Efficacy and safety of combined vs. Single renin-angiotensin-aldosterone system blockade in chronic kidney disease: A meta-analysis

American Journal of Hypertension

Volumn 26, Issue 3, 2013, Pages 424-441

  Susantitaphong, Paweena ^a,b,c   Sewaralthahab, Kamal ^a   Balk, Ethan M ^b,d   Eiam Ong, Somchai ^c   Madias, Nicolaos E ^a,b   Jaber, Bertrand L ^a,b  

^a ST ELIZABETH'S MEDICAL CENTER   (United States)

^b TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CHULALONGKORN UNIVERSITY   (Thailand)

^d TUFTS UNIVERSITY   (United States)

Author keywords

blood pressure; chronic kidney disease; Combined; GFR; hypertension; hypotension; potassium; proteinuria; RAAS blockade; randomized controlled trial

Indexed keywords

ALISKIREN; AMLODIPINE; BENAZEPRIL; CANDESARTAN; CREATININE; ENALAPRIL; EPLERENONE; FOSINOPRIL; FUROSEMIDE; IMIDAPRIL; IRBESARTAN; LISINOPRIL; LOSARTAN; OLMESARTAN; PERINDOPRIL; PLACEBO; POTASSIUM; PROTEIN; RAMIPRIL; SPIRONOLACTONE; TELMISARTAN; TEMOCAPRIL; VALSARTAN;

ALBUMINURIA; ARM; ARTICLE; BLOOD PRESSURE MONITORING; CHRONIC KIDNEY DISEASE; CREATININE BLOOD LEVEL; DIASTOLIC BLOOD PRESSURE; DRUG EFFICACY; DRUG SAFETY; GLOMERULUS FILTRATION RATE; HOSPITALIZATION; HUMAN; HYPERKALEMIA; LONG TERM CARE; MEAN ARTERIAL PRESSURE; META ANALYSIS; MONOTHERAPY; MORTALITY; POTASSIUM BLOOD LEVEL; PRIORITY JOURNAL; PROTEIN URINE LEVEL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTOLIC BLOOD PRESSURE; URINARY EXCRETION;

ADULT; AGED; ALBUMINURIA; ANGIOTENSIN RECEPTOR ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; BLOOD PRESSURE; CROSS-OVER STUDIES; GLOMERULAR FILTRATION RATE; HUMANS; HYPERKALEMIA; HYPOTENSION; MIDDLE AGED; MINERALOCORTICOID RECEPTOR ANTAGONISTS; PROTEINURIA; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RENAL INSUFFICIENCY, CHRONIC; RENIN; RENIN-ANGIOTENSIN SYSTEM;

EID: 84876590155     PISSN: 08957061     EISSN: 19417225     Source Type: Journal    
DOI: 10.1093/ajh/hps038     Document Type: Article

References (90)

1. Suckling R, Gallagher H. Chronic kidney disease, diabetes mellitus and cardiovascular disease: risks and commonalities. J Ren Care 2012;38 Suppl 1:4-11.
2. Juutilainen A, Kastarinen H, Antikainen R, Peltonen M, Salomaa V, Tuomilehto J,Jousilahti P, Sundvall J, Laatikainen T, Kastarinen M. Trends in estimated kidney function:the FINRISK surveys. Eur J Epidemiol 2012;27:305-313.
3. Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: approaches and initiatives-a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007;72:247-259. (Pubitemid 47172384)
4. Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L. US Renal Data System 2010 Annual Data Report. Am J Kidney Dis 2011;57(1 Suppl 1): A8,e1-526.
5. Hunsicker LG, Adler S, Caggiula A, England BK, Greene T, Kusek JW, Rogers NL, Teschan PE. Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int 1997;51:1908-1919. (Pubitemid 27252762)
6. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I. Renoprotective effect of the angiotensinreceptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-860.
7. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345: 861-869.
8. Li PK, Leung CB, Chow KM, Cheng YL, Fung SK, Mak SK, Tang AW, Wong TY, Yung CY, Yung JC, Yu AW, Szeto CC. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 2006;47:751-760.
9. Foundation NK. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45(4 Suppl 3): S1-153.
10. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Manolis A, Nilsson PM, Redon J, Struijker-Boudier HA, Viigimaa M, Adamopoulos S, Bertomeu V, Clement D, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, O'Brien E, Ponikowski P, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B, The task force for the management of arterial hypertension of the European Society of H, The task force for the management of arterial hypertension of the European Society of C. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28:1462-1536.
11. MacKinnon M, Shurraw S, Akbari A, Knoll GA, Jaffey J, Clark HD. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. Am J Kidney Dis 2006;48:8-20.
12. Catapano F, Chiodini P, De Nicola L, Minutolo R, Zamboli P, Gallo C, Conte G. Antiproteinuric response to dual blockade of the reninangiotensin system in primary glomerulonephritis: meta-analysis and metaregression. Am J Kidney Dis 2008;52:475-485.
13. Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 2008; 148:30-48. (Pubitemid 351688350)
14. Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol 2006;1:940-951.
15. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358:2433-2446. (Pubitemid 351793017)
16. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559. (Pubitemid 351522739)
17. Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsarinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008;372:547-553.
18. Haynes R, Mason P, Rahimi K, Landray MJ. Dual blockade of the reninangiotensin system: are two better than one? Nephrol Dial Transplant 2009; 24:3602-3607.
19. Slagman MC, Navis G, Laverman GD. Dual blockade of the renin-angiotensin-aldosterone system in cardiac and renal disease. Curr Opin Nephrol Hypertens 2010;19:140-152.
20. Krause MW, Fonseca VA, Shah SV. Combination inhibition of the renin-angiotensin system: is more better? Kidney Int 2011;80:245-255.
21. Mancia G, Grassi G. Impact of new clinical trials on recent guidelines on hypertension management. Ann Med 2011;43:124-132.
22. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12. (Pubitemid 26120810)
23. Seabra VF, Alobaidi S, Balk EM, Poon AH, Jaber BL. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol 2010;5:1734-1744.
24. Huedo-Medina TB, Sanchez-Meca J, Marin-Martinez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods 2006;11:193-206. (Pubitemid 44001277)
25. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634. (Pubitemid 27387172)
26. Jacobsen P, Andersen S, Rossing K, Hansen BV, Parving HH. Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. Nephrol Dial Transplant 2002;17:1019-1024. (Pubitemid 34746204)
27. Rossing K, Christensen PK, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Diabetes Care 2002;25:95-100. (Pubitemid 41070790)
28. Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 2003;63:1874-1880. (Pubitemid 36513336)
29. Jacobsen P, Andersen S, Jensen BR, Parving HH. Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. J Am Soc Nephrol 2003;14:992-999. (Pubitemid 36359280)
30. Rossing K, Jacobsen P, Pietraszek L, Parving HH. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized doubleblind crossover trial. Diabetes Care 2003;26:2268-2274. (Pubitemid 36993311)
31. Schjoedt KJ, Rossing K, Juhl TR, Boomsma F, Rossing P, Tarnow L, Parving HH. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int 2005;68:2829-2836. (Pubitemid 43251030)
32. Persson F, Rossing P, Reinhard H, Juhl T, Stehouwer CD, Schalkwijk C, Danser AH, Boomsma F, Frandsen E, Parving HH. Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria. Diabetes Care 2009;32:1873-1879.
33. Cetinkaya R, Odabas AR, Selcuk Y. Anti-proteinuric effects of combination therapy with enalapril and losartan in patients with nephropathy due to type 2 diabetes. Int J Clin Pract 2004;58:432-435. (Pubitemid 38786561)
34. Matos JP, de Lourdes Rodrigues M, Ismerim VL, Boasquevisque EM, Genelhu V, Francischetti EA. Effects of dual blockade of the renin angiotensin system in hypertensive type 2 diabetic patients with nephropathy. Clin Nephrol 2005;64:180-189. (Pubitemid 41263975)
35. Song JH, Cha SH, Lee HJ, Lee SW, Park GH, Kim MJ. Effect of lowdose dual blockade of renin-angiotensin system on urinary TGF-beta in type 2 diabetic patients with advanced kidney disease. Nephrol Dial Transplant 2006;21:683-689. (Pubitemid 43372915)
36. Joffe HV, Kwong RY, Gerhard-Herman MD, Rice C, Feldman K, Adler GK. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J Clin Endocrinol Metab 2007;92:2552-2558. (Pubitemid 47037357)
37. Swaminathan K, Davies J, George J, Rajendra NS, Morris AD, Struthers AD. Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles. Diabetologia 2008;51:762-768.
38. Russo D, Minutolo R, Pisani A, Esposito R, Signoriello G, Andreucci M, Balletta MM. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 2001;38:18-25. (Pubitemid 32611753)
39. Berger ED, Bader BD, Ebert C, Risler T, Erley CM. Reduction of proteinuria; combined effects of receptor blockade and low dose angiotensin-converting enzyme inhibition. J Hypertens 2002;20:739-743. (Pubitemid 34913719)
40. Ferrari P, Marti HP, Pfister M, Frey FJ. Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade. J Hypertens 2002;20:125-130. (Pubitemid 34913411)
41. Campbell R, Sangalli F, Perticucci E, Aros C, Viscarra C, Perna A, Remuzzi A, Bertocchi F, Fagiani L, Remuzzi G, Ruggenenti P. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int 2003;63:1094-1103. (Pubitemid 36315589)
42. Rutkowski P, Tylicki L, Renke M, Korejwo G, Zdrojewski Z, Rutkowski B. Low-dose dual blockade of the renin-angiotensin system in patients with primary glomerulonephritis. Am J Kidney Dis 2004;43:260-268. (Pubitemid 38146324)
43. Slagman MC, Waanders F, Hemmelder MH, Woittiez AJ, Janssen WM, Lambers Heerspink HJ, Navis G, Laverman GD. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ 2011;343:d4366.
44. Agarwal R. Add-on angiotensin receptor blockade with maximized ACE inhibition. Kidney Int 2001;59:2282-2289. (Pubitemid 32467622)
45. Kincaid-Smith P, Fairley K, Packham D. Randomized controlled crossover study of the effect on proteinuria and blood pressure of adding an angiotensin II receptor antagonist to an angiotensin converting enzyme inhibitor in normotensive patients with chronic renal disease and proteinuria. Nephrol Dial Transplant 2002;17:597-601. (Pubitemid 34308813)
46. Kim MJ, Song JH, Suh JH, Lee SW, Kim GA. Additive antiproteinuric effect of combination therapy with ACE inhibitor and angiotensin II receptor antagonist: differential short-term response between IgA nephropathy and diabetic nephropathy. Yonsei Med J 2003;44:463-472. (Pubitemid 36833898)
47. Song JH, Lee SW, Suh JH, Kim ES, Hong SB, Kim KA, Kim MJ. The effe ts of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy. Clin Nephrol 2003;60:318-326. (Pubitemid 37407689)
48. Esnault VL, Ekhlas A, Delcroix C, Moutel MG, Nguyen JM. Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents. J Am Soc Nephrol 2005;16:474-481. (Pubitemid 41725144)
49. Morales E, Huerta A, Gutierrez E, Gutierrez Solis E, Segura J, Praga M. [The antiproteinuric effect of the blockage of the renin-angiotensinaldosterone system (RAAS) in obese patients. Which treatment option is the most effective?]. Nefrologia 2009;29:421-429.
50. Meier P, Maillard MP, Meier JR, Tremblay S, Gauthier T, Burnier M. Combining blockers of the renin-angiotensin system or increasing the dose of an angiotensin II receptor antagonist in proteinuric patients: a randomized triple-crossover study. J Hypertens 2011;29:1228-1235.
51. Tutuncu NB, Gurlek A, Gedik O. Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study. Acta Diabetol 2001;38:157-161. (Pubitemid 34145694)
52. Andersen NH, Poulsen PL, Knudsen ST, Poulsen SH, Eiskjaer H, Hansen KW, Helleberg K, Mogensen CE. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care 2005; 28:273-277. (Pubitemid 40170925)
53. Krimholtz MJ, Karalliedde J, Thomas S, Bilous R, Viberti G. Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease. J Am Soc Nephrol 2005;16 Suppl 1:S42-47. (Pubitemid 41725082)
54. Atmaca A, Gedik O. Effects of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and their combination on microalbuminuria in normotensive patients with type 2 diabetes. Adv Ther 2006;23:615-622. (Pubitemid 44747441)
55. Ogawa S, Takeuchi K, Mori T, Nako K, Ito S. Spironolactone further reduces urinary albumin excretion and plasma B-type natriuretic peptide levels in hypertensive type II diabetes treated with angiotensinconverting enzyme inhibitor. Clin Exp Pharmacol Physiol 2006;33: 477-479.
56. Sengul AM, Altuntas Y, Kurklu A, Aydin L. Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. Diabetes Res Clin Pract 2006;71:210-219. (Pubitemid 43112114)
57. van den Meiracker AH, Baggen RG, Pauli S, Lindemans A, Vulto AG, Poldermans D, Boomsma F. Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function. J Hypertens 2006; 24:2285-2292. (Pubitemid 44611039)
58. Ogawa S, Takeuchi K, Mori T, Nako K, Tsubono Y, Ito S. Effects of monotherapy of temocapril or candesartan with dose increments or combination therapy with both drugs on the suppression of diabetic nephropathy. Hypertens Res 2007;30:325-334. (Pubitemid 46804317)
59. Mehdi UF, Adams-Huet B, Raskin P, Vega GL, Toto RD. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol 2009;20:2641-2650.
60. Kuriyama S, Tomonari H, Tokudome G, Horiguchi M, Hayashi H, Kobayashi H, Ishikawa M, Hosoya T. Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. Hypertens Res 2002;25:849-855. (Pubitemid 36024640)
61. Igarashi M, Hirata A, Kadomoto Y, Tominaga M. Dual blockade of angiotensin II with enalapril and losartan reduces proteinuria in hypertensive patients with type 2 diabetes. Endocr J 2006;53:493-501. (Pubitemid 44351500)
62. Uresin Y, Taylor AA, Kilo C, Tschope D, Santonastaso M, Ibram G, Fang H, Satlin A. Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst 2007;8:190-198. (Pubitemid 351166266)
63. Krairittichai U, Chaisuvannarat V. Effects of dual blockade of reninangiotensin system in type 2 diabetes mellitus patients with diabetic nephropathy. J Med Assoc Thai 2009;92:611-617.
64. Titan SM, M. Vieira J J, Dominguez WV, Barros RT, Zatz R. ACEI and ARB combination therapy in patients with macroalbuminuric diabetic nephropathy and low socioeconomic level: a double-blind randomized clinical trial. Clin Nephrol 2011;76:273-283.
65. Ruilope LM, Aldigier JC, Ponticelli C, Oddou-Stock P, Botteri F, Mann JF. Safety of the combination of valsartan and benazepril in patients with chronic renal disease. European Group for the Investigation of Valsartan in Chronic Renal Disease. J Hypertens 2000;18:89-95. (Pubitemid 30093713)
66. Tylicki L, Rutkowski P, Renke M, Rutkowski B. Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation. Am J Nephrol 2002;22:356-362.
67. Luno J, Barrio V, Goicoechea MA, Gonzalez C, de Vinuesa SG, Gomez F, Bernis C, Espinosa M, Ahijado F, Gomez J, Escalada P. Effects of dual blockade of the renin-angiotensin system in primary proteinuric nephropathies. Kidney Int Suppl 2002;82:S47-52. (Pubitemid 35356996)
68. Shoji T, Tomida K, Furumatsu Y, Kaneko T, Togawa M, Okada N, Imai E, Tsubakihara Y. The Long Term Influence of the Combination of Losartan andEnalapril on Erythropoiesis in Japanese Patients with Chronic Glomerulonephritis. J Am Soc Nephrol 2003;14:773A. Abstract.
69. Segura J, Praga M, Campo C, Rodicio JL, Ruilope LM. Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses. J Renin Angiotensin Aldosterone Syst 2003;4:43-47. (Pubitemid 36443386)
70. Renke M, Tylicki L, Rutkowski P, Rutkowski B. Low-dose angiotensin II receptor antagonists and angiotensin II-converting enzyme inhibitors alone or in combination for treatment of primary glomerulonephritis. Scand J Urol Nephrol 2004;38:427-433. (Pubitemid 39551354)
71. Scaglione R, Argano C, Corrao S, Di Chiara T, Licata A, Licata G. Transforming growth factor beta1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive subjects with minor renal abnormalities: a 24-week randomized controlled trial. J Hypertens 2005;23:657-664. (Pubitemid 40684726)
72. Chrysostomou A, Pedagogos E, MacGregor L, Becker GJ. Doubleblind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker. Clin J Am Soc Nephrol 2006;1:256-262.
73. Horita Y, Taura K, Taguchi T, Furusu A, Kohno S. Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy. Nephrology (Carlton) 2006;11: 462-466. (Pubitemid 44470097)
74. Kanno Y, Takenaka T, Nakamura T, Suzuki H. Add-on angiotensin receptor blocker in patients who have proteinuric chronic kidney diseases and are treated with angiotensin-converting enzyme inhibitors. Clin J Am Soc Nephrol 2006;1:730-737.
75. Nakamura T, Inoue T, Sugaya T, Kawagoe Y, Suzuki T, Ueda Y, Koide H, Node K. Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy. Am J Hypertens 2007;20: 1195-1201. (Pubitemid 47588815)
76. Mori-Takeyama U, Minatoguchi S, Murata I, Fujiwara H, Ozaki Y, Ohno M, Oda H, Ohashi H. Dual blockade of the rennin-angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis. Clin Exp Nephrol 2008;12:33-40.
77. Tokunaga M, Tamura M, Kabashima N, Serino R, Shibata T, Matsumoto M, Miyamoto T, Miyazaki M, Furuno Y, Nakamata J, Otsuji Y. Add-On Spironolactone in Patients with Advanced Chronic Kidney Disease Treated with Angiotensin II Receptor Blockers J Am Soc Nephrol 2008; Abstract.
78. Bianchi S, Bigazzi R, Campese VM. Intensive versus conventional therapy to slow the progression of idiopathic glomerular diseases. Am J Kidney Dis 2010;55:671-681.
79. Bakris GL, Ruilope L, Locatelli F, Ptaszynska A, Pieske B, de Champlain J, Weber MA, Raz I. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: results of the IMPROVE trial. Kidney Int 2007 72:879-885. (Pubitemid 47462081)
80. Menne J, Farsang C, Deak L, Klebs S, Meier M, Handrock R, Sieder C, Haller H. Valsartan in combination with lisinopril versus the respective high dose monotherapies in hypertensive patients with microalbuminuria: the VALERIA trial. J Hypertens 2008;2:1860-1867.
81. Ohishi M, Takeya Y, Tatara Y, Yamamoto K, Onishi M, Maekawa Y, Kamide K, Rakugi H. Strong suppression of the renin-angiotensin system has a renal-protective effect in hypertensive patients: high-dose ARB with ACE inhibitor (Hawaii) study. Hypertens Res 2010;33:1150-1154.
82. Luno J, Maria FG, de Vinuesa SG, Praga M. Effect of dual blockade of renin angiotensin system on the progression of type 2 diabetic nephropathy. J Am Soc Nephrol 2011;22 PMID:17699280
83. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-1305.
84. Di Angelantonio E, Chowdhury R, Sarwar N, Aspelund T, Danesh J, Gudnason V. Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study. BMJ 2010;341:c4986.
85. Eriksen BO, Ingebretsen OC. The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age. Kidney Int 2006;69:375-382. (Pubitemid 43323090)
86. De Nicola L, Minutolo R, Chiodini P, Zoccali C, Castellino P, Donadio C, Strippoli M, Casino F, Giannattasio M, Petrarulo F, Virgilio M, Laraia E, Di Iorio BR, Savica V, Conte G. Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention. Kidney Int 2006;69:538-545. (Pubitemid 43164447)
87. Irie F, Iso H, Sairenchi T, Fukasawa N, Yamagishi K, Ikehara S, Kanashiki M, Saito Y, Ota H, Nose T. The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population. Kidney Int 2006;69:1264-1271.
88. National Heart Foundation of Australia. Guide to management of hypertension 2010. http://www.heartfoundation.org.au/informationfor- professionals/Clinical-Information/Pages/hypertension.aspx
89. The Canadian Hypertension Education Program. Updated standardized recommendations and clinical practice guidelines to detect, treat and control hypertension, 2012. http://www.hypertension.ca/chep-recommendations.
90. Bakris GL, Kuritzky L. Monitoring and managing urinary albumin excretion: practical advice for primary care clinicians. Postgrad Med 2009;121:51-60.