Hypertensive End-Stage Renal Disease in Blacks:

The Role of End-Stage Renal Disease Surveillance

William McClellan, MD, MPH

• The end-stage renal disease (ESRD) networks and the United States Renal Data System recently have described
the epidemiology of ESRD and broadened our appreciation of the impact of ESRD in the United States. This surveillance
system also can be used to study the occurrence and control of ESRD. Among the epidemiologic study designs
available to conduct research on the etiology of renal failure, case-control studies are uniquely suited for this purpose.
The case of hypertensive ESRD illustrates this concept; risk factors for hypertensive ESRD, as a hypothetical exposure
in case-control studies, are briefly described. Case-control studies are an efficient and readily used means to study
causes of renal failure.
© 1993 by the National Kidney Foundation, Inc.

INDEX WORDS: End-stage renal disease; epidemiology; case control; surveillance; hypertension.

R ECENT REPORTS from the United States

Renal Data System (USRDS) and regional
end-stage renal disease (ESRD) networks have
advanced our understanding of the impact of
ESRD in the United States. These comprehensive
descriptions of the occurrence and treatment of
renal failure have resulted in increasing the rec-
ognition that ESRD is a significant health burden
and that considerable effort is warranted to im-
prove its treatment and control. 1 Furthermore,
they have stimulated interest in the use of epi-
demiologic research to improve our understand-
ing of the potential factors associated with the
occurrence, treatment, and control of ESRD.2
The USRDS and the ESRD networks will be a
major factor in the success of these efforts. This
report illustrates their role in the epidemiologic
study of factors for ESRD using the model of
hypertensive ESRD.
END-STAGE RENAL DISEASE SURVEILLANCE
Surveillance is the process of monitoring, an-
alyzing, and reporting the frequency of a disease
in a defined population to improve its treatment
and control. 3,4 End-stage renal disease is unique
in that it is the only chronic disease in the United
States for which a comprehensive national sur-
veillance system exists. This system comprises the
18 geographically defined ESRD networks in the
United States and the USRDS. A network con-
sists of a governing body, services to collect and
manage data, and a medical review board, which
conducts quality assurance activities. Each net-
work records and maintains information about
the occurrence of treated renal failure for new,
medicare-eligible patients. The record includes
demographic information and the cause of renal
failure as reported by the treatment facility.
Treatment and vital status are monitored and
updated periodically. Network data also are used
for the quality assurance activities conducted by
the networks. Information collected by the net-
works is sent to the USRDS and compiled in an
annual report. 1 An important feature of this sys-
tem is that it is ideally suited to conduct epide-
miologic investigations.
SURVEILLANCE AND DESCRIPTIVE
EPIDEMIOLOGY
The epidemiologic study of ESRD begins by
describing the incidence and prevalence within
a population, changes in incidence over time, and
geographic patterns of occurrence.4 United States
Renal Data System and ESRD network reports
of the epidemiology of hypertensive ESRD il-
lustrate this application of surveillance data
and show how useful descriptive epidemiology
can be.
Hypertension is identified by the nephrologist
as the primary cause of ESRD in 25% of new
cases reported to the networks. 1 Age-, sex-, and
race-specific incidence rates of hypertensive
ESRD show a disproportionate risk for blacks;
in addition, within races, males are at increased
risk compared with females. The ratio of the black
to white incidence rates, the relative risk, rises
from 2 in the youngest ages to a peak of 26 be-
tween ages 35 to 44 years, and then declines to
From the Division of Nephrology, Emory School of Medi-
cine, Atlanta, GA.
Presented at the Workshop on the Biology ofKidney Disease
and Hypertension in Blacks, Bethesda, MD, December 11-
13, 1991.
Address reprint requests to William McClellan, MD, MPH,
Clark Holder Clinic, 303 Smith St, La Grange, GA 30240.
© 1993 by the National Kidney Foundation, Inc.
0272-6386/93/2104-0106$3.00/0

American Journal of Kidney Diseases, Vol 21 , No 4, Suppl1 (April), 1993: pp 25-30 25

26
6 after the age of 65 years. 5 Incidence increases
with age until the eighth decade of life and de-
clines thereafter. The reported incidence of hy-
pertensive ESRD has been rising during the last
decade, particularly among the elderly. The age-,
sex-, and race-adjusted rates increased from 26.5
per million in 1984 to 36.5 per million in 1988. 1
While little is known about the geographic dis-
tribution of hypertensive ESRD, regional varia-
tions do occur. For example, in Georgia hyper-
tensive ESRD rates are higher than on the
southeastern coastal plain, a region with many
geologic and sociodemographic differences from
the Appalachian Piedmont to the west. 6
SURVEILLANCE AND
ETIOLOGIC INVESTIGATION
The next step in the epidemiologic study of a
disease is the investigation of factors that may be
associated with the disease occurrence. 4 A num-
ber of methods can be used, including case-con-
trol, cohort, and nested case-control designs. 7 The
case-control study, however, is uniquely suited
to a surveillance system.
Standard texts on the design and conduct of
case-control studies are available. 8,9 Case-control
studies are an efficient and cost-effective means
of exploring possible etiologic factors of a disease.
Briefly, cases are identified within a population
and nondiseased members from the same pop-
ulation are selected for comparison. Exposure
histories for putative risk factors are ascertained
in both groups, and the odds ratio is calculated.
The odds ratio estimates the degree of association
between exposure to the risk factor and the oc-
currence of the disease. Cases need not represent
all cases arising in the population nor be repre-
sentative of a previously defined population.
However, controls must be drawn from the same
source as the cases. Frequently, the most prob-
lematic feature of a case-control study design is
the identification of the cases. It is this aspect of
the ESRD surveillance system, the prompt iden-
tification of new cases of ESRD, that holds such
promise for future research.
RISK FACTORS FOR HYPERTENSIVE
END-STAGE RENAL DISEASE
A case-control study seeks to study the asso-
ciation between a potential etiologic factor and
the occurrence of a disease. This factor can be
suggested by basic, clinical, or epidemiologic re-
WILLIAM McCLELLAN
search. A large and growing list of risk factors
associated with the occurrence of hypertensive
ESRD that are suitable for the case-control study
design has been identified (Table I).
Race has been recognized as a risk factor for
hypertensive ESRD for some time. McCord first
reported that hypertensive black patients were
more likely than white patients to have renal fail-
ure from malignant hypertensive nephrosclero-
sis. 10 Subsequent studies reported a crude black
to white relative risk for hypertensive ESRD of
4 to I 7} 1·14 The greater prevalence and severity
of hypertension among blacks fail to completely
explain the increased risk of hypertensive
ESRD. 5,15
Familial aggregation may occur in hyperten-
sive ESRD. Grunfeld et al reported that a family
history of hypertension is associated with dimin-
ished renal functional reserve and increased
postprandial microalbuminuria. 16 Ferguson et al
found that among black patients on hemodialysis,
those with hypertensive ESRD were 14 times
more likely to report a family history of hyper-
tension than community controls. 17 Further-
more, a history of chronic renal failure in a first-
or second-degree relative was significantly more
frequent among dialysis patients.
Diabetes mellitus is associated with hyperten-
sive ESRD. Brancha et al found that patients with
essential hypertension and glucose intolerance
have lower glomerular filtration rates (GFRs) and
that when both glucose intolerance and hype-
ruricemia are present the GFR is even lower. 18
Patients with elevated blood sugar, hypertension,
and elevated uric acid experience a significant
decline in renal function during follow-up.15
Tierney and colleagues reported that 18.1 % of
6,880 hypertensive outpatients had evidence of
renal insufficiency during a mean follow-up of
7.2 years}9,20 The Hypertension Detection and
Follow-up Program (HDFP) reported an asso-
ciation between glucose intolerance and renal in-
sufficiency among essential hypertensives?1 Fac-
tors associated with increasing serum creatinine
in this cohort of treated essential hypertensives,
after controlling for blood pressure, included
baseline renal function, age, body mass cardio-
vascular risk factors, and comorbidity included
diabetes at entry and a fasting blood sugar level
of 140 mg/dL.
Lead exposure has been suggested as a risk fac-
tor for hypertensive renal failure?2.24 Bautman
ESRD SURVEILLANCE
Table 1. Risk Factors for Hypertensive
End-Stage Renal Disease
Age
Race
Family history
Diabetes
Lead exposure
Hyperuricemia
Proteinuria
NAG excretion rate
Kallikrein excretion rate
Potassium intake
LVH
Access to care
Degree of blood pressure control
Socioeconomic characteristics
Analgesic use
et al reported that patients with essential hyper-
tension and renal insufficiency had higher levels
of EDT A-mobilizable lead (860 J.lg) than did ei-
ther hypertensive patients with normal renal
function (340 J.lg) or patients with nonhyperten-
sive renal disease and comparable renal function
(440 J.lg). Wright et al reported 10 patients with
symptomatic gout, hypertension, and renal in-
sufficiency.25 These investigators found that seven
patients had a previous history of lead exposure,
five from illegal alcohol consumption and two
from an occupational exposure. Three of these
patients had elevated lead excretion with EDTA
chelation. Finally, the association between blood
pressure and blood lead levels found in the
NHANES II study suggests that hypertension and
lead exposure may precede significant renal dis-
ease. 26
Hyperuricemia has been associated with in-
creased risk of hypertensive renal disease. 27,28
Messerli et al examined renal hemodynamics in
individuals that was stratified by blood pressure
and uric acid. 29 Creatinine clearance was similar
in the different groups, but renal resistance was
higher and renal blood flow lower in those pa-
tients with increased levels of serum uric acid.
While these relationships were seen among nor-
motensive individuals, they were significant only
among patients with established hypertension
and a uric acid level higher than 9 mg/dLYu
and Berger studied 624 patients with gout. 30 The
mean inulin clearance among the 397 patients
with gout and no other comorbid factors was 100
mL/min. Patients with gout and either hyperten-
sion or ischemic heart disease or both had mean
27
clearance levels of 87 mL/min, while those with
gout and proteinuria had mean clearance levels
of 67 mL/min. The HDFP study found a similar
relationship between the level of uric acid and
serum creatinine at baseline. 21
Proteinuria was found to be a risk factor for
renal failure in patients with essential hyperten-
sion in the HDFP cohort. 21 Significant progres-
sion of renal insufficiency was associated with the
presence of proteinuria at baseline examination.
Morduchowicz et al reported that significant
degrees of proteinuria in biopsy-proven hyper-
tensive nephrosclerosis is associated with an
increased risk of developing renal failure. 31
Microalbuminuria has been associated with the
degree of blood pressure control and antihyper-
tensive treatment has been shown to reduce both
the rate of decline in the GFR and microalbumin
excretion rate. 32-34 Finally, Ruilope et al reported
that 17% of hypertensive patients with normal
renal function subsequently developed protein-
uria. 35 Baseline serum creatinine, blood glucose,
cholesterol, triglyceride, and creatinine clearance
in this study did not differ between patients who
developed proteinuria during follow-up and those
who did not. Importantly, creatinine clearance
levels were stable over 9 years of follow-up in
nonprotein uric patients, but declined signifi-
cantly in proteinuric patients after year 5. The
temporal association between the decline in renal
function and the onset of proteinuria was not
reported, but 60% of the patients with proteinuria
were identified before the decline in creatinine
clearance was noted. Interestingly, baseline uric
acid levels were higher among patients who de-
veloped proteinuria.
Increased excretion of N-acetyl-(beta)-gluco-
soaminidase (NAG) is a marker for incipient
renal injury in hypertensive patients. 36 Further
NAG excretion declined with antihypertensive
therapy. Urinary kallikrein excretion also has
been associated with risk of renal disease. Mitas
et al reported an inverse relationship between 24-
hour urinary kallikrein activity (UkA) and
GFR.37 The UkA, standardized for GFR, was
lower in hypertensive patients with renal paren-
chymal disease when compared with normoten-
sive subjects and hypertensive patients with nor-
mal renal function. These observations are of
interest since lower urinary kallikrein excretion
rates have been reported in black hypertensive
patients. 38-42 A recent study in renal transplant
28
patients indicated that UkA may be a marker of
renal reserve. 43
Dietary factors may be associated with the oc-
currence of hypertensive ESRD. Ford et al re-
ported that blacks in the HDFP cohort with blood
pressure levels in the lowest stratum had lower
serum and dietary potassium intakes as well as
higher creatinine levels when compared with
whites. 44 Horwitz et al reported an association
between kallikrein excretion and dietary potas-
sium. These investigators found that UkA is lower
in both normotensive and hypertensive black pa-
tients when compared with white patients and
that UkA in both races decreases with decreasing
levels of dietary potassium consumption. 45 To-
bian et al have reported that dietary potassium
is protective in rat models of hypertensive neph-
rosclerosis. 46,4 7
Left ventricular hypertrophy (LVH) also is a
risk factor for hypertensive renal disease. Messerli
and colleagues report that in patients with un-
complicated essential hypertension, reduced renal
blood flow was associated with LVH and in-
creased uric acid levels. 48 ,49 Cerasola et al also
have reported that microalbuminia is associated
with increased left ventricular mass and increased
GFR in uncomplicated essential hypertension. 50
The care of the hypertensive patient may be
associated with ESRD. For example, the degree
of blood pressure control may influence the risk
of hypertensive ESRD. 51 ,52 Kutner studied the
association between measures of access to care
and hypertensive ESRD using patients identified
through an ESRD network. 53 Prior to ESRD,
blacks were more likely to (1) report medication
and dietary noncompliance due to costs, (2) re-
port noncompliance with other medications, (3)
experience transportation and job-related barriers
to medical visits, (4) use outpatient clinics for
hypertensive care, and (5) be less familiar with
the adverse health consequences of hypertension.
Rostand et al reported that older age, black race,
visit noncompliance, and lower socioeconomic
status were associated with increased risk of de-
velopment of hypertensive renal disease in un-
complicated essential hypertension. 54 They also
noted that the risk of progression was not asso-
ciated with mean blood pressure level during fol-
low-up.
A CASE-CONTROL STUDY
There are few examples of case-control studies
ofESRD, but none that readily illustrate the use
WILLIAM McCLELLAN
of this method to study hypertensive ESRD. A
recent case-control study of the association be-
tween analgesic use and renal failure is relevant
to this issue. 55 Analgesic use has been associated
with increased risk of hypertensive ESRD in a
recent case-control study. 56 New cases of renal
failure in four medical centers were identified
over a 4-year period, yielding 709 eligible patients.
Control patients were identified by random digit
dialing in the communities served by the medical
centers. Patients and controls were interviewed
to assess various aspects of previous exposure to
the study factor, analgesics. Controls were
matched to cases for age, race, and gender, factors
that were felt to be likely risk factors for renal
disease and also related to patterns of anal-
gesic use.
Daily and weekly use of any analgesics, in-
cluding aspirin, acetaminophen, and phenacetin
mixtures, was associated with increased risk of
renal disease. The risk for chronic renal failure
increased with increasing levels of estimated total
lifetime analgesic consumption. Analgesic use
was associated with an eightfold increased risk of
interstitial nephritis. Of particular interest was
that analgesic use also was associated with in-
creased risk of hypertensive nephrosclerosis.
USING THE END-STAGE RENAL DISEASE
SURVEILLANCE SYSTEM TO STUDY
RISK FACTORS
The large numbers of new patients that can be
readily identified by the ESRD networks and the
USRDS will enable investigators to efficiently and
inexpensively study the association between pos-
sible risk factors and the occurrence ofhyperten-
sive ESRD. New patients with hypertensive
ESRD who are reported to an ESRD network
would serve as cases. Cases would be interviewed
about exposure to the suspected risk factor, as
well as about other known or suspected causal
factors. A comparison population would be cho-
sen from the same source as the cases and inter-
viewed about the same exposures. The frequency
of exposure in the control population compared
with that in the control group allows inferences
about the association between the risk factor and
the occurrence of ESRD. 55
It is important to emphasize that while simple
in concept, the design, conduct, and interpreta-
tion of a case-control study requires collaboration
ESRD SURVEILLANCE
between clinicians, epidemiologists, and biostat-
isticians to be successful.
CONCLUSION
Regional networks and the USRDS will be ex-
tremely useful means for efficiently and econom-
ically describing the epidemiology and investi-
gating the causes of ESRD in the US population.
The ultimate benefit of understanding hyperten-
sive ESRD will be to design primary and sec-
ondary preventive interventions that might di-
minish the occurrence of the disease. Initial efforts
to devise such a preventive strategy, informed by
clinical and epidemiologic research, already have
begun. s7
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