Michael J. Klag, M.D., M.P.H., Paul K. Whelton, M.D., Bryan L. Randall, M.S., James D. Neaton, Ph.D., Frederick L. Brancati, M.D., M.H.S., Charles E. Ford, Ph.D., Neil B. Shulman, M.D., and Jeremiah Stamler, M.D.
Background End-stage renal disease in the United States createsa large burden for both individuals and society as a whole.Efforts to prevent the condition require an understanding ofmodifiable risk factors.
Methods We assessed the development of end-stage renal diseasethrough 1990 in 332,544 men, 35 to 57 years of age, who werescreened between 1973 and 1975 for entry into the Multiple RiskFactor Intervention Trial (MRFIT). We used data from the nationalregistry for treated end-stage renal disease of the Health CareFinancing Administration and from records on death from renaldisease from the National Death Index and the Social SecurityAdministration.
Results During an average of 16 years of follow-up, 814 subjectseither died of end-stage renal disease or were treated for thatcondition (15.6 cases per 100,000 person-years of observation).A strong, graded relation between both systolic and diastolicblood pressure and end-stage renal disease was identified, independentof associations between the disease and age, race, income, useof medication for diabetes mellitus, history of myocardial infarction,serum cholesterol concentration, and cigarette smoking. As comparedwith men with an optimal level of blood pressure (systolic pressure<120 mm Hg and diastolic pressure <80 mm Hg), the relativerisk of end-stage renal disease for those with stage 4 hypertension(systolic pressure >210 mm Hg or diastolic pressure >120mm Hg) was 22.1 (P<0.001). These relations were not due toend-stage renal disease that occurred soon after screening and,in the 12,866 screened men who entered the MRFIT study, werenot changed by taking into account the base-line serum creatinineconcentration and urinary protein excretion. The estimated riskof end-stage renal disease associated with elevations of systolicpressure was greater than that linked with elevations of diastolicpressure when both variables were considered together.
Conclusions Elevations of blood pressure are a strong independentrisk factor for end-stage renal disease; interventions to preventthe disease need to emphasize the prevention and control ofboth high-normal and high blood pressure.
In 1991, about 190,000 persons in the United States either underwentdialysis or received a renal transplant for end-stage renaldisease.1 Hypertension was judged to be the underlying causeof the condition in 29 percent of these patients, second onlyto diabetes mellitus (36 percent).1 A striking association betweenmalignant hypertension and the development of renal diseasehas been recognized since the 19th century, but the risk ofrenal failure associated with less severe hypertension is lesscertain.2 Because of the relatively low incidence of end-stagerenal disease in the general population, prospective epidemiologicstudies of blood pressure and the disease have not been performed.
To determine the risks of renal failure associated with a widerange of blood-pressure levels, we prospectively studied 332,544men screened for the Multiple Risk Factor Intervention Trial(MRFIT) from 1973 to 1975. In this large cohort, followed for16 years, 814 cases of end-stage renal disease were identified.Mortality data from the MRFIT study also gave us an opportunityto identify subjects in the cohort who died of end-stage renaldisease without having received dialysis or a renal transplant.
Methods
MRFIT was a randomized, multicenter, primary-prevention trialdesigned to study the effects on the incidence of coronary heartdisease of an intervention program to control high blood pressure,lower serum cholesterol concentrations, and reduce cigarettesmoking.3,4 Between 1973 and 1975, 361,662 men from 35 to 57years of age in 18 U.S. cities were screened for entry intothe trial, of whom 12,866 eventually enrolled. Men with evidenceof end-organ damage noted in a medical history or physical examinationor with a serum creatinine concentration >2.0 mg per deciliter(177 µmol per liter) were excluded from the trial. Ofthe group screened for MRFIT, 3 men already being treated forend-stage renal disease at the time of screening and 29,115men for whom information about systolic blood pressure or incomewas not available were excluded from our study, leaving 332,544men for our analysis. Details concerning the recruitment andscreening procedures in MRFIT have been published elsewhere.5,6
Measurement
At screening for MRFIT, blood pressure was measured by trainedpersonnel according to a standardized protocol.7 Phases I andV of the Korotkoff sounds were used to determine systolic anddiastolic blood pressure, respectively. Three readings weretaken with a standard mercury sphygmomanometer; the mean ofthe last two readings was the blood-pressure measurement thatwe used in our analysis. In MRFIT, the serum cholesterol concentrationwas measured once in each participant at 1 of 14 laboratoriesthat met standardization requirements set by the Centers forDisease Control.8 A one-page questionnaire was administeredto determine the number of cigarettes smoked per day and torecord demographic characteristics. Information was also elicitedconcerning the following criteria for exclusion from the trial:expected geographic relocation, previous hospitalization lastingmore than two weeks due to heart attack (so termed), and thecurrent use of any medication for diabetes mellitus. For thepurposes of our analysis, we estimated subjects' socioeconomicstatus, using the median family incomes for black and whiteheads of family for each subject's ZIP Code of residence.
Outcome
The principal outcome examined in this analysis was end-stagerenal disease due to any cause, defined by treatment for end-stagerenal disease or death due to renal failure. Treated cases ofend-stage renal disease were ascertained from the national registryof the Health Care Financing Administration (HCFA). The MedicareEnd-Stage Renal Disease Program was initiated on January 1,1973, and contains records for 93 percent of all persons inthe United States who have received treatment for the conditionsince that date.9 Patients enrolled in the registry from 1973through 1990 were identified as having been screened for MRFITthrough matching of Social Security numbers and then by lastnames and dates of birth.
Data on death from renal failure were derived from the ongoingfollow-up of the MRFIT cohort. This information was compiledfrom the National Death Index (1979 to 1990) and the SocialSecurity Administration (1973 to 1990).10 Death certificateswere collected and coded by a trained nosologist using the InternationalClassification of Diseases, 9th Revision, Clinical Modification(ICD-9-CM).11 Deaths were classified as being due to renal failureif one of the ICD-9-CM codes listed in Table 1 was given onthe death certificate as the underlying cause. Hypertensiveend-stage renal disease was specifically examined as an outcomein our study and was considered to be present in cases of eitherentry into the HCFA registry, with an assigned underlying causeof hypertensive renal disease, or death from hypertensive renaldisease.
Table 1. Crude Rates of End-Stage Renal Disease in 332,544 Men Screened for MRFIT.
Statistical Analysis
The relation of blood pressure to end-stage renal disease wasinvestigated with time-to-event methods, including Kaplan–Meierestimation and proportional-hazards regression, stratified accordingto MRFIT center, with age, race, income, use of medication fordiabetes mellitus, history of heart attack, serum cholesterolconcentration, and cigarette smoking as covariates.12,13 Timeelapsed from screening for MRFIT until either entry into theHCFA registry or death from renal disease was examined as anoutcome. The incidence of outcomes per 100,000 person-yearsof observation was calculated and adjusted for age by the directmethod on the basis of the age distribution of all men screened.Because the analyses that considered treated end-stage renaldisease and death from renal disease as separate outcomes yieldedsimilar results, only those for the combined end point are presentedhere.
Blood pressure was categorized according to criteria for adults18 years of age and older modified from the Fifth Joint NationalCommittee Report on Detection, Evaluation, and Treatment ofHigh Blood Pressure.14,15 The categories were as follows: optimal:systolic blood pressure <120 and diastolic blood pressure<80 mm Hg; normal, not optimal: systolic 120 to 129 mm Hgand diastolic <84 mm Hg or diastolic 80 to 84 mm Hg and systolic<130 mm Hg; high normal: systolic 130 to 139 mm Hg and diastolic<90 mm Hg or diastolic 85 to 89 mm Hg and systolic <140mm Hg; stage 1 hypertension: systolic 140 to 159 mm Hg and diastolic<100 mm Hg or diastolic 90 to 99 mm Hg and systolic <160mm Hg; stage 2 hypertension: systolic 160 to 179 mm Hg and diastolic<110 mm Hg or diastolic 100 to 109 mm Hg and systolic <180mm Hg; stage 3 hypertension: systolic 180 to 209 mm Hg and diastolic<120 mm Hg or diastolic 110 to 119 mm Hg and systolic <210mm Hg; and stage 4 hypertension: systolic >210 mm Hg or diastolic>120 mm Hg.
The comparative strength of the association of end-stage renaldisease from any cause with systolic, as compared with diastolic,blood pressure was also examined. The relation between bloodpressure and end-stage renal disease from any cause was alsoinvestigated in the subgroup of screened men who actually enteredthe MRFIT study and whose blood pressure therefore was deemedunlikely to be elevated as a consequence of preexisting renaldisease. The availability of serum creatinine measurements anddipstick measurements of urinary protein excretion for thesemen at entry into MRFIT enabled us to analyze the relation ofblood pressure to the incidence of end-stage renal disease whiletaking into account renal function at base line.
Results
The characteristics of the men in this analysis are shown inTable 2. During the follow-up period (average length, 16 years),814 men either entered the Medicare End-Stage Renal DiseaseProgram or died of renal disease (Table 1). Of these, 649 enteredthe Medicare treatment program between the time of their screeningfor MRFIT and December 31, 1990, and 234 men died of renal disease,165 of whom did not receive long-term dialysis or a transplant.The cumulative percentages of men who either entered the registryor died of renal disease after 5, 10, and 15 years of follow-upwere 0.02 percent, 0.08 percent, and 0.22 percent, respectively.
Table 2. Age, Race, Income, and Risk Factors in 332,544 Men Screened for MRFIT.
Figure 1 shows the cumulative incidence during follow-up ofend-stage renal disease due to any cause, according to the sevenblood-pressure categories. The crude differences in the ratesfor the blood-pressure categories were reduced somewhat by adjustmentfor age and other covariates. The reduction occurred becauseall the factors considered were associated with a significantlyincreased risk of end-stage renal disease (P<0.001 for eachadjustment factor in the multivariate analysis) and, exceptfor cigarette smoking, were positively correlated with bloodpressure. The risk of end-stage renal disease associated withhigher blood pressure was strong, positive, and statisticallysignificant in all subgroups defined by age and other base-linecovariates. However, the positive associations were weaker amongolder men, blacks, and men with diabetes (data not shown).
Figure 1. Cumulative Incidence of End-Stage Renal Disease Due to Any Cause, According to Blood-Pressure Category in 332,544 Men Screened for MRFIT.
The age-adjusted incidence of end-stage renal disease and theestimated relative risk (adjusted for seven base-line factors)according to the seven blood-pressure categories are shown inTable 3. The risk of end-stage renal disease in men with hypertension,as compared with men with optimal levels of blood pressure,increased with each of the four successively more severe stagesof hypertension. Of the cases observed, 49 percent were attributableto hypertension of stage 1 or higher. Among men who survivedthe first 10 years after MRFIT screening without end-stage renaldisease, the relative risks of eventually having the conditionin men with hypertension as compared with men with optimal bloodpressure were 2.8 (stage 1 hypertension), 5.0 (stage 2), 8.4(stage 3), and 12.4 (stage 4).
Table 3. Base-Line Blood Pressure and the Incidence of End-Stage Renal Disease Due to Any Cause in 332,544 Men Screened for MRFIT.
The combined effects of various levels of systolic and diastolicpressure on the age-adjusted incidence of end-stage renal diseaseare shown in Figure 2. The differences in incidence attributableto differences in diastolic blood pressure were far less markedthan the steep risk gradient apparent for systolic blood pressure.For example, among the men in whom the diagnosis of stage 1hypertension was based on systolic blood pressure (140 to 159mm Hg), the rates of end-stage renal disease for the four lowercategories of diastolic blood pressure were similar. In contrast,for the men whose diagnosis of stage 1 hypertension was basedon high diastolic blood pressure (90 to 99 mm Hg), the incidencerates rose sharply from 9.8 to 16.4 per 100,000 person-years,even across the three categories of systolic blood pressurewithin the normotensive range. Overall, the rates of end-stagerenal disease were markedly higher for men with hypertensivelevels of both systolic and diastolic blood pressure.
Figure 2. Age-Adjusted Rate of End-Stage Renal Disease Due to Any Cause per 100,000 Person-Years, According to Systolic and Diastolic Blood Pressure in 332,544 Men Screened for MRFIT.
Data on men with stage 3 and stage 4 hypertension were combined because of their small number.
To compare systolic blood pressure with diastolic blood pressurein relation to the relative risk of end-stage renal disease,we divided the ranges of these blood-pressure variables intoquintiles (Table 4). Risk was not significantly increased inthe next-to-lowest quintile of either measure of blood pressure,as compared with the lowest quintile. For the third, fourth,and highest quintiles of both systolic and diastolic pressure,however, the relative risk rose progressively. After adjustmentfor age, race, serum cholesterol concentration, number of cigarettessmoked per day, use of medication for diabetes mellitus, andprevious myocardial infarction, the relative risk of end-stagerenal disease associated with a base-line blood pressure higherby 1 SD (systolic, 15.8 mm Hg; diastolic, 10.5 mm Hg) was similarfor systolic pressure (1.7; 95 percent confidence interval,1.7 to 1.8) and diastolic pressure (1.7; 95 percent confidenceinterval, 1.6 to 1.8). However, when systolic and diastolicpressure were considered together in the same proportional-hazardsmodel, with adjustment for all other variables, a base-linesystolic pressure higher by 1 SD had more predictive power (relativerisk, 1.6; 95 percent confidence interval, 1.5 to 1.7) thana similar increase in diastolic pressure (relative risk, 1.2;95 percent confidence interval, 1.1 to 1.2).
Table 4. Adjusted Relative Risk of End-Stage Renal Disease Due to Any Cause According to Quintile of Blood Pressure in 332,544 Men Screened for MRFIT.
The patterns of risk associated with blood-pressure levels weresimilar for hypertensive end-stage renal disease and for end-stagerenal disease due to any cause; 193 men had hypertensive end-stagerenal disease. After adjustment for the covariates listed above,the relative risk of end-stage renal disease attributed to hypertensionthat was associated with a blood pressure higher by 1 SD was2.0 (95 percent confidence interval, 1.8 to 2.1) for systolicblood pressure and 1.9 (95 percent confidence interval, 1.8to 2.2) for diastolic blood pressure.
Men Who Entered the MRFIT Study
Too few cases of end-stage renal disease (a total of 35) occurredamong the 12,866 men who entered MRFIT to permit classificationin the seven blood-pressure categories. Therefore, for thesemen, blood pressure was entered as a continuous variable inthe multivariate model. Among men who entered MRFIT, a systolicblood pressure higher by 1 SD was associated with a doublingof the risk of end-stage renal disease (P<0.001); for thosenot in the trial the risk increased by a factor of 1.8 (P<0.001).The results for diastolic blood pressure were similar. For menwho entered MRFIT, a diastolic blood pressure higher by 1 SDwas associated with a 2.5-fold increase in the risk of end-stagerenal disease (P<0.001); for men not in the trial, the riskwas increased 1.7-fold (P<0.001). When the serum creatinineconcentration and urinary protein excretion at entry into thetrial were included as covariates in multivariate models, therelative risks of end-stage renal disease associated with ablood pressure higher by 1 SD did not change (for systolic bloodpressure: 2.0; 95 percent confidence interval, 1.5 to 2.7; fordiastolic pressure: 2.5; 95 percent confidence interval, 1.4to 4.3). Moreover, when the analysis was confined to the 7817men who entered MRFIT with a serum creatinine concentrationof less than 1.2 mg per deciliter (106 µmol per liter)and a urinary protein excretion of less than 1+, among whomend-stage renal disease developed in 19, estimates of relativerisk associated with a blood pressure higher by 1 SD (for systolicblood pressure: 1.8; 95 percent confidence interval, 1.2 to2.7; for diastolic pressure: 1.7; 95 percent confidence interval,0.8 to 3.4) were not significantly different from those forthe total MRFIT cohort of 12,866 men.
Discussion
Our study extends knowledge of the link between blood pressureand renal disease in several ways. Higher blood pressure, asmeasured carefully on a single occasion, was a strong independentrisk factor for end-stage renal disease. The increase in riskassociated with higher blood pressure was graded and continuousthroughout the distribution of blood-pressure readings abovethe optimal level. Our results demonstrate the validity of usingthe Joint National Committee's categories in the predictionof end-stage renal disease. Risk estimates were graded for bothsystolic and diastolic blood pressure considered separately,but systolic pressure was the stronger predictor of subsequentdisease when both variables were considered together. Theserelations, including the pattern of interactions with age anddiabetes mellitus, are very similar to those between coronaryheart disease or stroke and blood pressure.15-17 Older age,lower income, higher serum cholesterol concentrations, cigarettesmoking, diabetes mellitus, a history of hypertension, and blackrace were also associated with an increased risk of end-stagerenal disease.
Accelerated and malignant hypertension have long been knownto be linked with an increased risk of renal failure, and clinicaltrials studying patients with this diagnosis have demonstratedthat antihypertensive-drug therapy prolongs survival and slowsthe progression of renal disease.18-21 The risk of renal failureassociated with less severe hypertension has been investigatedonly recently.2 In an analysis of 26 geographic areas in Maryland,the incidence of hypertensive end-stage renal disease correlatedclosely with the prevalence of hypertension, especially severehypertension.22 During a 15-year follow-up of 11,912 hypertensivemale veterans, systolic blood pressure before treatment wasa stronger predictor of end-stage renal disease than was diastolicpressure.23 The results of our study are consistent with observationalstudies of blood pressure in patients with mild-to-moderateimpairment of renal function.24-30 Observational studies andclinical trials involving patients with established renal insufficiencyhave also demonstrated that lowering blood pressure preservesrenal function.31-36
The most important barrier to studying the relation of bloodpressure to end-stage renal disease is the low incidence ofend-stage disease. The large size of the MRFIT screening cohortand the 15-to-17-year follow-up period produced a large numberof cases for study. The availability of comprehensive data ondeath from renal disease and treatment for end-stage diseasemeans that differences in the incidence of the disease accordingto blood-pressure levels are unlikely to be due to systematicdifferences either in the assessment of outcome or in the subjects'access to care. Likewise, our use of end-stage renal diseasedue to any cause as the primary outcome precludes the possibilityof misclassifying the causes of the condition.37,38
Our study, however, has several limitations. No women were included.Blood pressure was measured on only one occasion, resultingin an underestimation of the strength of the association ofend-stage renal disease with blood pressure.39 A more precisemeasure — for example, an average of blood-pressure readingsfrom several visits made over a longer period — wouldyield greater differences in the incidence of end-stage renaldisease associated with higher blood pressure. We also collectedno information on antihypertensive therapy. Misclassificationof a treated hypertensive person as normotensive or less severelyhypertensive would also tend to weaken the estimated risk associatedwith higher blood pressure. Most of the men were studied beforethe widespread use of angiotensin-converting–enzyme inhibitors,a class of antihypertensive drugs that may offer special renalprotection.
An additional limitation of our study is that renal functionwas not assessed at base line except in the subgroup of menwho entered the MRFIT trial. Thus, for the majority of men screened,we do not know whether renal insufficiency was already presentin those in whom end-stage renal disease later developed. Thesimilar relation in the two groups — all men screenedfor MRFIT and those who actually entered that study —between blood pressure and end-stage renal disease due to anycause; the independence of that relation from base-line serumcreatinine concentrations and urinary protein excretion in themen entering the MRFIT trial; and the persistence of the relationafter 10 years of follow-up in the group of all screened menargue against viewing preexisting renal disease as an importantcontributor to the observed associations. However, the earlyincrease in the incidence of end-stage renal disease in menwith the highest blood pressures (Figure 1) may reflect preexistingrenal disease in this subgroup. The lack of information on renalfunction, both at base line and during follow-up, does mean,however, that we cannot say definitively whether the strongassociation between blood pressure and the incidence of end-stagerenal disease was due to the initiation of renal disease orto the accelerated progression of preexisting disease.
The costs of end-stage renal disease to the individual and tosociety make the identification of modifiable risk factors forthe condition an important public health priority. Interventionsto prevent end-stage renal disease need to emphasize the preventionand control of high blood pressure. The importance of the primaryprevention of hypertension, by slowing or stopping the increasein blood pressure from youth to middle age, has received widespreadrecognition as one means of addressing the epidemic of cardiovasculardisease40,41; primary prevention also has the potential to preventa large proportion of cases of end-stage renal disease. In addition,the need to prevent end-stage renal disease dictates continuedefforts to achieve the early identification of persons withhypertension and to provide them with effective antihypertensivetherapy.
Supported by grants (RO1 DK41837 and RO1 HL28715) from the NationalInstitutes of Health. Dr. Klag is an Established Investigatorof the American Heart Association.
We are indebted to Dr. Paul Eggers and Dr. Marshall McBean ofthe Health Care Financing Administration for their assistancein the study and to Ms. Barbara Pawloski for editorial help.
Source Information
From the Departments of Medicine and Epidemiology (M.J.K., P.K.W., F.L.B.) and the Department of Health Policy and Management (M.J.K.), Johns Hopkins University School of Medicine and Johns Hopkins University School of Hygiene and Public Health, Baltimore; the Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis (B.L.R., J.D.N.); the University of Texas Health Science Center at Houston, Houston (C.E.F.); the Department of Medicine, Emory University, Atlanta (N.B.S.); and the Department of Preventive Medicine, Northwestern University Medical School, Chicago (J.S.).
Address reprint requests to Dr. Klag at the Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21205-2223.
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(2008). Vildagliptin, a Novel Dipeptidyl Peptidase IV Inhibitor, Has No Pharmacokinetic Interactions With the Antihypertensive Agents Amlodipine, Valsartan, and Ramipril in Healthy Subjects. J Clin Pharmacol
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O'Hare, A. M., Choi, A. I., Bertenthal, D., Bacchetti, P., Garg, A. X., Kaufman, J. S., Walter, L. C., Mehta, K. M., Steinman, M. A., Allon, M., McClellan, W. M., Landefeld, C. S.
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Franciosi, M., Pellegrini, F., Sacco, M., De Berardis, G., Rossi, M. C.E., Strippoli, G. F.M., Belfiglio, M., Tognoni, G., Valentini, M., Nicolucci, A., on behalf of the IGLOO (Impaired Glucose tolerance,
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Dickinson, B. D., Havas, S., for the Council on Science and Public Health, Amer,
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Ninomiya, T., Kubo, M., Doi, Y., Yonemoto, K., Tanizaki, Y., Tsuruya, K., Sueishi, K., Tsuneyoshi, M., Iida, M., Kiyohara, Y.
(2007). Prehypertension Increases the Risk for Renal Arteriosclerosis in Autopsies: The Hisayama Study. J. Am. Soc. Nephrol.
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Elsayed, E. F., Tighiouart, H., Griffith, J., Kurth, T., Levey, A. S., Salem, D., Sarnak, M. J., Weiner, D. E.
(2007). Cardiovascular Disease and Subsequent Kidney Disease. Arch Intern Med
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(2007). A Population-Based, Prospective Study of Blood Pressure and Risk for End-Stage Renal Disease in China. J. Am. Soc. Nephrol.
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Hou, F. F., Xie, D., Zhang, X., Chen, P. Y., Zhang, W. R., Liang, M., Guo, Z. J., Jiang, J. P.
(2007). Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency. J. Am. Soc. Nephrol.
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Shankar, A., Klein, R., Klein, B. E.K., Nieto, F. J., Moss, S. E.
(2007). Relationship Between Low-Normal Blood Pressure and Kidney Disease in Type 1 Diabetes. Hypertension
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Ruggenenti, P., Perna, A., Ganeva, M., Ene-Iordache, B., Remuzzi, G., for the BENEDICT Study Group,
(2006). Impact of Blood Pressure Control and Angiotensin-Converting Enzyme Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes: A Post Hoc Analysis of the BENEDICT Trial. J. Am. Soc. Nephrol.
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(2006). Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease. Journal of Renin-Angiotensin-Aldosterone System
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van Bemmel, T., Woittiez, K., Blauw, G. J., van der Sman-de Beer, F., Dekker, F. W., Westendorp, R. G.J., Gussekloo, J.
(2006). Prospective Study of the Effect of Blood Pressure on Renal Function in Old Age: The Leiden 85-Plus Study. J. Am. Soc. Nephrol.
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(2006). The Association among Smoking, Heavy Drinking, and Chronic Kidney Disease. Am J Epidemiol
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Ishani, A., Grandits, G. A., Grimm, R. H., Svendsen, K. H., Collins, A. J., Prineas, R. J., Neaton, J. D., for the MRFIT Research Group,
(2006). Association of Single Measurements of Dipstick Proteinuria, Estimated Glomerular Filtration Rate, and Hematocrit with 25-Year Incidence of End-Stage Renal Disease in the Multiple Risk Factor Intervention Trial. J. Am. Soc. Nephrol.
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Garrett, M. R., Joe, B., Yerga-Woolwine, S.
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Hsu, C. C.-c., Bray, M. S., Kao, W.H.L., Pankow, J. S., Boerwinkle, E., Coresh, J.
(2006). Genetic Variation of the Renin-Angiotensin System and Chronic Kidney Disease Progression in Black Individuals in the Atherosclerosis Risk in Communities Study. J. Am. Soc. Nephrol.
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Appel, L. J., Brands, M. W., Daniels, S. R., Karanja, N., Elmer, P. J., Sacks, F. M.
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O'Hare, A. M., Rodriguez, R. A., Bacchetti, P.
(2005). Low Ankle-Brachial Index Associated With Rise in Creatinine Level Over Time: Results From the Atherosclerosis Risk in Communities Study. Arch Intern Med
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He, J., Gu, D., Wu, X., Chen, J., Duan, X., Chen, J., Whelton, P. K.
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Johnson, R. J., Segal, M. S., Srinivas, T., Ejaz, A., Mu, W., Roncal, C., Sanchez-Lozada, L. G., Gersch, M., Rodriguez-Iturbe, B., Kang, D.-H., Acosta, J. H.
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Contreras, G., Greene, T., Agodoa, L. Y., Cheek, D., Junco, G., Dowie, D., Lash, J., Lipkowitz, M., Miller, E. R. III, Ojo, A., Sika, M., Wilkening, B., Toto, R. D., for the African American Study of Kidney Disease a,
(2005). Blood Pressure Control, Drug Therapy, and Kidney Disease. Hypertension
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Whelton, P. K., Barzilay, J., Cushman, W. C., Davis, B. R., IIamathi, E., Kostis, J. B., Leenen, F. H. H., Louis, G. T., Margolis, K. L., Mathis, D. E., Moloo, J., Nwachuku, C., Panebianco, D., Parish, D. C., Pressel, S., Simmons, D. L., Thadani, U., for the ALLHAT Collaborative Research Group,
(2005). Clinical Outcomes in Antihypertensive Treatment of Type 2 Diabetes, Impaired Fasting Glucose Concentration, and Normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med
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Hsu, C.-y., McCulloch, C. E., Darbinian, J., Go, A. S., Iribarren, C.
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Rahman, M., Pressel, S., Davis, B. R., Nwachuku, C., Wright, J. T. Jr, Whelton, P. K., Barzilay, J., Batuman, V., Eckfeldt, J. H., Farber, M., Henriquez, M., Kopyt, N., Louis, G. T., Saklayen, M., Stanford, C., Walworth, C., Ward, H., Wiegmann, T., for the ALLHAT Collaborative Research Group,
(2005). Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med
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Verhave, J. C., Fesler, P., du Cailar, G., Ribstein, J., Safar, M. E., Mimran, A.
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Stuveling, E. M., Bakker, S. J. L., Hillege, H. L., de Jong, P. E., Gans, R. O. B., de Zeeuw, D.
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Domrongkitchaiporn, S., Sritara, P., Kitiyakara, C., Stitchantrakul, W., Krittaphol, V., Lolekha, P., Cheepudomwit, S., Yipintsoi, T.
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Morrison, R. G., Carpenter, A. B., Adams, V. L., Mangiarua, E. I., Wehner, P. S., McCumbee, W. D.
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Young, B. A., Katon, W. J., Von Korff, M., Simon, G. E., Lin, E. H. B., Ciechanowski, P. S., Bush, T., Oliver, M., Ludman, E. J., Boyko, E. J.
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Coyle, J. D, Gardner, S. F, White, C M.
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Jung, O., Bickel, M., Ditting, T., Rickerts, V., Welk, T., Helm, E. B., Staszewski, S., Geiger, H.
(2004). Hypertension in HIV-1-infected patients and its impact on renal and cardiovascular integrity. Nephrol Dial Transplant
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(2004). From Finland to Fatland: Beneficial Effects of Statins for Patients with Chronic Kidney Disease. J. Am. Soc. Nephrol.
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Siegel, A.-K., Kossmehl, P., Planert, M., Schulz, A., Wehland, M., Stoll, M., Bruijn, J. A., de Heer, E., Kreutz, R.
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Smith, D. H., Gullion, C. M., Nichols, G., Keith, D. S., Brown, J. B.
(2004). Cost of Medical Care for Chronic Kidney Disease and Comorbidity among Enrollees in a Large HMO Population. J. Am. Soc. Nephrol.
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Abbott, K., Basta, E., Bakris, G. L.
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(2004). A 43-Year-Old Woman With Chronic Renal Insufficiency. JAMA
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Kivimaki, M., Kinnunen, M.-L., Pitkanen, T., Vahtera, J., Elovainio, M., Pulkkinen, L.
(2004). Contribution of Early and Adult Factors to Socioeconomic Variation in Blood Pressure: Thirty-Four-Year Follow-up Study of School Children. Psychosom. Med.
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Fox, C. S., Larson, M. G., Leip, E. P., Culleton, B., Wilson, P. W. F., Levy, D.
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Vupputuri, S., Batuman, V., Muntner, P., Bazzano, L. A., Lefante, J. J., Whelton, P. K., He, J.
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Wright, J. T. Jr, Rahman, M., Scarpa, A., Fatholahi, M., Griffin, V., Jean-Baptiste, R., Islam, M., Eissa, M., White, S., Douglas, J. G.
(2003). Determinants of Salt Sensitivity in Black and White Normotensive and Hypertensive Women. Hypertension
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Zeller, T., Frank, U., Muller, C., Burgelin, K., Sinn, L., Bestehorn, H.-P., Cook-Bruns, N., Neumann, F.-J.
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Haroun, M. K., Jaar, B. G., Hoffman, S. C., Comstock, G. W., Klag, M. J., Coresh, J.
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Feig, D. I., Johnson, R. J.
(2003). Hyperuricemia in Childhood Primary Hypertension. Hypertension
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(2003). Management of Uncontrolled Hypertension in a Nurse-Led Clinic Compared With Conventional Care for Patients with Type 2 Diabetes. Diabetes Care
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Bakris, G. L., Weir, M. R., Shanifar, S., Zhang, Z., Douglas, J., van Dijk, D. J., Brenner, B. M.
(2003). Effects of Blood Pressure Level on Progression of Diabetic Nephropathy: Results From the RENAAL Study. Arch Intern Med
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Gassman, J. J., Greene, T., Wright, J. T. Jr., Agodoa, L., Bakris, G., Beck, G. J., Douglas, J., Jamerson, K., Lewis, J., Kutner, M., Randall, O. S., Wang, S.-R.
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(2003). Progression of Chronic Renal Failure. Arch Intern Med
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(2003). Blood Pressure Predicts Risk of Developing End-Stage Renal Disease in Men and Women. Hypertension
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Fesler, P., du Cailar, G., Ribstein, J., Mimran, A.
(2003). Left Ventricular Remodeling and Renal Function in Never-Treated Essential Hypertension. J. Am. Soc. Nephrol.
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Douglas, J. G., Bakris, G. L., Epstein, M., Ferdinand, K. C., Ferrario, C., Flack, J. M., Jamerson, K. A., Jones, W. E., Haywood, J., Maxey, R., Ofili, E. O., Saunders, E., Schiffrin, E. L., Sica, D. A., Sowers, J. R., Vidt, D. G., the Hypertension in African Americans Working Grou,
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Chen, J., Muntner, P., Hamm, L. L., Fonseca, V., Batuman, V., Whelton, P. K., He, J.
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