Nephrol Dial Transplant (2002) 17: Editorial Comments
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Nephrol Dial Transplant (2002) 17: 1163–1165
Dietary salt restriction and drug-free treatment of hypertension
in ESRD patients: a largely abandoned therapy
Stanley Shaldon
Le Michelangelo, Avenue des Papalins, Monaco
‘Be not the first by whom the new are tried, nor yet
the last to lay the old aside’ Alexander Pope,
‘Essay on Criticisms’ 1711
Historical reviews have a tendency to be dinosaurian
and consequently, if read at all, have little impact upon
therapeutic paradigms. However, the neglect of old
knowledge may lead to therapeutic tragedies, and
I believe that throughout the world today dialysis
patients are being incorrectly managed with respect to
dietary salt intake and the concentration of dialysate
sodium to control hypertension. The word ‘salt’ is used
in this article to mean sodium chloride. However,
a ‘salt-restricted intake’ and a ‘dialysate sodium concentration’ refer to all sodium salts, including sodium
bicarbonate.
The problem of poor control of hypertension in
dialysis patients with the associated increase in
mortality from cardiovascular causes has been recognized in the US by the National Kidney Foundation.
It created a task force to investigate these ‘epidemic’
causes of death. It recommended 11 clinical studies
to evaluate and control the epidemic, and yet it
rejected the proposal by Scribner w1x of an evaluation
of ‘the drug-free salt restriction ultrafiltration method
of blood pressure control’.
Historically, the first reported benefit of a reduced
dietary salt intake in controlling hypertension in
patients with chronic renal failure was published in
1944 by Kempner w2x. Its success was undoubtedly
due to the paternalism of Kempner in persuading
patients to stick to a rice diet with added fruit that
contained only 250–300 mg salt, 350 g rice and 20 g
protein. Drinking water was to be distilled if it contained more than 20 mgul sodium. With this draconian
diet, he was able to control patient blood pressures
dramatically (Figure 1).
The question as to whether the history of the world
would have been different if President Roosevelt, dying
from uncontrollable malignant hypertension, had
been treated with a low-salt diet whilst attending the
Yalta conference in February 1945 will always remain
speculative.
Correspondence and offprint requests to: Dr Stanley Shaldon, MA,
MD, FRCP, 25 Le Michelangelo, 7 Avenue des Papalins, Monaco
98000. Email: [email protected]
#
Fig. 1. The blood pressure of patient ML, a male aged 23, suffering from chronic renal failure was reduced from 230u145 to
135u90 mmHg in 8 weeks with symptomatic improvement of
headache, nausea and vomiting, remarkable improvement in eyesight and with reduction of macula papilloedema. Modified from
reference w2x.
The first mention of the ability to control hypertension in haemodialysis patients without the use of
drugs was in 1961 w3x. The first four patients treated by
long-term dialysis in Seattle were hypertensive, and
their hypertension was well controlled by a low sodium
diet and ultrafiltration alone. Drug therapy had been
stopped in three patients as it was producing too many
2002 European Renal Association–European Dialysis and Transplant Association
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Nephrol Dial Transplant (2002) 17: Editorial Comments
Fig. 2. Blood pressure, body weight and exchangeable sodium volume during 6 months of haemodialysis with a salt restricted diet.
Arrow indicates the lag phenomenon. Modified from reference w5x.
side effects and was relatively ineffective w3x. Two years
later, we reported our initial success with a low-salt
diet and adequate ultrafiltration in a 32-year-old
patient whose eye-sight was restored when the severe
drug-resistant malignant hypertension was relieved
by haemodialysis, ultrafiltration and a reduced salt
intake w4x. We subsequently reported our results in
eight hypertensive patients with ESRD. We measured
exchangeable sodium and total body water during
the initial months of dialysis treatment whilst the
patients were maintained on a daily intake of 5 g of
salt without any hypertensive drug therapy w5x. An
initial dramatic improvement in blood pressure control was seen during the first month with progressive ultrafiltration and a 10% reduction in dry body
weight (Figure 2). In addition, there was a significant
reduction in exchangeable sodium.
This component of hypertension in the ESRD
patient which responds to ultrafiltration has been
called volume-sensitive hypertension w6x. However, the
most interesting finding was a lag response of
several months between the lowest level of exchangeable sodium and the ultimate lowest maintenance
blood pressure. This suggested that an adaptive
phenomenon to the reduction in total body sodium
was occurring at a later time interval, and was not the
direct effect of volume control. A more recent
publication has confirmed the observation of the lag
phenomenon but still believes that it is a consequence
of strict extracellular volume control w7x.
However, in the following three decades, the use of
a salt-restricted diet has largely been abandoned. Only
three research groups w8–10x have reported remarkable
blood pressure control in over 95% of their patients
for prolonged periods of time without the use of antihypertensive drugs. The most quoted has been the
group of Laurent from Tassin w8x and, although they
prescribe salt restriction (5.0 guday) and use a dialysate
sodium of 138 mmolul, there has been a tendency to
attribute the excellent long-term survival to long
dialysis durations, without stressing the importance
of salt restriction, until recently. Indeed, salt restriction
was not emphasized in any publications from Tassin
between 1983 and 1998.
The lengthening of dialysis time implies a considerable increase in cost for in-centre dialysis and is
therefore largely impractical for the majority of
patients. Hence, my colleagues and I w11x decided to
evaluate the role of a salt restriction of 5–6 guday
(no added salt in cooking and avoidance of all foods
that taste salty) combined with a sodium dialysate of
135 mmolul, (following patient compliance; with substantial reduction in post-dialysis thirst), without any
increase in dialysis time (4–5 h), in a group of selected
hypertensive patients who had been treated with
haemodialysis for between 1 and 18 years. The results
of this pilot study were limited. In four out of the seven
patients, all hypertensive therapy could be stopped and
their mean arterial pressure was reduced to less than
100 mmHg. In the remaining three patients, who were
clearly unable to comply with a 5–6 guday salt intake,
drug therapy was required, although it was reduced,
and intolerance of a sodium dialysate of 135 mmolul
was observed. Nevertheless, these results suggested
that in compliant patients, a mean arterial pressure of
less than 100 mmHg could be obtained and maintained
by a simple reduction in salt intake, without any drug
therapy or reduction in dry body weight. In addition,
interdialytic weight gain was reduced to less than
2.0 kg and dialysis tolerance was improved with
reduction in post-dialysis fatigue.
It may be useful at this stage to emphasize that the
only reliable method of judging patient compliance
with a low-salt (5 guday) diet is to accurately measure
the interdialytic weight gain. In an anuric 70 kg patient
this should average 1.5 kg. If the patient is compliant
with the salt restriction it is not necessary to stress a
restricted fluid intake because the patient drinks less
as their thirst is reduced, and the interdialytic weight
gain is reduced significantly w12,13x. The success of
dietary instruction is dependent upon an increase in
the ability to taste salt which tends to be reduced
in patients dialysed with a dialysate sodium concentration of 140 mmolul or even higher concentrations
w14,15x. Lowering the dialysate sodium prior to confirming patient compliance by a reduction in the
interdialytic weight gain can prove dangerous and
can lead to severe symptoms on dialysis.
Nephrol Dial Transplant (2002) 17: Editorial Comments
The mechanism underlying this phenomenon is only
partially understood. It is associated with a reduction
in peripheral vascular resistance, without a decrease
in cardiac output w16x. Current thinking suggests
that the mechanism may be a reduction in plasma
1-asymmetric dimethyl arginine (ADMA), a known
inhibitor of nitric oxide synthetase, which is usually
retained in ESRD patients and would be removed by
dialysis w17x. Alternatively, sodium overload could lead
to a reversal of the inhibition of NaquKq-ATPase via
an endogenous digitalis-like substance, the result of
which would be an increase in the intracellular sodium
and calcium concentrations, with an increase in the
tone of vascular smooth muscle cells. Reducing the
sodium load could reverse this mechanism w18x. A
recent observation in salt-sensitive hypertension without renal involvement has shown that salt-loading
increased plasma ADMA levels and reduced plasma
nitric oxide concentrations w19x. In contrast, salt restriction reversed this effect and produced a reduction in
blood pressure with a lowering of peripheral resistance
consistent with increased release of nitric oxide.
Perhaps, it might be useful to consider the majority
of ESRD patients as suffering from salt-sensitive
hypertension w20x.
Whatever the rational explanation for the empirical
benefit of salt restriction in the hypertensive dialysis
patient proves to be, the clinical benefit is undeniable
and associated with the best survival data in the world.
It can be achieved with virtually no added cost and
does not necessarily impose a boring and unpalatable
diet upon the patient. Indeed, it is worth remembering
that in Tuscany, where regional Italian cuisine arguably reaches its pinnacle, the regular bread sold in the
bakeries is salt-free. Perhaps the time has come to cast
aside Neptune’s poisoned chalice and give the welldialysed patient a longer and healthier life with fewer
complications with no added expense.
The tragedy lies in the abandonment of this method
of treating hypertension in ESRD patients. Indeed,
in a recent review of the strategies and feasibilty of
hypertension control in ESRD patients, salt restriction
was not even mentioned w21x.
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