Renoprotective Effect of Small Doses of Losartan and Enalapril in Patients with Primary Glomerulonephritis
Background: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The...
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Published in | American journal of nephrology Vol. 22; no. 4; pp. 356 - 362 |
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Format | Journal Article |
Language | English |
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Basel, Switzerland
01.04.2002
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Abstract | Background: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. Methods: Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. Results: Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. Conclusions: These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy. |
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AbstractList | Background: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. Methods: Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. Results: Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. Conclusions: These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy. |
Author | Rutkowski, Przemyslaw Renke, Marcin Rutkowski, Boleslaw Tylicki, Leszek |
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Cites_doi | 10.1097/00004872-200018010-00013 10.1159/000013417 10.1056/NEJM199604113341502 10.1056/NEJM199311113292004 10.1046/j.1523-1755.1998.00164.x 10.1046/j.1523-1755.2000.00224.x |
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Keywords | Angiotensin-converting enzyme inhibitors Glomerulonephrits Kidney Angiotensin II receptor blockers Proteinuria |
Language | English |
License | Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. https://www.karger.com/Services/SiteLicenses |
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References | Andersen S, Tarnow L, Rossing P, Hansen BV, Parving HH: Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy. Kidney Int 2000;57:601-606.10652037 Kohzuki M, Yasujima M, Liu PF, Obara K, Kanazawa M, Yoshida K, Saito T, Sato T, Abe K: Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus. Clin Exp Pharm Physiol 1995;22:S366-S367. Hebert LA, Falkenhain ME, Nahman NS, Cosio FG, O'Dorisio TM: Combination ACE inhibitor and angiotesin II receptor antagonist therapy in diabetic nephropathy. Am J Nephrol 1997;19:1-6.10.1159/000013417 Nielsen S, Dollerup J, Nielsen B, Jensen H, Mogensen CE: Losartan reduces albuminuria in patients with essential hypertension: An enalapril controlled 3 months study. Nephrol Dial Transplant 1997;12(suppl 2):S19-S23. Zoccali C, Valvo E, Russo D, Panichi V, Zuccala A: Antiproteinuric effects of losartan in patients with chronic renal diseases (letter). Nephrol Dial Transplant 1997;12:234-235.9027813 Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zuchelli P: Effect of angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency: The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Eng J Med 1996;334:939-945.859659410.1056/NEJM199604113341502 Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-2446.9385294 Ots M, Mackenzie HS, Troy JL, Rennke HG, Brenner BM: Effects of combination therapy with enalapril and losartan on the rate of progression of renal injury with 5/6 renal mass ablation. J Am Soc Nephrol 1998;9:224-230.9527398 Veelken R, Hilgers KF, Mann JFE: The acute renal effects of angiotensin II receptor blockers. Nephrol Dial Transplant 1998;13:1928-1929.9719141 Edwards RM: Response of isolated renal arterioles to acetylocholine, dopamine and bradykinin. Am J Physiol 1985;248:F181-F189. Ruiz-Ortega M, Lorenzo O, Ruperez M, Egido J: ACE inhibitors and AT1 receptor antagonists - beyond the haemodynamic effect. Nephrol Dial Transplant 2000;15:561-565.10809789 Peters H, Border WA, Noble NA: Targeting TGF-β overexpression in renal disease: Maximizing the antifibrotic action of angiotensin II blockade. Kidney Int 1998;54:1570-1580.984413310.1046/j.1523-1755.1998.00164.x Conlin PR: Angiotensin II antagonists in the treatment of hypertension: More similarities than differences. J Clin Hypertens 2000;2:253-257. Hollenberg NK: Impact of angiotensin II on the kidney: Does an angiotensin II receptor blocker make sense? Am J Kidney Dis 2000;36:S18-S23.10986155 Gansevoort RT, De Zeeuw D, De Jong PE: Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? Kidney Int 1994;45:861-867.8196289 Taal MW, Brenner B: Renoprotective benefits of RAS inhibition: From ACEI to angiotensin II antagonists. Kidney Int 2000;57:1803-1817.10792600 Ruilope LM, Aldigier JC, Ponticelli C, Oddou-Stock P, Botteri F, Mann JF on behalf of the European Group for the Investigation of Valsartan in Chronic Renal Disease: Safety of the combination of valsartan and benazepril in patients with chronic renal diseases. J Hypertens 2000;18:89-95.1067854810.1097/00004872-200018010-00013 Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-1462.841345610.1056/NEJM199311113292004 Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M, Minutolo R: Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 1999;33:851-856.10213639 El Nahas AM: Renal scarring: The role of angiotensin II. Nephrol Dial Transplant 1995;10(suppl 9): 28-32. Tylicki L, Renke M, Rutkowski P, Rutkowski B: Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis - pilot study. J Ren Nutr 2002, in press. Edwards RM, Trizna W, Stack EJ, Weinstock J: Interaction of nonpeptide angiotensin II receptor antagonists with the urate transporter in rat renal brush-border membranes. J Pharmacol Exp Ther 1996;276:125-129.8558420 Perico N, Remuzzi A, Sangalli F, Azzollini N, Mister M, Ruggenenti P, Remuzzi G: The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indometacin. J Am Soc Nephrol 1998;9:2308-2317.9848785 Lacourciere Y, Belanger A, Godin C, Halle JP, Ross S, Wright N, Marion J: Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int 2000;58:762-769.1091610010.1046/j.1523-1755.2000.00224.x ref2 ref1 ref4 ref3 ref6 ref5 |
References_xml | – reference: Lacourciere Y, Belanger A, Godin C, Halle JP, Ross S, Wright N, Marion J: Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int 2000;58:762-769.1091610010.1046/j.1523-1755.2000.00224.x – reference: Zoccali C, Valvo E, Russo D, Panichi V, Zuccala A: Antiproteinuric effects of losartan in patients with chronic renal diseases (letter). Nephrol Dial Transplant 1997;12:234-235.9027813 – reference: Kohzuki M, Yasujima M, Liu PF, Obara K, Kanazawa M, Yoshida K, Saito T, Sato T, Abe K: Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus. Clin Exp Pharm Physiol 1995;22:S366-S367. – reference: Perico N, Remuzzi A, Sangalli F, Azzollini N, Mister M, Ruggenenti P, Remuzzi G: The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indometacin. J Am Soc Nephrol 1998;9:2308-2317.9848785 – reference: Andersen S, Tarnow L, Rossing P, Hansen BV, Parving HH: Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy. Kidney Int 2000;57:601-606.10652037 – reference: Ruiz-Ortega M, Lorenzo O, Ruperez M, Egido J: ACE inhibitors and AT1 receptor antagonists - beyond the haemodynamic effect. Nephrol Dial Transplant 2000;15:561-565.10809789 – reference: Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zuchelli P: Effect of angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency: The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Eng J Med 1996;334:939-945.859659410.1056/NEJM199604113341502 – reference: Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-2446.9385294 – reference: Gansevoort RT, De Zeeuw D, De Jong PE: Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? Kidney Int 1994;45:861-867.8196289 – reference: Veelken R, Hilgers KF, Mann JFE: The acute renal effects of angiotensin II receptor blockers. Nephrol Dial Transplant 1998;13:1928-1929.9719141 – reference: Nielsen S, Dollerup J, Nielsen B, Jensen H, Mogensen CE: Losartan reduces albuminuria in patients with essential hypertension: An enalapril controlled 3 months study. Nephrol Dial Transplant 1997;12(suppl 2):S19-S23. – reference: Ots M, Mackenzie HS, Troy JL, Rennke HG, Brenner BM: Effects of combination therapy with enalapril and losartan on the rate of progression of renal injury with 5/6 renal mass ablation. J Am Soc Nephrol 1998;9:224-230.9527398 – reference: Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-1462.841345610.1056/NEJM199311113292004 – reference: Hebert LA, Falkenhain ME, Nahman NS, Cosio FG, O'Dorisio TM: Combination ACE inhibitor and angiotesin II receptor antagonist therapy in diabetic nephropathy. Am J Nephrol 1997;19:1-6.10.1159/000013417 – reference: Ruilope LM, Aldigier JC, Ponticelli C, Oddou-Stock P, Botteri F, Mann JF on behalf of the European Group for the Investigation of Valsartan in Chronic Renal Disease: Safety of the combination of valsartan and benazepril in patients with chronic renal diseases. J Hypertens 2000;18:89-95.1067854810.1097/00004872-200018010-00013 – reference: Conlin PR: Angiotensin II antagonists in the treatment of hypertension: More similarities than differences. J Clin Hypertens 2000;2:253-257. – reference: Edwards RM, Trizna W, Stack EJ, Weinstock J: Interaction of nonpeptide angiotensin II receptor antagonists with the urate transporter in rat renal brush-border membranes. J Pharmacol Exp Ther 1996;276:125-129.8558420 – reference: Hollenberg NK: Impact of angiotensin II on the kidney: Does an angiotensin II receptor blocker make sense? Am J Kidney Dis 2000;36:S18-S23.10986155 – reference: El Nahas AM: Renal scarring: The role of angiotensin II. Nephrol Dial Transplant 1995;10(suppl 9): 28-32. – reference: Russo D, Pisani A, Balletta MM, De Nicola L, Savino FA, Andreucci M, Minutolo R: Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 1999;33:851-856.10213639 – reference: Edwards RM: Response of isolated renal arterioles to acetylocholine, dopamine and bradykinin. Am J Physiol 1985;248:F181-F189. – reference: Taal MW, Brenner B: Renoprotective benefits of RAS inhibition: From ACEI to angiotensin II antagonists. Kidney Int 2000;57:1803-1817.10792600 – reference: Peters H, Border WA, Noble NA: Targeting TGF-β overexpression in renal disease: Maximizing the antifibrotic action of angiotensin II blockade. Kidney Int 1998;54:1570-1580.984413310.1046/j.1523-1755.1998.00164.x – reference: Tylicki L, Renke M, Rutkowski P, Rutkowski B: Short-term effects of angiotensin II receptor blockade in patients with primary glomerulonephritis - pilot study. J Ren Nutr 2002, in press. – ident: ref6 doi: 10.1097/00004872-200018010-00013 – ident: ref5 doi: 10.1159/000013417 – ident: ref2 doi: 10.1056/NEJM199604113341502 – ident: ref1 doi: 10.1056/NEJM199311113292004 – ident: ref3 doi: 10.1046/j.1523-1755.1998.00164.x – ident: ref4 doi: 10.1046/j.1523-1755.2000.00224.x |
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Title | Renoprotective Effect of Small Doses of Losartan and Enalapril in Patients with Primary Glomerulonephritis |
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