Brief Article
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World J Nephrol. Nov 6, 2013; 2(4): 129-135
Published online Nov 6, 2013. doi: 10.5527/wjn.v2.i4.129
A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease
Keng-Thye Woo, Hui-Lin Choong, Kok-Seng Wong, Han-Kim Tan, Marjorie Foo, Fook-Chong Stephanie, Evan JC Lee, Vathsala Anantharaman, Grace SL Lee, Choong-Meng Chan
Keng-Thye Woo, Hui-Lin Choong, Kok-Seng Wong, Marjorie Foo, Grace SL Lee, Choong-Meng Chan, Han- Kim Tan, Department of Renal Medicine, Singapore General Hospital, 169608, Singapore
Fook-Chong Stephanie, Department of Clinical Research, Singapore General Hospital, 169608, Singapore
Evan JC Lee, Vathsala Anantharaman, Department of Nephrology, National University of Singapore, 169608, Singapore
Author contributions: Woo KT, Main author, coordinated study, recruited patients and preparation of manuscript; Choong HL helped in designing data bases and strategy, recruited patients and helped in writing; Wong KS involved in recruiting and participation in trial and helped in editing paper; Tan HK helped in recruiting, participation of trial , preparation of references and tables; Foo M helped in recruitment of patients and their treatment, preparation of paper; Stephanie FC, Statistician involved in design and analysis of data, writing of relevant part of paper; Lee EJC contributed patients and participated in treatment and follow of patients; Anantharaman V helped to recruit and treat patients, advised on paper; Lee GSL, Co-author and Co ordinator for patient recruitment, helped in editing of paper; Chan CM recruited and treatment of trial patients, editing manuscript.
Supported by Singhealth Cluster with IRB approval, CIRB Ref: 569E
Correspondence to: Keng-Thye Woo, Professor, Department of Renal Medicine Singapore General Hospital, Outram Road, 169608, Singapore. woo.keng.thye@sgh.com.sg
Telephone: +65-63266049 Fax: +65-62202308
Received: May 28, 2013
Revised: August 2, 2013
Accepted: August 28, 2013
Published online: November 6, 2013
Processing time: 160 Days and 1.8 Hours
Abstract

AIM: To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD).

METHODS: This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure.

RESULTS: Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001).

CONCLUSION: This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

Keywords: Aliskiren; Chronic kidney disease disease; Clinical trial

Core tip: The Aliskiren trial in type 2 diabetes using Cardio-Renal Endpoints (ALTITUDE) study was able to unmask serious adverse events like ischemic heart disease and strokes because it had included Cardio-Renal Endpoints among its primary end points. It may be advisable to require future trials on drugs which could impact on the kidneys, heart and brain to have similar Cardio-Renal Endpoints or Cardio-Neuro-Renal End points to further ensure therapeutic safety of the trial drug. Our modest study compared to the magnitude of the ALTITUDE study still managed to detect the problem of hyperkalaemia in the group treated with Combination therapy with Aliskiren and ARB. Based on our study it would appear that the findings of the ALTITUDE study would also apply to non-diabetic Chronic Kidney Disease patients.