**Part 3**

**The Renin-Angiotensin-Aldosterone Pathway** 

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**7** 

*Japan* 

**The Renin-Angiotensin-Aldosterone** 

Hypertension (HT) and cardiovascular disease (CVD) are common in dialysis-dependent chronic kidney disease (DD-CKD) patients. The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of HT in DD-CKD patients. Activated RAAS also increases inflammatory mediators, which was shown to be an independent predictor of CVD in DD-CKD patients. Recent meta-analyses suggested that antihypertensive pharmacotherapy may reduce CVD in DD-CKD patients. This review focuses on the physiological roles and blockade effects of RAAS for HT and CVD in DD-

The role of RAAS in hypertensive DD-CKD patients was confirmed by the normalization of blood pressure (BP) upon administration of an angiotensin antagonist, saralasin. Normally, volume overload and elevation of BP result in suppression of RAAS production. Since this feedback is often incomplete in CKD patients, CKD patients often show HT and high or normal RAAS. Weidmann et al. reported that the renin levels of hypertensive hemodialysis-dependent CKD (HDD-CKD) patients were approximately twice as high as those of normal subjects. Parenchymal renal injury and renovascular disease may cause increased renin secretion in end-stage CKD. The prevalence of renal artery stenosis may be as high as 40% in patients starting HD, although the diagnosis was determined in only one-quarter of such a group before entering a dialysis program. Kimura et al. reported that plasma rennin activity (PRA) increased from 2.3±0.5 ng/ml/hr at just before initiation of HD to 6.5±1.3 ng/ml/hr over an 8- to 10-year period in HDD-CKD patients. These data suggested that renin secretion continued even after disuse

atrophy of kidney with almost complete deterioration of its excretory function.

Activated RAAS increased inflammatory mediators, which is an independent risk factor for CVD. The mechanism is thought to be as follows. Activated RAAS directly increases pro-

**2. The physiological roles of RAAS in DD-CKD patients** 

**1. Introduction** 

CKD patients.

 \*

Corresponding Author

**System in Dialysis Patients** 

Yoshiyuki Morishita\* and Eiji Kusano *Division of Nephrology, Department of Medicine,* 

*Jichi Medical University, Tochigi,* 
