Dietary salt restriction and drug-free treatment of hypertension in ESRD patients: a largely abandoned therapy

‘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 1 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 2. 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 mg/l 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. The first mention of the ability to control hypertension in haemodialysis patients without the use of drugs was in 1961 3. 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 side effects and was relatively ineffective 3. 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 4. 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 5. 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 6. 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 7. However, in the following three decades, the use of a salt‐restricted diet has largely been abandoned. Only three research groups 8–10 have reported remarkable blood pressure control in over 95% of their patients for prolonged periods of time without the use of anti‐hypertensive drugs. The most quoted has been the group of Laurent from Tassin 8 and, although they prescribe salt restriction (5. 0 g/day) and use a dialysate sodium of 138 mmol/l, 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 11 decided to evaluate the role of a salt restriction of 5–6 g/day (no added salt in cooking and avoidance of all foods that taste salty) combined with a sodium dialysate of 135 mmol/l, (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 g/day salt intake, drug therapy was required, although it was reduced, and intolerance of a sodium dialysate of 135 mmol/l 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 g/day) 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 12, 13. 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 mmol/l or even higher concentrations 14, 15. 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. 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 16. 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 17. Alternatively, sodium overload could lead to a reversal of the inhibition of Na+/K+‐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 18. 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 19. 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 20. 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 well‐dialysed 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 21. The blood pressure of patient, ML, a male aged 23, suffering from chronic renal failure was reduced from 230/145 to 135/90 mmHg in 8 weeks with symptomatic improvement of headache, nausea and vomiting, remarkable improvement in eye‐sight and with reduction of macula papilloedema. Modified from reference 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 5. Correspondence and offprint requests to: Dr Stanley Shaldon, MA, MD, FRCP, 25 Le Michelangelo, 7 Avenue des Papalins, Monaco 98000. Email: stanleyₛhaldon@monaco377. com