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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1245-1253
Evaluation of visual evoked potentials and brain-stem auditory evoked response in patients of chronic kidney disease


Department of Medicine, Division of Nephrology, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India

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Date of Web Publication29-Jan-2021
 

   Abstract 


Chronic kidney disease (CKD) is associated with functional changes in the central nervous system (CNS) which, in the initial stages do not manifest clinically. Early involvement of the CNS can be identified by the assessment of the electrocortical activity. Visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) are useful tests for the early diagnosis of CNS involvement in CKD and are more sensitive compared to electroencephalography. One hundred adult CKD patients (stage 3–5 and 5D) and 50 controls were included in the study. Clinical and biochemical parameters were assessed and all the patients and controls underwent VEP and BAER evaluation. Evaluation of the VEP showed prolonged latencies of all the three peaks (N75, P100, and N145) compared to controls. Furthermore, all the absolute and interpeak BAER latencies for the CKD patients were similarly prolonged compared to controls. CNS dysfunction is common in CKD patients. The electrophysiological tests of VEP and BAER can be used for the early diagnosis of these disorders, even in the sub-clinical stages, thus allowing for their better management.

How to cite this article:
Aggarwal H K, Jain D, Bhatia S. Evaluation of visual evoked potentials and brain-stem auditory evoked response in patients of chronic kidney disease. Saudi J Kidney Dis Transpl 2020;31:1245-53

How to cite this URL:
Aggarwal H K, Jain D, Bhatia S. Evaluation of visual evoked potentials and brain-stem auditory evoked response in patients of chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 May 12];31:1245-53. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1245/308333



   Introduction Top


Chronic kidney disease-(CKD) induced uremic syndrome produces changes in the cerebral tissue leading to encephalopathy. However, the clinical features of neurologic involvement in CKD occurs late and initial subtle changes are difficult to identify. With chronic renal insufficiency, changes in the function of the central nervous system (CNS) occur in both dialyzed and non-dialyzed patients. Organic and inorganic substances which are not adequately excreted in patients with CKD, including urea, uric acid, hippurate, guanidine, indolic acid, polyamines, carnitine, glucuronate, acetone, phosphate, sulfate, and myoinositol, have adverse effects on the entire nervous system.[1] This includes CNS disorders such as stroke, cognitive dysfunction, and encephalopathy, as well as peripheral nervous system conditions such as peripheral and autonomic neuropathies. The presence of these complications has a significant impact on patient morbidity and mortality. Although neurologic dysfunction is usually identified in end-stage disease, diagnosis, and management of these conditions before significant decline in renal function can help mitigate their impact at later stages.[2]

Early involvement of the CNS can be identified using assessment of the electrocortical activity, which also provides an objective measurement of the severity of the uremic syndrome.[3],[4] Sophisticated electrophysiological techniques are used for detecting chronic uremia-induced abnormalities affecting the CNS, without any evident clinical symptoms. Visual evoked potentials (VEPs) are a useful test in the early diagnosis of CNS involvement in CKD and are more sensitive compared to electroencephalography.[5],[6],[7] VEPs are the electrical responses (amplitudes and latencies) of the brain to visual stimulation. The most important parameter in VEPs is P100 latency which is 100 ms in healthy people. Peak latencies are relatively consistent, and accurate normative data are available; amplitude data are less consistent and thus less useful. Demyelination of the optic nerve results in increased latency of the P100 waveform, without significant effect on amplitude; compressive and toxic damage reduce amplitude primarily, with less effect on latency. Another electrophysiological test for the evaluation of CNS function in CKD patients is brain-stem auditory evoked responses (BAER). BAER is an early evoked response that assesses neural function along the ascending auditory pathway, from the cochlea to the inferior colliculus. In addition, patients with CKD are predisposed to sensorineural hearing loss due to damage to the auditory pathway at both the sensory organ and neuronal levels.[8]

With the progressive decline in renal function, there is an increase in the prevalence of cognitive impairment to the tune of 60% among end-stage renal disease (ESRD) patients. Memory, attention, and executive functioning are the areas of cognitive functioning comm.-only affected among patients with CKD.[9] Contributing factors for this cognitive impairment in ESRD patients include a high prevalence of traditional risk factors causing sub-clinical neurologic damage, and uremia with its associated metabolic disturbances.[10],[11] Cognitive impairment adversely affects functioning in numerous domains of life including work, school, family, social relationships, leisure activities, or maintenance of health and hygiene. Cognitive impairment leads to deterioration in quality of life, increases resource utilization, escalates medical costs, and causes medical care to be sub-optimal because the patients are unable to follow the caregiver’s recommendations properly.[12],[13] Therefore, identifying cognitive impairment may lead to the institution of supportive measures that improve outcomes and decrease disease burden.[14],[15]

The intricate association of the functioning of the CNS and the degree of renal dysfunction indicates that sensitive electrophysiological tests can aid in the evaluation of patients of CKD. The use of electrophysiological tests not only help in early diagnosis of CNS dysfunction and sensorineural hearing loss in CKD patients but also helps in the timely institution of advanced therapeutic modalities to improve the outcome as well as the quality of life of patients with CKD.[16]


   Material and Methods Top


This prospective observational study was conducted on 100 adult patients with CKD and 50 healthy controls on regular follow-up at the Kidney and Dialysis Clinic, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India. The study was duly approved by the Ethical Committee and the postgraduate board of studies of the institution. The inclusion criteria of the CKD patients were; age between 18 and 75 years, CKD stages 3, 4, and 5, and patients on maintenance hemodialysis (HD) for at least three months. Patients excluded were those who had congenital hearing loss or middle ear alterations, history of excessive exposure to noise, history of use of ototoxic medications, patients using any type of hearing aids, and post-renal transplant patients. Patients with corrected visual acuity <6/60, patients with retinal lesions, multiple sclerosis, preexisting psychiatric illness, and patients with multi-organ failure disease were also excluded from the study.

The study participants were divided into two groups:

  1. Group I consisted of 50 healthy controls and Group II consisted of 100 patients with CKD (stages 3 to 5D)
  2. Group II was further subdivided into four groups A, B, C, and D based on CKD staging by NKF-K/DOQI guidelines.[17]


    • Group A consisted of 25 patients with an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/ 1.73 m2 (CKD Stage 3)
    • Group B consisted of 25 patients with eGFR between 15 and 29 mL/min/ 1.73 m2 (CKD Stage 4)
    • Group C consisted of 25 patients with of eGFR <15 mL/min/1.73 m2, not on HD (CKD stage 5)
    • Group D consisted of 25 patients with of eGFR <15 mL/min/1.73 m2 on HD (CKD stage-5 D).


After enrolment, all patients and controls included in the study underwent a battery of investigations which included a complete blood count, blood urea, serum creatinine, blood sugar, serum calcium and phosphorus, serum uric acid, serum albumin, serum electrolytes, urine routine examination, 24-h urine for proteinuria, viral markers (HIV/HBsAg/ Anti HCV), electrocardiogram, chest X-ray posteroanterior view, and ultrasound abdomen for bilateral kidney size and echotexture. Visual acuity was assessed using Snellen’s chart. All the patients and controls underwent pure tone audiometry, VEP and BAER. VEP was taken for each eye separately and the average was taken for analysis.

At the end of the study, the data were expressed as mean ± standard deviation (SD) or range. P <0.05 were considered to be significant in all the analyses. Independent t-test and ANOVA tests were used to analyze differences in quantitative variables between the groups. The correlations were tested using Pearson correlation coefficient analysis. All statistical calculations were carried out using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA).


   Results Top


Out of the total of 100 patients, 64 were male and 36 were female while out of the 50 controls 26 were male and 24 were female. As depicted in [Table 1], statistically significant differences between Groups I and II were found for systolic blood pressure, hemoglobin, random blood sugar, blood urea, serum creatinine, eGFR, serum sodium, serum calcium, serum phosphate, and serum uric acid levels. Except for systolic blood pressure all these values were significantly different among different stages of CKD as well [Table 2]. The comparison of mean hearing threshold between group I and II showed values of 8.6 ± 2.33 dB and 19.33 ± 4.55 dB at 4.0 kHz, respectively, and 10.82 ± 2.37 dB and 28.96 ± 5.97 dB at 8.0 kHz, respectively, with statistically significant difference. This shows patients with CKD have sensorineural deafness at higher frequencies.
Table 1: Baseline demographic and clinical parameters of cases vis-à-vis controls.

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Table 2: Baseline demographic and clinical parameters among different stages of chronic kidney disease.

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In the present study, evaluation of the VEP showed prolonged latencies of all the three peaks namely N75, P100, and N145 in CKD patients compared to controls. The values showed a delay of about 4 s for N75 and a delay of about 3 s for P100 and N145 [Table 3]. There was a progressive increase in latencies of all the three peaks from group A to group D which was statistically significant only for P100 and N145 [Table 4].
Table 3: Comparison of visual evoked potentials parameters of cases vis-à-vis controls.

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Table 4: Comparison of visual evoked potentials parameters among different groups of chronic kidney disease patients.

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All the absolute and interpeak BAER latencies for the CKD patients were significantly prolonged compared to controls in the present study [Table 5]. On comparison, different stages of CKD revealed significant differences for waves I and III, III-V and I-V interpeak latencies [Table 6].
Table 5: Comparison of brain-stem auditory evoked potentials latencies (absolute and interpeak) of cases vis-à-vis controls.

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Table 6: Comparison of brain-stem auditory evoked potentials latencies (absolute and interpeak) among different groups of chronic kidney disease patients.

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The correlation of VEP of CKD patients with serum creatinine was significant for the P100 and N145 peaks while the correlation with eGFR was significant for all the three peaks i.e., N75, P100, and N145. The correlation of BAER with serum creatinine and eGFR was significant only for peak III and III-V interpeak latency [Table 7]. A multivariate regression model was prepared to compare BAER - N75, P100, N145 in cases versus controls while adjusting for age. This revealed statistically significant correlation (P <0.001) for BAER abnormalities in the case group. Furthermore, comparison of the non-dialyzed versus dialyzed patients resulted in significant difference for the N145 peak of VEP as well as wave I, and interpeak latencies III-V and IV of BAER.
Table 7: Correlation of visual evoked potentials and brain-stem auditory evoked potentials of chronic kidney disease patients with serum creatinine and estimated glomerular filtration rate.

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   Discussion Top


Investigational techniques for early diagnosis of CNS involvement in CKD patients have long been searched for. VEPs represent a noninvasive electrophysiological tool for the assessment of CNS dysfunction.[18] VEP parameters in CKD patients are deranged with increased amplitudes and prolonged latencies representing the extent of neurologic dysfunction and also provide quantitative information about the degree of renal insufficiency.[5]

In BAER, the impulses are generated by the brain-stem which, when the recorded result in a series of waves designated by roman numerals I-VII. Waves I and II originate from the cochlear nerve, wave III from the cochlear nucleus, wave IV from superior olivary complex, wave V from nuclei of the lateral lemniscus, and waves VI and VII from the inferior colliculus.

An association between CKD and hearing loss was first described in patients with Alport syndrome.[19] There are physiologic, ultrastructural, and antigenic similarities between the kidney and the cochlea indicating that the association between inner ear damage and kidney failure is more than serendipitous.[20] Both the organs are involved in intricate processes of water and ion regulation through different proton-pump systems.[21] Further strengthening the relationship between the kidney and cochlea is the fact that antibodies generated against the nephron are also deposited in the stria vascularis.[22] Sensori-neural hearing loss, particularly at high frequencies, is common among CKD patients, with dysfunction of both the cochlea and the auditory pathway.[23]

Results of the present study are consistent with Lewis et al who studied eight patients undergoing HD using Flash-VEP and demonstrated that there were prolonged latencies in the study cases compared to controls.[6] Results of the study by Azar et al also showed prolonged latencies of P100 and N140 in patients undergoing HD compared to controls.[24] Kuba et al assessed pattern reversal VEP in three groups with CKD treated by HD, drug treatment, and renal transplantation. The authors mentioned that there was significant prolonged P100 latency in HD group compared to controls.[25] Rossini et al assessed VEP parameters in 11 CKD patients on HD by using Flash-VEP. P100 latency was found to be longer in 63.6% of patients under HD.[7]

The prolonged latencies of P100 and N145 but not of N75 were found to be correlated with blood urea and serum creatinine values in the present study. Similar association of prolonged latencies with blood urea nitrogen was found by Rossini et al and Teschan et al.[7],[16] Many authors assess the validity of CNS testing with VEPs in uremic patients by looking for correlations between peak latencies and amplitude parameters of the VEPs and the levels of creatinine and urea. They assume a causal dependence between these indicators of the stage of uremia and the degree of CNS disorder. However, Lewis et al, Kuba et al and Hamel et al stated that no association existed between evoked potential results and blood biochemical results.[5],[6],[25] The present study showed an association between serum potassium levels and prolonged latencies of all the three peaks. Similar association of serum potassium with P100 latency was found by Azar et al which was not corroborated by other studies.[24] Furthermore, correlation was found between peak latencies of P100 and N145 and serum phosphate levels in the present study, although none of the previous studies have mentioned such an association.

Compared with healthy controls, a highly significant delay was observed in CKD patients in both absolute and interpeak BAER latencies in the present study. This is in agreement with Rossini et al who reported prolongation of all ABR waves following wave I. Pagani et al also noted the prolongation of ABR wave III and V latencies among patients with ESRD.[26] According to Gafter et al, patients with ESRD had prolonged wave III and V latency and I-V interpeak latency before and following HD.[27]

The present study showed the correlation of the absolute latencies of peaks I and III, and of interpeak latencies III to V and I to V with blood urea levels. However, only the absolute latency of peak III, and interpeak latency III to V were found correlated with serum creatinine values. Blood urea nitrogen was the unique chemical index to correlate with BAER parameters in the study by Rossini et al.[28] These findings are in contrast with those of Aspris et al,[8] Baldini et al,[29] Gafter et al[27] and Niedzielska et al[30] who found no correlations between biochemical measures and changes in BAER absolute and interpeak latencies. There was no correlation of absolute or interpeak latencies with serum calcium or albumin levels in the present study. However, Antonelli et al reported that ABR wave latency was correlated to albumin and calcium levels.[31] In addition, Pratt et al. reported changes in absolute and interpeak latency that were correlated to calcium ion changes prior to and following HD.[32]

CKD patients on dialysis showed an insignificant increase in the absolute latencies of waves I and III compared to the non-dialyzed group which is similar to the results of Bains et al in which the absolute latencies were increased as well.[33]

Till date, no concrete evidence of the relationship between urea and creatinine levels and the degree of CNS involvement in CKD has been documented. In addition, some authors have investigated other potential factors affecting uremia including aluminum calcium and parathormone, soluble brain proteins however, the relationship between these factors and VEP parameters has not been established.[34],[35]

The remarkable improvement in the treatment of CKD patients over the past decades can help prevent the detrimental effects on the CNS encountered during the initial stages of renal impairment. CNS dysfunctions can be diagnosed early and additional therapeutic approaches followed using VEP and BAER during the treatment of CKD.

The limitation encountered in the present study is the absence of any intervention to treat the CNS dysfunction encountered on either VEP or BAER in these patients of CKD.


   Conclusion Top


From the present study, it can be concluded that CNS dysfunction is common in patients with CKD. The electrophysiological tests of VEP and BAER can be used for the early diagnosis of these disorders, even in the sub-clinical stages, thus allowing for their timely management thereby improving the quality of life of these patients. There is an unmet need to develop specific therapeutic approaches which can halt and possibly reverse the neurologic dysfunction associated with renal insufficiency.

Conflict of interest: None declared.



 
   References Top

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Sehgal AR, Grey SF, DeOreo PB, Whitehouse PJ. Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am J Kidney Dis 1997;30:41-9.  Back to cited text no. 14
    
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Teschan PE, Ginn HE, Bourne JR, et al. Quantitative indices of clinical uremia. Kidney Int 1979;15:676-97.  Back to cited text no. 16
    
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33.
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Correspondence Address:
Deepak Jain
Department of Medicine, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana
India
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DOI: 10.4103/1319-2442.308333

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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