|Year : 2016 | Volume
| Issue : 2 | Page : 53-58
Oral conditions, periodontal status and periodontal treatment need of chronic kidney disease patients
Modupeoluwa Omotunde Soroye1, Patricia Omowunmi Ayanbadejo2
1 Department of Preventive Dentistry, Faculty of Dentistry, College of Health Sciences, University of Port Harcourt, Port Harcourt, Rivers State, Nigeria
2 Department of Preventive Dentistry, Faculty of Dentistry, College of Medicine, University of Lagos, Lagos State, Nigeria
|Date of Web Publication||13-Oct-2016|
Modupeoluwa Omotunde Soroye
Department of Preventive Dentistry, Faculty of Dentistry, College of Health Sciences, University of Port Harcourt, Port Harcourt, Rivers State
Source of Support: None, Conflict of Interest: None
Objective: To evaluate the periodontal status and periodontal treatment need (TN) of patients with chronic kidney disease (CKD).
Methodology: All the patients with CKD who presented at the renal out-patient clinic of the University of Lagos University Teaching Hospital were recruited into the study. Data were collected using self-administered questionnaire with open and closed questions comprising demographic details such as age and gender, year of diagnosis, and stage of kidney disease and dialysis. Simplified oral hygiene index (OHI-S) of Green and Vermilion and Community Periodontal Index of TN were used to assess the patients' periodontal status.
Results: Participants' age ranged between 21 years and 73 years with a mean age of 45.14 14.14. Of the 65 participants, males were 64.6% and females were 35.5%. More than half of the participants were diagnosed within the last 5 years (54.6%). The cause of renal disease in 41 of them (63.1%) was hypertension. Other causes such as chronic glomerular nephritis (4.6%), diabetes mellitus (4.6%), and hypertensive heart disease (3.1%) were also mentioned. Nearly, 6.2% had no known cause. About a fifth of the participants (16.9%) had other systemic conditions such as diabetes. Their mean OHI-S was 1.96 0.90. About two-thirds of the participants had CPI score of 2, and the major treatment needed was code 2 consisting of scaling, polishing, and root planing.
Conclusion: Majority of the CKD patients reviewed had poor periodontal status with code 2 TN. We, therefore, recommend nonsurgical periodontal treatment for all CKD patients to improve their oral health and forestall the systemic effects of periodontal pathology.
Keywords: Chronic kidney disease, periodontal status, periodontal treatment need
|How to cite this article:|
Soroye MO, Ayanbadejo PO. Oral conditions, periodontal status and periodontal treatment need of chronic kidney disease patients. J Oral Res Rev 2016;8:53-8
|How to cite this URL:|
Soroye MO, Ayanbadejo PO. Oral conditions, periodontal status and periodontal treatment need of chronic kidney disease patients. J Oral Res Rev [serial online] 2016 [cited 2021 Sep 23];8:53-8. Available from: https://www.jorr.org/text.asp?2016/8/2/53/192176
| Introduction|| |
Periodontal disease has been highlighted as an important potential risk factor for noncommunicable diseases (NCDs) such as diabetes mellitus, cardiovascular diseases, pulmonary diseases, and chronic kidney diseases (CKD). , It is a destructive chronic inflammatory and infectious destruction of the gingiva, periodontal ligaments, and alveolar bone, predominantly caused by Gram-negative bacteria residing in dental plaque biofilm.  On the other hand, CKD, also known as chronic renal disease, is a progressive and irreversible loss in kidney function over a period of months leading to a decline in the glomerular filtration rate.  Some studies have reported an association between chronic renal disease and periodontitis while others did not find any association between them. ,,,, In some situations, a bidirectional model has also been observed where the presence of one condition increases the chances of the other and controlling one condition may benefit the patient as regarding the other condition.  In CKD, the kidneys are not removing urea from the blood and this is broken down into ammonia, thus people with CKD may have bad taste and mouth odor. They can also have loose and painful teeth because the body cannot absorb calcium properly.  Other oral complications of renal disease include dry mouth, periodontal disease, and inflammation of the salivary glands.  A study reported that patients suffering from end-stage renal failure (ESRF) and those receiving dialysis are more prone to periodontal disease and other oral health problems.  It revealed that the renal failure groups had higher gingival index and bleeding, probing depths, attachment loss, enamel hypoplasia, pulp obliteration, and less caries, than the control. Plaque was also found to be higher in the dialysis and predialysis groups, and it was concluded that the correlation between dialysis and ESRF and gingivitis, probing depth, attachment loss, and enamel hypoplasia is significant.  Dialysis patients may form calculus more rapidly than healthy individuals possibly due to high salivary urea and phosphate levels, and a significant correlation between plaque scores and gingival inflammation in renal dialysis patients has been reported. ,, Elevated parathyroid hormone synthesis is also common in ESRF which causes accelerated bone loss that can exacerbate periodontal disease.
Periodontitis is an inflammatory disease and contributes to systemic diseases due to increased inflammatory burden, leading to the worsening of CKD.  Periodontal pathogens can cause the destruction of periodontal tissues resulting in detachment of tissues from around the teeth and the entry of pathogens and their products into systemic circulation leading to increased systemic inflammation.  The mechanism proposed for the effect of periodontitis on the development of kidney disease is systemic inflammation. , Both periodontitis and kidney diseases are associated with inflammatory markers such as C-reactive protein and the chronic low level of inflammation that is associated with periodontitis may lead to endothelial dysfunction which may play a role in the pathogenesis of kidney disease.  The unpleasant effects of systemic inflammation on kidney function could occur during the period of active periodontal infection and accumulate throughout the life time of the individual. In addition, inflammation is an important predictor of low-serum albumin levels among dialysis patients.  Detailed literature reviews yielded few studies performed to assess the periodontal status and treatment need (TN) of CKD patients. The aim of this study, therefore, is to evaluate the periodontal status of those with kidney disease and assess their TN.
| Methodology|| |
Study population and design
A cross-sectional study carried out among patients already diagnosed with CKD who attended the renal outpatient clinic in Lagos University Teaching Hospital (LUTH), Idi-araba, Lagos, in October and November, 2011, were recruited for this study after getting written consent from them.
All patients who were 18 years and above and have been diagnosed with CKD for at least 6 months and who consented for the study.
Ethical approval was collected from the Research and Ethics Committee of the LUTH.
Self-administered questionnaire with open and closed questions were used to collect the participants' demographic details such as age, gender, ethnicity, and educational status. Also collected were details on participants' cause of kidney disease, stage of kidney disease, year of diagnosis, when dialysis was started, type of medication, and presence of any other systemic disease. The participants' oral conditions were recorded by asking questions like if there is a change in their taste and if they have mouth dryness as well as by using the following periodontal indices:
1. The Simplified Oral Hygiene Index (OHI-S) 
2. The Community Periodontal Index of TNs (CPITN). 
Simplified oral hygiene index
This index is one of the most commonly used indices for assessing the oral hygiene status. The OHI-S is a composite index that scores debris and calculus deposition on selected teeth. Six surfaces were examined for the OHI-S.  These are the buccal surfaces of the upper right and left first permanent molars, the lingual surfaces of the lower right and left first permanent molars, and the labial surfaces of the upper right and lower left permanent central incisors. Oral debris was scored as follows:
0 = No debris or stain present
1 = Soft debris covering not more than one-third of the tooth surface or presence of extrinsic stains without other debris regardless of surface area covered
2 = Soft debris covering more than one-third, but not more than two-thirds of the exposed tooth surface
3 = Soft debris covering more than two-thirds of the exposed tooth surface.
Calculus was scored as follows:
0 = No calculus present
1 = Supragingival calculus covering not more than one-third of the exposed tooth surface
2 = Supragingival calculus covering more than one-third, but not more than two-thirds of the exposed tooth surfaces or presence of individual flecks of subgingival calculus around the cervical portion of the tooth
3 = Supragingival calculus covering more than two-thirds of the exposed tooth surface or a continuous heavy band of subgingival calculus around the cervical portion of the tooth.
After recording the debris and calculus scores for the patient, the index values were then calculated. This was achieved by totaling the debris scores and dividing by the number of surfaces examined. The average score for debris is the simplified debris index (DI-S) and that for calculus is simplified calculus index (CI-S).
The DI-S and CI-S were added to obtain the OHI-S. The OHI-S values range from 0 to 6 and interpreted as such:
0-1.2 = Good
1.3-3.0 = Fair
3.1-6.0 = Poor
The community periodontal index of treatment needs
The CPITNs is an epidemiologic tool developed by the World Health Organization (WHO) for the evaluation of periodontal disease in population surveys, throughout the world. It was adopted by Ainamo et al. in 1982.  It is a tool used to measure periodontal disease and is valuable because it allows rapid examination of population groups to determine their periodontal TNs. E-probe was used in this study. Since the participants were older than 20 years, 10 specified index teeth were examined.
0 - healthy gingiva
1 - bleeding observed, directly or by using mouth mirror, after probing
2 - calculus detected during probing, but all the black band on the probe visible
3 - pocket 4-5 mm (gingival margin within the black band on the probe)
4 - pocket 6 mm or more (black band on the probe not visible)
X - excluded sextant (<2 teeth present).
0 - no care required
I - oral hygiene instruction,
II - oral hygiene instruction, and professional removal of dental plaque
III - specialized treatment required.
Data analysis was done using Epi info version 3.5.1; 2008 (CDC) (http://www.cdc.gov/epiinfo/index.html), August, 2008 statistical software. A descriptive analysis was generated for all comparisons, and the level of significance was set at 5%.
| Results|| |
[Table 1] shows the sociodemographic characteristics of the participants. Sixty-five participants with CKD participated in the study. Their age ranged between 21 and 73 years with a mean age of 45.1 years (±standard deviation 14.1). There were more men than women (M = 42 [64.6%], W = 23 [35.4%]).
Multiple Nigerian ethnic groups were represented: Igbos 26 (40.0%), Yoruba 24 (36.9%), and Hausa 1 (1.5%).
More than half of the participants, i.e., 35 (53.8%) had tertiary education. Only 4 (6.2%) had no formal education. The participants' occupation varies. About one-third, i.e. eighteen (27.7%) were traders, seven were (10.7%) professionals, nine were (13.9%) artisans, and nine were pensioners (13.9%).
[Table 2] shows the oral conditions of the participants. Twenty-six (40%) of them had dry mouth, 24 (36.9%) had slight to moderate change in taste (unpleasant taste), while halitosis was present in 12 (18.5%) of them. Only 1 (1.5%) participant had candidiasis and 4 (6.2%) had mobile teeth. [Table 3] shows that the cause of CKD in majority, i.e., 41 (63.1%) participants was hypertension. Other causes were diabetes mellitus 3 (4.7%), chronic glomerulonephritis 3 (4.7%), and hypertensive heart disease 2 (3.1%). The cause was unknown in 4 (6.1%) participants. About three quarters (47 [72.3%]) of the participants were in Cockcroft-Gault stage 1 of the disease and two-fifth (7 [10.8%] in stage 2). About one-fifth of the participants (12 [18.5%]) were on dialysis and more than half (8 [55.7%]) of those on dialysis had been on dialysis for more than 1 year. [Table 4] shows the oral hygiene status of the participants. Majority, i.e., 45 (69.2%) of them had fair oral hygiene, one-fifth, i.e., 13 (20%) had good oral hygiene, and 7 (10.8%) had poor oral hygiene. The mean oral hygiene score of the participants was 1.97 ± 0.90. Two-third (41 [63.1%]) of the participants had periodontal status of CPITN code 2 and 9 (13.9%) had code 3. The TN for half (50 [77%]) of the participants was oral hygiene instructions, scaling and polishing, and sub-gingival scaling and root planing. Only 1 (1.5%) participant needed specialized periodontal treatment [Table 5].
|Table 3: Participants' aetiology, stage of chronic kidney disease and dialysis status |
Click here to view
| Discussion|| |
Chronic medical conditions that are not spread by infections are called NCDs, and oral diseases were classified among NCDs by WHO in 2005 since they serve as a source of infection to other body organs. , Although NCDs such as diabetes mellitus, pulmonary diseases, osteoporosis, cardiovascular diseases, and CKDs affect the life of individuals in terms of morbidity, mortality, and financial crises, its been said that 40% of total deaths can be controlled by eliminating the risk factors.  Furthermore, a global survey predicted that by 2020, seven out of every ten deaths will be due to NCDs in the developing countries.  Many studies have reported increased prevalence and severity of periodontal disease in patients with CKD, however majorly on patients undergoing dialysis. ,, The present study assessed the periodontal status and TN of patients diagnosed with CKD, since there is a lack of adequate knowledge on this issue. There were 65 participants in this study with male (64.6%) more than females (35.4%). This is similar to a study done in Albania that recorded a higher number of males (54.7%) than females (45.3%), and it is in contrast with that done in Saudi Arabia that reported more females (58.9%) than males (41.1%). , This difference can be explained by the different sample populations. Although age is a risk factor for CKD, in this study, participants' age ranged from 21 to 65 years with a mean age of 45.1 ± 14.1 years. This is comparable to a study done in Saudi Arabia which had a mean age of 45.63 ± 16.77.  However, other studies done in Iran, Albania, and Poland recorded a higher mean age of 47.9 ± 15.3 years, 51.2 ± 16.1 years, and 51 years, respectively. ,,,, Studies have shown that with the progression of CKD, some oral symptoms arise. , CKD affects the oral health status of patients by inducing gingival xerostomia, hyperplasia, calcification of root canals, and relayed eruption of teeth.  Dry mouth (xerostomia) is caused by limited fluid intake that has to be controlled, since the kidneys are unable to remove excess fluid and waste products and azotemia, in which there is a high level of urea nitrogen and if uncontrolled can lead to uremia.  In this study, 40% of the patients had dry mouth. This is lower than that reported by the studies done in the United Kingdom, in which 50% and 69% of their participants had dry mouth, but compares with the studies done in Brazil (40%) and Mexico (44.4%, 43.7%). ,,,, Other oral conditions recorded in this study included halitosis (18.5%), candidiasis (1.5%), and mobile teeth (6.2%). The percentage of the participants with unpleasant taste in this study was 37%. This is lower than that reported by de la Rosa et al. among Mexicans (45.5%), but higher than that reported by Bots et al. (31%). , The etiology of CKD has been documented to be many and could either be a manifestation of another chronic disease that cause end-organ failure such as hypertension and diabetes mellitus or could be due to an intrinsically renal disease such as polycystic kidney disease. , Our study recorded the etiology of CKD in about two-third of the participants (63.1%) as hypertension, diabetes in 4.7%, and idiopathic (unknown) in 6.1%. Other studies done in Nigeria, Cameroon, and the United States of America likewise recorded hypertension as the most prevalent etiology among their participants. ,,, Almost three-quarters of the participants (72.3%) in our study were in stage 1 of the Cockcroft-Gault Stage of Kidney disease, 10.8% in stage 2, and 1.5% in stage 5. Though many studies reported that the oral hygiene status of patients having CKD is poor due to negligence of their oral health as the disease progresses due to stress, xerostomia, gingival hyperplasia, malnutrition, and drugs such as anti-depressants and anti-coagulants, in this study, only 10.8% of participants had poor oral hygiene and 69.1% had fair oral hygiene status. ,, This compares to a study done among Indians which reported that 73.7% of their participants had fair oral hygiene.  The fair oral hygiene status in our study may be accounted by the fact that most of the participants used in this study were at the early stages of their disease and their oral hygiene may get poor with time. However, it is important that early intervention in oral care should be emphasized as early as possible for CKD patients. Almost all the participants (90.8%) in our study had periodontal disease, though not all were on dialysis. This could only mean that not only CKD patients on dialysis have periodontal disease, but also those yet to require it. The high prevalence of periodontal disease among our participants compares to other studies which reported the same. ,,,,,,, The majority of the participants (63.1%) in this study had CPITN code 2 (supra- and sub-gingival calculus detected during probing, but all the black band on the probe visible, that is, periodontal pocket <3.5 mm). This compares with an Indian study that also reported that most of their participants had CPITN code 2 score.  Suprith et al. reported that most of their participants had code 4.  The TN recorded for about two-third of the participants in this study was CPITN code 2 (oral hygiene instruction, scaling, and root planing).
A small sample size was used in this study, though it is comparable to most previous studies and it may not be large enough to represent the CKD population.
| Conclusion|| |
This study agrees with the findings of other studies that periodontal disease is common, prevalent, and unrecognized among CKD patients. However, periodontal disease was not only present among patients undergoing dialysis, but also found among predialyzed ones. Thus, there is a need to incorporate oral care in the management of patients with CKD so as to improve their oral health and their quality of life as well as forestall the systemic effects of periodontal pathology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wahid A, Chaudhry S, Ehsan A, Butt S, Ali Khan A. Bidirectional relationship between chronic kidney disease and periodontal disease. Pak J Med Sci 2013;29:211-5.
Bokhari SA, Khan AA. Growing burden of noncommunicable diseases: The contributory role of oral diseases, Eastern Mediterranean Region perspective. East Mediterr Health J 2009;15:1011-20.
Lucas VS, Roberts GJ. Oro-dental health in children with chronic renal failure and after renal transplantation: A clinical review. Pediatr Nephrol 2005;20:1388-94.
Ots M, Pechter U, Tamm A. Characteristics of progressive renal disease. Clin Chim Acta 2000;297:29-41.
Kshirsagar AV, Offenbacher S, Moss KL, Barros SP, Beck JD. Antibodies to periodontal organisms are associated with decreased kidney function. The dental atherosclerosis risk in communities study. Blood Purif 2007;25:125-32.
Borawski J, Wilczynska-Borawska M, Stokowska W, Mysliwiec M. The periodontal status of pre-dialysis chronic kidney disease and maintenance dialysis patients. Nephrol Dial Transplant 2007;22:457-64.
Shultis WA, Weil EJ, Looker HC, Curtis JM, Shlossman M, Genco RJ, et al.
Effect of periodontitis on overt nephropathy and end-stage renal disease in type 2 diabetes. Diabetes Care 2007;30:306-11.
Castillo A, Mesa F, Liébana J, García-Martinez O, Ruiz S, García-Valdecasas J, et al.
Periodontal and oral microbiological status of an adult population undergoing haemodialysis: A cross-sectional study. Oral Dis 2007;13:198-205.
Vesterinen M, Ruokonen H, Leivo T, Honkanen AM, Honkanen E, Kari K, et al.
Oral health and dental treatment of patients with renal disease. Quintessence Int 2007;38:211-9.
Davidovich E, Schwarz Z, Davidovitch M, Eidelman E, Bimstein E. Oral findings and periodontal status in children, adolescents and young adults suffering from renal failure. J Clin Periodontol 2005;32:1076-82.
Epstein SR, Mandel I, Scopp IW. Salivary composition and calculus formation in patients undergoing hemodialysis. J Periodontol 1980;51:336-8.
Naugle K, Darby ML, Bauman DB, Lineberger LT, Powers R. The oral health status of individuals on renal dialysis. Ann Periodontol 1998;3:197-205.
Atassi F, Al-Shammery RA, Al-Ghamdi S. Gingival health among individuals on hemodialysis in Saudi population. Saudi Dent J 2001;13:82-6.
Loos BG. Systemic effects of periodontitis. Int J Dent Hyg 2006;4 Suppl 1:34-8.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366:1809-20.
Bascones-Martínez A, Muñoz-Corcuera M, Noronha S, Mota P, Bascones-Ilundain C, Campo-Trapero J. Host defence mechanisms against bacterial aggression in periodontal disease: Basic mechanisms. Med Oral Patol Oral Cir Bucal 2009;14:e680-5.
Rahmati MA, Craig RG, Homel P, Kaysen GA, Levin NW. Serum markers of periodontal disease status and inflammation in hemodialysis patients. Am J Kidney Dis 2002;40:983-9.
Grubbs V, Plantinga LC, Crews DC, Bibbins-Domingo K, Saran R, Heung M, et al.
Vulnerable populations and the association between periodontal and chronic kidney disease. Clin J Am Soc Nephrol 2011;6:711-7.
Greene JC, Vermillion JR. The simplified oral hygiene index. J Am Dent Assoc 1964;68:7-13.
Ainamo J, Barmes D, Beagrie G, Cutress T, Martin J, Sardo-Infirri J. Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J 1982;32:281-91.
Boutayeb A, Boutayeb S. The burden of non communicable diseases in developing countries. Int J Equity Health 2005;4:2.
Gavaldá C, Bagán J, Scully C, Silvestre F, Milián M, Jiménez Y. Renal hemodialysis patients: Oral, salivary, dental and periodontal findings in 105 adult cases. Oral Dis 1999;5:299-302.
Al-Wahadni A, Al-Omari MA. Dental diseases in a Jordanian population on renal dialysis. Quintessence Int 2003;34:343-7.
Jenabian N, Ghazi Mirsaeed AM, Ehsani H, Kiakojori A. Periodontal status of patient's underwent hemodialysis therapy. Caspian J Intern Med 2013;4:658-61.
Atassi F, Almas K. Oral hygiene profile of subjects on renal dialysis. Indian J Dent Res 2001;12:71-6.
Merita R, Saimir S, Elizana P, Myftar B, Dritan M, Nereida S, et al
. Is the periodontitis a source of systemic inflammation in patients undergoing peritoneal dialysis or hemodialysis? BANTAO J 2011;9:36-41.
Kho HS, Lee SW, Chung SC, Kim YK. Oral manifestations and salivary flow rate, pH, and buffer capacity in patients with end-stage renal disease undergoing hemodialysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:316-9.
Murtagh FE, Addington-Hall JM, Edmonds PM, Donohoe P, Carey I, Jenkins K, et al.
Symptoms in advanced renal disease: A cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J Palliat Med 2007;10:1266-76.
Murtagh FE, Addington-Hall J, Edmonds P, Donohoe P, Carey I, Jenkins K, et al.
Symptoms in the month before death for stage 5 chronic kidney disease patients managed without dialysis. J Pain Symptom Manage 2010;40:342-52.
Cunha FL, Tagliaferro EP, Pereira AC, Meneghim MC, Hebling E. Oral health of a Brazilian population on renal dialysis. Spec Care Dentist 2007;27:227-31.
de la Rosa E, Cruz S, Mondragón A. Tooth loss in diabetic patients with and without chronic kidney disease and dialysis. Nefrologia 2008;28:645-8.
de la Rosa García E, Mondragón Padilla A, Aranda Romo S, Bustamante Ramírez MA. Oral mucosa symptoms, signs and lesions, in end stage renal disease and non-end stage renal disease diabetic patients. Med Oral Patol Oral Cir Bucal 2006;11:E467-73.
Bots CP, Poorterman JH, Brand HS, Kalsbeek H, van Amerongen BM, Veerman EC, et al.
The oral health status of dentate patients with chronic renal failure undergoing dialysis therapy. Oral Dis 2006;12:176-80.
Amira CO, Braimoh RW, Bello BT. Pattern of intradialytic complications at the Lagos University Teaching Hospital. Afr J Med Med Sci 2012;41:411-6.
Arogundade FA, Sanusi AA, Hassan MO, Akinsola A. The pattern, clinical characteristics and outcome of ESRD in Ile-Ife, Nigeria: Is there a change in trend? Afr Health Sci 2011;11:594-601.
Halle MP, Takongue C, Kengne AP, Kaze FF, Ngu KB. Epidemiological profile of patients with end stage renal disease in a referral hospital in Cameroon. BMC Nephrol 2015;16:59.
Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al
. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038-47.
Tadakamadla J, Kumar S, Mamatha GP. Comparative evaluation of oral health status of chronic kidney disease (CKD) patients in various stages and healthy controls. Spec Care Dentist 2014;34:122-6.
de Souza CM, Braosi AP, Luczyszyn SM, Olandoski M, Kotanko P, Craig RG, et al.
Association among oral health parameters, periodontitis, and its treatment and mortality in patients undergoing hemodialysis. J Periodontol 2014;85:e169-78.
Lacson E Jr., Levin NW. C-reactive protein and end-stage renal disease. Semin Dial 2004;17:438-48.
Parkar SM, Ajithkrishnan CG. Periodontal status in patients undergoing hemodialysis. Indian J Nephrol 2012;22:246-50.
Suprith SS, Setty S, Tharku S. Assessment of periodontal status in chronic kidney disease patients. Dent Sci 2015;4:163-5.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]