International Journal of Pediatric Otorhinolaryngology

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1 International Journal of Pediatric Otorhinolaryngology 75 (2011) Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology journal homepage: Auditory brain stem response and otoacoustic emission results in children with end-stage renal disease Masoud Naderpour a, Fakhrossadat Mortazavi b,*, Yalda Jabbari-Moghaddam a, Mohammad H. Sharifi-Movaghar a a Department of Otolaryngology Head and Neck Surgery, Pediatric Health Research Center, Tabriz University of Medical Sciences, Iran b Department of Pediatric Nephrology, Pediatric Health Research Center, Tabriz University of Medical Sciences, Iran A R T I C L E I N F O Article history: Received 24 August 2010 Received in revised form 19 December 2010 Accepted 21 February 2011 Available online 21 March 2011 Keywords: End stage renal disease Pediatrics Hemodialysis Auditory brain stem response Otoacoustic emission AB S TR AC T Background: Abnormalities in auditory system are frequent in patients with end stage renal disease (ESRD). There is not yet any consensus for the effect of renal failure and hemodialysis on auditory complications. The aim of this study was to evaluate the auditory abnormalities in pediatric ESRD patients undergoing long term hemodialysis and compare the results with those of nondialytic chronic renal failure (CRF) children and controls. Methods: Children aged 1 16 years were evaluated in three groups: 25 ESRD patients undergoing hemodialysis, 25 nondialytic patients with CRF, and 25 age and sex-matched normal counterparts. Patients with history of otological diseases, ear trauma, diabetes mellitus, receiving ototoxic drugs and syndromes with hearing abnormalities were excluded. The auditory brainstem response (ABR) and otoacoustic emission (OAE) were tested in all subjects. Frequency of cases with abnormal findings was compared between the groups. Results: The ABR testing was abnormal in 11 (44%) dialytic patients with normal results in all nondialytic CRF cases and controls (p < 0.001). The OAE testing was abnormal in all dialytic patients with abnormal ABR testing results (44%), in 1 (4%) nondialytic CRF patient and in no controls (p < 0.001). There ware no significant differences with regard to age, gender, height, weight, blood pressure, serum levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium, glomerular filtration rate (GFR), duration of dialysis and dialysis adequacy between dialytic patients with and without abnormal results of ABR/OAE testing. Conclusion: Sensorineural hearing loss is rare among nondialytic pediatric patients with CRF but very common in ESRD children undergoing long term dialysis Elsevier Ireland Ltd. All rights reserved. 1. Introduction Chronic renal failure (CRF) and end stage renal disease (ESRD) can cause malfunction of multiple organs, including auditory and vestibular systems [1]. Although the etiology of this malfunction is not definitely described, multiple factors have been proposed. Electrolyte disturbances, elevated serum urea level, episodes of hypotension, hypoxia, altered pharmacodynamics of ototoxic drugs, dysfunction or loss of hair cells, collapse of the endolymphatic space, edema and atrophy of specialized auditory cells, neuropathy, and in some patients, dialysis and its associated complications such as wide fluctuation in blood pressure during * Corresponding author at: Tabriz University of Medical Sciences, Children s Hospital of Tabriz, Sheshgelan Street, Tabriz, Iran. Tel.: / ; fax: address: Mortazavi_fakhri@yahoo.co.uk (F. Mortazavi) /$ see front matter 2011 Elsevier Ireland Ltd. All rights reserved. doi: /j.ijporl

2 hemodialysis (HD) and accumulation of contaminants from dialysate water are some assumed ethiopathologies [2 6]. Selecting an appropriate testing method of the hearing organ is a pivotal step. The auditory brainstem response (ABR) reflects neural function along the ascending auditory pathway, from the cochlea to the inferior colliculus [7]. The otoacoustic emission (OAE) is a low level sound 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 [8]. By now, there have been various number of studies focused on association between CRF and dialysis with abnormalities in hearing system in adult patients. Baldini et al. demonstrated elongation of wave III and V in ABR tests of CRF patients. They assumed a central and peripheral damage of hearing organ due to uremia [9]. Pagani et al. confirmed disorders of latency of wave III and V and IPL I III and I V in ABR testing of patients treated with chronic HD [10]. Based on different studies, frequency of hearing loss ranges between 20% and 77% in

3 M. Naderpour et al./international Journal of Pediatric Otorhinolaryngology 75(2011) adult CRF patients and between 15% and 79% in dialytic ones [11 15]. There is only limited number of studies evaluating hearing abnormalities in children with CRF or ESRD. Bergstrom and Thompson [16] reported that 47% of 151 children with ESRD had hearing loss. Mancini et al. [17] investigated the incidence of sensorineural hearing loss in 68 patients who reached CRF in childhood and found that 29% of patients on conservative treatment and 28% of patients on HD had sensorineural hearing loss. There is a concern about possible differences between the pediatric and adult populations in this regard. Moreover, auditory complications in children with CRF or ESRD are more important than those in adults, because the deficits present during the childhood may deeply influence the growth, development and future life [18]. The aim of this study is to evaluate the auditory abnormalities in pediatric ESRD patients undergoing long term HD and to compare the results with those of nondialytic CRF children and control group. 2. Methods In this cross-sectional study, children aged 1 16 years were recruited in three groups; dialytic group including 25 children with non-syndromic ESRD (GFR < 15 ml/min/1.73 m 2 body surface area) under maintenance HD for 4 h, 2 3 times a week, nondialytic group including children with non-syndromic CRF (15 <GFR < 30 ml/min/1.73 m 2 body surface area) on conservative management, and controls including 25 normal healthy children. The three groups were matched for age and sex. GFR was calculated by applying Shwartz formula using height (cm) and serum creatinine (mg/dl) [19]. This study was conducted during an 18-month period between November 2008 and May 2010 in Children s Hospital of Tabriz in northwest of Iran. All subjects were thoroughly examined by an ear, nose and throat (ENT) specialist. Patients with history of otological diseases, ear trauma, diabetes mellitus, receiving ototoxic drugs, syndromes with hearing abnormalities (Alport syndrome, for example) and mental retardation were excluded. Only subjects with normal middle ear function as confirmed by tympanometric measurement were enrolled. The audiological tests including ABR and OAE were performed bilaterally by an expert audiologist blind to the group of subjects in an outpatient ward. The audiological tests carried out between HD sessions at least 24 h after dialysis. For measuring the hearing threshold we used ABR. Standards of employed ABR were 90 db nhl, 30 impulses, click 125 ms half-wave square in frequencies between 1000 and 4000 Hz. The criteria for abnormal ABR defined as any rise in the hearing thresholds (cut-off value). The OAEs were measured using MADSEN Capella Oto Acoustic Analyzer, T1 LA. Cases with no response in OAE were reported as abnormal (cut-off value). Other studied variables were age, gender, height and weight and their percentiles according to growth charts provided by the Ministry of Health and Medical Education, systolic and diastolic blood pressures, duration of CRF, duration of dialysis and dialysis adequacy, glomerular filtration rate (GFR), serum levels of blood urea nitrogen (BUN), creatinine, sodium (Na) and potassium (K). Kt/V ratio (Kis the dialyzer clearance of urea, t is the dialysis time, and Vis the patient s total body water) as an indicator of dialysis adequacy was calculated from pre and post dialysis blood urea, weight and ultra filtration volume [20]. All ESRD patients were dialysed by polysulphan dialyzers. Informed consents were signed by the parents of recruited children. This study was approved by the Ethics Committee of Tabriz University of Medical Sciences. Statistical analysis was performed using the SPSS software (Chicago, IL), version Data are presented as mean ± standard deviation (median) or frequency (percent). Independent samples T-test, Mann Whitney U-test, Chi-square test or Fishers Exact test were used for comparisons. P-value of <0.05 was considered significant. 3. Results Patients characteristics, general data and on-admission laboratory results are summarized in Table 1. The mean duration of CRF was 3.21 ± 4.12 years (range: 1 6 years) in nondialytic group and 4.05 ± 5.32 years (range: 2 7 years) in dialytic group (p = 0.12). The mean duration of dialysis was ± months (range: 4 48, median: 18 months). The mean Kt/V was 1.26 ± 0.08 (range: , median: 1.20). In dialytic patients, ABR testing showed that 11(44%) patients had bilateral symmetric increased V latency (by 35 db amplitude in frequencies between 1000 and 4000) which indicated mild increased hearing thresholds in these cases. We found normal ABR in other two groups (p < 0.001). The OAE testing was abnormal in the same 11 patients in dialytic group (who had abnormal ABR), in 1(4%) patient in nondialytic group and in no one in the control group (p < 0.001). There was not any child with normal tests in one ear and abnormal tests in the opposite ear. Different variables are compared between the dialytic patients with and without abnormal ABR/OAE testing results in Table 2. Accordingly, no significant difference was found between these two groups. 4. Discussion In current study we found that abnormal ABR and OAE testing results were significantly more frequent in dialytic patients (44%) than the other two groups. Nikolopoulos et al. [12] studied hearing acuity in 46 children and adolescents suffering from renal insufficiency. Sensorineural hearing loss was found in 30.4% of their patients. Samir et al. [21] studied 34 children with CRF; 27 on regular HD and 7 on conservative treatment. Twenty normal healthy children served as controls. OAE testing was failed in 11.1% of patients on HD but in none of the patients on conservative Table 1 General data in different studied groups. Variable Dialytic patients (n = 25) Nondialytic patients (n = 25) Controls (n = 25) Gender (male) 18 (%72) 16 (%64) 16 (%64) Age (year) 9.98±3.19 (4 16, 10) 8.72±3.09(3 14,9) 8.56±2.97(3.5 14,9) Height (cm) ±17.39 (92 158, 124) ±25.83 (90 140, 112) ±17.22 (95 155, 125) Weight (kg) 24.62±7.79 (13 41, 26) 21.32±7.15 (11 40, 20) 23.98±5.95 (14 32, 25) SBP (mmhg) ±17.72 ( , 150) ±20.50 (90 170, 110) ±10.77 (85 120, 100) DBP(mmHg) 93.80±10.13 (70 110, 95) 69.40±14.24 (50 110, 70) 66.20±8.45 (50 80, 65) BUN (mg/dl) ± (89 165, 114) 71.44±18.82 (43 110, 65) ±3.97 (10 25, 18) Creatinine(mg/dl) 7.18±0.93 ( , 7.3) 3.03 ±1.14( , 2.8) 0.66±0.12 ( , 0.65) Na (meq/l) ±2.81 ( , 130) ±4.97 ( , 137) ±3.81 ( , 139) K (meq/l) 5.69 ± 0.55 ( , 5.8) 4.86 ± 0.65 (3 6.1, 4.8) 4.57 ± 0.40 ( , 4.5) GFR 8.46±1.53 ( , 8.20) 21.41±6.89( ,19.1) 95.87±13.85 ( , 94.54) BUN: blood urea nitrogen, DBP: diastolic blood pressure, GFR: glomerular filtration rate (ml/min/1.73 m 2 body surface area), SBP: systolic blood pressure. Data are shown as mean ± standard deviation (range, median) or frequency (percent).

4 706 M. Naderpour et al./international Journal of Pediatric Otorhinolaryngology 75(2011) Table 2 Different variables in dialytic patients with and without ABR/OAE testing results. Variable Normal ABR/OAE (n= 14) Abnormal ABR/OAE (n= 11) P-value a OR 95%CI b Gender (male) 10 (%71.41) 8 (%72.7) Age (year) 10.21±2.76 (10) 9.68±3.80 (10) 0.72 Height (<25th percentile) 14(100) 11(100) Weight (<25th percentile) 11 (%78.6) 11 (%100) SBP (mm Hg) ± (150) ±20.05 (150) 0.64 DBP (mmhg) ±8.05 (97.5) 91.36±12.27 (95) 0.41 BUN (mg/dl) ±22.30 (110) ±19.51 (125) 0.35 Creatinine (mg/dl) 7.07±1.10(7.2) 7.31 ± 0.68 (7.5) 0.49 Na (meq/l) ±2.15 (130) ±3.53 (130) 0.66 K (meq/l) 5.8±0.34 (5.85) 5.55±0.74 (5.8) 0.76 GFR (ml/min/m 2 ) 8.82± 1.37 (8.35) 8± 1.66 (7.60) 0.12 Disease duration (years) 4.11 ±3.08 (4.06) 4± 5.87 (4.02) 0.78 Dialysis duration (month) 24±10.33 (25.5) ± (14) 0.34 Dialysis adequacy (Kt/V) 1.25±0.08 (1.2) 1.27±0.08 (1.25) 0.57 ABR: auditory brainstem response, BUN: blood urea nitrogen, DBP: diastolic blood pressure, GFR: glomerular filtration rate (ml/min/1.73 m 2 body surface area), OAE: otoacoustic emissions testing, OR: odds ratio, SBP: systolic blood pressure. Data are shown as mean ± standard deviation (median) or frequency (percent). a Nonparametric test for numerical data. b Confidence interval for the odds ratio. treatment or in controls. Summing up some published reports, frequency of sensorineural hearing loss is between 0% and 30.4% in pediatric nondialytic CRF patients and between 11% and 47% in dialytic cases [11,12,16,17,21]. Our results are also in the reported ranges. Different reasons may be proposed to justify the heterogeneity and wide range of reports in this regard including small sample sizes, flawed methodology specially in matching the patients and controls, and various methods with different accuracies in documenting the hearing loss. To the best of our knowledge, the current study is the first one which is evaluating three well-matched groups of dialytic, nondialytic and normal children simultaneously. Combined ABR and OAE testing provides a comprehensive evaluation of the hearing system in children [11]. All of our dialytic subjects with the increased bilateral and symmetric wave V latency results had concomitant abnormal OAE finding. Abnormal OAE indicates dysfunction or loss of hair cells in the organ of corti [22]. Increased bilateral and symmetric wave V latency (by 35 db amplitude in Hz frequency) is mostly a reflection of sensorinural hearing loss due to cochlear hearing impairment. Orendorz-Fraczkowska et al. [23] evaluated 20 children with CRF, aged years. They also showed abnormalities in OAE testing results and concluded that there are disturbances in auditory cells on the level of the cochlea in these children. Despite the large number of studies, there is still an ongoing debate about the effect of dialysis on hearing system in the literature. The role of hemodialysis in causation of sensorineural hearing loss is controversial; some authors have reported a depression in hearing threshold after hemodialysis while others have the opinion that there was no relation between HD and hearing threshold [24 26]. Based on Lasisi s opinion disturbances of hearing tests in HD patients may be due to a combination of changes in fluid and electrolyte composition of endolymph and possibly exposure to aged cellulose acetate membranes of dialyzers used, allowing acetate degradation product to enter the blood [27]. Hajduk et al. [28] assessed hearing acuity in 22 CRF children aged 9 17 years and 18 age-matched healthy counterparts. They revealed significantly lower mean OAE amplitudes in CRF children when compared to healthy children, at all frequencies measured. On the other hand, no differences in ABR evaluation were observed. We showed that the abnormal OAE and ABR testing results were rare in nondialytic CRF patients. Another finding in present study was hearing loss in high frequencies in dialytic patients. This is in line with previous reports in adults [26]. Nonetheless, according to our findings the hearing abnormalities were associated with dialysis rather than the CRF itself. However, comparing differentvariables such as patients demographics, blood pressure, serum electrolytes, GFR, duration of dialysis and renal disease and dialysis adequacy between dialytic patients with and without hearing abnormalities did not reveal a significant difference. Lasisi et al. [27] also found no correlation between the hearing threshold and the diastolic blood pressure and creatinine level of the patients. Small sample size is a limitation of current study with regard to determining possible risk factors of hearing loss in dialytic patients. 5. Conclusion Based on results of this study, sensorineural hearing loss is rare among nondialytic pediatric patients with CRF but very common in ESRD children undergoing long term dialysis. Further investigations with larger sample sizes may be helpful for determining the risk factors of auditory impairments in dialytic ESRD patients. Acknowledgements The authors would like to appreciate all staff of HD ward and audiometry laboratory who were involved in managing the patients and in performing the auditory tests. References [1] A.A. Sazgar, F. Ahmadi, K. Akrami, S. Akrami, M.R. Abbasi, F. Rasool, Vestibular evoked myogenic potentials of haemodialysed patients with end stage renal disease, Eur. Arch. Otorhinolaryngol. 265 (4) (2008) [2] P. Stavroulaki, T.P. Nikolopoulos, I. Psarommatis, N. Apostolopoulos, Hearing evaluation with distortion-product otoacoustic emissions in young patients undergoing haemodialysis, Clin. Otolaryngol. Allied Sci. 26 (3) (2001) [3] M.A. Sobh, M.M. El Koussi, M.S. Bakr, Value of otoacoustic emission in monitoring hearing acuity in chronic renal failure patients, Saudi J. Kidney Dis. Transpl. 10(2) (1999) [4] D.W.Johnson, R.H. Mathog, Hearing function and chronic renal failure, Ann. Otol. Rhinol. Laryngol. 85 (1 Pt 1) (1976) [5] C. Thodi, E. Thodis, V. Danielides, P. Pasadakis, V. Vargemezis, Hearing in renal failure, Nephrol. Dial. Transplant. 21(11) (2006) [6] A.K. Aspris, C.D. Thodi, D.G. Balatsouras, E.D. Thodis, V. Vargemezis, V. Danielides, Auditory brainstem responses in patients under treatment of hemodialysis, Ren. Fail. 30 (4) (2008) [7] J.W. Hall, Handbook of Auditory Evoked Responses, 1st ed., Allyn & Bacon, USA, [8] M.S. Robinette, Tj. Glattke, Otoacoustic Emissions: Clinical Applications, 3rd ed., Thieme, USA, [9] S. Baldini, R. Radicioni, M. Melappioni, M. Baldassari, N. Panichi, G. Pelliccioni, M. Guidi, L. Rosa, R. Magnaterra, O. Scarpino, Utility of electrophysiologic study using the blink reflex and brainstem evoked potentials for the evaluation of the course of uremic polyneuropathy, Minerva Urol. Nefrol. 47 (1) (1995)

5 M. Naderpour et al./international Journal of Pediatric Otorhinolaryngology 75(2011) [10] C. Pagani, C. Bazzi, G. Arrigo, C.T. Venturini, G. D Amico, Evoked potentials (VEPs and BAEPs) in a large cohort of short- and long-term haemodialysed patients, Nephrol. Dial. Transplant. 8 (10) (1993) [11] G. Niedzielska, E. Katska, P. Sikora, I. Szajner-Milart, ABR differences before and after dialyses, Int. J. Pediatr. Otorhinolaryngol. 48 (April (1)) (1999) [12] T.P. Nikolopoulos, D.C. Kandiloros, J.V. Segas, P.N. Nomicos, E.A. Ferekidis, K.E. Michelis, N.J. Apostolopoulos, G.K. Adamopoulos, Auditory function in young patients with chronic renal failure, Clin. Otolaryngol. Allied Sci. 22 (June (3)) (1997) [13] A.O. Lasisi, B.L. Salako, M.A. Kodiya, M.A. Amusat, W.P. Osisanya, Hearing threshold in patients with chronic renal failure, Saudi Med. J. 28 (May (5)) (2007) [14] O. Ozturan, S. Lam, The effect of hemodialysis on hearing using pure-tone audiometry and distortion-product otoacoustic emissions, ORLJ. Otorhinolaryngol. Relat. Spec. 60 (November December (6)) (1998) [15] B.S. Zeigelboim, P.L. Mangabeira-Albernaz, Y. Fukuda, High frequency audiometry and chronic renal failure, Acta Otolaryngol. 121 (January (2)) (2001) [16] L. Bergstrom, P. Thompson, Hearing loss in pediatric renal patients, Int.J. Pediatr. Otorhinolaryngol. 5 (July (3)) (1983) [17] M.L. Mancini, L. Dello Strologo, P.M. Bianchi, L. Tieri, G. Rizzoni, Sensorineural hearing loss in patients reaching chronic renal failure in childhood, Pediatr. Nephrol. 10 (February (1)) (1996) [18] C. Bazzi, C.T. Venturini, C. Pagani, G. Arrigo, G. D Amico, Hearing loss in short- and long-term haemodialysed patients, Nephrol. Dial. Transplant. 10 (10) (1995) [19] B.A. Vogt, E.D. Avner, Chronic kidney disease, in: R.M. Kliegman, R.E. Behrman, H.B. Jenson, B.F. Stanton (Eds.), Nelson Textbook of Pediatrics, 18th ed., Saunders, USA, 2007, pp [20] F.A. Gotch, J.A. Sargent, A mechanistic analysis of the National Cooperative Dialysis Study (NCDS), Kidney Int. 28 (3) (1985) [21] M. Samir, H. Riad, M. Mahgoub, Z. Awad, N. Kamal, Transient otoacoustic emissions in children with chronic renal failure, Clin. Otolaryngol. Allied Sci. 23 (1) (1998) [22] P.W. Flint, B.H. Haughey, V.J. Lund,J.K. Niparko, M.A. Richardson, K.T. Robbins,J.R. Thomas, Cummings Otolaryngology Head and Neck Surgery, 5th ed., Mosby, USA, [23] K. Orendorz-Fraczkowska, I. Makulska, L. Pos piech, D. Zwoliñska, The influence of haemodialysis on hearing organ of children with chronic renal failure, Otolaryngol. Pol. 56 (5) (2002) [24] P. Stavroulaki, T.P. Nikolopoulos, I. Psarommatis, N. Apostolopoulos, Hearing evaluation with distortion-product otoacoustic emissions in young patients undergoing haemodialysis, Clin. Otolaryngol. Allied Sci. 26 (June (3)) (2001) [25] D. Gatland, B. Tucker, S. Chalstrey, M. Keene, L. Baker, Hearing loss in chronic renal failure-hearing threshold changes following haemodialysis, J. R. Soc. Med. 84 (October (10)) (1991) [26] J.C. Hutter, M.J. Kuehnert, R.R. Wallis, A.D. Lucas, S. Sen, W.R.Jarvis, Acute onset of decreased vision and hearing traced to hemodialysis treatment with aged dialyzers, JAMA 283 (April (16)) (2000) [27] A.O. Lasisi, B.L. Salako, O. Osowole, W.P. Osisanya, M.A. Amusat, Effect of hemodialysis on the hearing function of patients with chronic renal failure, Afr.J. Health Sci. 13 (2006) [28] A. Hajduk, G. Lisowska, G. Namysłowski, K. Szprynger, M. Szczepañska, A. Widziszowska, Hearing evaluation in chronic renal failure children, Otolaryngol. Pol. 60(1) (2006)