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443
Brief Reviews
Lipids and the Kidney
Bertram L. Kasiske, Michael P. O'Donnell, William Cowardin, and William F. Keane
E
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pidemiological studies have shown that hypertension and hypercholesterolemia are both
risk factors for the development of cardiovascular disease.1-5 Although most investigations
have focused on the independent nature of the risks
resulting from hypertension and hypercholesterolemia, the data have also indicated a possible synergism in the combined influences of these and other
risk factors on vascular disease.6 In addition, several
studies have found a more frequent than expected
occurrence of hypertension and hypercholesterolemia in the same individuals.7-9 It is unlikely that this
association is the result of hypertension causing
abnormalities in lipid metabolism. On the other hand,
lipid abnormalities could participate in the pathogenesis of hypertension in a number of ways. The elevated
systemic vascular resistance resulting from advanced
atherosclerotic vascular disease, for example, may
contribute to the development of hypertension in the
elderly. However, recent experimental data have also
suggested that lipid abnormalities associated with
hypercholesterolemia may be involved in the pathogenesis of essential hypertension through mechanisms
not dependent on the presence of overt vascular
disease.10-13 This intriguing possibility casts a new light
on what is already known about the synergistic effects
of hypercholesterolemia and elevated blood pressure
on atherosclerosis.
The kidney may be an important link in our
understanding of the interactions between abnormalities in lipid metabolism, blood pressure, and vascular disease (Figure 1). There is now abundant evidence demonstrating that the kidney is a major target
organ for both hypertension and lipid-induced injury.
In addition, the kidney may have an important role in
the pathogenesis of essential hypertension, and it is
possible that lipid-induced renal alterations could
contribute to the development and maintenance of
elevated blood pressure. Although it is well known
that advanced renal vascular disease may cause
hypertension, it is also possible that earlier, more
From the Department of Medicine, Hennepin County Medical
Center, University of Minnesota, Minneapolis, Minnesota.
Supported by United States Public Health Service grants RO1
AM37396, R23 AM37112, and KO8 DK01628. M.P.O. is the
recipient of a New Investigator Award. B.L.K. is the recipient of a
Clinical Investigator Award from the National Institutes of Health.
Address for correspondence: Bertram L. Kasiske, MD, Department of Medicine, Hennepin County Medical Center, 701 Park
Avenue, Minneapolis, MN 55415.
subtle, lipid-induced alterations could influence renal
resistance, sodium chloride handling, or the release of
vasoactive mediators from the kidney. These early
lipid-associated alterations could be important in the
pathogenesis of essential hypertension. Moreover,
recent evidence has suggested that the kidney may
play a role in lipoprotein metabolism. Thus, sufficient
renal damage caused by hypertension and abnormalities in lipid metabolism could result in additional
deleterious effects on circulating lipoproteins.
A clue to the potential importance of the kidney in
the complex interrelation between cholesterol, blood
pressure, and vascular disease is to be found in
several recent epidemiological studies. In these
investigations, the presence of urinary protein excretion, even in amounts not detectable by the usual
clinical methods, was found to be an important
predictor of cardiovascular disease mortality.14-16
Moreover, in at least one study, the relation between
proteinuria and vascular disease was found to be
statistically independent of hypertension and
hypercholesterolemia.16 Several different mechanisms could explain the. independent association
between urinary protein excretion and cardiovascular
disease. Indeed, the kidney could be both a target
organ for, and a cause of, increased blood pressure
and lipid abnormalities. Regardless of the underlying
mechanisms, the relative strength of the association
between proteinuria and vascular disease indicates
the potential importance of the kidney in the pathogenesis or consequences, or both, of hypercholesterolemia and hypertension.
Histological studies have also pointed to a strong
relation between systemic atherosclerosis and renal
damage. When two groups of otherwise normal individuals with different degrees of systemic atherosclerosis were compared (patients with renal artery stenosis were excluded), the group with more severe
atherosclerosis was found to have a higher incidence
of nephron obsolescence and intrarenal vascular
disease.17 Although it is possible that the glomerular
sclerosis and nephron destruction were caused by the
intrarenal vascular disease, it is also possible that the
same factors causing systemic atherosclerosis (e.g.,
hypertension and hyperlipidemia) resulted in the
greater degree of nephron destruction. In addition,
differences in the amount of renal damage may have
caused differences in the incidence and severity of
systemic hypertension that, in turn, could also help
444
Hypertension
Vol 15, No 5, May 1990
^Systemic Atherosclerosisj-
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FIGURE 1. Schematic diagram showing possible relations
between hyp'ercholesterolemia, hypertension, vascular disease,
and renal injury. Lipid abnormalities associated with hypercholesterolemia may contribute to both atherosclerosis and
renal damage. Decreased renal function may lead to lipid
abnormalities directly, or indirectly through the effects of
proteinuria. Lipid abnormalities and renal injury may also be
involved in the pathogenesis of hypertension. Elevated blood
pressure may, in turn, cause further renal damage and atherosclerosis. PVR, peripheral vascular resistance; RVR, renal
vascular resistance.
explain the observed association between renal damage and systemic atherosclerosis.
Effects of Hypertension on the Kidney
It has long been appreciated that hypertension
causes renal injury. Early histological investigations
emphasized the deleterious effects of elevated systemic blood pressure on small intrarenal arteries and
arterioles.18'19 In contrast, larger, interlobar arteries
appeared to be affected by age-related, atherosclerotic vascular disease that was not solely the result of
hypertension.18 In these early investigations, it was
noted that the number of histologically intact nephrons appeared to be diminished in kidneys with
vascular disease.1820 This loss of functioning nephrons to glomerulosclerosis was generally attributed to
ischemia caused by vascular occlusion.20-21 More
recent studies have challenged the notion that glomerular obsolescence is entirely the result of occlusive intrarenal vascular changes and have suggested,
as an alternative explanation, that there may be other
factors common to the pathogenesis of both.17
Recent investigations have also attempted to more
precisely define the pathogenesis of hypertensioninduced renal injury. The capillaries within the renal
glomerulus are unique because they have both preglomerular and postglomerular arterioles. Increases
in preglomerular resistance tend to decrease intraglomerular pressure and the rate of glomerular filtration. Conversely, unopposed increases in postglomerular resistance raise glomerular capillary
pressure and the filtration rate. A number of micropuncture experiments have been carried out in animal models of hypertension, and these experiments
have demonstrated that the amount of nephron
damage is largely dependent on the extent to which
systemic arterial pressure is transmitted to glomerular capillaries.2223 Thus, in hypertensive rats with
high preglomerular vascular resistance and normal
intraglomerular pressures, little glomerular injury
occurred.22-24 However, in hypertensive rats with
lower preglomerular resistance and high glomerular
capillary pressure, a large amount of glomerular
sclerosis resulted.22-23-25 Moreover, in the rat twokidney, one clip model of hypertension, elevated
systemic pressure is transmitted to the glomeruli of
the undipped, but not the clipped kidney.26 As a
result, hypertensive renal injury is confined to the
undipped kidney.23
It should also be recognized that the effects of
systemic blood pressure and glomerular capillary
pressure can be dissociated, and the importance of
intraglomerular pressure in the pathogenesis of renal
injury may explain why similar pharmacological
reductions in systemic blood pressure may not yield
equivalent decreases in renal damage. Indeed, it has
been found that treatment of hypertensive rats with
converting enzyme inhibitors, which reduce both
systemic and intraglomerular pressure, ameliorates
the amount of renal injury.27 However, an equivalent
reduction in blood pressure using pharmacological
agents that lowered systemic pressure without reducing intraglomerular pressure left a substantially
greater amount of renal injury.27
Despite the recent advances in our understanding
of the pathogenesis of renal injury in experimental
models of hypertension, a number of questions
remain unanswered. Because micropuncture experiments cannot be carried out in humans, the importance of intraglomerular pressure in the pathogenesis
of hypertensive renal injury is still a matter of speculation. Short-term studies in diabetic patients with
nephropathy have suggested that converting enzyme
inhibitors may reduce urine protein excretion and
retard the progression of renal disease.2829 However,
carefully controlled trials comparing converting
enzyme inhibitors with other antihypertensive agents
have not been carried out, and the long-term effects
of these agents on renal injury are unknown.
The mechanism whereby increased glomerular
pressure may cause renal injury is also unknown. It is
possible that increased glomerular capillary pressure
may damage endothelial cells directly. Alternatively,
an increased flux of plasma proteins across basement
membranes subjected to elevated glomerular pressure could result in cell injury through direct or
indirect mechanisms. In this regard, it is important to
note that, in animal models of hypertension, renal
damage was often accompanied by both proteinuria
and plasma lipid abnormalities. In the two-kidney
Goldblatt model, in the remnant kidney model, and in
the Dahl salt-sensitive rat, the development of proteinuria is accompanied by increasing plasma lipid levels
(see below).30-31 It is important, therefore, to examine
the possible independent, additive, or synergistic effects
of abnormal lipid metabolism on the renal injury associated with hypertension and proteinuria.
Kasiske et al Lipids and the Kidney
Effects of Hypercholesterolemia on the Kidney
Many patients with renal disease who have a
pronounced reduction in functional renal mass
recover enough function through compensatory
mechanisms to survive a number of years. However, a
slow, progressive deterioration in renal function that
eventuates in end-stage renal failure frequently
develops in these patients.32"34 A number of mechanisms have been proposed to explain this chronic,
progressive renal destruction.35-37 Because patients
with renal disease almost invariably have alterations
in lipid metabolism, it is important to determine
whether lipid abnormalities could participate in the
pathogenesis of chronic renal injury.
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Recent experimental data have suggested that
lipid abnormalities may indeed influence the development and progression of renal injury. Studies
carried out in several animal models of endogenous
hyperlipidemia demonstrated that the pharmacological reduction of serum lipid levels was associated
with a reduction in the amount of glomerular injury.
Rats subjected to a surgical reduction in the number
of functioning nephrons, the so-called remnant kidney model of chronic renal failure, developed proteinuria, hypercholesterolemia, systemic hypertension, and progressive renal injury.27-30'38 When
remnant kidney rats were treated with either of two
structurally unrelated antilipemic agents (clofibric
acid and lovastatin), serum cholesterol was reduced
and the amount of renal injury diminished.39 Moreover, micropuncture experiments demonstrated that
the reduction in renal injury resulting from the
antilipemic agents could not be explained by reduced
glomerular pressures.39 Similar investigations were
carried out in the obese Zucker rat, which is a model
of hyperlipidemia, type II diabetes, and progressive
renal injury.40 Treatment of obese Zucker rats with
clofibric acid or lovastatin effectively reduced serum
lipids and ameliorated the proteinuria and renal
injury.41 Thus, these investigations indicated that
endogenous hyperlipidemia may be important in the
development and progression of chronic, progressive
renal injury.
Other animal models of endogenous hyperlipidemia have also been shown to develop progressive
renal injury.4243 An interesting exception is the
Watanabe heritable hyperlipidemic rabbit. The
Watanabe rabbit lacks the normal number of low
density lipoprotein receptors, and as a result, develops pronounced hyperlipidemia. Renal injury was
not found in this model.44 Understanding the unique
resistance of the Watanabe rabbit to progressive
renal damage may ultimately help unravel the pathogenesis of lipid-induced renal injury.
In a number of experimental investigations, dietinduced hypercholesterolemia has also been shown
to cause renal injury. Rats, rabbits, and guinea pigs
fed diets containing cholesterol or increased amounts
of saturated fat, or both, developed hypercholesterolemia.45-49 The lipid abnormalities in these experi-
445
ments were accompanied by proteinuria and progressive renal injury. Although blood pressure was not
systematically evaluated in these studies, others have
shown that high fat, high cholesterol diets may
increase systemic blood pressure.12-50'51
The possible mechanisms whereby lipid abnormalities cause renal injury have recently been reviewed
in detail.52-53 Many of these mechanisms may be
analogous to those believed important in the pathogenesis of atherosclerosis. Investigations have shown
that renal injury in models of hyperlipidemia is
accompanied by glomerular lipid deposition and the
appearance of foam cells.41-45'47-49-54 In addition, lipid
analysis has indicated that cholesterol-induced injury
is associated with increased amounts of cholesterol
and cholesteryl esters in renal tissue.45-49-55 Pronounced changes in renal fatty acids, similar to the
relative essential fatty acid deficiency profile associated with the development of atherosclerosis, have
also been described in models of lipid-induced renal
injury.55 These fatty acid changes could lead to
alterations in the renal production of vasoactive and
inflammatory mediators that could be important in
the pathogenesis of injury. Finally, investigations
have also shown that renal lipid deposition is accompanied by the infiltration of the kidney with monocytes and macrophages.45-56 Research into the pathogenesis of atherosclerosis has demonstrated the
pivotal role that macrophages play in this process,
and similar mechanisms could be important in lipidinduced renal injury.
There are also clinical data pointing to an association between abnormalities in lipid metabolism and
renal injury. Indeed, renal lipid deposition has long
been known to accompany glomerular injury in a
number of different kidney diseases.57-60 Glomerular
and interstitial foam cells have also been found in
patients with renal disease.61-62 Moreover, the spontaneous development of renal disease has been
reported in patients with uncommon forms of
dyslipoproteinemias.62-65 On the other hand, the
prevalence of renal abnormalities in patients with the
more common types of hyperlipidemias, although
unknown, is probably not very high. Overt renal
disease does not develop in most patients with hypercholesterolemia, which suggests that other predisposing factors (e.g., immune-mediated glomerular injury
or glomerular hypertension) may have to be present
for significant renal damage to occur.
Possible Interactive Effects of Lipid Abnormalities
and Glomerular Hypertension on Renal Injury
The experimental evidence suggests that both
increased intraglomerular pressures and hyperlipidemia may independently cause renal injury. However, these two risk factors are often seen together.
Thus, it is important to determine how abnormalities
in lipid metabolism could interact with alterations in
glomerular pressures to cause renal injury. Although
experiments have shown that lipid abnormalities can
cause renal injury in the absence of alterations in
446
Hypertension
TABLE 1.
Vol 15, No 5, May 1990
Effects of Cholesterol Feeding on Rats With Two-Kidney, One Clip Hypertension
Weeks of age
Variable and experimental group
14 weeks
20 weeks
26 weeks
Body weight (g)
Hypertension
Hypertension and cholesterol
397 ±29
475 ±50
352±52*
445±61
516±69
485 ±76
161 + 15
166±14
190±35
183±27
198±30
192±30
51±8
230±102*
68 ±39
280±130*
340±131*
76±16
68±13
94±52
80±16
101±45
78±13
3±4
26 ±22*
37±59
68±34*
58 ±70
107±65*
Blood pressure
Hypertension
Hypertension and cholesterol
Serum cholesterol (mg/dl)
Hypertension
Hypertension and cholesterol
Serum triglycerides (mg/dl)
Hypertension
Hypertension and cholesterol
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Urine albumin (mg/24 hr)
Hypertension
Hypertension and cholesterol
87+38
Values are mean±SD.
*p<0.05 compared with hypertension group (urine albumins were analyzed after logarithmic normalization).
intraglomerular pressure, it is also possible that
pronounced changes in serum lipids can cause
increased glomerular pressure. To investigate this
possibility, micropuncture experiments were carried
out in Sprague-Dawley rats fed a high cholesterol
diet. Rats were studied at a time when there was
proteinuria and mild expansion of the glomerular
mesangium but before there was evidence of glomerular sclerosis. Preliminary results have shown a pronounced increase in serum cholesterol levels after 4
weeks of diet.66 Glomerular filtration and plasma
flow rates were not significantly affected by the diet.
However, glomerular capillary pressure was increased by 10-20% in rats fed the high cholesterol
diet compared with control rats fed standard chow.66
Thus, although lipid abnormalities may cause renal
injury without elevating glomerular pressure, pronounced hypercholesterolemia may cause glomerular
hypertension that could exaggerate the amount of
injury.
The reason for the increase in glomerular capillary
pressure associated with hypercholesterolemia is
unclear. The glomerular hemodynamic changes
could have been the result of the altered plasma
viscosity or decreased red blood cell deformability
that is known to occur in hyperlipidemia.67-68 It is
interesting, however, that whole kidney vascular
resistance after cholesterol feeding was found to be
increased in isolated kidneys perfused without red
blood cells or plasma lipoproteins.69 This latter
observation suggested the possibility that factors in
addition to altered blood rheology could have played
a role in the glomerular hemodynamic changes. In
this regard, it is possible that the increased number of
mesangial cells or glomerular macrophages that are
associated with cholesterol feeding could release
vasoactive mediators and contribute to increased
glomerular capillary pressures.
Additional experiments have been carried out to
determine the extent to which alterations in glomerular pressure and serum lipids could act additively, or
synergistically, to accelerate renal injury. The twokidney Goldblatt model of systemic hypertension
offers a unique opportunity to examine the possible
interactive effects of alterations in intraglomerular
pressure and lipid abnormalities on renal injury. By
placing a single clip on the left renal artery of normal
rats, a pronounced elevation in systemic blood pressure occurs. Compensatory vasodilation exposes the
glomeruli in the undipped kidney to pressures that
are much higher than normal.26 In contrast, intraglomerular pressure in the clipped kidney is actually
lower than normal.26 By comparing the renal histology in clipped and undipped kidneys from the same
rats, the glomerular hemodynamic modulation of
cholesterol-induced renal injury can be examined.
Normal, 6-week-old male Sprague-Dawley rats
were fed standard chow (n=16) or standard chow
supplemented with 4% cholesterol and 2% sodium
cholate («=13). After 4 weeks of diet (i.e., at 10
weeks of age) a single clip was placed on the right
renal artery of all rats. Systolic blood pressures were
elevated in both diet groups and serum cholesterol
levels were markedly increased in the cholesterol-fed
rats (Table 1). In contrast, serum triglycerides were
not significantly different between the two groups
(Table 1). Compared with normal Sprague-Dawley
rats (data not shown), albumin excretion was
increased in both diet groups (Table 1). Moreover,
the cholesterol-fed rats had a significantly higher
urine albumin excretion rate (Table 1).
The glomerular areas of undipped kidneys, determined by planar morphometry, were greater in
Kasiske et al
g
30.0
(18)
• S t a n d a r d Diet
ESJHigh Cholesterol
(13)
u
10
5
20.0
i
10.0
(8)
(13) (1«)
<fl
f^j
Clipped
Kidneys
Normal
Kidneys
I
Undipped
Kidneys
FIGURE 2. Bar graph showing relation between reduced,
normal, or elevated perfusion pressure and glomerulosclerosis
in rats fed a standard diet (open bars) or high cholesterol
(hatched bars). Clipped kidneys of Goldblatt hypertensive rats
with low renal perfusion pressure are compared with kidneys
from rats with normal renal perfusion pressure56 and
undipped kidneys that have glomeruli exposed to systemic
hypertension.
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cholesterol-fed rats (ll,200± 1,700 /xm2) compared
with standard chow rats (8,440±898 ju,m2, p<0.01).
The glomeruli in the clipped kidneys were smaller
compared with undipped kidneys, but the glomeruli
in the clipped kidneys were larger in cholesterol-fed
rats (8,500±l,300 jam2) compared with those of
standard chow controls (6,400±440 jam2, p<0.Ql).
There was no glomerulosclerosis in clipped kidneys
from rats fed standard chow. However, in the clipped
kidneys from rats fed high cholesterol, 0.4±0.5% had
glomerulosclerosis (p<0.05 compared with those of
standard chow rats). In the undipped kidneys, where
glomerular pressures have been reported to be
elevated,26 the percent of glomeruli with sclerosis was
19±19% in the standard chow group versus 32±20%
in the cholesterol-fed group (/?<0.05).
It is interesting that the amount of glomerular
injury in the clipped kidneys of rats fed a high
cholesterol diet was less than that previously
observed in normotensive Sprague-Dawley rats fed
the same high cholesterol diet for the same length of
time (Figure 2). Although glomerular hemodynamic
measurements were not carried out in these experiments, others demonstrated that glomerular pressures were actually reduced in the clipped kidneys in
the rat, two-kidney Goldblatt model.26 Thus, these
data suggest that a reduction in normal glomerular
pressures may have resulted in a decrease in the
amount of cholesterol-induced glomerular injury. Of
course, other changes in the clipped kidneys could
have also caused the observed differences in injury. It
is also significant that the amount of glomerular
injury in the undipped kidneys was increased compared with clipped and normal kidneys in both
standard chow and cholesterol-fed rats (Figure 2).
Moreover, the injurious effects of combining the
glomerular hemodynamic changes (i.e., increased
pressure) in the undipped Goldblatt hypertensive rat
kidney with diet-induced hypercholesterolemia
appeared to be additive but not synergistic in this
model (Figure 2).
Lipids and the Kidney
447
It is also interesting that the amount of injury was
proportional to the size of remaining intact glomeruli, and that cholesterol was associated with an
increase in glomerular size in both clipped and
undipped kidneys. The effects of the clip and of the
cholesterol diet could reflect differences in glomerular hemodynamic function (i.e., increased pressure)
or could reflect differences in the compensatory
hypertrophic response to the different amounts of
glomerular injury in the experimental groups. The
latter could be particularly important, as it has
recently been suggested that the renal hypertrophic
response per se may be important in the pathogenesis
of renal injury.70-71
A similar investigation has been carried out by others
using a diet that produced a much milder degree of
hypercholesterolemia.49 Indeed, normal rats fed a high
cholesterol, high fat diet had serum total cholesterol
levels that were not significantly different from rats fed
a control, high carbohydrate diet.49 In that investigation, as in the present study, the greatest amount of
damage was seen in undipped kidneys of rats fed the
high cholesterol, high fat diet.49 Altogether these data
suggest that the relatively mild cholesterol-induced
injury seen in normal kidneys may become severe when
combined with other injurious factors such as increased
glomerular pressure.
Possible Impact of Renal Abnormalities on
Hypertension and Hypercholesterolemia
Experimental and clinical evidence suggest that
hypercholesterolemia and associated lipid abnormalities may be important in the pathogenesis of essential hypertension. It has been postulated that alterations associated with hypercholesterolemia could
increase smooth muscle cell contractility by altering
endothelial-dependent relaxing factors, changing
membrane cation transport, or affecting vascular
eicosanoid production.10-13'72-73 Alterations in
smooth muscle contractility could, in turn, affect
peripheral vascular resistance and systemic arterial
pressure. Because the kidney has a unique role in the
regulation of systemic blood pressure, it is also
possible that cholesterol-induced alterations in renal
function could be important in the pathogenesis of
essential hypertension.
It is known that severe renal vascular disease
caused by hypertension and hypercholesterolemia
can contribute to elevated systemic blood pressure.
However, the results of studies carried out using
isolated kidneys from rats fed a high cholesterol diet
for only 4 weeks, indicated that cholesterol may
induce changes in renal vascular resistance at a
time when the only histological change apparent is
a mild glomerular mesangial expansion.69 Renal
vascular resistance was significantly elevated in the
isolated, perfused kidneys from rats fed the high
cholesterol diet, and the filtration fraction was
reduced.69 These hemodynamic changes were similar to those reported in individuals with essential
hypertension.74-76 Because the kidneys in these
448
Hypertension
Vol 15, No 5, May 1990
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experiments were isolated from lipoproteins and
other possible systemic influences of the diet, the
cholesterol was the apparent cause of intrinsic renal
alterations that resulted in the increased resistance.
Histologically, only a small amount of mesangial
matrix expansion and increased mesangial cellularity
were seen after 4 weeks of cholesterol feeding (personal observations). There was no glomerulosclerosis
evident at this time, and no vascular abnormalities
were seen (personal observations). The mechanism
for these early alterations in renal resistance with
cholesterol feeding is unknown. However, other
investigations have shown that cholesterol feeding
may directly, or indirectly, alter smooth muscle cell
contractility.11'73 These data suggested that hypercholesterolemia may cause early alterations in renal
vascular resistance that could participate in the
pathogenesis of essential hypertension.
Although patients with untreated essential hypertension are more likely to have hypercholesterolemia,7-9 certainly not all hypercholesterolemic
patients have elevated blood pressure. Likewise,
changes in serum cholesterol in experimental models
of hyperlipidemia have not been uniformly associated
with alterations in systemic blood pressure.39-41 These
data raise the possibility that hypercholesterolemia
may not cause increased blood pressure per se but
may be a marker for other associated abnormalities
in lipoprotein or fatty acid metabolism. Alternatively,
lipoprotein abnormalities associated with hypercholesterolemia may combine with other factors to cause
increased blood pressure.
It is also possible that renal alterations resulting
from hypercholesterolemia and hypertension could
contribute to elevated plasma lipoprotein levels.
Although the mechanisms are still uncertain, it is well
known that patients with large amounts of urinary
protein excretion have pronounced hyperlipidemia.
Whether low levels of urinary protein excretion also
contribute to plasma lipid abnormalities is unknown.
To the extent that urinary protein excretion may
reflect abnormal renal lipoprotein metabolism, it is
possible that even low levels of proteinuria could
contribute to abnormalities in plasma lipids. Moreover, it has also been shown that declines in glomerular
filtration rate are associated with abnormalities in lipid
metabolism. Indeed, individuals with glomerular filtration rates less than 50-60 ml/min begin to manifest
abnormalities in circulating lipoproteins.7778 The effect
of this renal functional reduction on lipid metabolism
suggests that the normal, age-related decline in glomerularfiltrationrate could play a role in the propensity for
cholesterol levels to increase with age.79
In summary, a substantial body of evidence points
to the potentially important role of the kidney in the
complex relation between hypercholesterolemia,
hypertension, and mortality from vascular disease. It
is generally accepted that the kidney is a major target
organ for the deleterious effects of hypertension.
However, recent data suggest that lipid abnormalities
associated with hypercholesterolemia may also cause
renal damage. In addition, alterations in renal function resulting from hypercholesterolemia or hypertension may contribute to the maintenance of elevated blood pressure and abnormal lipid metabolism.
Taken all together, these data suggest that the treatment of both hypercholesterolemia and hypertension
may best preserve renal function. Moreover, cholesterol and blood pressure reduction strategies that best
preserve renal function may be the most effective in
reducing the incidence of cardiovascular disease.
Acknowledgment
We thank Jan Lovick for her assistance in preparing this manuscript.
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KEY WORDS
renal function
hypercholesterolemia
glomerulonephritis
essential hypertension
Lipids and the kidney.
B L Kasiske, M P O'Donnell, W Cowardin and W F Keane
Hypertension. 1990;15:443-450
doi: 10.1161/01.HYP.15.5.443
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