JN a T

Kidney senescence and renal function evaluation in the elderly
JNEPHROL 2010; 23 (S15): S46-S54
www.sin-italy.org/jnonline – www.jnephrol.com
How to assess renal function in the geriatric
population
Filippo Aucella, Claudio Carmine Guida,
Vincenzo Lauriola, Michele Vergura
Nephrology and Dialysis Unit, IRCCS “Casa Sollievo della
Sofferenza” Hospital, San Giovanni Rotondo, Foggia Italy
Nephrology and Dialysis Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
Nephrology and Dialysis Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
Nephrology and Dialysis Unit, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Foggia - Italy
Abstract
The myth of the inexorable decline of
The progressive decline of renal function with aging
is not inevitable, because it is mainly due to comorbid conditions such as hypertension and diabetes.
However, in the elderly there is a high prevalence of
chronic kidney disease leading to the need for strategies to control cardiovascular risk – death being far
more common than dialysis at all stages of kidney
function. Serum creatinine, the most widely used surrogate marker of glomerular filtration rate (GFR), is
inaccurate with increasing age, particularly in sick
and/or malnourished elderly people; it shows the socalled creatinine blind area, and substantial variation
between laboratory analytical methods. An alternative
endogenous marker is serum cystatin C: it correlates
better with renal function and has the potential advantage of improved precision of the assay, but its measurement is still much more expensive. Current guidelines recommend that the 2 most commonly used
equations to estimate GFR – the Modification of Diet
in Renal Disease Study or Cockcroft-Gault equations
– be used to estimate GFR in the clinical setting. Both
show relevant bias, with underestimation of GFR in
subjects with normal or mild renal impairment, a bias
limited by using the more recent Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Nonetheless, keeping in mind that a decreased renal
function in the elderly is not benign, current GFR equations facilitate detection, evaluation and management
of the disease, and they should result in improved patient care and better clinical outcomes.
Key words: Aging, Cockcroft-Gault equation, Creatinine
clearance, Cystatin C, Estimated glomerular filtration
rate, Modification of Diet in Renal Disease equation
S46
renal function with senescence
When we talk about physiology, we refer to the normal
function of organs, whereas “insufficiency” or “failure” is a
pathological status. In this regard, we should keep in mind
that renal aging is a physiological rather than a pathological
process. Therefore, it is not correct to speak about the aging
kidney function as a “physiological renal insufficiency”: that
represents a gross conceptual error because the aging kidney is able to maintain the extracellular volume equilibrium
in conditions of health, although its resources and ability to
adapt to challenges of restriction or overload are limited (1).
Old uncontrolled observations, including in individuals with
comorbid conditions, suggested that the average kidney
weight decreases by up to 40% from young adulthood to senescence (2). These findings clearly disagree with observations where no significant decrease in renal mass was found
in elderly patients who had suffered traumatic death and in
whom renal disease and/or important comorbid conditions
were excluded (3). Moreover, imaging studies investigating
changes of renal size and structure showed only a modest decrease until the age of 75 years, whereas thereafter
kidney size, calculated volume and parenchymal thickness
were clearly lower (4). So the loss of renal mass with aging
is moderate, preferentially affecting the renal cortex, at least
until the age of 70 years. Glomerulosclerosis is the main
age-associated change of renal hemodynamics (5). The degree of age-related glomerulosclerosis is clearly related to
the severity of systemic atherosclerosis, and the presence
of glomerulosclerosis is indicative of subclinical renal injury
from comorbid conditions affecting renal structure (6).
The kidneys of elderly people are more sensitive to negative influences from other coexisting comorbid conditions,
and aging causes the appearance of albuminuria most often
© 2010 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2010; 23 (S15): S46-S54
together with other coexisting factors such as male sex or
uncontrolled hypertension. But advanced age alone is not
harmful for the kidneys (7). Based on all of this, Danilo Fliser
has clearly defined as a myth the inexorable decline of renal
function with senescence (8).
Decline of renal function in normal
aging: rate and clinical impact
The Baltimore Longitudinal Study of Aging (BLSA), the
first continuing scientific examination of human aging,
was started in 1958 and has been an important source of
information on the aging kidney (9). This seminal study,
with an observation period of at least 5 years using ageadjusted standards for creatinine clearance, apparently
confirmed the previously postulated progressive decline
of renal function with aging. The estimated average annual change in creatinine clearance (CrCl) was 0.26 ml/min
per 1.73 m2 in the age group 20 to 39 years and became
1.51 ml/min per 1.73 m2 after the age of 80.
However, Lindeman and coworkers could identify 3 subgroups of these elderly persons above 65 years: one of
these showing apparently no change in glomerular filtration rate (GFR), a second group with hypertension and mild
reduction of GFR and a third with edema and proteinuria,
probably due to unrecognized cardiac and renal disease,
showing a relevant impairment of renal function with aging
(Fig. 1) (9). So, clearly it was shown that comorbidity has an
important impact on changes in GFR with age. In fact, while
BLSA participants were selected to be “healthy,” the diagnostic technology available at that time may have failed to
detect subclinical cardiovascular and kidney disease. This
is important because the distinction between age-unrelated
renal changes and progressive renal insufficiency is associated with a different prognosis. Moreover, one of the most
important findings of the BLSA was that kidney function varied between persons at all ages, and when declines with aging were noted, they occurred at substantially different rates.
In some individuals with an accelerated decline in CrCl, the
presence of undetected, subclinical diseases could not be
excluded. Indeed, Rowe et al (10) showed that in restricting
the analysis to individuals without diabetes or any degree
of hypertension, the decline was much less accentuated.
Perhaps more important for nephrologists is the fact that
some BLSA participants showed periods of 5 years or even
10 years without a significant decline of renal function. Although the number of these individuals was small, and few
were older than 70 years of age, they challenge the notion
that the decline of kidney function with age is unavoidable.
Another recent large, community-based study from Cana-
da with about 10,000 subjects above the age of 66 years,
investigated the same issue, and the major finding was that
the majority of elderly subjects have no or minimal progression of kidney disease over 2 years (11). An increased risk
of death, as opposed to dialysis, was also evident, with a
risk of death 6 or 60 times greater than the risk of dialysis in
subjects with a mean study estimated glomerular filtration
rate (eGFR) of 30-59 ml/min. Thus, among the vast majority
of older persons with chronic kidney disease (CKD), even
when this is quite advanced (i.e., eGFR 15-29 ml/min per
1.73 m2), death is a more common outcome than progression to end-stage renal disease (ESRD).
The results from the Cardiovascular Health Study also indicate little or no progression of CKD in the majority of older
adults; a deterioration in kidney function of 426.5 mmol/L
(0.3 mg/dL) was seen in less than 3% of subjects (mean
age 73 years) who were followed for at least 3 years (12).
These results are consistent with a prior study (13) based
on 28,000 health maintenance organization enrollees (mean
age 65) with a baseline eGFR of 90 ml/min per 1.73 m2 followed for 5 years, in whom death once again was far more
common than dialysis at all stages of kidney function.
All of above-mentioned studies underline the low rate of
progression of kidney dysfunction in the majority of community-dwelling elderly subjects without diabetes mellitus,
which is reassuring given the high prevalence of CKD in this
population (14). So, strategies aimed at slowing progression
of kidney disease should consider the underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older adults. However, the
higher rates of progression for subjects with mean study
eGFR of 30 ml/min per 1.73 m2 or less, both with and without diabetes mellitus, emphasize the importance of targeted
provision of care in patients with CKD. All CKD patients require aggressive cardiovascular risk reduction (15), but not
all elderly CKD patients require an emphasis on therapy to
delay progression of kidney disease. These high-risk patients can be identified by the presence of diabetes mellitus,
substantial proteinuria and a mean eGFR of 30 ml/min 1.73
m2 or less. It is these same patients who are likely to receive
the most benefit with referral to specialized and multidisciplinary care (11).
Factors affecting GFR with aging
Nowadays, patients 75 years and older currently represent
one of the fastest growing contingents of the ESRD population, most likely reflecting both population aging and the
high overall prevalence of CKD in the elderly (16). Thus,
a critical challenge for health systems and providers carS47
Aucella et al: Assessment of renal function in the elderly
Fig. 1 - Rate loss of renal function, glomerular filtration
rate as measured by creatinine clearance (CrCl), in healthy
subjects (group A), in patients with arterial hypertension
(group B) and in patients with proteinuria (group C) (data
from Lindeman et al (9)).
ing for older patients with CKD lies in identifying the relatively small proportion, but large absolute number, of older
patients with CKD who are at greatest risk for progressive
loss of renal function and ultimate need for dialysis. The
main factors affecting GFR with aging were investigated in
several studies (Tab. I).
Bleyer at el (12) published a retrospective study, the Cardiovascular Health Cohort, of more than 4,000 nondiabetic
subjects above the age of 65 years. They made an analysis
3 years apart with 2 measurements of serum creatinine, and
suggested that 3 very preventable or treatable conditions
– hypertension, smoking and vascular disease – which are
associated with large and small vessel disease, are highly
associated with clinically important changes in renal function in an older population. It is important and significant
that current smoking habits and elevated systolic blood
pressure, two conditions amenable to treatment, were significant predictors of renal functional decline in individuals
at least 65 years of age. These findings discourage the notion that years of hypertension and smoking have already
resulted in damage in this age group and that, therefore,
their continued presence in the older population is unlikely
to affect outcomes. The results of this study indicate that
cessation of smoking and reduction in systolic blood pressure in people over 65 could result in decreased risks of
renal insufficiency in this older group.
A large study from Japan (17) included 120,000 subjects,
and about 15% of them were older than 70 years – a quite
large part of the population, about 15,000 people. There
was an age-specific incidence of CKD stage 1 or 2 in the
elderly compared with those 40 years of age or younger,
but the difference was not dramatic – about 6% versus 3%.
Moreover, the usual suspects were identified as risk factors for progression: high blood pressure defined by any
variable, treated hypertension, diabetes and impaired glucose tolerance. Importantly, current smoking and obesity
also came out to be important confounders of age-related
changes in GFR (17). The Systolic Hypertension in the Elderly Program (SHEP) study (18) also showed that in the
elderly population with isolated systolic hypertension, systolic blood pressure was clearly a determinant of the progression of CKD.
TABLE I
FACTORS AFFECTING RENAL FUNCTION WITH AGING
Physiological
Pathological
• Low protein diet
• Vegetarian habit
•
•
•
•
•
•
•
•
•
S48
Atherosclerosis/glomerulosclerosis
Hypertension
Heart failure
Diabetes/glucose intolerance
Obesity
Smoking habit
Drugs
Inflammation markers
Hyperlipemia
JNEPHROL 2010; 23 (S15): S46-S54
More recently, the relationship between renal function
estimated by different equations and all-cause and cardiovascular mortality over a 6-year follow-up was investigated among participants in the Invecchiare in Chianti
(InCHIANTI) study (19), and a clear influence of renal function on risk of death was shown.
Finally, the Health, Aging, and Body Composition Study
(20), which included men and women older than 70 years,
has shown a correlation between inflammatory markers
known to be increased in patients with atherosclerosis
and cardiac disease, and thus markers of microinflammation in the cardiovascular system, and cystatin C, but
not with creatinine or eGFR. It may be argued that serum
cystatin C is a more sensitive marker than eGFR for detecting the association of inflammation with kidney disease, especially among persons without CKD.
Serum marker of renal function
GFR estimation based on serum creatinine alone is not
an ideal method, especially in elderly persons, because it
is influenced by a number of variables such as age, sex
of individual, muscle mass, diet and medications that
block creatinine’s tubular secretion. Moreover, this easyto-measure GFR marker has one important limitation, the
so-called creatinine blind area: when serum creatinine
increases above the normal range, GFR has already decreased by at least 40% in a younger person and even
more so in an elderly person (Fig. 2) (21). It is also to be
underlined that the rate of creatinine production is lower in
elderly people due to the age-related diminution of muscle mass and that the normal range of serum creatinine
for the general population may be inappropriately high for
senescent people. As a consequence, serum creatinine
in the upper normal range may already indicate severe
impairment of renal function in elderly people (22).
Cystatin C is a cysteine proteinase inhibitor that is produced
by nearly all human cells and released into the bloodstream,
from which it is freely filtered by the kidney glomerulus and
metabolized by the proximal tubule. Although the relative
contribution of factors other than GFR, to serum cystatin C
concentrations remains to be determined, the association of
serum cystatin C with GFR seems to be independent of age,
sex and muscle mass, in contrast to serum creatinine (23).
Whereas elevated serum creatinine levels detect only the
small subset of elderly individuals with the most impaired
kidney function who are at increased risk for cardiovascular
disease (CVD), cystatin C has a linear association with clinical CVD (15, 24). Studies have shown cystatin C to be an
accurate marker of subtle changes in GFR in elderly people
Fig. 2 - The blind area of creatinine as marker of glomerular
filtration rate.
and diagnostically superior to serum creatinine with a significantly better correlation with GFR (23, 25).
In CKD stages 2-3, the correlation between the gold standard Cr 51 ethylenediaminetetraacetic acid (51Cr-EDTA)
clearance and serum cystatin C was better than the correlation between 51Cr-EDTA clearance and serum creatinine,
and also than the reciprocal of serum creatinine (26). It has
been reported that cystatin C correlates better with 51CrEDTA clearance than creatinine clearance calculated from
the Cockcroft-Gault (CG) and Modification of Diet in Renal
Disease (MDRD) Study formulas. Another potential advantage of cystatin C is the improved precision of the assay
compared with that for creatinine, but it must be emphasized that its measurement is still much more expensive
than that of creatinine, which precludes its widespread and
repetitive use. Estimation of serum cystatin C is no longer
technically difficult: it should be used to minimize diagnostic errors in patients with mild to moderate impairment of
kidney function or in female patients. Finally, the results of
recent large prospective epidemiological studies indicated
that increased serum cystatin C levels, even in the range of
relatively normal kidney function, independently predict cardiovascular outcome in the elderly, and therefore may also
indicate unsuccessful aging (27).
Glomerular filtration rate assessment
Although measured GFR is considered the best overall
measurement of kidney function, it is often not practical
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Aucella et al: Assessment of renal function in the elderly
in clinical or epidemiological settings. Thus, there are few
studies of measured GFR in older adults, and they have
small sample sizes (28).
Creatinine clearance as measured from a 24-hour urine
collection can be used to measure GFR, but it is vital to
remember the high likelihood of inaccurate collection, especially in some elderly people with cognitive impairment
or who are bedridden. It is important therefore to check
for adequacy of urinary collection before interpretation of
clearance. Twenty-four-hour urine collection for the estimation of GFR has been shown by many studies to be not
any more reliable and frequently less reliable than serum
creatinine–based equations. Moreover, it may overestimate GFR because creatinine is also secreted, particularly with advanced renal insufficiency.
However, in individuals with variations in dietary intake
(e.g., vegetarian diet or creatine supplements) or muscle
mass (e.g., amputation, malnutrition or muscle wasting),
as is seen in many elderly persons, 24-hour urine collection may be a preferred method because many of these
factors are not specifically taken into account in prediction equations.
GFR assessment may also be performed by invasive methods. The most reliable method is the measurement of the
renal clearance of specific markers of GFR, for example
inulin, radioactive markers including 51Cr-EDTA or 99mTc diethylenetriamine pentaacetic acid (DTPA) or radio-contrast
agents including 125I-iothalamate, because these markers
are excreted only by glomerular filtration. However, they are
invasive, time-consuming, costly and cumbersome. Their
use is therefore mostly restricted to research purposes, but
they may be required in elderly people when an accurate
measurement of GFR is essential: for example, for the calculation of drug doses for chemotherapy (21).
Glomerular filtration rate estimation
GFR is usually estimated (eGFR) from serum levels of endogenous filtration markers, most commonly creatinine
and recently cystatin C; however, factors other than filtration, including generation, tubular secretion or reabsorption and extrarenal elimination affect these markers.
Thus current guidelines recommend that the 2 most commonly used equations to estimate GFR, which are both
serum creatinine–based – the Cockcroft-Gault (CG) or
Modification of Diet in Renal Disease (MDRD) Study equation – be used to estimate GFR in the clinical setting (29).
Essentially, compared with serum creatinine, these equations increase the accuracy of eGFR vis-a-vis measured
GFR by accounting for variables such as age and weight
S50
in the former equation, and age, sex and race in the latter
one. Their main limitation is the underestimation of GFR
in patients with normal and moderately reduced levels of
renal function. In fact, they have been reported to be less
accurate in patients without kidney disease, muscle wasting or inflammation, all conditions that might interfere with
the accuracy of creatinine or cystatin C–based estimating
equations in older people with frailty or comorbidities.
In elderly people, the CG formula may severely underestimate GFR, particularly in the oldest old (30). Moreover,
these 2 equations can yield disparate estimates of renal
function in a given individual. Inconsistency in the estimates provided by these 2 equations not only influences
population-based estimates of CKD prevalence, but also
has the potential to complicate patient management. Gill
et al clearly reported that elderly patients were assigned
to a different stage of CKD 60% of the time when the CG
equation was used instead of the MDRD equation. Overall,
these authors estimated that 20% fewer patients would
be qualified for a dose reduction of amantadine based on
MDRD eGFR versus CG estimates of CrCl (31). A similar
report was made by Carnevale et al comparing the Mayo
Clinic equation as well (32).
The MDRD formulas for GFR estimation were derived by
computer modeling from the 1,628 patients of the MDRD
Study population (33). There have been some validation
studies of the MDRD equation in the elderly concluding
that it is better than the CG equation (34-36).
However, there are also papers reporting a better performance for the CG formula (19). The InChianti study addressed the question of whether measured and estimated
CrCl in older individuals is a significant predictor of mortality. The 24-hour CrCl, CG and MDRD-derived equations (full
and simplified) were calculated at enrollment, and all-cause
mortality and cardiovascular mortality were prospectively
ascertained by Cox regression over a 6-year follow-up. In
a Cox model adjusted for demographics, physical activity,
comorbidities, proteinuria and inflammatory parameters,
participants with CrCl 60-90 ml/min per 1.73 m2 and CrCl
<60 ml/min per 1.73 m2 were, respectively, 1.70 and 1.91
times more likely to die over the follow-up, compared with
those with CrCl >90 ml/min 1.73 m2. Using the CG equation,
the group with values <60 ml/min per 1.73 m2 had a significantly higher all-cause mortality compared with those with
values >90 ml/min per 1.73 m2. The classification based on
the MDRD formulas did not provide any significant prognostic information. As suggested by the authors, CrCl and
CG eGFR may be better prognostic indicators than MDRDderived equations because they incorporate a stronger effect of age.
JNEPHROL 2010; 23 (S15): S46-S54
In any case, at this time, the majority of papers agree that
the MDRD Study equation shows better performance than
the CG equation (34-36). The most widely used form of the
MDRD Study equation in elderly people is the 4-variable
version or the version that was abbreviated from the original 6-variable version. This is especially advantageous for
elderly patients compared with the CG formula or CrCl
measurement, because it only requires serum creatinine,
age, sex and race, and not weight or any urine collections. Although the MDRD formula may be more precise
in elderly patients with CKD, it has not been shown to be
without bias in patients with GFR greater than 60 ml/min
per 1.73 m2.
A new cystatin and creatinine-based estimating equation
(37), developed in a pooled sample in which the mean age
was 52 years, reduces bias by 50% and offers small but
consistent improvements in precision and accuracy, compared with the most commonly used equation. In addition, accuracy of creatinine-based equations does not differ significantly from that of cystatin C–based equations
in populations studied thus far, but equations based on
the combination of the 2 markers might provide the best
accuracy (37, 38). Non-GFR determinants affecting each
marker, such as low muscle mass and possibly obesity,
might lead to systematic overestimation or underestimation of GFR in specific individuals.
Another Italian study compared the MDRD and Mayo
Clinic quadratic estimate of GFR (MCQ) estimates of GFR
with the measurement of CrCl in 24-hour urine collection
in 73 oldest old patients (32). The main finding was that
the tested equations for estimation of GFR and the measured 24-hour CrCl provide significantly different results,
so that they may not be used interchangeably in clinical
practice. It has also to be noted that differences in calibration of creatinine assays between laboratories can lead
to differences in GFR estimation and thus is an important
limitation of estimation equations in general.
Recently a new equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, to estimate
GFR in adults, from serum creatinine by using a large database pooled from 10 studies was developed (39). The
CKD-EPI equation was shown to be more accurate than
the widely used MDRD Study equation: it has lower bias,
especially at an eGFR greater than 60 ml/min per 1.73 m2;
however, its precision remains limited. The improved accuracy of the CKD-EPI equation overcomes some of the
limitations of the MDRD Study equation and has important
implications for public health and clinical practice. Improved accuracy of the CKD-EPI equation could have important implications for public health and clinical practice.
Nowadays the CKD-EPI equation might be considered the
new gold standard, and it could replace the MDRD Study
equation in general clinical use to estimate GFR.
Finally, a simple method to estimate CrCl at the bedside
that might allow caregivers to approximate renal function without formally replacing the standard formulas has
recently been proposed (40). The new formulas, eCCr,
are eCCr (male) = weight/creatinine; and eCCr (female)
= weight × 0.84/creatinine; both with weight in kg. eCCr
appears to give a good rough estimate of CrCl, easily
calculated at the bedside, which might alert clinicians to
the need to assess a change in drug dosing, or to more
formally estimate the patient’s level of renal function.
The MDRD Study formulas should, of course, be used
for CKD staging.
Clearly, improved measures of kidney function in older
patients are needed to better estimate the prevalence of
CKD (41).
Not one size for all ages
To address this objective and better define the overall
risk of the geriatric patient, Roderick et al (42) suggested
the division of CKD stage 3 into 2 substages: 3a (eGFR
45-59 ml/min per 1.73 m2) and 3b (eGFR 30-44 ml/min
per 1.73 m2). They found that in people 75 years and
older, an eGFR less than 45 ml/min per 1.73 m2 was an
independent predictor of poor survival, especially in the
first 2 years of follow-up, largely because of increased
cardiovascular mortality. The same finding was also noted in previous studies (43) which suggested not using
the same eGFR cutoff points in the elderly as for younger
age groups, and that the former group would probably
benefit from a finer categorization of the 30-59 ml/min
per 1.73 m2 eGFR groups (Fig. 3).
We should probably redefine the present CKD classification system in which everybody with an eGFR <60 ml/
min is defined as at-risk. In this setting, 2 main options
has been suggested: either introduce age- and sex-specific cutoff values or define only subjects with an eGFR
below 45 as always at-risk. The level of 45 should be
chosen because at that level metabolic derangements
arise in our patients. So it is not only the risk for cardiovascular end points and the risk for ESRD that we should
consider but also age and quality of life. At higher levels, over 45, we should pay more attention to additional
signs of chronic kidney damage such as microalbuminuria, macroalbuminuria, erythrocyturia or abnormalities on
an ultrasound.
The term preclinical has been used to describe conditions
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Aucella et al: Assessment of renal function in the elderly
Conclusions
Fig. 3 - Mortality rate by age and estimated glomerular filtration rate (eGFR, in ml/min per 1.73 m2) (data from O’Hare et
al (43)).
that predate the development of clinical disease and are
directly associated with adverse health consequences.
So, preclinical kidney disease clearly shows a direct
analogy to prehypertension and prediabetes. It has been
proposed to describe patients with a creatinine-based
eGFR >60 ml/min per 1.73 m2 and a cystatin C level >1.0
mg/L (equivalent to an eGFR of approximately 75 ml/min
per 1.73m2) as suffering from preclinical kidney disease.
On the basis of these criteria, 39% of the Cardiovascular
Health Study sample, in which the mean age is 75 years,
do not meet the GFR-based criteria for CKD, but have
preclinical kidney disease. The incidences of death and
CKD, defined on the basis of creatinine-based eGFR, is
higher among these patients than it is among patients
with eGFR >60 ml/min per 1.73 m2 and low cystatin C
(44). Not only did these participants have increased mortality and cardiovascular risk compared with those with
cystatin C levels less than 1.0 mg/L, but they were also
at substantially increased risk for progression to CKD after 4 years of follow-up. Furthermore, participants with
elevated cystatin C concentrations who progressed to
subsequent CKD had statistically significantly increased
mortality and cardiovascular risk compared with participants with elevated cystatin C levels who did not progress to CKD. Taken together, these findings suggest that
elevated cystatin C concentrations capture a state of
preclinical kidney disease that is highly prevalent among
community-dwelling elderly persons.
S52
First of all, it needs to be underlined that the so-called ageassociated loss of GFR critically depends on comorbid conditions such as hypertension and diabetes. Evidence from
the Cardiovascular Health Study (44) strongly suggests that
unlike standard cardiovascular risk factors, which become
less predictive in older adults, markers of kidney function are
strong risk factors for a wide range of adverse outcomes. So,
it needs to be recognized that a decreased kidney function in
the elderly, either clinical or preclinical, is not benign (45).
Because the measurement of serum creatinine is notoriously unreliable as an indicator of GFR in elderly patients,
more reliable GFR estimates should be employed whenever
indicated: for example, timed creatinine clearance, estimated GFR using a serum creatinine–based formula or serum
cystatin C. Except in situations such as drug dosage adjustment and in some cases of offering transplant options, in
practical terms, the change in GFR is more important than
the absolute cutoff value. Although novel methods such as
cystatin C–based measures are being explored, GFR estimation is still largely creatinine-based.
It needs to emphasized that reporting eGFR, although having
limitations, is especially useful in the elderly whose serum creatinine so poorly reflects GFR. Recognizing CKD in the elderly
should benefit them even if ESRD is unlikely, because it should
improve drug dosing and reduce nephrotoxin exposure.
The MDRD Study equation identified large numbers of patients who met Kidney Disease Outcomes Quality Initiative
(KDOQI) criteria for moderate CKD. Most of these patients
were elderly, and many had “very” moderate reductions in
eGFR that were not associated with an increased relative or
absolute risk for death. The main limitation of current GFR
estimates is the greater inaccuracy in populations without
known CKD than in those with the disease. Nonetheless,
current GFR estimates facilitate detection, evaluation and
management of the disease, and they should result in improved patient care and better clinical outcomes.
Financial support: The present study did not receive any financial
support.
Conflict of interest statement: None declared.
Address for correspondence:
Filippo Aucella, MD
Chief of the Nephrology and Dialysis Unit
IRCCS “Casa Sollievo della Sofferenza” Hospital
Viale Cappuccini
IT-71013, San Giovanni Rotondo (FG), Italy
f.aucella@operapadrepio.it
JNEPHROL 2010; 23 (S15): S46-S54
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