Brain renin-angiotensin system: Is it important in dialysis patients?

Abstract

Sir, Excessive inter dialytic weight gain (IDWG) is an important clinical problem and portends a poor outcome in haemodialysis patients [1]. Treatment is based on the restriction of salt and water intake. However, the compliance is usually poor and one-third of patients treated with maintenance haemodialysis are chronically overhydrated. The cardiovascular and haemodynamic effects of the peripheral renin–angiotensin system (RAS) are well documented. Conversely, the current knowledge regarding the effects of the brain RAS on blood pressure and thirst is mainly based on experimental studies. It was shown in experimental models that the stimulation of centrally located angiotensin 1 receptors (AT1-R) causes a rise in blood pressure, a release of vasopressin [2], thirst and thereby an increase in salt [3] and water [4] intake. In this respect, the effects of the RAS system on the brain could be important in haemodialysed patients. The brain RAS system upregulation is likely to increase the patients’ drinking behaviour, along with an increase in salt and water intake causing excessive IDWG. Therefore, the brain RAS represents a potential target for RAS inhibitors to counteract these centrally related effects. Dipsogenic activity is mediated only by AT-1 receptors. Brain tissue, with the exception of the circumventricular organs, is separated from the circulation by the blood–brain barrier. AT-1 receptors are widespread in the brain, and their stimulation in circumventricular structures causes drinking and pressor responses. In addition to circumventricular organs, AT1 receptors are also located in the inside compartment of the blood–brain barrier, and the activation of these AT1 receptors also causes drinking and pressor responses [5]. One is allowed to speculate that inhibiting centrally related effects of brain RAS with lipophilic angiotensin-converting enzyme and/or AT1-R blockers exerts a favourable effect on the IDWG. In a prospective, self-controlled and interventional study that included 30 anuric haemodialysed patients, we compared the IDWG in a period of 3 consecutive months without and with administration of telmisartan. We showed that the IDWG significantly decreased following telmisartan at a dosage of 40 mg/day [6]. These results suggest that the treatment of hypertension in haemodialysed patients with AT1-R inhibitors does not only aim at reducing the blood pressure—a short-term effect. In the long run, it also diminishes thirst, salt and water intake and hence the extracellular fluid volume and tissue sodium concentrations that are essentially responsible for high blood pressure and left ventricular hypertrophy in these patients. Conflict of interest statement. None declared.