American Society of Nephrology Presidential Address 2006: Chronic Kidney Disease as a Public Health Threat—New Strategy for a Growing Problem
Thomas D. DuBose, Jr.
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina
Address correspondence to: Dr. Thomas D. DuBose, Jr., Chair of Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1052. Phone: 336-716-2715; Fax: 336-716-2273; E-mail: tdubose{at}wfubmc.edu
On behalf of the officers and council of the American Societyof Nephrology, our dedicated professional staff, and membersof the Program Committee, I welcome you to the 39th annual meetingof the American Society of Nephrology (ASN).
The program that is about to be launched is a result of thetalent and perseverance of the outstanding chair of the 2006Annual Meeting Program Committee, Dr. Lisa Guay-Woodford, andthe innovative and conscientious members of the Program Committee.The theme they have chosen for this program conveys recognitionof the immense potential for rapid advances in the field ofnephrology through translational investigation. The programhighlights major advances in biomedical and clinical sciences.Expect a glimpse into the future toward what can be accomplished.
As president, this year it has been my privilege to work veryclosely with a dedicated and responsible ASN Council and withour extraordinarily devoted professional staff, led by KarenCampbell, our executive director, and Robert Fulcher, chiefoperating officer. This group is responsible for most of whatthe society accomplishes during the year. All of us are indebtedto the members of our board of advisors, made up of ASN advisorygroups and committees for their effort on behalf of the society.
While this has been an exceptional year in many respects, unfortunately,the last year was not without great loss. Several prominentmembers died this year and include, Mackenzie Walser in November;Louis Tobian, a recipient of the Peters Award in 1990, diedin September, and Nancy Gary, founding president of Women inNephrology, died in May.
Our dear friend and colleague Norman Siegel died suddenly inApril. Dr. Siegel served as president of the ASN in 2002 andof the American Society of Pediatric Nephrology in 1989. Aspresident of the ASN, Norm's contributions resulted in a moreeffective organization and one that better serves its members.To commemorate his service and example, the ASN Council hasdesignated one of our Career Development Awards in his honor.The first ASN-ASPN Norman Siegel Career Development Grant isawarded this year to a pediatric nephrologist, Fangming Lin.
I refer you to the on-site publication ASN Highlights for adetailed president's report. Let me review a few of the highpoints of our activities this year.
By establishing the Public Policy Board, our society has notonly bolstered advocacy for kidney research but has extendedour effort to a broader public policy. The Public Policy Boardis under the capable direction of Jonathan Himmelfarb, MD, Chair,and Paul Smedberg, our full-time director of public policy.Board members include Connie Davis, MD; Thomas Hostetter, MD;Eric Neilson, MD; Brian Pereira, MD; and Donald Wesson, MD.
The Public Policy Board is engaged in building a platform forthe ASN in the public health arena related to the importanceand consequences of kidney disease. The council has endorsedexpansion of our public policy efforts and will encourage cooperativeadvocacy with our sister renal organizations.
This has been an active year for filling key positions. PaulKimmel began as the new full-time director of education in September.Eric Nielsen and his deputy and associate editors will takeover the reins at JASN beginning July 2007, and Stanley Goldfarbwill become the new editor of NephSAP beginning July 2007. Withthe publication of CJASN in January of this year, the ASN nowprovides a unique compendium of journals covering nephrologyfrom bench to bedside. We thank Bill Couser and Dick Glassockfor their visionary and capable leadership of JASN and NephSAP,respectively. These journals have advanced successfully duringtheir term as editor.
Everyone in this audience is aware that we are witness to anepidemic of chronic kidney disease (CKD). There are currentlyapproximately 387,000 patients with end-stage kidney diseasein the United States and 1.8 million patients worldwide whorequire dialysis therapy or a transplant for survival (1–4).Forty-two percent of the 100,000 new patients in the UnitedStates annually have diabetes mellitus as a cause of their kidneydisease, and over 90% of the diabetics have type 2 diabetes(4) (Table 1). The economic burden of this population on healthcare expenditures is forecast to be staggering. If, for example,the number of dialysis patients in the United States in 2010reaches 650,000 as predicted, the public expenditure for dialysiscare from Medicare alone will increase from $17 to $28 billionper year (4).
Paradoxically, while we are spending a staggering amount onend-stage kidney care, our health care system has not yet developeda comprehensive approach for the care of the 11% of the US population,approximately 19 million people, who have CKD at some stage(5). More important, most of the CKD patients are not awarethey have kidney disease, yet they are at risk for developingend-stage kidney disease and/or dying prematurely of one ofits major complications, cardiovascular disease (CVD). Unfortunately,no federal agency has yet officially declared that CKD is apublic health threat.
Schoolwerth et al. (6,7) published an informative and relevantarticle earlier this year and defined the conditions that mustbe met for a health problem to be considered a public healthissue (Table 2). These include:
High burden of disease; "burden"is experienced in terms ofmortality and morbidity, qualityof life, and cost.
Problem is distributed unfairly (i.e.,affects minorities anddisadvantaged individuals to a greaterextent).
Evidence exists that upstream preventive strategiescould reducethe burden of the condition.
CKD clearly meets all criteria, and it is time that it be considereda threat to the health of the public. Although formal programsare not yet in place, the efforts of nephrologists are makinga difference.
Recent US Renal Data System data indicate slowing of the annualincrease in the incidence of end-stage disease, experiencedsince the 1980s (7) (Figure 1). The fact that the incident ratesseem to be declining is very encouraging, especially since thisprogress has been made in the absence of a fully integratednational program to slow progression of CKD. Therefore, thepotential for achieving current treatment goals in at-risk patientswith a more focused approach promises a much greater reductionin incidence in the future.
Disturbingly, the increase in the incidence of ESRD continuesto mount in young African Americans (7) (Figure 2). AfricanAmericans make up only 13% of the US population yet constitute32% of patients with ESRD. Although the risk for developingESRD is at least three-fold higher in African Americans, over43% of African Americans with kidney failure are not aware ofkidney disease until 1 wk before their kidneys fail entirely.Hispanic Americans have a high prevalence of diabetes. Amongdiabetics, Hispanic patients are six times more likely to developCKD and to advance to end-stage disease (1,7). Expect the dialysisincidence to grow in this expanding population in the future.Therefore, the burden of this disease is borne disproportionatelyby certain ethnic groups in which worse outcomes and highercosts are typical.
The incidence of ESRD in older patients is increasing (Figure 3).In addition, as many as 11% of Americans aged 65 or older havemoderate to severe CKD (7). With the increase in life expectancyin the United States, the epidemic of both ESRD and CKD willincrease.
Figure 3. Incident and prevalent rates, by age. Incident ESRD patients 75 yr and older at initiation, and December 31 point prevalent ESRD patients, 75 yr and older. Rates adjusted for gender and race. Source: USRDS, 2006 ADR (http://www.usrds.org/2006/slides/html/02_incid_prev_06_files/frame.htm).
The ASN was challenged 8 years ago by then-president ThomasHostetter (8) to raise awareness of CKD through education ofphysicians, patients, and communities. Another ASN president,Roland Blantz, encouraged a CKD initiative that involved thecooperation of all of the major kidney organizations (9).
A plan of action was conceived to solve some of the problemsassociated with obtaining the best outcomes for patients withCKD. The committee ranked highly the need to develop and promulgatesimple guidelines for distribution to both patients and providersand to devise effective screening strategies.
Things have changed since 2003. The federal government is takinga much more active role in 2006. Specifically, the Centers forMedicare and Medicaid Services (CMS) and the Centers for DiseaseControl and Prevention are recognizing the need for a qualityassurance agenda around CKD. Moreover, several recent studiescompel us to be part of a more coordinated effort in the UnitedStates.
It is well appreciated that the incidence of ESRD is significantlylower in Europe, compared with the United States, yet the prevalenceof CKD is similar. A recent study by Hallan et al. (10) comparedthe relationship between CKD and the prevalence of ESRD in twowell-studied populations in the United States and Norway (Table 3).While the incidence of CKD is essentially identical, the relativerisk for progression from stage 3 or 4 CKD to stage 5 kidneydisease in Caucasian patients from the United States is almostthree-fold higher than in Norwegian patients with CKD, evenwhen the higher prevalence of diabetes in the United Statesis taken into consideration. Obviously, differences in healthcare access between Norway and the United States might be acontributor to variations in the prevalence of end-stage disease.Referral to a nephrologist occurs at an earlier juncture, andthe management of patients with CKD is better coordinated betweenthe primary and secondary physicians. This results in a higherfrequency of erythropoietin administration, higher levels ofserum albumin, and better nutrition in the Norwegian with CKD(Table 4).
Table 4. CKD is not being recognized or treated by PCP (17)a
That there are significant differences in CKD care in this countrywas substantiated by Boulware et al. (11) through use of a questionnairedirected to primary care physicians and nephrologists in theUnited States. The study revealed that primary care physiciansin this country recognize and recommend specialist care forprogressive kidney disease less often than nephrologists anddiffer significantly in their clinical evaluations and expectationsfor referral. Fewer than 20% of primary care physicians routinelyscreen for CKD those diabetics or hypertensives in their practices,and less than one third with CKD receive angiotensin-convertingenzyme inhibitors (ACE-I). Late referral to nephrology is common,especially among young African American men (4) (Table 4). Thesedata, taken together, suggest that we have a serious problemwith quality of care for CKD in the United States and provideevidence for meeting the fourth requirement for a public healthcrisis; that is, preventive strategies are not in place. Unfortunately,however, for the population at risk, with a nephrology workforceof only 5000 specialists in the United States, direct involvementof nephrologists early in the course of treatment for CKD isuntenable.
If the health care system in this country is to blame, in part,for poor outcomes of patients with CKD, should we not advocatefor funding from CMS and private payers for wide applicationof therapy specifically designed to impede progression? Severaleconomic analyses of existing databases suggest that significantsavings for the health care system are possible. Alexander etal. (12) estimated the cost savings for specific therapy, afteraccounting for drug costs, of $3522 per patient over 3 years.Trivedi et al. (13) analyzed the impact of availability of ACE-Ior angiotensin receptor blocker (ARB), assuming the rate ofdecline in GFR could be slowed by as little as 10% in all patientswith estimated GFR of <60 ml/min. The cumulative direct healthcare savings by postponing dialysis could be as astonishingas $18.6 billion dollars over a 10-yr span. Rosen's (14) analysisprojected the cost savings for full Medicare coverage of ACE-Ifor beneficiaries under Medicare Part D. If out-of-pocket expensesare completely eliminated, Medicare could save more than $1600per beneficiary per year. The findings suggest we should advocatefor wider application of proven pharmacologic intervention inCKD. In other words, this country needs a policy that valueshealth care and is based on the long-term benefits to the society.
The optimal care of patients with CKD will require coordinatedmanagement (Table 5). Certainly, it is fair to say that, atpresent, CKD care is highly fragmented (15,16). Existing clinicalguidelines for CKD are simply too complex to be accomplishedin the limited office encounter of the primary care physician.If we agree that we should work with primary care physicianson CKD, then we as nephrologists will need to develop partnershipswith primary care physicians in our own communities. Ideally,patients could be identified in the earlier stages of kidneydisease and managed by primary care physicians and non-nephrologyspecialists with little input from individual nephrologistsuntil later in stage 3 kidney disease (15,17–19). Levin(20) emphasized that the ability to deliver optimal care mustbe coupled with heightened public awareness and education andhealth care system redesign. Obviously, care plans for primarycare physicians should include clinical strategies that arewell known to nephrologists (20,21) (Table 5).
To respond to the challenges of CKD, a special meeting of thepresidents and presidents-elect of the major kidney societieswas held in Chicago on August 28, 2006, at the invitation ofthe Renal Physicians Association (RPA). All those representedagreed that we need to formulate a simple, unified message thatshould resonate with the public and primary care physicians.It was further agreed that to serve the public health, we havethe opportunity to develop a cooperative plan that transcendssocietal interests by focusing on a broader public health agenda.We agreed we need to work together to develop a consistent themewhen it comes to dealing with Congress, federal agencies, andprimary care societies and in our messages to the public.
It is widely appreciated by this audience that CKD is a majorrisk factor for the development of progressive CVD (22–26)(Figure 4). This figure shows the risks for CVD at various levelsof kidney function. Actually, as you know, most patients withearly-stage kidney disease do not reach the point of dialysisbecause of death from CVD (22,24,27).
Figure 4. Chronic kidney disease is a multiplier of cardiovascular disease. Reprinted from Go et al. (23), with permission.
Perhaps a message that emphasizes the major role that kidneydisease plays in increasing the risk for death from CVD mayresonate more effectively with both primary care physiciansand with federal funding agencies (26). Such an approach couldplace CKD into the framework of the overall public health agenda(Table 6). To have a greater impact on the CKD–CVD connection,we will need additional data.
Table 6. CKD–CVD connection: Time for a broader strategya
Coca et al. (27) recently explored large, randomized, controlledclinical trials on congestive heart failure and acute myocardialinfarction published from 1985 through 2005. This analysis showedthat 60% of major cardiovascular trials exclude patients withkidney disease and 90% do not provide adequate information onthe kidney function of enrollees or the effect of interventionson patients with kidney disease (28). The VALIANT trial showedthat the use of aspirin, blockers, statins, or coronary revascularizationwas much lower among those patients with CKD (29) (Table 7).Clinical guidelines published by the American College of Cardiology/AmericanHeart Association actually discourage ACE-I/ARB therapy forpatients with CKD and CVD.
The CRIC (Chronic Renal Insufficiency Cohort) study, anticipatedto be complete by December 2009, is a large, multicenter, observationalcohort study of risk factors associated with progression ofCKD and CVD that should provide helpful observational data (30).We should be better able to understand the CKD–CVD relationship.However, it seems obvious that we badly need interventionalclinical trials designed exclusively for patients with bothCVD and CKD. These trials should make every effort to includeminorities. Certainly, patients who are at the highest riskfor cardiovascular events should not be denied lifesaving therapywithout sufficient evidence for harm or benefit.
New Research Funding Strategies around link of CKD–CVD
Poor outcomes in patients with progressive kidney disease appearto be the result of two adversaries, fibrosis in the kidneyand accelerated CVD. Basic research is needed to delineate effectivetherapy for treating CKD that goes beyond blockade of the renin-angiotensin-aldosteronesystem and to discover specific therapy for treating vascularcomplications (31,32). Better methods are needed to identifyand treat those patients at risk for progression of kidney disease(Table 8).
Table 8. Research funding strategies around link of CKD–CVD
Figure 5 summarizes current knowledge of the various pathwaysinvolved in the pathogenesis of CKD. If the goal is to stabilizeor improve kidney function, additional research will be neededon regression and remission of fibrosis. Several new conceptsand potential therapeutic targets, some of which are highlightedon this slide, will be reviewed in detail in presentations atthis meeting.
Figure 5. Newer pathways and therapeutic targets: Chronic kidney disease. Reprinted from Eddy and Neilson (31), with permission.
If we can align clinical and basic research objectives in thisarea, we may stimulate new research funding opportunities. Researchprograms that might be jointly funded by the National Instituteof Diabetes and Digestive and Kidney Diseases and the NationalHeart, Lung, and Blood Institute, for example, were encouragedby introduction of the National Institutes of Health ReformBill, encouraging cooperative funding by institutes.
Let me conclude by summarizing some of the suggestions madetoday.
Shift advocacy from detection and prevention of CKD alone toCKD within the framework of CVD and diabetes (i.e., as a publichealth issue).
That we align public health advocacy and professionaleducationopportunities within this broader framework.
Joinwith all kidney societies and members to develop a truepartnershipwith primary care physicians to advance the conceptof coordinatedcare.
Advocate for the incorporation of care plans for CKDinto existingCVD and diabetes clinical guidelines. To be effective,we shouldpartner with the National Kidney Foundation, RPA,American HeartAssociation, and American Diabetes Associationto develop guidelinessuitable for primary care physicians.
Advocate for application of quality assurance measures forCKDcare by CMS and other payers.
Encourage collaborationand resource sharing by the Centersfor Disease Control andPrevention and National Kidney DiseaseEducation Program (forenhanced surveillance and education,respectively).
Work withthe National Kidney Disease Education Program to focuson educationalapproaches to reduce CKD disease burden in ethnicminorities.
Direct the National Institute of Diabetes and Digestive andKidney Diseases to raise the priority for funding of neededbasic and clinical research in kidney disease. We can bolsteradvocacy for investigator-initiated research by stressing thesignificant return on investment by the National Institutesof Health in translational studies of fundamental measurementsof glomerular hemodynamics that resulted in substantive advancesin the care of CKD patients.
Participate in organization ofa multisociety initiative onWorld Kidney Day, March 8, 2007.For 2007, the ASN will participatein simultaneous congressionallobbying events with the NationalKidney Foundation and RPA.
Develop the educational resources needed by our members toprovideinstructive presentations on the coordinated managementof CKDand CVD at the level of local medical societies and hospitalgrand rounds. The ASN will develop a set of instructional slidesfor use by our members in their own communities.
A great deal of progress on the understanding of the pathogenesisof CKD has been made in a short time, and limited interventionalstrategy has been successful, but we have not yet successfullyprojected the view that CKD is a public health issue, and wehave not offered a method to approach CKD in the populationat risk. I have suggested today that it is time for us to takeownership of the CKD problem by changing our focus.
I owe a debt of gratitude to my colleagues at Wake Forest inNephrology, especially Barry Freedman and Mike Rocco for theirencouragement, but especially for their collegiality and support.In addition, I thank Tom Hostetter for assistance. I acknowledgethe unwavering support of my wife, Linda, during this year notonly to me personally but for her support of the ASN.
Footnotes
Published online ahead of print. Publication date availableat www.jasn.org.
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blockers, statins, or coronary revascularization was much lower among those patients with CKD (29) (Table 7). Clinical guidelines published by the American College of Cardiology/American Heart Association actually discourage ACE-I/ARB therapy for patients with CKD and CVD. 
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Introduction
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