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 Table of Contents  
Year : 2022  |  Volume : 34  |  Issue : 3  |  Page : 272-275

Evaluation of serum urea, uric acid and creatinine in OSMF patients: A clinical and biochemical stusdy

1 Dental Surgeon and Oral and Maxillofacial Radiologist, Aarogya Hospital, Vaishali, Ghaziabad, Uttar Pradesh, India
2 Department of Oral Medicine and Radiology, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (Deemed University), Sawangi, Wardha, Maharashtra, India

Date of Submission02-Jun-2022
Date of Decision14-Aug-2022
Date of Acceptance06-Sep-2022
Date of Web Publication26-Sep-2022

Correspondence Address:
Swati Verma
Oral and Maxillofacial Radiologist, Aarogya Hospital, Vaishali, Ghaziabad, Uttar Pradesh; Permanent Address: Flat No-B-1403, Apex Acacia Valley, Vaishali Sector 3, Ghaziabad - 201 010, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_151_21

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Introduction: Oral submucous fibrosis (OSMF) is described as a chronic debilitating disease of the submucosal tissue. Leaching out compounds from areca nut is the main etiology for OSMF. Biochemical examinations have concentrated on demarcating changes in the blood, serum, or tissues of patients with this disease. Such examinations have given insights into the possible pathogenesis of OSMF. Aim: Estimation of serum urea, uric acid (UA), and creatinine (Cn.) in OSMF patients. Objective: To estimate the level of serum urea, UA, and Cn. in OSMF patients and compare them with habitual betel nut chewers. Materials and Methods: The purposive samples were selected from patients attending the OPD of the Oral Medicine and Radiology (OMR) Department. In total 180 patients were included and divided into three groups. Group I-Patients suffering from OSMF, Group II-Habitual control, and Group III-Healthy control. Results: The mean value of serum UA (mg/dL) in Group I was 7.82 ± 2.18, Group II was 5.83 ± 1.22, and Group III was 5.28 ± 1.10. The mean value of serum Cn. (mg/dL) in Group I was 1.05 ± 0.27, Group II was 1.15 ± 0.22, and Group III was 0.72 ± 0.21. One-way analysis of variance (ANOVA) was applied between the groups and significant differences were found for both serum UA and Cn. with P < 0.0001, whereas no significant difference was found for serum urea. Conclusion: It can be concluded from this study that serum urea, UA, and Cn. of OSMF patients should be evaluated for liver and renal involvement and for overall improving the disease prognosis.

Keywords: Cn, OSMF, UA, urea
Key Message: Areca nut habit is associated with multiple systemic disorders because of areca nut alkaloids. One should always check for systemic involvement in OSMF and betel nut chewers, which will help in treatment modality.

How to cite this article:
Verma S, Bhowate RR. Evaluation of serum urea, uric acid and creatinine in OSMF patients: A clinical and biochemical stusdy. J Indian Acad Oral Med Radiol 2022;34:272-5

How to cite this URL:
Verma S, Bhowate RR. Evaluation of serum urea, uric acid and creatinine in OSMF patients: A clinical and biochemical stusdy. J Indian Acad Oral Med Radiol [serial online] 2022 [cited 2022 Dec 10];34:272-5. Available from: http://www.jiaomr.in/text.asp?2022/34/3/272/356950

   Introduction Top

Potentially malignant disorders (PMD) tend to convert into malignancies. The areca nut chewing is the main etiological factor in the pathogenesis of oral submucous fibrosis (OSMF). Other are nutritional deficiency, autoimmunity, and genetic susceptibility, which are important.[1]

Protein catabolism leads to the breakdown of proteins into amino acids and the formation of urea. The excretion of urea is combined with considerable body water loss due to osmotic pressure.[2]

Uric acid (UA) is the end product of purine metabolism in humans. UA is a widely accepted known antioxidant and it prevents cancer by mopping up free radicals that may cause injury at cellular and genetic levels.[3]

Creatine phosphokinase is an enzyme that is released in the body due to muscle damage in different diseases and is used as a potent biomarker for finding out the extent of muscle damage in the disease.[4] The muscular creatine (Cr) and phosphocreatine (PCr) are converted to creatinine (Cn.), which diffuses out of the cells and is excreted by the kidneys into the urine as a waste product.[5]

The prevalence of OSMF with increasing potential toward malignant conversion is seen in the third and fourth decades of life.[6] Considering the liver dysfunction in areca nut habitual due to reactive oxygen adducts (superoxide dismutases, hydrogen peroxide) may lead to alteration in level of urea, uric acid and creatinine and may cause renal involvement. Hence, this study was conducted to investigate serum, urea, UA, and Cn. in OSMF, habitual and healthy control.

   Materials and Methods Top

This cross-sectional cohort study was conducted in the Department of Oral Medicine and Radiology, SPDC Sawangi (Meghe), Wardha, Maharashtra, after approval of the Institutional Ethics Committee (Ref. No-DMIMS (DU)/IEC/2015-16/2039) (18/04/2016). The duration of the study was 2 years. A total of 180 participants were included after obtaining informed consent who were clinically diagnosed with different grades of OSMF, habitual, and healthy control groups. Each patient's detailed case history was recorded in the structured proforma. Kerr's[7] grading system was adopted for clinical diagnosis of the OSMF. A total of 180 subjects were divided into three groups.

  • Group I - 60 participants who were suffering from OSMF.
  • Group II - 60 (habitual control).
  • Group III - 60 (healthy control).

Patients with precancerous conditions or lesions other than OSMF, patients suffering from systemic diseases and other malignancies, and patients under medications for OSMF in the last 6 months were excluded from the study. Serum urea in patients was estimated by the Berthelot method, serum UA by the uricase method, and serum Cn. by the Jaffe reaction. Reagents were obtained, for S.urea - ENZOPAK, Reckon Diagnostics (Mfg–Lic no- G/1008), S.uric acid– Priman Liquigold (Mfg.Lic no-26/UA/SC/-2008), Serum creatinine - Siddham Diagnostics (C-493).

Statistical analysis

Evaluation of the results and statistical analysis was done by SPSS 17.0 and GraphPad Prism 5.0 version. All variables from this study were analyzed statistically for the mean values, standard deviation (SD), frequency, percentage, and P value, and the results obtained were analyzed statistically using the Chi-square test and the analysis of variance (ANOVA) test. The cut-off P value was to be considered statistically significant.

   Results Top

The mean age in Group I was found to be 29.88 ± 8.54 (18–48 years), in Group II was found to be 34.86 ± 11.26 (18–70 years), and in Group III was found to be 30.51 ± 9.82 (18–65 years). The M: F ratio in Group I was (6.45:1); in Group II was 7.55:1, and in Group III was 1.5:1, respectively [Table 1]. The maximum number of patients (50, 83.33%) in Group I and in Group II (43, 71.67%) were habitual of kharra with a mean frequency/day of 4.95 ± 1.50 in Group I and 3.61 ± 1.57 in Group II and duration of habit in a year was 5.78 ± 3.50 in Group I and 5.18 ± 3.76 in Group II [Table 2]. The mean inter-incisal opening was found to be 24.81 ± 4.89 mm in Group I (OSMF) [Table 3]. Out of 60, 53 (88.33%) patients belonged to Grade II OSMF, 5 (8.33%) belonged to Grade I OSMF, and 2 (3.33%) belonged to Grade III; this grading system is according to Kerr A.R.
Table 1: Demographic details of Group I, II, and III subjects

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Table 2: Characteristics of Areca Nut habit in Group I and Group II

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Table 3: Clinical characteristics in OSMF (Group I) patients

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The mean value of serum UA (mg/dL) in Group I was 7.82 ± 2.18, in Group II was 5.83 ± 1.22, and in Group III was 5.28 ± 1.10. One-way ANOVA was applied in groups with P < 0.0001, which is highly significant [Graph 1].

The mean value of serum Cn. (mg/dL) in Group I was 1.05 ± 0.27, in Group II was 1.15 ± 0.22, and in Group III, the mean value of serum Cn. was 0.72 ± 0.21. One-way ANOVA was applied between the groups and showed P < 0.000,1 which was highly significant [Graph 1].

The mean value of serum urea (mg/dL) in Grade I OSMF was 27.00 ± 3.41, in Grade II OSMF was 28.89 ± 7.1, and in Grade III was 26.73 ± 3.25. The mean value of serum UA (mg/dL) in Grade I OSMF was 8.76 ± 3.88, in Grade II OSMF was 7.78 ± 2.01, and in Grade III OSMF was 6.51 ± 0.75. The mean value of serum Cn. in Grade I OSMF was 1.04 ± 0.20, in Grade II OSMF was 1.06 ± 0.27, and in Grade III OSMF was 0.92 ± 0.53. Results showed no statistical major difference in serum urea, serum UA, and serum Cn. with Grades of OSMF [Graph 2].

   Discussion Top

In OSMF, the main culprit is areca nut. The areca nut-induced production of reactive oxygen species (ROS) increases by Fe +2, Fe +3 and Cu +2, but is suppressed by Mn +2. The generated ROS from betel quid chewing may cause cellular injury leading to oxidative damage to the DNA of oral mucosal cells.[8]

In the present study, the mean age in Group I (OSMF) was 29.88 ± 8.54 years, which was in accordance with the study conducted by Raina.[9] The majority of patients suffering from OSMF were males (52, 86.67%) with M: F ratio of 6.45:1, which is similar to the study by Zameera.[10] All OSMF patients were regular habitual of areca nuts with tobacco and lime. Fifty (83.33%) out of 60 subjects with OSMF had a kharra chewing habit. Kharra is a local preparation of white half-cut areca nuts mixed with tobacco and lime. In the present study, the mean duration of chewing areca nuts in any form was 5.78 ± 3.50 years, which is similar to the study by Tilakaratne.[11] The mean frequency of habit in the majority of patients of Group I (OSMF) was found to be 4.95 ± 1.50. The duration of chewing habit was significantly associated with daily consumption. A similar finding was reported by Maher, Lee, and Warnakalasuriya[12] who stated that with respect to the risk of OSMF, daily consumption appeared to be much more significant than life-long duration of the habit but Ahmad and Ali[13] reported that the habitual use of areca quid for 5 years or more predisposes the oral mucosa to OSMF.

In the present study, the majority of the patients suffering from OSMF were in Grade II 53 (88.33), 5 (8.33%) in Grade I, and 2 (3.33%) in Grade III, which is in accordance with the study by Rooban.[14]

Various studies established an association between betel nut chewing habit with metabolic syndrome,[15] cardiovascular disease, hypertension,[16] chronic kidney disease, and proteinuria.[17]

Urea, which is commonly known as blood urea nitrogen (BUN), is a non-protein nitrogenous (NPN) waste product.[18] Therefore, the aqueous extract of areca nut can lead to breakage in the DNA of kidney cells. A diminished glomerular filtration rate (GFR) has been reported for subjects consuming 40 areca nuts/day.[19]

The mean value of serum UA (mg/dL) in Group I was 7.82 ± 2.18, in Group II was 5.83 ± 1.22, and in Group III was 5.28 ± 1.10. Intergroup correlation was found to be significant, which is the same as that by Narang[1] and Sung.[20] A close relationship has been proved between hyperuricemia and metabolic syndrome,[21] CVD, hypertension,[22] chronic kidney disease,[23] and epidemiological diseases. Verdecchia et al.[24] correlated hyperuricemia with a high risk of cardiovascular events and Chang[23] found a positive correlation between hyperuricemia with chronic kidney disease in persons older than 40 years of age. The present study in both Group I and Group II showed increased UA levels compared to the healthy group, this may be due to betel nut chewing with tobacco and mixed dietary habit in all OSMF and without OSMF. Raised UA level causes endothelial cell dysfunction through nitric oxidase synthetase[25] and vascular smooth muscle proliferation. UA may stimulate the renin–angiotensin system responsible for renal disorder and higher blood pressure.[26]

In the present study, the mean value of serum Cn. (mg/dL) in Group I was 1.05 ± 0.27, in Group II was 1.15 ± 0.22, and in Group III was 0.72 ± 0.21. Intergroup correlation was found to be significant.

In Group 2, there was a statistically significant difference between serum UA and serum Cn. Dietary creatine supplements metabolize to creatine phosphate by phosphorylation and then to Cn.

In Group II, all individuals were areca nut habitual, where chewing is responsible for increased activity of masticatory muscles and may be responsible for the association of Cn. and UA. The current article emphasizes the comparison among different grades of OSMF, habitual control, and normal control, which show the relationship between disease progression in established and developing cases. Altered levels of biomarkers play a significant role in diagnosing and planning the treatment, which results in a better prognosis and improvement in the quality of life.


As the study used serum urea, UA, and Cn. as prognostic markers, it might not give much requisite information in patients suffering from inflammatory disorders such as gout and chronic kidney disease.

Future recommendations

Further multi-centric evaluation of OSMF for liver and renal involvement is required in Indian areca nut habitual along with 24 h urine analysis for urea, UA, and Cn.

   Conclusion Top

Areca nut habit is associated with metabolic syndrome, CVS, renal, and liver disorders because of areca nut alkaloids. Increase in serum urea, UA, and Cn. predispose to the functional disorder of CVS and renal system. Serum Cn. level primarily reflects GFR as it passes without being reabsorbed through the renal tubules. Areca nut alkaloids have a para sympathomimetic effect and may result in disproportionate reabsorption of urea. Therefore, the patient suffering from OSMF should be evaluated for the involvement of the liver and renal disorder, which will help in planning the treatment protocol.

Declaration of patient consent

The authors certify that they have obtained all the appropriate consent from patients in their consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their clinical information to be reported in the journal. The patients understand that their names will not be published and due efforts will be made to conceal their identity, but their anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

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Satyanarayan U, Chakrapani U. Biochemistry. 4th ed, Chapter 15. Elsevier; 2013. p. 330-79.  Back to cited text no. 3
Lang H, Wurzburg U. Creatinekinase, an enzyme of many forms. Clin Chem 1982;28:1439-47.  Back to cited text no. 4
Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism.Physiol Rev 2000;80:1107-213.  Back to cited text no. 5
Gupta PC, Mehta FS. Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 1980;8:287-333.  Back to cited text no. 6
Kerr AR, Warnakulasuriya S. A systematic review of medical interventions for OSMF and future research opportunities. Oral Dis 2011;17:42–57.  Back to cited text no. 7
Liu TY, Chen CL. Oxidative damage to DNA induced by areca nut extract. Mutat Res- Genet Toxicol Environ Mutagen 1996;367:25-31.  Back to cited text no. 8
Raina C, Raizada RM.Clinical profile and serum beta carotene levels in OSMF. Indian J Otolaryngol 2005;57:191-5.  Back to cited text no. 9
Zameera A, Mamtha GP. Serum proteins, transaminases and blood urea in patients with OSMF- A preliminary study. Int J Oral Sci 2012:1-5.doi: 10.13140/RG.2.2.19524.17287.  Back to cited text no. 10
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Maher R, Lee AJ, Warnakalasuriya KAAS, Ewis JA, Johnson NW. Role of areca nut in causation of OSMF: A case control study in Pakistan. J Oral Pathol Med 1994;23:65-9.  Back to cited text no. 12
Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological and etiological study of OSMF among Gutkha chewers of Patna, Bihar, India. J Indian Soc Pedod Prev Dent 2006;24:84-9.  Back to cited text no. 13
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  [Table 1], [Table 2], [Table 3]


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