Antiproteinuric Effect of Aliskiren versus Losartan in Primary Glomerulonephritis

Abdul Halim Abdul Gafor, Azrini Abdul Aziz, Rozita Mohd, Rizna Abdul Cader, Kong Wei Yen, Shamsul Azhar Shah, Norella C. T. Kong

Department of Epidemiology and Biostatistics, University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala, Lumpur, Malaysia.
Nephrology Unit, Department of Medicine, University Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala, Lumpur, Malaysia.

DOI: 10.4236/ojneph.2014.42009                

Abstract

Introduction: Treatment with renin-angiotensin-aldosterone-system (RAAS) blockers plays a major role in halting chonic kidney disease (CKD) progression. Aliskiren is the first orally available direct renin inhibitor (DRI). Objective: We studied the efficacy of aliskiren compared to losartan in patients with primary GN. Design and Method: This was a prospective open-label randomized control trial in patients with primary GN. Patients were randomized to receive either aliskiren or losartan to maximum tolerated doses for 24 weeks. Blood and urine investigations were measured at baseline and at 4-weekly intervals. Adverse effects were recorded. Results: 22 patients were recruited (aliskiren-11 and losartan-11). Their baseline characteristics were comparable with the exception of a higher proteinuria (uPCI) in the aliskiren arm. There were no significant differences in proteinuria, blood pressure and other renal parameters between both groups. At end-study, only patients in the aliskiren arm showed significant reductions in both the systolic blood pressure and in proteinuria. There were no changes in the other parameters of renal function over time and no adverse events occurred. Conclusion: Aliskiren appears to be as efficacious and tolerable as losartan both as an antihypertensive and antiproteinuric agent in this study.

Keywords

Primary Glomerulonephritis, Hypertension, Proteinuria, Aliskiren, Losartan

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	McGrogan, A., Franssen, C.F. and de Vries, C.S. (2011) The Incidence of Primary Glomerulonephritis Worldwide: A Systematic Review of the Literature. Nephrology Dialysis Transplantation, 26, 414-430. http://dx.doi.org/10.1093/ndt/gfq665
[2]	Sunita Bavanandan, L.S.K. (2009) 3rd Report on the Malaysian Registry of Renal Biopsy on Primary Glomerulonephritis.
[3]	Couchoud, C., Stengel, B., Landais, P., Aldigier, J.C., de Cornelissen, F., Dabot, C., et al. (2006) The Renal Epidemiology and Information Network (REIN): A New Registry for End-Stage Renal Disease in France. Nephrology Dialysis Transplantation, 21, 411-418. http://dx.doi.org/10.1093/ndt/gfi198
[4]	Hooi, L.S., Wong, H.S. and Morad, Z. (2005) Prevention of Renal Failure: The Malaysian Experience. Kidney International Supplements, 94, S70-S74. http://dx.doi.org/10.1111/j.1523-1755.2005.09418.x
[5]	Philibert, D. and Cattran, D. (2008) Remission of Proteinuria in Primary Glomerulonephritis: We Know the Goal but Do We Know the Price? Nature Clinical Practice Nephrology, 4, 550-559. http://dx.doi.org/10.1038/ncpneph0915
[6]	Hsu, C.Y., Iribarren, C., McCulloch, C.E., Darbinian, J. and Go, A.S. (2009) Risk Factors for End-Stage Renal Disease: 25-Year Follow-Up. Archives of Internal Medicine, 169, 342-350. http://dx.doi.org/10.1001/archinternmed.2008.605
[7]	Astor, B.C., Matsushita, K., Gansevoort, R.T., van der Velde, M., Woodward, M., Levey, A.S., et al. (2011) Lower Estimated Glomerular Filtration Rate and Higher Albuminuria Are Associated with Mortality and End-Stage Renal Disease. A Collaborative Meta-Analysis of Kidney Disease Population Cohorts. Kidney International, 79, 1331-1340. http://dx.doi.org/10.1038/ki.2010.550
[8]	Ruggenenti, P., Perna, A., Mosconi, L., Pisoni, R. and Remuzzi, G. (1998) Urinary Protein Excretion Rate Is the Best Independent Predictor of ESRF in Non-Diabetic Proteinuric Chronic Nephropathies. “Gruppo Italiano di Studi Epidemiologici in Nefrologia” (GISEN). Kidney International, 53, 1209-1216. http://dx.doi.org/10.1046/j.1523-1755.1998.00874.x
[9]	Iseki, K., Ikemiya, Y., Iseki, C. and Takishita, S. (2003) Proteinuria and the Risk of Developing End-Stage Renal Disease. Kidney International, 63, 1468-1474. http://dx.doi.org/10.1046/j.1523-1755.2003.00868.x
[10]	Keane, W.F. (2000) Proteinuria: Its Clinical Importance and Role in Progressive Renal Disease. American Journal of Kidney Diseases, 35, S97-S105. http://dx.doi.org/10.1016/S0272-6386(00)70237-X
[11]	Rutkowski, P., Tylicki, L., Renke, M., Korejwo, G., Zdrojewski, Z. and Rutkowski, B. (2004) Low-Dose Dual Blockade of the Renin-Angiotensin System in Patients with Primary Glomerulonephritis. American Journal of Kidney Diseases, 43, 260-268. http://dx.doi.org/10.1053/j.ajkd.2003.10.032
[12]	Renke, M., Tylicki, L., Rutkowski, P. and Rutkowski, B. (2004) Low-Dose Angiotensin II Receptor Antagonists and Angiotensin II-Converting Enzyme Inhibitors Alone or in Combination for Treatment of Primary Glomerulonephritis. Scandinavian Journal of Urology and Nephrology, 38, 427-433. http://dx.doi.org/10.1080/00365590410015687
[13]	Praga, M., Andrade, C.F., Luno, J., Arias, M., Poveda, R., Mora, J., et al. (2003) Antiproteinuric Efficacy of Losartan in Comparison with Amlodipine in Non-Diabetic Proteinuric Renal Diseases: A Double-Blind, Randomized Clinical Trial. Nephrology Dialysis Transplantation, 18, 1806-1813. http://dx.doi.org/10.1093/ndt/gfg284
[14]	Tylicki, L., Rutkowski, P., Renke, M. and Rutkowski, B. (2002) Renoprotective Effect of Small Doses of Losartan and Enalapril in Patients with Primary Glomerulonephritis. Short-Term Observation. American Journal of Nephrology, 22, 356-362. http://dx.doi.org/10.1159/000065227
[15]	Tylicki, L., Renke, M., Rutkowski, P., Rutkowski, B. and Lysiak-Szydlowska, W. (2005) Randomized, Controlled Study of the Effects of Losartan versus Enalapril in Small Doses on Proteinuria and Tubular Injury in Primary Glomerulonephritis. Medical Science Monitor, 11, PI31-PI37.
[16]	Persson, F., Rossing, P., Reinhard, H., Juhl, T., Stehouwer, C.D., Schalkwijk, C., et al. (2009) Renal Effects of Aliskiren Compared with and in Combination with Irbesartan in Patients with Type 2 Diabetes, Hypertension, and Albuminuria. Diabetes Care, 32, 1873-1879. http://dx.doi.org/10.2337/dc09-0168
[17]	Lizakowski, S., Tylicki, L., Renke, M., Rutkowski, P., Heleniak, Z., Slawinska-Morawska, M., et al. (2012) Effect of Aliskiren on Proteinuria in Non-Diabetic Chronic Kidney Disease: A Double-Blind, Crossover, Randomised, Controlled Trial. International Urology and Nephrology, 44, 1763-1770. http://dx.doi.org/10.1007/s11255-011-0110-z
[18]	Moriyama, T., Tsuruta, Y., Kojima, C., Itabashi, M., Sugiura, H., Takei, T., et al. (2012) Beneficial Effect of Aliskiren Combined with Olmesartan in Reducing Urinary Protein Excretion in Patients with Chronic Kidney Disease. International Urology and Nephrology, 44, 841-845. http://dx.doi.org/10.1007/s11255-011-9991-0
[19]	Li, S.Y., Chen, Y.T., Yang, W.C., Tarng, D.C., Lin, C.C., Yang, C.Y., et al. (2012) Effect of Add-On Direct Renin Inhibitor Aliskiren in Patients with Non-Diabetes Related Chronic Kidney Disease. BMC Nephrology, 13, 89. http://dx.doi.org/10.1186/1471-2369-13-89
[20]	Tang, S.C., Lin, M., Tam, S., Au, W.S., Ma, M.K., Yap, D.Y., et al. (2012) Aliskiren Combined with Losartan in Immunoglobulin A Nephropathy: An Open-Labeled Pilot Study. Nephrology Dialysis Transplantation, 27, 613-618. http://dx.doi.org/10.1093/ndt/gfr349
[21]	Persson, F., Rossing, P., Schjoedt, K.J., Juhl, T., Tarnow, L., Stehouwer, C.D., et al. (2008) Time Course of the Antiproteinuric and Antihypertensive Effects of Direct Renin Inhibition in Type 2 Diabetes. Kidney International, 73, 1419-1425. http://dx.doi.org/10.1038/ki.2008.68
[22]	Parving, H.H., Brenner, B.M., McMurray, J.J., de Zeeuw, D., Haffner, S.M., Solomon, S.D., et al. (2012) Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. The New England Journal of Medicine, 367, 2204-2213. http://dx.doi.org/10.1056/NEJMoa1208799
[23]	Parving, H.H., Persson, F., Lewis, J.B., Lewis, E.J. and Hollenberg, N.K. (2008) Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. The New England Journal of Medicine, 358, 2433-2446. http://dx.doi.org/10.1056/NEJMoa0708379
[24]	Persson, F., Rossing, P., Reinhard, H., Juhl, T., Stehouwer, C.D., Schalkwijk, C., et al. (2010) Optimal Antiproteinuric Dose of Aliskiren in Type 2 Diabetes Mellitus: A Randomised Crossover Trial. Diabetologia, 53, 1576-1580. http://dx.doi.org/10.1007/s00125-010-1789-6
[25]	Gupta, A., Khaira, A., Singh, B., Bhowmik, D.M. and Tiwari, S.C. (2009) Aliskiren as an Antiproteinuric Add-On Therapy in Primary Membranous Nephropathy. Clinical and Experimental Nephrology, 13, 402-403. http://dx.doi.org/10.1007/s10157-009-0130-5
[26]	Laverman, G.D., Henning, R.H., de Jong, P.E., Navis, G. and de Zeeuw, D. (2001) Optimal Antiproteinuric Dose of Losartan in Nondiabetic Patients with Nephrotic Range Proteinuria. American Journal of Kidney Diseases, 38, 1381-1384. http://dx.doi.org/10.1053/ajkd.2001.29262
[27]	Peterson, J.C., Adler, S., Burkart, J.M., Greene, T., Hebert, L.A., Hunsicker, L.G., et al. (1995) Blood Pressure Control, Proteinuria, and the Progression of Renal Disease. The Modification of Diet in Renal Disease Study. Annals of Internal Medicine, 123, 754-762. http://dx.doi.org/10.7326/0003-4819-123-10-199511150-00003
[28]	Foundation, N.K. (2012) KDOQI Clinical Practice Guidelines for Diabetes and Chronic Kidney Disease: 2012 Updates American Journal of Kidney Diseases, 60, 850-886.
[29]	Reich, H.N., Troyanov, S., Scholey, J.W. and Cattran, D.C. (2007) Remission of Proteinuria Improves Prognosis in IgA Nephropathy. Journal of the American Society of Nephrology, 18, 3177-3183. http://dx.doi.org/10.1681/ASN.2007050526
[30]	Oparil, S., Yarows, S.A., Patel, S., Fang, H., Zhang, J. and Satlin, A. (2007) Efficacy and Safety of Combined Use of Aliskiren and Valsartan in Patients with Hypertension: A Randomised, Double-Blind Trial. Lancet, 370, 221-229. http://dx.doi.org/10.1016/S0140-6736(07)61124-6
[31]	Gradman, A.H., Schmieder, R.E., Lins, R.L., Nussberger, J., Chiang, Y. and Bedigian, M.P. (2005) Aliskiren, a Novel Orally Effective Renin Inhibitor, Provides Dose-Dependent Antihypertensive Efficacy and Placebo-Like Tolerability in Hypertensive Patients. Circulation, 111, 1012-1018. http://dx.doi.org/10.1161/01.CIR.0000156466.02908.ED
[32]	Solomon, S.D., Appelbaum, E., Manning, W.J., Verma, A., Berglund, T., Lukashevich, V., et al. (2009) Effect of the Direct Renin Inhibitor Aliskiren, the Angiotensin Receptor Blocker Losartan, or Both on Left Ventricular Mass in Patients with Hypertension and Left Ventricular Hypertrophy. Circulation, 119, 530-537. http://dx.doi.org/10.1161/CIRCULATIONAHA.108.826214
[33]	Hellemons, M.E., Persson, F., Bakker, S.J., Rossing, P., Parving, H.H., De Zeeuw, D., et al. (2011) Initial Angiotensin Receptor Blockade-Induced Decrease in Albuminuria Is Associated with Long-Term Renal Outcome in Type 2 Diabetic Patients with Microalbuminuria: A Post Hoc Analysis of the IRMA-2 Trial. Diabetes Care, 34, 2078-2083. http://dx.doi.org/10.2337/dc11-0324
[34]	Ito, S., Nakura, N., Le Breton, S. and Keefe, D. (2010) Efficacy and Safety of Aliskiren in Japanese Hypertensive Patients with Renal Dysfunction. Hypertens Research, 33, 62-66. http://dx.doi.org/10.1038/hr.2009.175