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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1303-1309
Myringosclerosis in hemodialysis patients with hyperparathyroidism


1 Department of internal Medicine, Head and Neck Surgery, Faculty of Medicine, Zagazig University, Sharkia Governorate, Egypt
2 Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, Zagazig University, Sharkia Governorate, Egypt

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Date of Web Publication29-Jan-2021
 

   Abstract 


Myringosclerosis is the final stage of the middle ear lamina propria inflammation or trauma; it starts with collagen production in excess amounts in the lamina propria of the middle ear mucosa. Then, hyalinization and calcification occur. Later on, metaplasia of bone or cartilage can occur. A similar sequence occurs with hyperparathyroidism in chronic kidney disease. This study is aimed to detect the prevalence of myringosclerosis in patients of our hemodialysis (HD) unit and find out any association between hyperparathyroidism and myringosclerosis in chronic HD patients. A total number of 86 patients were selected according to the inclusion criteria. They were divided into two groups: Group 1 (58 patients myringosclerosis free patients on regular HD), Group 2 (28 patients myringosclerosis-positive patients on regular HD). No statically significant difference was found in serum parathyroid hormone levels between the two studied groups. Serum creatinine was significantly higher in Group 2, serum ferritin was significantly lower in Group 2, and mean corpuscular volume of red blood cells was highly significantly lower in Group 2. Myringosclerosis affects 32% of our HD patients and we could not detect any strong correlation between myringosclerosis and hyperparathyroidism.

How to cite this article:
Alnahal A, Waheed M, Abdelhamid WA. Myringosclerosis in hemodialysis patients with hyperparathyroidism. Saudi J Kidney Dis Transpl 2020;31:1303-9

How to cite this URL:
Alnahal A, Waheed M, Abdelhamid WA. Myringosclerosis in hemodialysis patients with hyperparathyroidism. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Feb 28];31:1303-9. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1303/308339



   Introduction Top


Myringosclerosis or sclerosis of the tympanic membrane can be easily identified during otoscopic examination. It starts with hyaline degeneration of the middle ear mucosa, then deposition of calcium and phosphorus in the submucosa.[1] Furthermore, there are several kinds of pathological calcification similar to tympano-sclerosis in involving matrix vesicles, macro-phages, fibroblasts, and various enzymes.[2] Chronic kidney disease (CKD) patients have pathological calcification due to dysregulation in metabolism of calcium and phosphorus resulting in excess matrix vesicles within the collagen.[3]


   Objective Top


The aim of the current study was to detect prevalence of myringosclerosis in patients of our hemodialysis (HD) unit and find out a possible association of hyperparathyroidism and myringosclerosis in chronic HD patients and to survey the relation of myringosclerosis to other laboratory results in those patients.


   Materials and Methods Top


This cross-sectional study was conducted on 86 HD patients (aged ≥18 years) who underwent regular HD for six months at least in HD unit of the Internal Medicine Department, Faculty of Medicine, Zagazig University during the year 2018. Syndromic patients and patients who underwent any type of ear intervention before or were exposed to ear trauma were excluded. All patients shared in the study signed written formal consents. The study was performed in accordance with the Declaration of Helsinki.

The patients were classified into two main groups according to the presence or absence of myringosclerosis:

Group 1: Included 58 patients who did not have myringosclerosis. They were 30 males and 28 females with age ranging from 17 to 70 years with mean ± SD 44.9 ± 14.5 years. Group 2: Included 28 patients who had myringosclerosis. They were 16 males and 12 females with age ranging from 20 to 70 years with mean ± SD 47.3 ± 14.5 years.

All patients of the study were subjected to full history taking, general and local examination, routine laboratory investigations (complete blood picture, serum alanine aminotransferase, aspartate aminotransferase, serum creatinine, blood urea, prothrombin time, partial thrombin time, international normalized ratio, serum calcium, serum phosphorus, serum intact parathyroid hormone (iPTH), serum iron, total iron-binding capacity (TIBC), serum ferritin, hepatitis C virus antibodies, HIV antibodies, and HbsAg). All patients were on regular HD three times weekly by low flux membrane dialyzers.

Otoscopic examination was done for all patients. Myringosclerosis was considered to be positive if the tympanic membrane showed a typical plaque. The diffuse opacification of the tympanic membrane occurring in old patients was not considered as myringosclerosis.

Myringosclerosis was graded as:

  1. Grade I: Involving less than one quadrant (25%) of the pars tensa of the tympanic membrane
  2. Grade II: Involving from one quadrant (25%) up to two quadrants (50%) of the pars tensa
  3. Grade III: Involving more than two quadrants (50%) up to three quadrants (75%) of the pars tensa
  4. Grade IV: Involving more than three quadrants (75%) of the pars tensa.



   Statistical Analysis Top


The results were analyzed using the Statistical Package for the Social Sciences (SPSS) program version 19.0 (SPSS Inc., Chicago, Illinois, USA). The Chi-square test was used as a nonparametric test to compare between qualitative data, and t-test was used to compare between mean and standard deviation (SD) values. P <0.05 is considered statistically significant and highly significant if <0.01. Spearman’s rank correlation analysis was done between selected study parameters. We consider (+) sign as an indication for direct correlation and (-) sign as an indication for inverse correlation, also we consider values near to 1 as strong correlation and values near 0 as weak correlation.


   Results Top


There were no statistically significant differences between Group 1 and Group 2 regarding age, sex, and dialysis duration [Table 1].
Table 1: Comparison between the two groups regarding age, sex, and dialysis duration.

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The comparison of routine laboratory investigations between the two groups revealed mean corpuscular volume (MCV) is lower, which was highly significant, in Group 2, serum creatinine is significantly higher in Group 2, and ferritin is significantly lower in Group 2. There were no significant differences regarding White blood cells (WBC’s) count, hemoglobin, MCH, mean corpuscular hemoglobin concentration (MCHC), platelets count, blood urea nitrogen (BUN), serum calcium, serum phosphorous, iPTH, serum iron, and TIBC [Table 2].
Table 2: Comparison between the two groups regarding laboratory data.

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We also found that the severity of myringo-sclerosis in Group 2 patients is strongly correlated to age of patients and their dialysis duration [Table 3]. [Figure 1] shows the positive correlation of myringosclerosis severity to age of the patients in Group 2. [Figure 2] shows the positive correlation of myringosclerosis severity to the duration of dialysis of the patients in Group 2.
Figure 1: Correlation between myringosclerosis severity and age in group 2.

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Figure 2: Correlation between myringosclerosis severity and dialysis duration in group 2.

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Table 3: Correlation between myringosclerosis severity and selected study parameters of group 2 patients.

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   Discussion Top


Tympanosclerosis is the final stage of the middle ear lamina propria trauma or inflammation either acute or chronic.[4] Tympano-sclerosis starts with collagen production in excess amounts in the lamina propria of the middle ear mucosa. Then hyalinization and calcification occur. Later on, metaplasia of bone or cartilage can occur.[2] The pathogenesis of this process is still not well understood. Some authors suggest autoimmune process in genetic predisposed patients.[5]

That process of calcification is like other kinds of pathological calcification which are either metastatic or dystrophic. Metastatic calcification happens when serum calcium phosphate ratio is elevated, so excessive deposition in tissues other than bone occurs while dystrophic calcification occurs through active cellular mechanisms in damaged or necrotic tissue in the presence of normal calcium level.[6]

The markedly diminished glomerular filtration rate in chronic kidney disease causes retention of phosphate in the body leading to elevated serum phosphorus, that binds to free calcium resulting in ectopic calcification and calcium in the blood gets consumed. The low serum calcium stimulates production of parathyroid hormone (PTH). Secondary hyper-parathyroidism demineralizes bone, releases calcium in bloodstream leading to new calcification.[7] In addition, another important hormone is fibroblast growth factor-23 (FGF-23) that steadily increases with the progress of CKD and it plays important role to regulate urinary phosphate excretion. However, there is a growing evidence of probable detrimental effect of FGF-23 on the structure and function of the heart and vascular system, leading to cardiac dysfunction and sudden death.[8]

Aim of our study was to detect prevalence of myringosclerosis in patients of our HD unit and find out any association of hyperpara-thyroidism and myringosclerosis in chronic HD patients.

In our study, 86 patients on regular HD were examined for the presence of myringosclerosis and classified into Group 1 subjects who did not have myringosclerosis and Group 2 patients who had myringosclerosis.

The prevalence of myringosclerosis in our HD patients was 32%. The two groups were similar relative to age and sex distribution. There was no significant difference between the two groups regarding the duration of dialysis (P = 0.543). Kabaya et al[9] were also unable to discover any impact from the dialysis vintage on the incidence of vascular calcification in chronic HD patients. Leskinen et al[10] also observed no significant difference in carotid calcification in patients with chronic renal failure either before or following dialysis. Our results showed that the dialysis duration did not have a significant role in the prevalence of myringosclerosis.

As regard laboratory data of Group 1 and Group 2, there were no significant differences regarding WBC’s count, hemoglobin, MCH, MCHC, platelets count, BUN, serum calcium, serum phosphorous, iPTH, serum iron, and TIBC.

In our study, MCV and serum ferritin were significantly lower in Group 2 (P = 0.000, P = 0.05), as shown in [Table 2]. The markedly low MCV may be due to the associated low ferritin levels. Ferritin has important role for activity of Heme oxygenase (HO) enzyme. The low ferritin level results in downregulation of HO-1 and ferritin system that has important defensive mechanism against vascular calcification. Thus, downregulation of HO enzyme stimulates cytotoxicity, leading to hastened vascular calcification and atherosclerosis.[11]

In our study, Group 2 patients had significantly higher serum creatinine pointing to the correlation of poor dialysis to the development of tympanosclerosis. Elevated serum creatinine in CKD causes vascular calcification and ectopic calcification in a dynamic process resembling bone formation. Recent studies showed that there are distinct gene products that enhance or suppress the process of ectopic calcification. The key regulatory proteins preventing vascular and ectopic calcification in CKD are matrix Gla-protein, fetuin, osteo-protegerin, and osteopontin and they are inhibited in uremic patients. On the other hand, elevated serum creatinine independently of phosphate concentrations induces excess production of stimulating proteins (Alkaline phosphatase, Osteocalcin, Osteonectin, and Bone matrix protein 2a). In addition, changes in serum level of phosphate had no further impact on calcification.[12]

In addition, our study showed that severity of myringosclerosis in Group 2 patients is positively correlated to age of patients. In older patients, Wnt/β-catenin signaling is increased as reported by Bryan et al.[13] Wnt pathway performs a vital part in the process of bone homeostasis. Its stimulation enhances bone genesis and its decreased activity inhibits bone genesis. In older patients, Dickkopf-related protein 1 (DKK1) expression becomes lower resulting in less suppression of Wnt signalling pathway, as there’s an inverse correlation between the DKK1 level and Wnt signalling activity. That downregulation of DKK1 leads to development of tympanosclerosis.[14]

Furthermore, we found that severity of myringosclerosis in Group 2 patients is positively correlated to HD duration. This is in agreement with El-Anwar et al who found that longer duration of HD is associated with significantly more myringosclerosis in chronic renal failure in children.[15] This may be explained by that longer HD period is associated with more accumulation of advanced glycation end products (AGEs) due to the decreased hemofiltration of AGE precursors, oxidative stress and nonenzymatic glycation. Excess production of AGEs results in simulation of microinflammatory environment and plays important role in cellular aging.[16]

Myringosclerosis is mostly not associated with conductive hearing loss,[17] particularly in patient on HD who has high prevalence of sensory-neural hearing loss.[18] However, such easily detected myringosclerosis could direct to investigate for other remote calcifications.


   Conclusion Top


Myringosclerosis affects 32% of our HD patients. We could not detect any strong correlation between myringosclerosis and hyperparathyroidism in chronic HD patients. On the other hand we detected strong positive correlation of myringosclerosis to serum creatinine, and strong negative correlation of myringosclerosis to serum ferritin and mean corpuscular volume of red blood cells in our study.

Also, the severity of myringosclerosis was strongly correlated positively to age of patients and HD duration.

Conflict of interest: None declared.



 
   References Top

1.
Ozbay C, Dundar R, Kulduk E, Soy KF, Aslan M, Katilmis H. A post-tympanoplasty evaluation of the factors affecting development of myringosclerosis in the graft: A clinical study. J Int Adv Otol 2014;10:102-6.  Back to cited text no. 1
    
2.
Forséni Flodin M. Macrophages and possible osteoclast differentiation in the rat bullar bone during experimental acute otitis media, with reference to tympanosclerosis. Otol Neurotol 2001;22:771-5.  Back to cited text no. 2
    
3.
Anderson HC. Mechanisms of pathological calcification. Rheum Dis Clin North Am 1988; 14:303-19.  Back to cited text no. 3
    
4.
Forséni M, Bagger-Sjöbäck D, Hultcrantz M. A study of inflammatory mediators in the human tympanosclerotic middle ear. Arch Otolaryngol Head Neck Surg 2001;127:559-64.  Back to cited text no. 4
    
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Koç A, Uneri C. Genetic predisposition for tympanosclerotic degeneration. Eur Arch Otorhinolaryngol 2002;259:180-3.  Back to cited text no. 5
    
6.
Li Q, Sundberg JP, Levine MA, Terry SF, Uitto J. The effects of bisphosphonates on ectopic soft tissue mineralization caused by mutations in the ABCC6 gene. Cell Cycle 2015;14:1082-9.  Back to cited text no. 6
    
7.
Caldas Neto S, Lessa FJ, Alves G Jr., Caldas N, Gouveia Mde C. Myringosclerosis in patients with chronic renal failure: Comparative analysis with a control group. Braz J Otorhinolaryngol 2008;74:494-502.  Back to cited text no. 7
    
8.
Razzaque MS. Does FGF23 toxicity influence the outcome of chronic kidney disease? Nephrol Dial Transplant 2009;24:4-7.  Back to cited text no. 8
    
9.
Kabaya T, Nitta K, Kimura H, Kawashima A, Narusawa K, Nihei H. Increased aortic calcification index in hemodialysis patients. Nephron 1999;81:354-5.  Back to cited text no. 9
    
10.
Leskinen Y, Lehtimäki T, Loimaala A, et al. Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden. Atherosclerosis 2003;171:295-302.  Back to cited text no. 10
    
11.
Ishikawa K, Sugawara D, Wang Xp, et al. Heme oxygenase-1 inhibits atherosclerotic lesion formation in ldl-receptor knockout mice. Circ Res 2001;88:506-12.  Back to cited text no. 11
    
12.
Cozzolino M, Brancaccio D, Gallieni M, Slatopolsky E. Pathogenesis of vascular calcification in chronic kidney disease. Kidney Int 2005;68:429-36.  Back to cited text no. 12
    
13.
White BD, Nguyen NK, Moon RT. Wnt signaling: It gets more humorous with age. Curr Biol 2007;17:R923-5.  Back to cited text no. 13
    
14.
Zhang Y, Wang S, Zheng Y, Liu A. Possible role of Dickkopf-1 protein in the pathogenesis of tympanosclerosis in a rat model. J Laryngol Otol 2017;131:860-5.  Back to cited text no. 14
    
15.
El-Anwar M, El-Aassar A, El-Sayed H. Myringosclerosis in children with chronic renal failure on regular hemodialysis. Indian J Otol 2015;21:238-42.  Back to cited text no. 15
  [Full text]  
16.
Meerwaldt R, Zeebregts CJ, Navis G, Hillebrands JL, Lefrandt JD, Smit AJ. Accumulation of advanced glycation end products and chronic complications in ESRD treated by dialysis. Am J Kidney Dis 2009; 53:138-50.  Back to cited text no. 16
    
17.
Zheng Y, Dong X, Zhao Y, Lu D, Lei L, Ren J, et al. Clinical analysis of audiology in two hundred seventy-seven patients with myringo-sclerosis. Clin Otolaryngol 2019;44:465-70.  Back to cited text no. 17
    
18.
El-Anwar MW, Elsayed H, Khater A, Nada E. Audiological findings in children with chronic renal failure on regular hemodialysis. Egypt J Otolaryngol 2013;29:182-8.  Back to cited text no. 18
  [Full text]  

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Correspondence Address:
Walid Ahmed Ragab Abdelhamid
Department of Internal Medicine, Faculty of Medicine, Zagazig University, Sharkia Governorate
Egypt
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DOI: 10.4103/1319-2442.308339

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