave latencies in these groups.

To study the effect of duration of disease on wave latencies, all patients of CRF were divided into two groups - Group I included 28 cases of CRF with duration of disease less than 2 years and Group II included 18 cases of CRF with duration of disease more than 2 years. The mean wave latencies were compared in both the groups. The significant differences between the hearing thresholds of these two groups were assessed using student's t test for unequal samples.

To study the correlation between blood urea level and mean wave latencies, the patients of CRF with blood urea less than 200 mg% were grouped in one group and patients of CRF with blood urea more than 200 mg% were grouped in the other group. The mean wave latencies of the two groups were correlated by student's t test for unequal samples.

To study the correlation between severity of renal impairment and mean hearing threshold, all patients of CRF included in the study were divided into two groups: Group A included patients with GFR of 60 mL/min/1.73 m 2 but more than 10 mL/min/1.73 m 2 (managed by conservative treatment; 24 patients) and Group B included patients with GFR less than 10 mL/min/1.73 m 2 (managed by hemodialysis CRF:-22 patients). The mean wave latencies and mean blood urea and serum creatinine were calculated in both groups, and statistical analysis was done to evaluate correlation between hearing loss and severity renal impairment.

The result of the study group and control group are presented as the number of ears.


  Results Top


  1. The characteristics of the study group are as shown in [Table 1]. Of the 46 patients, 29 (63.04%) were males and 17 (36.96%) were females, and 80.43% (37/52) of the patients were in 21 to 40 year age group. The mean age group was 36.84 years with a standard deviation of 4.21.
    Table 1: Showing age and sex distribution of patients of chronic renal failure in the study group (Number of patients 46)

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  2. The mean absolute wave latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V in 92 ears of CRF with normal hearing are as shown in [Table 2]. The mean wave latencies were compared with the corresponding mean wave latencies in the control group. There was a statistically significant (P<0.01) difference in absolute wave latencies of wave I, III, and V and inter-peak latencies I-III, III-V, and I-V.
    Table 2: Showing absolute latencies and inter-peak latencies in Case and Control group

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  3. Cases of CRF with wave latencies more than mean ± 2 SD of control were considered abnormal, and cases with wave latencies less than mean ± 2 SD were considered normal. Cases with a delay even in one absolute latency or inter-peak latency were considered abnormal. Absolute wave latencies were abnormal in 63.05% cases and inter-peak latencies were abnormal in 67.39% [Figure 1].
    Figure 1: Showing normal and abnormal absolute latencies and inter-peak latencies in patients of chronic renal failure with normal hearing

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  4. The number of ears with duration of CRF less than 2 years was 56 (60.86%) while number of ears with duration of CRF more than 2 years was 36 (39.14%). The mean absolute wave latencies and inter-peak latencies are as shown in [Table 3]. There was a significant difference (P<0.05) in absolute wave latency of wave V and significant difference in inter-peak latencies of I-III, III-V, and wave I-V. There was a non-significant difference in absolute wave latency of wave I and wave III in both groups.
    Table 3: Showing mean absolute latencies and inter-peak latencies in patients of chronic renal failure with duration of disease < than 2 years and > than 2 years

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  5. To evaluate the correlation between blood urea level and wave latencies, all cases were divided into two groups as shown in [Table 4]. Cases with blood urea level less than 200 mg% were in one group and cases with blood urea more than 200 mg% were in the other group. A total of 69.56% of cases had blood urea less than 200 and 30.44 % of cases had blood urea more than 200. Statistical analysis showed there was a significant delay in mean wave latency of wave III and wave V and non-significant delay in absolute wave latency of wave I. There was a significant difference in inter-peak latency of wave I-III, III-V, and I-V.
    Table 4: Showing mean absolute latencies and inter-peak latencies in patients of chronic renal failure with blood urea level < than 200 mg% and > than 200 mg%

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  6. The mean absolute wave latencies I, III, and V and inter-peak wave latencies I-III, III-V, and I-V of 48 ears (52.17%) of CRF with GFR less than 60 mL/min/1.73 m 2 but more than 10 mL/min/1.73 m 2 (Group A - mean age 33.42±14.23, mean blood urea concentration was 177.23±80.29, and mean serum creatinine was 9.58±6.63) were compared with mean hearing threshold of 44 ears (47.83%) with GFR less than 10 mL/min/1.73 m 2 (Group B - mean age 41±7.28 years, mean blood urea concentration 230.65±98.01, and mean serum creatinine concentration 15.46±7.91) as shown in [Table 5]. There was no significant difference in absolute wave latencies of wave I and significant difference in absolute wave latencies of wave III and V in group A and group B. There was no statistically significant difference in inter-peak latencies of wave I-III, III-V, and I-V in group A and group B.
    Table 5: Showing mean absolute latencies and inter-peak latencies in patients of Chronic Renal Failure with glomerular filtration rate (GFR) less than 60 but more than 10 and with GFR less than 10

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  Discussion Top


CRF is characterized by the gradually progressive destruction of nephrons. When the renal reserve exhausts, it leads to an increase in plasma level of urea and creatinine Possible cause of uremic manifestations in CRF is due to accumulation of toxins due to impairment of renal function. As a result, the blood becomes too acidic, bones starts losing calcium, and nerves starts degenerating. One of the common manifestations of uremia is neuropathy. Uremic neuropathy is mainly due to axonal degeneration and demyelination. [3],[4] Thomas et al.[4] suggested that uremic neuropathy is a multiple neuropathy due to axonal degeneration of the sensory and motor nerves, and it starts from lower extremities. Sensorineural hearing loss in patients of CRF is relatively higher in comparison with the general population. Quite a good number of studies show that patients of CRF have sensorineural hearing loss. [5],[6] The study group in the present study included normal hearing patients of CRF to evaluate the involvement of auditory end organ and central neuropathy.

Pure tone audiometry is a subjective method of hearing assessment. Mohammad et al.[7] suggested transient evoked otoacoustic emission as a more sensitive method as compared with pure tone audiometry (27.2% v/s 19.2% respectively) for evaluation of hearing acuity in patients of CRF. The present study incorporated brainstem evoked response audiometry for evaluating the involvement of auditory end organ and auditory pathway in patients of CRF, as it provides more accurate and objective assessment.

Absolute wave latencies and inter-peak latencies

There was a statistically significant difference in the mean absolute latency of wave I, III, and V and mean inter-peak latency I-III, III-V, and I-V in patients of CRF with normal hearing as compared with age- and sex-matched controls. A significant delay in absolute wave latencies is suggestive of end organ lesion and a significant delay in inter-peak latency is suggestive of axonal neuropathy. As the patients included in the study included those with normal hearing, delay in wave latencies is suggestive of subclinical involvement of auditory end organs and auditory nerve. Rossini [8] and Pratt [9] established that patients of CRF have hearing loss on the basis of pure tone audiometry and brainstem evoked response audiometry. Almost similar results were seen in a study by Aspris et al.[10] and Balzer. [11] Aspris et al.[10] found delay in all wave latencies except inter-peak latency I-III and Balzer et al.[11] found delay in all wave latencies in patients of CRF. Antonielli et al.[2] found a delay in wave latency of I-III and I-V in patients of CRF with normal hearing. Yu et al.[1] reported normal brainstem evoked potentials and subclinical peripheral neuropathy (nerve conduction deficit) in cases of terminal renal failure.

Niedzielska et al.[12] in a similar study on ABR in patients with normal nearing suggested that delay in wave latencies is because of deranged biochemical parameters of uremia. Orendorz - Fraczkowska et al.[13] reported subclinical disturbances in neural conduction of auditory pathway. A variety of causes like uremic toxins, [13] hyperkalemia, [13] electrolyte imbalance, [14] vitamin deficiency, [14] and inhibition of Na + K + activated ATPase enzyme [14] (important for maintaining cationic gradients in cochlea) have been suggested for sensorineural hearing loss in patients of chronic renal failure.

Correlation in hearing loss with duration of disease

There was a statistically significant delay in mean absolute latency of wave V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with duration of disease more than 2 years as compared with patients of CRF with duration of disease less than 2 years. The findings are suggestive of end organ lesion at inferior colliculus (wave V) and demyelination of the auditory pathway as the duration of disease increases. However, there was no significant difference in absolute latency of wave I and Wave III in patients of CRF with duration of disease less than 2 years as compared with the patients of CRF with duration of disease more than 2 years.

The results are suggestive of the fact that uremic neuropathy worsens as the duration of disease increases with significant delay in absolute latency of wave V and inter-peak latencies of wave I-III, III-V, and I-V. The findings are suggestive of progression of subclinical neuropathy as the duration of disease increases. Henrich et al.[15] showed found that 75% of patients showed no deterioration of hearing in pure tone audiometry during a 4-year time of follow-up.

Correlation between wave latencies and blood urea level

There was a significant delay in mean absolute latency of wave III and V and mean inter-peak latency of wave I-III, III-V, and I-V in patients of CRF with blood urea level more than 200 mg% as compared with patients of CRF with blood urea level less than 200 mg%. The findings are suggestive of the progression of uremic neuropathy as the level of blood urea increases. The delay in absolute wave latencies of wave III and V suggests that superior olivary nucleus and inferior colliculus are more prone to damage in patients with higher blood urea level (more than 200 mg%). The delay in inter-peak latencies I-III, III-V, and I-V is suggestive of diffuse axonal neuropathy when blood urea level increases above 200 mg%. Johnson [16] reported that there is no relationship between hearing and serum urea nitrogen.

Correlation between wave latencies and severity of disease

Since the patients of CRF with GFR less than 10 mL/min/1.73 m 2 have relatively less number of nephrons as compared with the patients of CRF with GFR less than 60 mL/min/1.73 m 2 but more than 10 mL/min/1.73 m 2 , they form a group with more severe illness. GFR is the most important predictor of the severity of CRF. This is also a commonly used criterion for planning treatment (conservative treatment or dialysis) in these patients.

There was a statistically significant difference in mean absolute latency of wave III and V and in patients of CRF with GFR less than 10 as compared with patients of CRF with GFR less than 60 but more than 10, suggesting that wave III and wave V generators (superior olivary nucleus and inferior colliculus) are more prone for damage by uremic neuropathy as the severity of disease increases. There is statistically non-significant delay in inter-peak latencies I-III, III-V, and I-V, suggesting that damage to neural pathway does not progress as the disease progresses. This is the first study to make GFR as a criterion for the severity of the disease. Other studies have correlated it with BUN and creatinine level. Kusakari [17] and Jorgenson [15] reported that there is no correlation between auditory dysfunction and serum creatinine and BUN.


  Conclusions Top


The study suggests the presence subclinical uremic neuropathy in patients of CRF with normal hearing. It further establishes that brainstem evoked response audiometry provides earlier detection of involvement of auditory end organ (delayed absolute latencies) and auditory nerve (delayed inter-peak latencies) in patients of CRF.

Correlation in hearing loss with duration of disease

The results suggest that uremic neuropathy worsens as the duration of disease increases. The findings are suggestive of progression of subclinical neuropathy involving inferior colliculus and auditory pathway as the duration of disease increases.

Correlation between wave latencies and blood urea level


The findings are suggestive of the progression of uremic neuropathy (especially superior olivary nucleus and inferior colliculus) and diffuse axonal neuropathy as the level of blood urea increases.

Correlation between wave latencies and severity of disease

Considering GFR as a criterion for the severity of disease, the study suggests that superior olivary nucleus and inferior colliculus in auditory pathway are more prone to damage by uremic neuropathy as the severity of disease increases.

 
  References Top

1.Yu YL, Cheng IK, Chang CM, Bruce IC, Mok KY, Zhong WY, et al. A multimodal neurophysiological assessment in terminal renal failure. Acta Neurol Scand 1991;83:89-95.  Back to cited text no. 1
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2.Antonelli AR, Bonfioli F, Garrubba V, Ghisellini M, Lamoretti MP, Nicolai P, et al. Audiological findings in elderly patients with chronic renal failure. Acta Otolaryngol Suppl 1990;476:54-68.  Back to cited text no. 2
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3.Yasuda T, Sohue G. Pathophysiology and origin of a neuropathy. J Med Technol 1996;40:760-6.   Back to cited text no. 3
    
4.Thomas PK, Hollinrake K, Lascelles RG, O'Sullivan DJ, Baillod RA, Moorhead JF, et al. The polyneuropathy of chronic renal failure. Brain 1971;94:761-80.   Back to cited text no. 4
    
5.Mancini M, Dello Strologo L, Bianchi P, Tieri L, Rizzoni G. Sensorineural hearing loss in patients reaching chronic renal failure in childhood. Pediatr Nephrol 1996;10:38-40.  Back to cited text no. 5
    
6.Antonelli AR, Bonfioli F, Garrubba V, Ghisellini M, Lamoretti MP, Nicolai P, et al. Audiological findings in elderly patient with chronic renal failure. Acta Otolaryngol 1990;476 (Suppl):54-68.   Back to cited text no. 6
    
7.Sobh MA, El Koussi MM, Bakr MS. Value of otoacoustic emission in monitoring hearing acuity in chronic renal failure patients. Saudi J Kidney Dis Transpl 1999;10:144-7.   Back to cited text no. 7
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8.Rosini M, Stefano D, Febbo A, Paolo D, Bascini M. Brainstem auditory responses in patients with chronic renal failure. Electroencephalography and Clinical Neurology 1984;57:507- 14.   Back to cited text no. 8
    
9.Pratt H, Brodsky G, Goldsher M, Ben-David Y, Harari R, Podoshin L, et al. Auditory brain-stem evoked potentials in patients undergoing dialysis. Electroencephalogr Clin Neurophysiol 1986;63:18-24.   Back to cited text no. 9
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10.Aspris AK, Thodi CD, Balatsouras DG, Thodi ED, Vergemezis V, Danielides V. Auditory Brainstem responses in patients under treatment of hemodialysis. Renal Fail 2008;30:383-90.  Back to cited text no. 10
    
11.Balzer Z, Kuttner K Early auditory evoked potential. A diagnostic parameter in uremic encephalopathy. HNO 1996;44:559-66.   Back to cited text no. 11
    
12.Niedzielska G, Katska E, Sikora P, Szajner-Milart I. ABR differences before and after dialyses. Int J Pediatr Otorhinolaryngol 1999;48;27-9.   Back to cited text no. 12
    
13.Orendorz-Fraczkowska K, Makulska I, Pospiech L, Zwolinska D. The influence of hemodialysis on hearing organ of children with chronic renal failure. Otolaryngol Pol 2002;56:597-602.  Back to cited text no. 13
    
14.Brookes GB. Vitamin D deficiency and deafness: 1984 update. Am J Otol 1985;6:102-7.  Back to cited text no. 14
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15.Henrich W, Thompson P, Bergstrom LV, Lum GM. Effect of dialysis on hearing acuity. Nephron 1977;18:348-51.  Back to cited text no. 15
    
16.Johnson DW, Wathen RL, Mathog RH. Effect of hemodialysis on hearing threshold. ORL J Otorhinolaryngol Relat Spec 1976;38:129-39.  Back to cited text no. 16
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17.Kusakari J, Kobayashi T, Rokugo M, Arakawa E, Ohyama K, Kawamoto K, et al. The inner ear dysfunction in hemodialysis patients. Tohoku J Exp Med 1981;135:359-69.  Back to cited text no. 17
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    Tables

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



 

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