Aliskiren Reduces Proteinuria Through Changes in Central and Peripheral Hemodynamics in Chronic Kidney Disease Patients

Research Article

Austin J Nephrol Hypertens. 2014;1(3): 1011.

Aliskiren Reduces Proteinuria Through Changes in Central and Peripheral Hemodynamics in Chronic Kidney Disease Patients

Hiromichi Suzuki*, Tsutomu Inoue, Tomohiro Kikuta, Tsuneo Takenaka and Hirokazu Okada

Department of Nephrology, Saitama Medical University, Japan

*Corresponding author: Hiromichi Suzuki, Department of Nephrology, Saitama Medical University, 38 Moroyama-machi, Iruma-gun, Saitama, 350-0495 Japan

Received: August 12, 2014; Accepted: August 20, 2014; Published: August 22, 2014


Recently, a newly developed direct rennin inhibitor (DRI), aliskiren, has been shown to have a persistent depressor action throughout the day in hypertensive patients. However, only a few reports compared Reno protection by aliskiren to angiotensinogen receptor blockers (ARBs) in proteinuric chronic kidney disease (CKD) patients.

Methods: Measurements of urinary protein excretion (Upro) were carried out before and 6 months after the change from other ARBs to aliskiren. Twenty three patients who persistently had values of Up ro >1.0 g daily despite the treatment with antihypertensive drugs including ARBs were considered as candidates. Initially, aliskiren was started at 150 mg once daily in the evening, and increased up to 300 mg once daily in the evening. Home BP was utilized for determination of BP control. In addition to BP measurements, pulse wave velocity (PWV) and second SBP (SBP2), an index of central BP, were evaluated before and 6 months after aliskiren administration. Renal function was evaluated by estimated glomerular filtration rate (eGFR).

Results: Administration of aliskiren reduced Upro (2.16 ± 0.91 to 1.62 ± 1.08 g/day, P<0.05), accompanied with decreases in systolic BP, SBP2 and PWV. Moreover, reduction of Upro was positively correlated with those of changes in SBP (r=0.46, P<0.05), SBP2 (r=0.48, p<0.05) and PWV (r=0.48, P<0.05). Renal dysfunction evaluated by eGFR did not progress during the study period (before 70.46 ± 9.56, after 68.00 ± 12.24 ml/min/1.73m2).

Conclusion: The results of the present study suggest that aliskiren exerted its renoprotective action through improvement of central and peripheral hemodynamics.

Keywords: Chronic kidney disease(CKD); Pulse wave velocity(PWW); central arterial pressure, home blood pressure


CKD: Chronic Kidney Disease; PWW: Pulse Wave Velocity


Blockade of the Renin-Angiotensin-Aldosterone System (RAAS) using angiotensinogen converting enzyme inhibitors (ACEi) and angiotensinogen receptor blockers (ARB) has been advocated for the management of proteinuria in chronic kidney disease (CKD) patients [1]. Aliskiren, a direct renin inhibitor (DRI) inhibits the enzyme renin by binding to its catalytic site, thus blocking the RAAS at its point of activation. Angiotensinogen I, angiotensin II, and aldosterone levels decrease, and their hemodynamic effects are abolished. Aliskiren impedes efferent arteriolar vasoconstriction and diminishes the glomerular filtration fraction, salt and water absorption [2-4]. Although the effects of ACEi and ARBs result in an increase in plasma renin concentration and activity, the inhibition of the RAAS might be incomplete. In this regard, aliskiren might be superior to ACEis and ARBs. Recently, Lizakowski et al. [5] reviewed several small studies on the antiproteinuric effects of aliskiren and found marked reduction of proteinuria and albuminemia in diabetic and non-diabetic CKD patients. Previous reported studies were mainly carried out in the protocol of add-on style [6]. However, there are no definitive studies comparing the renoprotective effects of aliskiren with that of available ARBs. In the present study, the efficacy of aliskiren was assessed on blood pressure (BP) control and renoprotection in CKD patients in whom reductions of proteinuria were more than 1.0 g daily in spite of administration of ARBs.


This study was performed in accordance with the Declaration of Helsinki and written informed consent was obtained from all patients.,/

This study was a prospective and observational cohort study conducted in a 6 months treatment period with aliskiren.


CKD patients in stages 2 and 3 who had proteinuria >1.0 g daily despite treatment with ARBs for more than 1 year, were considered as candidates for the change from ARBs (10 patients on olmesartan, 6 patients on candesartan, 5 patients on valsartan, and 2 patients on telmisartan) to aliskiren. CKD stages 2 and 3 were defined as the estimated glomerular filtration rate (eGFR) being >30 mL/ min/1.73m2. Exclusion criteria were as follows: types 1 and 2 diabetes mellitus, hypokalemia (>5.5 mEq/L), severe cardiovascular diseases, treated with corticosteroid or immunosuppressant, past history of a major surgery within 6 months, and other diseases that physicians had elected to treat.

Office BP was not measured and patients were given instructions on how to measure and record their own BP at home. BP measurements were recorded at least twice a week at home in the sitting position - once in the morning before breakfast within 30 min of awakening, and once in the evening just before dinner. Home BP measurements were made using the HEM 401C (Omron Life Science Co. Ltd, Tokyo, Japan), a semi-automatic device that operates on the cuff-oscillometric principle and generates a digital display of systolic and diastolic BP and pulse rate [7]. Pulse wave velocity (PWV) was measured using an automatic waveform analyzer (form PWV/ ABI; Omron Colin, Co., Ltd., Komaki, Japan). All individuals were examined after resting in the supine position for at least 5 minutes and radial artery pulse waveform was recorded by an automated tonometric system HEM-9000AI (Omeron Healthcare, Kyoto, Japan) with patients in a sitting position. The HEM-9000AI algorithm automatically performed online detection of the second peak (late systolic inflection) based on the second maxima of the fourth derivative of the radial pressure wave form to determine the late or second SBP (SBP2), an index of central BP [8]. SBP2, an index of CAP, is well correlated with central arterial pressure (CAP) measured simultaneously by the direct catheter method [9,10].

BP was evaluated by the average of 20 measurements at home during a month and doses of antihypertensive agents except aliskiren were adjusted. The target levels of BP were less than 130/80 mm Hg.

All of the subjects were registered to replace their single daily morning ARBs to aliskiren when their daily proteinuria was >1.0 g regardless of the levels of BP.

The serum creatinine, 24-hr urinary excretions of creatinine and protein (Upro), and hematologic and serum tests including urea, uric acid, blood urea nitrogen (BUN), electrolytes, etc. were obtained at the beginning and end of the baseline period and during every month of follow-up.

Statistical analysis

Data are expressed as mean ± standard deviation. The differences from baseline to 6 months were tested using the Student’s test for paired data.

Correlations between various characteristics were determined using Pearson’s correlation test. All statistical tests were two-sided with significance level of 0.05, and were performed using the SAS Release 8.2 (SAS Institute Inc., Cary, NC, USA).


The mean age of all subjects was 59.0 ± 16.3 years and female to male ratio was 6/17. Underlying renal diseases were: Ig A nephropathy, 7; nephrosclerosis, 6; membranous nephropathy, 2; and unknown, 8. Patient baseline values are presented in Table 1. Before the start of aliskiren, average values were: SBP at home was 142.6/75 ± 10.8/0 mm Hg; PWV was 1675.7 ± 329.3 cm/sec; eGFR was 70.4 ± 9.5 ml/min/1.73 m2; and urinary protein excretion was 2.16 ± 0.91/g Cr. Administration of aliskiren resulted in significant reductions of SBP, SBP2 and PWV with a significance.