Background: Treatment of hypertension slows the progression of non-diabetic nephropathies, but the optimal regimen is unknown. Angiotensin-converting enzyme inhibitors are more effective than β-blockers, but their merits relative to calcium channel blockers are less clear. Methods: 73 hypertensive patients with progressive non-diabetic nephropathies were prospectively randomised to open-label quinapril (Q, n = 28), amlodipine (A, n = 28) or both drugs (Q&A, n = 17). Therapy was increased to achieve a diastolic blood pressure <90 mm Hg. Patients were followed for 4 years or until death. The primary outcome was the combined endpoint of doubling serum creatinine, starting renal replacement therapy or death. Results: There was no significant difference in the primary outcome, or in the change of glomerular filtration rate. Blood pressure was equally controlled throughout the study period. 29 (40%) patients were withdrawn from the allocated therapy (Q 39%, A 36%, Q&A 47%). Because of the large crossover between trial arms, the data were re-analysed per protocol. The effect on preventing the need for renal replacement therapy then approached significance between the groups (p = 0.089) and the combined quinapril-containing groups were less likely than the amlodipine group to achieve the primary endpoint (p = 0.038), or the individual endpoints of renal replacement therapy (p = 0.030) or doubling creatinine (p = 0.051). Conclusions: Quinapril is more effective than amlodipine at reducing the incidence of dialysis in patients with progressive renal failure, but only if they can tolerate the drug. The tolerability of these drugs in patients with advanced renal failure is poor.

Keywords:
Angiotensin-converting enzyme inhibitors, Calcium channel blockers, Drug side effects, Hypertension, Chronic kidney failure, Proteinuria
1.
Mackenzie HS, Taal MW, Luyckx VA, Brenner BM: Adaptation to nephron loss; in Brenner BM (ed): Brenner & Rector’s The Kidney, ed 6. Philadelphia, Saunders, 2000, pp 1901–1942.
2.
Wilmer WA, Rovin BH, Hebert CJ, Rao SV, Kumor K, Hebert LA: Management of glomerular proteinuria: a commentary. J Am Soc Nephrol 2003;14:3217–3232.
3.
Klahr S, Levey A, Beck J, et al: The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N Engl J Med 1994;330:877–884.
4.
Maschio G, Alberti D, Janin G, et al: Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996;334:939–945.
5.
Zucchelli P, Zuccalà A, Borghi M, et al: Long-term comparison between captopril and nifedipine in the progression of renal insufficiency. Kidney Int 1992;42:452–458.
6.
The GISEN Group: Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857–1863.
7.
Hannedouche T, Landais P, Goldfarb B, et al: Randomised controlled trial of enalapril and β blockers in non-diabetic chronic renal failure. BMJ 1994;309:833–837.
8.
Himmelmann A, Hansson L, Hansson BG, et al: ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension. Blood Press 1995;4:85–90.
9.
Remuzzi G, Ruggenenti P, Perico N: Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition. Ann Intern Med 2002;136:604–615.
10.
Jafar TH, Schmid CH, Landa M, et al: Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med 2001;135:73–87.
11.
McLaughlin KJ, Harden PN, Ueda S, Boulton-Jones JM, Connell JMC, Jardine AG: The role of genetic polymorphisms of angiotensin-converting enzyme in the progression of renal diseases. Hypertension 1996;28:912–915.
12.
Perna A, Ruggenenti P, Testa A, et al: ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies. Kidney Int 2000;57:274–281.
13.
Epstein M: Calcium antagonists and renal disease. Kidney Int 1998;54:1771–1784.
14.
Harris DC, Hammond WS, Burke TJ, Schrier RW: Verapamil protects against progression of experimental chronic renal failure. Kidney Int 1987;31:41–46.
15.
Bianchi S, Bigazzi R, Baldari G, Campese VM: Long-term effects of enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up. Am J Nephrol 1991;11:131–137.
16.
Okamura M, Kanayama Y, Negoro N, Inoue T, Takeda T: Long-term effects of calcium antagonists and angiotensin-converting enzyme inhibitors in patients with chronic renal failure of IgA nephropathy. Contrib Nephrol. Basel, Karger, 1991, vol 90, pp 161–165.
17.
Bannister KM, Weaver A, Clarkson AR, Woodroffe AJ: Effect of angiotensin-converting enzyme and calcium channel inhibition on progression of IgA nephropathy. Contrib Nephrol. Basel, Karger, 1995, vol 111, pp 184–192.
18.
Kanno Y, Suzuki H, Okada H, Takenaka T, Saruta T: Calcium channel blockers versus ACE inhibitors as antihypertensives in polycystic kidney disease. Quart J Med 1996;89:65–70.
19.
Acone D, Cante D, Cillo F, Giordano G, Giordano C: Blood pressure and progression of renal failure in the elderly. Kidney Int 1996;49(suppl 55):S75–S77.
20.
Pedersen EB, Bech JN, Nielsen CB, et al: A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years. Scand J Clin Lab Invest 1997;57:673–681.
21.
Kumagai H, Hayashi K, Kumamaru H, Saruta T: Amlodipine is comparable to angiotensin-converting enzyme inhibitor for long-term renoprotection in hypertensive patients with renal dysfunction: a one-year, prospective, randomized study. Am J Hypertens 2000;980–985.
22.
Ecder T, Chapman AB, Brosnahan GM, Edelstein CL, Johnson AM, Schrier RW: Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2000;35:427–432.
23.
Herlitz H, Harris K, Risler T, et al: The effects of an ACE inhibitor and a calcium antagonist on the progression of renal disease: the Nephros study. Nephrol Dial Transplant 2001;16:2158–2165.
24.
Petersen LJ, Petersen JR, Talleruphuus U, et al: A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension. Clin Nephrol 2001;55:375–383.
25.
Rose GW, Kanno Y, Ikebukuro H, et al: Cilnidipine is as effective as benazepril for control of blood pressure and proteinuria in hypertensive patients with benign nephrosclerosis. Hypertens Res 2001;24:377–383.
26.
Hayashi K, Kumagai H, Saruta T: Effect of efonidipine and ACE inhibitors on proteinuria in human hypertension with renal impairment. Am J Hypertens 2003;16:116–122.
27.
Marin R, Ruilope LM, Aljama P, Aranda P, Segura J, Diez J: A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease. J Hypertens 2001;19:1871–1876.
28.
Agodoa LY, Appel L, Bakris GL, et al: Effect of ramipril vs. amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. J Am Med Assoc 2001;285:2719–2728.
29.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–470.
30.
Traynor JP, Simpson K, Geddes CC, Deighan CJ, Fox JG: Early initiation of dialysis fails to prolong survival in patients with end-stage renal failure. J Am Soc Nephrol 2002;13:2125–2132.
31.
Klahr S, Breyer JA, Beck GJ, et al: Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group. J Am Soc Nephrol 1995;5:2037–2047.
32.
Van Dijk MA, Breuning MH, Duiser R, van Es LA, Westendorp RG: No effect of enalapril on progression in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 2003;18:2314–2320.
33.
Ruggenenti P, Perna A, Remuzzi G: ACE inhibitors to prevent end-stage renal disease. When to start and why possibly never to stop: a post-hoc analysis of the REIN trial results. J Am Soc Nephrol 2001;12:2832–2837.
34.
Payton CD, McLay A, Boulton-Jones JM: Progressive IgA nephropathy: the role of hypertension. Nephrol Dial Transplant 1988;2:138–142.
35.
Brazy PC, Stead WW, Fitzwilliam JF: Progression of renal insufficiency: role of blood pressure. Kidney Int 1989;35:670–674.
36.
Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE: Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. Nephrol Dial Transplant 1995;10:1963–1974.
37.
Ruggenenti P, Perna A, Benini R, Remuzzi G: Effects of dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibition, and blood pressure control on chronic, nondiabetic nephropathies. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). J Am Soc Nephrol 1998;9:2096–2101.
38.
Bakris GL, Weir MR, DeQuattro V, McMahon FG: Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy. Kidney Int 1998;54:1283–1289.
39.
Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T: Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 2003;361:117–124.
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2005
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