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Periodontal Disease and Other Nontraditional Risk Factors for CKD

Monica A. Fisher, PhD, DDS, MPH,1 George W. Taylor, DMD, DrPH,2 Brent J. Shelton, PhD,3

Kenneth A. Jamerson, MD,2 Mahboob Rahman, MD, MS,1 Akinlolu O. Ojo, MD, PhD,2 andAshwini R. Sehgal, MD1

Background: Chronic kidney disease, undiagnosed in a significant number of adults, is a publichealth problem. Given the systemic inflammatory response to periodontal disease, we hypothesized

that periodontal disease could be associated with chronic kidney disease.

Study Design: Cross-sectional.

Setting & Participants: We identified 12,947 adults 18 years or older with information for kidney

function and at least one risk factor in the Third National Health and Nutrition Examination Survey.

Predictor: The main predictor was periodontal status. Other nontraditional and traditional risk factors

included socioeconomic status, health status, health behavior, biomarker levels, anthropometric assess-

ment, and health care utilization.

Outcomes & Measurements: Chronic kidney disease was defined using the Kidney Disease

Outcomes Quality Initiative stages 3 and 4 with a moderate to severe decrease in kidney function

(glomerular filtration rate, 15 to 59 mL/min/1.73 m2). Univariable and multivariable logistic regression

models assessed the associations between chronic kidney disease and periodontal disease and other

nontraditional risk factors.

Results:Chronic kidney disease prevalence was 3.6%; periodontal disease prevalence was 6.0%;

and edentulism prevalence was 10.5%. Adults with periodontal disease and edentulous adults weretwice as likely to have chronic kidney disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.16

to 2.21; adjusted odds ratio, 1.85; 95% confidence interval, 1.34 to 2.56, respectively) after simulta-

neously adjusting for other traditional and nontraditional risk factors.

Limitations: Temporal association is unknown.

Conclusions: Periodontal disease and its severe consequence, edentulism, were independently

associated with chronic kidney disease after adjusting for other traditional and nontraditional risk factors.

This model could contribute to identifying individuals at risk of chronic kidney disease and reduce its

burden.

Am J Kidney Dis51:45-52.2007 by the National Kidney Foundation, Inc.

INDEX WORDS: Chronic kidney disease; diabetes mellitus; edentulism; glomerular filtration rate;

hypertension; macroalbuminuria; periodontal disease.

Chronic kidney disease (CKD) is a publichealth problem that is undiagnosed in a

significant number of those affected in the UnitedStates.1-3 Serious sequelae related to CKD in-

clude end-stage kidney failure, cardiovasculardisease, and premature death, with death andcardiovascular events more common than pro-gression to kidney failure.4-6 The risk of theseserious sequelae increases as glomerular filtra-tion rate (GFR) decreases to less than 60 mL/min/1.73 m2 (1.0 mL/s/1.73 m2).4-6 This level of

moderate to severe decrease in kidney functioncorresponds to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiativestages 3 and 4 CKD, defined as a GFR of 15 to 59mL/min/1.73 m2 (0.25 to 0.98 mL/s/1.73 m2).1

Identification of undiagnosed high-risk indi-viduals is needed to provide the opportunity forearly detection and intervention to prevent or

delay the onset of end-stage renal disease andcardiovascular events. Other than one recently

reported prediction model,7 high-risk subgroups

for CKD typically were identified through a

single traditional risk factor: age older than 60

years,1,7,8 hypertension,2,8,9-15 diabetes,2,7-16 poorglycemic control,1,11,12 obesity,2,12-16 macroalbu-

minuria,1,3,8,17 smoking,1,9,12,14-16 C-reactive

protein level,14,18,19 elevated total choles-

terol level,1,12,14 low high-density lipoprotein

1From Case Western Reserve University, Cleveland, OH;2University of Michigan, Ann Arbor, MI; and3University ofKentucky, Lexington, KY.

Received June 2, 2007. Accepted in revised form Septem-ber 18, 2007.

This work was done at Case Western Reserve University.Address correspondence to Monica A. Fisher, PhD, DDS,

MPH, Associate Professor, Case Western Reserve Univer-sity, 10900 Euclid Ave, Cleveland, OH 44106-4905.E-mail:monica.fisher@case.edu

2007 by the National Kidney Foundation, Inc.0272-6386/07/5101-0007$34.00/0doi:10.1053/j.ajkd.2007.09.018

American Journal of Kidney Diseases,Vol 51, No 1 (January), 2008: pp 45-52 45

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level,1,10,12,15 elevated low-density lipoproteincholesterol level,15 race/ethnicity,1,11,13,14,16 gen-der,1,7,9,12,14-16and income/poverty.1,13 Recently,nontraditional risk factors were reported that

may contribute to CKD, such as periodontaldisease,20-22 education,13,16 and health care utili-zation.13,23

The rationale for considering periodontal dis-ease as a nontraditional risk factor for CKDcenters around the inflammatory response to peri-odontal disease adding to the chronic systemicinflammatory burden associated with CKD. Therole of chronic inflammatory burden in patientswith CKD was reported through the associationbetween C-reactive protein level and CKD.19,24

Thus, we speculate that periodontal disease maycontribute to CKD because periodontal disease,more specifically chronic periodontitis, is achronic infectious disease caused by gram-negative bacteria with a persistent host inflamma-tory response. The loss of attachment of theperiodontal ligament and bony support of theteeth can lead to tooth loss. In adults, periodontaldisease is a major cause of edentulism.25 Theresponse to periodontal pathogens leads to alocal tissue-destructive immunoinflammatory re-sponse thought to create a chronic systemic in-flammatory burden secondary to the systemicdissemination of periodontal pathogenic bacte-

ria, their products (eg, lipopolysaccharides), andlocally produced inflammatory mediators (eg,interleukin 1, tumor necrosis factor, interleu-kin 6, prostaglandin E2, and thromboxaneB2).26,27 Furthermore, an acute-phase inflamma-tory response, measured by using elevated C-reactive protein level, is associated with periodon-tal disease and edentulism after controlling forotherrisk factors for elevated C-reactive proteinlevel.28

A similar focus on the systemic inflammatoryburden of chronic periodontal disease was hypoth-

esized to contribute to endothelial injury andatherogenesis.29An increasing body of epidemio-logical evidence supports a significant associa-tion between periodontal disease and cardiovas-cular diseases.30,31 Additionally, several clinicalstudies involving the treatment of patients withchronic periodontitis reported an improvementin secondary end points considered important incardiovascular disease risk,27 including a re-cently reported randomized clinical trial show-

ing a significant improvement in endothelial func-tion after periodontal treatment.29

Chronic inflammation is one of the commonrisk factors for both atherosclerotic cardiovascu-

lar disease and CKD. Evidence also exists tosupport chronic inflammation contributing to thepathogenesis of hypertension and diabetes melli-tus, both major riskfactors for cardiovasculardisease and CKD.32 Based on the current evi-dence that periodontal disease is a source ofsystemic inflammatory burden, it is biologicallyplausible to hypothesize that periodontal diseaseis a risk factor for CKD.

The use of single risk factors to identify sub-groups at high risk of CKD is a major limitationthat can be addressed by simultaneously consid-ering a set of risk factors. Recently, Bang et al7

proposed a multivariable prediction model forCKD and also reported that no other multivari-able method existed to predict CKD. Our studycontributes to helping health care providers iden-tify patients at high risk of CKD by simulta-neously considering recognized traditional riskfactors and suspected nontraditional risk factors,including periodontal disease and one of its im-portant sequelae, edentulism, in a representativesample of the US population.

The objective of our study is to investigate therole of periodontal disease and other nontradi-

tional risk factors in patients with CKD by: (1)describing and quantifying the relationship be-tween CKD and periodontal disease, along withthe relationship between CKD and other nontra-ditional and traditional risk factors, in the ThirdNational Health andNutrition Examination Sur-vey (NHANES III)33; and (2) developing a mul-tivariable model for the association between CKDand periodontal disease and other nontraditionalrisk factors, adjusting for traditional risk factorsto identify risk factors independently associatedwith the presence of CKD.

MATERIALS

Study Population

This cross-sectional study was deemed exempt by theinstitutional review board, and all investigators compliedwith the Data Use Restrictions for the NHANES III public-use data set collected by the National Center for HealthStatistics, Centers for Disease Control and Prevention.NHANES III, 1988-1994, is a complex, multistage, strati-fied, clustered sample of the civilian noninstitutionalized USpopulation representative of the US population. NHANES

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includes questionnaire, laboratory-assay, and clinical-exami-nation measures of health outcomes and explanatory vari-ables. Data used in this study are: (1) responses to questionsregarding age, race/ethnicity, gender, income, education,smoking, diabetes, and hypertension; (2) laboratory assays

of serum cotinine, glycated hemoglobin, plasma glucose,serum C-reactive protein, serum creatinine, serum totalcholesterol, serum high-density lipoprotein cholesterol, se-rum low-density lipoprotein cholesterol, urinary albumin,and urinary creatinine; and (3) clinical examination data forsystolic and diastolic blood pressure, height, weight, andperiodontal status. We identified 12,947 adults 18 years orolder representing 140.2 million Americans with informa-tion for kidney function and at least one risk factor, of which11,955 had information for kidney function and all riskfactors tested in multivariable modeling.

Description of Main Outcome

The main outcome was stages 3 and 4 CKD with moder-

ate to severe decrease in kidney function, defined as GFR of15 to 59 mL/min/1.73 m2 (0.25 to 0.98 mL/s/1.73 m2).1 Thisdefinition was reported to be a more precise estimate ofdecreased kidney function.3 Henceforth, we refer to thisdefinition of stages 3 and 4 CKD simply as CKD. GFR wasestimated by using the 4-variable Modification of Diet inRenal Disease Study equation: GFR 186.3 (serumcreatinine [mg/dL])1.154 age0.203 (0.742 if female)

(1.21 if black). Serum creatinine value was calibrated bysubtracting the value of 0.23 to align the NHANES measureswith creatinine assays in the aforementioned equation.34

Description of Risk Factors

The principal exposure or predictor for this analysis isperiodontal status based on a clinical examination, andcategorized as no periodontal disease, periodontal disease,or edentulous. Periodontal disease is defined as one or moresites with both 4 mm or greater loss of attachment andbleeding on the same tooth (bleeding as an indicator ofactive inflammation).35 Edentulous is defined as having lostall natural teeth. Other traditional and suspected nontradi-tional risk factors for CKD included in the analyses aresocioeconomic status (age, race/ethnicity, gender, income,and education), health status (diabetes mellitus and systemichypertension), health behavior and biomarker levels (smok-ing, macroalbuminuria, C-reactive protein, total cholesterol,high-density lipoprotein cholesterol, and low-density lipopro-tein cholesterol), anthropometric assessment (body massindex), and health care utilization (self-report of an annualphysician visit or hospitalization in the past year).

Lower income is defined as less than $20,000 annualhousehold income. Diabetes mellitus status is categorized asno diabetes, diabetes with good control (7% glycatedhemoglobin), and diabetes with poorer control (7% gly-cated hemoglobin). Diabetes mellitus is defined as fastingplasma glucose level of 126 mg/dL or greater (7.0 mmol/L)or 200 mg/dL or greater (11.1 mmol/L) after an oralglucose tolerance test, or self-reported physician-diagnoseddiabetes. Systemic hypertension is defined as systolic bloodpressure greater than 140 mm Hg or diastolic blood pressuregreater than 90 mm Hg, or being told on two or more

different visits that one had hypertension. Macroalbuminuria

is defined as urinary albumin-creatinine excretion ratio of

300 mg/g or greater. Self-reported smoking status is current,

former, or never, excluding those who reported former or

never smoking but were current smokers based on the gold

standard of serum cotinine levels of 15 ng/mL or greater(85 nmol/L).36 Obesity is defined as a body mass index

greater than 27 kg/m2. High C-reactive protein level is

defined as greater than 3.0 mg/dL.

Statistical Analyses

Tests of the hypothesis that CKD is associated with

traditional and nontraditional risk factors used univariable

and multivariable logistic regression modeling. Covariates

were selected by using a stepwise regression approach with

Pvalue less than 0.05 as the selection criterion to enter and

remain in the model. This approach simultaneously took into

account the statistically significant risk factors determined

by means of univariable analyses, with statistical signifi-

cance reported as a 95% confidence interval (CI). Theindependent association between CKD and risk factors,

namely, socioeconomic status, health status, health behavior

and biomarker levels, and health care utilization, was quanti-

fied by calculating the adjusted odds ratio (ORAdj). Model fit

was assessed by means of the Satterthwaite-adjusted F

statistic test, accounting for the complex study design. Thus,

we compared the final full model with periodontal disease to

the reduced model with all the same covariates excluding

periodontal status. Analyses were conducted using SAS-

Callable SUDAAN, version 9.0.1(Research Triangle Insti-

tute, Research Triangle Park, NC)37 and SAS Systems for

Windows, version 9.1 (SAS Institute Inc, Cary, NC) to

account for complex survey design and sample weights and

to produce national estimates.

RESULTS

Overall Descriptive Summary

Table 1 presents important characteristics ofthe study population and their unadjusted associa-tion with CKD. Overall, 3.6% of the study popu-lation had CKD, 6.0% had periodontal disease,10.5% were edentulous, 23.5% were hyperten-sive, and 36.4% were obese. The univariablemodels reported in Table 1 are similar to thetypical approach that reports a single risk factorwithout adjusting for potential confounders. Forexample, an adult with the nontraditional riskfactor edentulism was over 10 times more likelyto have CKD (odds ratio [ORCrude], 10.38; 95%CI, 7.87 to 13.70) than an adult without periodon-tal disease. Likewise, an adult with periodontaldisease was 4 times more likely to have CKD(ORCrude, 3.93; 95% CI, 2.95 to 5.24) than anadult without periodontal disease.

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Table 1. Descriptive Summary and Association Between CKD and Periodontal Disease and Other Risk Factors

No CKD CKD ORCrude

Risk Factors (n 12,330; 96.4%) (n 617; 3.6%) (95% CI)

Socioeconomic statusAge (y)

18-59 (n 9,575; 81.4%) 83.9% 16.3% 1.00

60 (n 3,372; 18.6%) 16.1% 83.7% 26.78 (17.74-40.43)*

Race/ethnicity

Non-Hispanic white (n 5,051; 82.2%) 81.9% 91.3% 5.57 (3.88-8.01)*

Non-Hispanic black (n 3,472; 11.5%) 11.7% 7.4% 3.18 (2.11-4.79)*

Mexican-American (n 3,890; 6.3%) 6.4% 1.3% 1.00

Gender

Female (n 6,922; 52.5%) 52.1% 61.8% 1.49 (1.11-1.99)*

Male (n 6,025; 47.5%) 47.9% 38.2% 1.00

Lower income

Yes (n 6,004; 32.0%) 31.1% 56.7% 2.90 (2.31-3.65)*

No (n 6,725; 68.0%) 68.9% 43.3% 1.00

High school graduate

Yes (n 7,826; 76.6%) 77.5% 53.8% 1.00No (n 5,040; 23.4%) 22.5% 46.2% 2.95 (2.31-3.78)*

Health status and health behavior

Periodontal status

Edentulous (n 1,610; 10.5%) 9.2% 41.8% 10.38 (7.87-13.70)*

Periodontal disease (n 1,271; 6.0%) 5.8% 11.2% 3.93 (2.95-5.24)*

No periodontal disease (n 10,066; 83.5%) 85.0% 47.0% 1.00

Diabetes

Poor control (n 642; 3.1%) 2.8% 12.1% 5.22 (3.19-8.53)*

Good control (n 512; 3.0%) 2.7% 9.7% 4.32 (2.98-6.27)*

No diabetes (n 11,784; 93.9%) 94.5% 78.2% 1.00

Hypertension

Yes (n 3,659; 23.5%) 21.7% 70.8% 8.73 (6.93-10.99)*

No (n 9,274; 76.5%) 78.3% 29.2% 1.00

Macroalbuminuria

Yes (n 231; 1.0%) 0.7% 8.4% 12.71 (7.92-20.42)*

No (n 12,716; 99.0%) 99.3% 91.6% 1.00

Obesity

Yes (n 5,463; 36.4%) 36.0% 47.4% 1.61 (1.27-2.03)*

No (n 7,460; 63.6%) 64.0% 52.6% 1.00

High C-reactive protein

Yes (n 171; 1.0%) 0.9% 2.8% 3.14 (1.56-6.33)*

No (n 12,767; 99.0%) 99.1% 97.2% 1.00

High cholesterol

Yes (n 2,403; 18.0%) 17.2% 38.9% 3.06 (2.45-3.83)*

No (n 10,505; 82.0%) 82.8% 61.1% 1.00

Low high-density lipoprotein

Yes (n 1,560; 12.9%) 12.6% 20.5% 1.78 (1.34-2.36)*

No (n 11,256; 87.1%) 87.4% 79.5% 1.00

High low-density lipoproteinYes (n 948; 16.3%) 15.8% 32.2% 2.53 (1.72-3.70)*

No (n 4,600; 83.7%) 84.2% 67.8% 1.00

Smoking status

Never (n 6,739; 48.2%) 48.3% 44.9% 1.96 (1.40-2.74)*

Former (n 2,753; 22.4%) 21.7% 40.8% 3.95 (2.83-5.53)*

Current (n 3,455; 29.4%) 30.0% 14.3% 1.00

Hospitalized in past year

Yes (n 1,661; 11.3%) 10.8% 23.0% 2.45 (1.89-3.18)*

No (n 11,250; 88.7%) 89.2% 77.0% 1.00

Annual physician visit

Yes (n 10,190; 80.8%) 80.4% 92.2% 2.90 (1.87-4.50)*

No (n 2,656; 19.2%) 19.6% 7.8% 1.00

Note:Unweighted number with weighted percent. Excludes those who reported never or former smoking with serum

cotinine level indicating current smoker. Inclusion criteria were periodontal examination or edentulous.

Abbreviations: CKD, chronic kidney disease; ORCrude, unadjusted odds ratio for the association between CKD and thesuspected/recognized risk factors; CI, confidence interval.

*P 0.05.

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Multivariable Logistic Regression Modelfor the Association Between CKD andPeriodontal Disease and OtherNontraditional Risk Factors

Table 2presents the most parsimonious modelwe estimated for the association between CKDand periodontal disease and other nontraditionalrisk factors, simultaneously adjusting for thelisted risk factors and reporting ORAdjand 95%CI for each risk factor. Adults with periodontal

disease and edentulous adults were approxi-mately twice as likely to have CKD (ORAdj,1.60; 95% CI, 1.16 to 2.21; ORAdj, 1.85; 95% CI,1.34 to 2.56, respectively) than adults withoutperiodontal disease after simultaneously adjust-ing for age, race/ethnicity, gender, income, smok-ing status, macroalbuminuria, hypertension, totalcholesterol level, high-density lipoprotein choles-terol level, and hospitalizations, and physicianvisits in the past year. It is also noted that older

adults were over 10 times more likely to haveCKD (ORAdj, 10.32; 95% CI, 6.97 to 15.27) thanyounger adults after simultaneously adjusting forthe other statistically significant risk factors or

risk indicators.The fit of the final full model with periodontal

status listed inTable 2is improved compared tothe reduced model with the same risk factorsexcluding periodontal status, based on the Satter-thwaite-adjusted F statistic P value of 0.0005.This indicates that including periodontal status inthe model provides a statistically significant con-tribution to a model that excluded periodontalstatus.

DISCUSSION

In our US population-based study, periodontaldisease and edentulism, as well as the nontradi-tional risk factors that included having an annualphysician visit and being hospitalized in the pastyear, were independently associated with CKDafter simultaneously adjusting for the followingtraditional risk factors: age, race/ethnicity, gen-der, smoking status, income, hypertension, mac-roalbuminuria, total cholesterol level, and high-density lipoprotein cholesterol level. Ourunivariable unadjusted models support the previ-ous studies that described high-risk subgroups byusing a single risk factor.1-3,8-23Additionally, our

study of a sample representative of the US popu-lation provides a basis to extend the list ofpotential nontraditional risk factors to includeperiodontal disease status in a multivariablemodel for the outcome CKD.

The findings of this study suggest the impor-tance of simultaneously taking into account otherrisk factors, rather than the typical approach ofidentifying high-risk subgroups for CKD basedon a single risk factor. By comparing the ORCrudewith the ORAdj, the need to consider these othercovariates is evident. For example, when age

was the only risk factor considered, older adultswere 27 times more likely to have CKD. How-ever, when the other risk factors were simulta-neously taken into account, older adults were 10times more likely to have CKD. Likewise, whenperiodontal status was the only risk factor consid-ered, adults with edentulism were over 10 timesmore likely to have CKD, and adults with peri-odontal disease were 4 times more likely to haveCKD. However, when the other risk factors were

Table 2. Multivariable Model for the Association

Between CKD and Periodontal Disease and Other

Risk Factors

Risk Factors Final Model ORAdj(95% CI)

Age60 y 10.32 (6.97-15.27)*

Macroalbuminuria 5.13 (2.74-9.63)*

Race/ethnicity

Non-Hispanic white

Non-Hispanic black

3.53 (2.36-5.28)*

2.40 (1.57-3.68)*

Hypertension 2.12 (1.66-2.71)*

Smoking status

Former smoker

Never smoker

1.99 (1.41-2.79)*

1.55 (1.10-2.20)*

Periodontal status

Edentulous

Periodontal disease

1.85 (1.34-2.56)*

1.60 (1.16-2.21)*

Low high-density lipoprotein 1.80 (1.24-2.60)*

Hospitalized in past year 1.68 (1.24-2.27)*

Low income 1.65 (1.29-2.11)*Annual physician visit 1.65 (1.10-2.50)*

High cholesterol level 1.47 (1.14-1.90)*

Female 1.45 (1.05-2.01)*

Note:The following risk factors were not included in the

final model because they were not statistically significant:

education, diabetes status, high C-reactive protein level,

and high low-density lipoprotein cholesterol level. Ex-

cludes those who reported never or former smoking with

serum cotinine level indicating current smoker.

Abbreviations: CKD,chronickidney disease;ORAdj, odds

ratio for the association between CKD, simultaneously

takinginto account allthe listed potentialor recognized risk

factors; CI, confidence interval.

*P 0.05.

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simultaneously considered, adults with edentu-lism were almost twice as likely, and adults withperiodontal disease were over 1 times morelikely to have CKD. In addition, when diabetes

status, obesity, C-reactive protein level, and edu-cation were considered separately, they weresignificant. However, after simultaneously tak-ing into account the other risk factors, includingperiodontal disease status, they were no longersignificant.

Although African Americans were reported tobe more likely to have CKD than whites,4,11 thiswas not found in our study or in a previousNHANES III study.3 This inconsistency may bepartly explained by racial disparity in survival,such that the prevalence of CKD may be greaterin non-Hispanic whites than non-Hispanic blacks,whereas the incidence is greater in non-Hispanicblacks, but they do not survive as long. In addi-tion, our findings of greater racial disparities inunadjusted than adjusted analyses indicate thatresults are partly explained by confounding dueto health status, health behaviors, socioeconomiccharacteristics, and health care utilization.

An important limitation of this study is itscross-sectional design, which did not allow forassessment of temporality. To establish causality,it is imperative to show that periodontal disease,as the exposure, precedes the development or

progression of CKD. This cannot be determinedin a cross-sectional study. Another limitation toconsider is that factors that lead to CKD couldalso lead to periodontal disease. These are bothchronic conditions that progress in severity. Simi-lar to the 5 progressive stages of CKD, periodon-tal disease progresses with increasing loss ofconnective tissue attachment and bony support,often ultimately resulting in tooth loss. Based onthe review of traditional and nontraditional riskfactors for CKD reported herein, and a thoroughrecent review of risk factors for periodontal

disease,38

and more recent publications,29,30

thefollowing potential confounders/risk factors arein common for both diseases and were consid-ered in our modeling: age, race/ethnicity, gender,income, education, poorly controlled diabetes,smoking, obesity, C-reactive protein level, cho-lesterol level, high-density lipoprotein choles-terol level, and low-density lipoprotein choles-terol level. Support for periodontal status havingan independent association with CKD comes in

part from our analytical modeling approach thatinvolved the simultaneous assessment of poten-tial confounders/risk factors common to bothperiodontal disease and CKD.

Although we make no claims of causality,several other features of this study warrant fur-ther consideration of periodontal disease as apotential risk factor for CKD. First, we foundthat the strength of the unadjusted association forthe nontraditional risk factors edentulism andperiodontal disease is similar to the unadjustedassociation between the traditional risk factorpoorly controlled diabetes. Second, the signifi-cant association we found is consistent withprevious studies finding a significant associationbetween periodontal disease and renal dis-ease.20-22 Third, there is biological plausibilityfor chronic periodontal disease as a source ofsystemic inflammatory burden28 contributing tothe chronic inflammation associated with CKD.Fourth, our results are consistent with a dose-response for periodontal status. When we as-sessed a dose-response ranging from no periodon-tal disease to mild to moderate periodontal diseaseto severe periodontal disease with 6 mm orgreater loss of attachment,35 or 80th percentile ofthe highest percentage of teeth with periodontaldisease, to edentulous, we found a dose-responsein which the odds of CKD increased as the

severity or extent of periodontal disease in-creased, similar to that previously reported.20

Our study has several other strengths. First,we focused on the simultaneous assessment ofrecognized and suspected risk factors for CKD,finding that some previously recognized factorswere no longer significant, whereas infrequentlystudied nontraditional risk factors, namely peri-odontal disease and edentulism, remained signifi-cant in the final multivariable model. Second, thefinal model simultaneously considered 12 riskfactors for CKD rather than looking at only a

single factor at a time. Third, we addressed thepossibility that patients may deny smoking byincorporating anobjective smoking measure (ie,serum cotinine).39 Fourth, NHANES III sam-pling methodology is designed to represent theUS population. Fifth, questionnaire, examina-tion, and laboratory data were collected in anunbiased manner such that participants were un-aware of our study of risk factors for CKD. Thisallowed us to investigate multiple recognized

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traditional and suspected nontraditional risk fac-tors. Sixth, data were available for adults whodid not have an annual physician visit, unlikeother studies limited to patients who visited

health care providers.The next step is to test our model in longitudi-

nal studies. Periodontal therapy may be consid-ered along with the recommendation to counselhigh-risk individuals to reduce their risk by modi-fying theirbehavior, such as smoking-cessationcounseling,40 diet modification, and exercise,along with antihypertensive drug therapy.1,11,41

In summary, our findings support the conclu-sion that periodontal disease and edentulism arepotential nontraditional risk factors indepen-dently associated with CKD in US adults. Theseresults support the importance of oral healthbecause adults with periodontally diseased teethand adults who lost all their teeth were morelikely to have CKD after controlling for tradi-tional and nontraditional risk factors. As morestudies of CKD assess the role of periodontaldisease, data will accumulate to support or refutethe inclusion of periodontal therapy in preven-tive targeted approaches to impede the increas-ing numbers of individuals with CKD. Addi-tional research is needed from prospective studiesto help assess the causal inference and fromintervention studies to assess a decrease in inci-

dence, progression, and complications of CKD.

ACKNOWLEDGEMENTS

Support: This study was supportedby grantsDE016031-03and DE016031-04 from the National Institutes of Health.

Financial Disclosure:None.

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