Opinion How Can Survival of the Well-Dialyzed Patient Be Increased? Stanley Shaldon Monaco Neptune’s Poisoned Chalice: A Tragedy of Modern Therapeutics The Oxford University Dictionary definition of opin- ion is as follows: “A judgement or belief based upon grounds short of proof.” The title of this opinion implies that an adequate dose of dialysis, whatever that may be according to the paradigm of the day, has been pre- scribed. Therefore I am not going to discuss any efforts to increase the dose or frequency of dialysis, however, topical they may be. I am devoting this opinion entirely to a method of curing hypertension in dialysis patients without the use of drugs. The first mention of the ability to control hypertension without the use of drugs was in 1961. The first four patients treated by long-term dialysis in Seattle were hy- pertensive. The hypertension was well controlled by a low sodium diet and ultrafiltration. Drug therapy had been stopped in three patients, as it was producing too many side effects and was relatively ineffective (1). Two years later we reported our initial success with a low salt diet and adequate ultrafiltration in a 32-year-old patient whose eyesight was restored when the severe drug- resistant malignant hypertension was relieved by ultra- filtration and reduced salt intake (2). We subsequently reported our results in a further nine patients in whom we measured exchangeable sodium and total body water during the initial months involved in treating their hy- pertension (3). The most interesting finding was a lag response of several months between the lowest level of exchangeable sodium and the lowest maintenance blood pressure ultimately achieved. This suggested that an adaptive phenomenon to the reduction in total body so- dium was occuring at a later time interval, and was not the direct effect of volume control. In the following three decades, the use of a salt re- stricted diet has largely been abandoned. Only three groups (4–6) have reported remarkable blood pressure control in more than 95% of their patients for prolonged periods of time without the use of hypotensive drugs. The most quoted group has been the group from Tassin, France (4), and although they practice 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 hours of dialysis without stressing until recently the importance of salt restriction. Indeed, no mention of salt restriction occurs in any publication from Tassin between 1983 and 1998. As the lengthening of dialysis time would imply a considerable increase in cost for in-center dialysis and is therefore largely impractical for the majority of patients, we decided to evaluate the role of salt restriction (5–6 g/day) and a dialysate sodium of 135 mmol/L without any increase in dialysis time (4–5 h) in a group of selected hypertensive patients treated by hemodialysis for between 1 and 18 years (7). The results of this pilot study were limited. In four of seven patients, all hypertensive therapy could be stopped and mean ar- terial pressure was reduced to less than 100 mm Hg in these four patients. In the three patients who were clearly unable to comply with a 5–6 g/day salt intake, drug therapy (although reduced) was required, and intolerance of a sodium dialysate of 135 mmol/L was observed. Nev- ertheless, the results suggested that in compliant patients, a mean arterial pressure less than 100 mm Hg could be obtained and maintained by a simple reduction in salt intake, without any drug therapy or reduction in dry body weight. However, interdialytic weight gain was reduced to less than 2 kg and dialysis tolerance was improved, with reduction in postdialysis fatigue. The mechanism underlying this phenomenon is only partially understood. It is associated with a reduction in peripheral vascular resistance, without a decrease in car- diac output (8). Current thinking suggests that the flavor of the month may be a reduction in plasma 1-ADMA (asymmetric dimethyl arginine), a known inhibitor of nitric oxide synthetase (9). Alternatively, sodium over- load could lead to a reversal of the inhibition of the Na + /K + -ATPase via an endogenous digitalis-like sub- stance, the result of which would be an increase in the intracellular sodium and calcium concentration with an increased tone of vascular smooth muscle cells; reducing the sodium load could reverse this mechanism (10). Fi- nally, a link between sympathetic overactivity as it is found in hemodialysis patients and the sodium overload could be an alternative hypothesis. Whatever the rational explanation for the empiric ben- efit of salt restriction in the hypertensive dialysis patient proves to be, the clinical benefit is undeniable and asso- ciated with the best survival data in the world. It can be achieved with virtually no added cost and does not im- pose a boring and unpalatable diet upon the patient. In- deed, it is worth remembering that in Tuscany, where regional Italian cuisine arguably reaches its pinnacle, salt-free bread is the regular bread sold in bakeries. Per- haps the time has come to cast aside Neptune’s poisoned chalice and give the well-dialyzed patient a longer and healthier life with fewer complications and no added expense. Address correspondence to: Stanley Shaldon, MD, 7 Av- enue des Papalins, Monaco 98000, or e-mail: shaldon@ webstore.mc. Seminars in Dialysis—Vol 13, No 1 (January-February) 2000 pp. 11–12 11