Hypertension in Hemodialysis Patients

Hypertension occurs in 90% of patients starting hemodialysis and persists in 70-90% of hemodialysis patients in the US [57]. In the large, multicenter Hemodialysis (HEMO) Study more than 70% of patients were hypertensive by JNC VI guidelines, and almost 75% required antihypertensive medications [58]. This is contrary to the situation in the late 1960s, when strict control of true dry body weight was practiced and the majority of patients did not require antihypertensive agents [59]. There is a consensus that most patients on dialysis have volume-dependent hypertension. Only a small proportion of patients have vasoconstrictive hypertension requiring bilateral nephrectomy in the past [59] or blood pressure medications at present. The problem is how to achieve normovolemia and control blood pressure without medications.

Blood Pressure Control by Dietary Measures and Low

Dialysate Sodium

The possibility of controlling blood pressure in a reno-prival state by drastic reduction in dietary salt intake was first shown by Kempner [60, 61] in the 1940s. It was subsequently shown that the beneficial effect of the 'rice diet' on hypertension was related to the lowering of plasma volume and extracellular fluid space [62]. In the 1960s it was considered as mandatory to restrict dietary salt intake in hemodialysis patients to control blood pressure. This restriction was combined with long dialysis sessions and relatively low dialysate sodium. The achievement of blood pressure control was very gradual. It was not surprising for the hemodialysis pioneers as this phenomenon was already observed by Kempner [ 60, 61] in the 1940s. In the first patient on a 'rice diet' containing less than 500 mg of salt, blood pressure was lowered gradually from 230/145 to 135/90 mm Hg in 8 weeks [60]. Even achievement of dry body weight does not lead immediately to controlling blood pressure because the relationship between extracellular volume status and blood pressure is not simple and linear, but complex because of a lag of several weeks between the normalization of the time-averaged extracellular volume and the decrease in blood pressure ('lag phenomenon') [63]. The exact pathomech-anism of the lag phenomenon is not clear. It is likely that this may be caused by the retention of circulating factors, such as asymmetric dimethyl-L-arginine, a potent inhibitor of nitric oxide synthesis and Na+,K+-ATPase inhibitors that may remain elevated because of a large volume of distribution and ineffective removal [64]. Elevated sodium may remain in the arterial smooth muscles and be responsible for vasoconstriction. It may take several weeks of normovolemia for the intracellular sodium to escape. Regardless of the mechanism, the normalization of blood pressure by volume control is tricky requires patience and a good understanding of the problem [56, 63, 64], Several groups have tried to lower extracellular volume and blood pressure without lengthening dialysis duration by dietary measures and low dialysate sodium [65], In 8 patients Krautzig et al. [66] tried a regime of gradual lowering of the dialysate sodium concentration from 140 to 135 mEq/l at a rate of 1 mEq/l every 3-4 weeks and restricting dietary salt intake while maintaining dialysis duration of 4-5 h/session. It is worth stressing that dialysis duration was longer that practiced in the US.

The authors reported lowering blood pressure in these patients with a possibility of stopping blood pressure medications in 4 patients and only a moderate increase in the frequency of cramps during dialysis. The control of extracellular volume by a low sodium diet without prolongation of dialysis duration and low dialysate sodium is difficult; it increases intradialytic symptoms and requires a very strict adherence to an unpalatable diet.

Blood Pressure Control and Duration of Dialysis

Hypertension is less frequent in Europe and Japan where dialysis time is longer. The lowest mortality related to cardiovascular causes is reported from the Centre de Rein artificial, Tassin, France [56]: where long duration hemodialysis is practiced. Long-term mortality in this center is lower in patients with lower mean blood pressures. In addition, gentle ultrafiltration and proper estimation of dry body weight allows the achievement of good blood pressure control in the majority of patients [56]. Hypotension, in patients dialyzed thrice weekly for 8 h, is a strong indicator that the patient weight dropped below the true dry body weight [56]. With rapid ultrafiltration, hypotension is dependent mostly on hypovole-mia, which occurs long before the dry body weight is achieved. In spite of clear evidence that short dialysis is associated with poor blood pressure control, the blame is commonly put on suboptimal drug therapy, excessive in-terdialytic weight gains ('patient noncompliance'), and the practice of withholding antihypertensive medications before dialysis [67].

With long-duration hemodialysis sessions, blood pressure could be controlled without antihypertensive therapy in 90-95% of patients [56, 68]. These patients have volume-dependent hypertension. The remaining 5-10% of patients has 'refractory' hypertension, treated with bilateral nephrectomy in the past, but nowadays these patients respond to antihypertensive therapy with converting enzyme inhibitors [69]. The originator of chronic dialysis is Belding H. Scribner, who practiced long-duration dialysis sessions in the 1960s, and in recent years advocated forcefully departure from short dialysis and better attention to volume management for blood pressure control [63, 70-72]. Other groups also advocate longer dialysis sessions for better blood pressure control [73-75]: A recent randomized crossover study of long (6-8 h) dialysis thrice weekly at home and short (3.5-4.5 h) thrice weekly in the dialysis center showed much better control of blood pressure and a reduction in hypotensive episodes with longer dialysis sessions [76]. Even moderate prolongation of dialysis sessions from 253 8 15 to 273 8 25 min together with strict control of sodium balance over 3-4 months allowed control of blood pressure in 10 of 16 patients with 'dialysis-resistant' hypertension [77].

The K/DOQI guidelines do not recommend the duration of dialysis as an independent measure of dialysis adequacy. After discussing all arguments for and against the importance of dialysis duration, the work group could not reach a consensus on this subject and did not include it in the final recommendations [45]. Some work group members felt strongly that the time of dialysis should not fall below 2.5 h, but a duration of dialysis of >4 h was not recommended [45]. However, I see no good explanation for why duration of dialysis is dismissed as unimportant.

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