Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Jacobsen, Peter Karl; Andersen, Steen; Jensen, Bente; Parving, Hans‐Henrik

doi:10.1097/01.asn.0000054495.96193.bf

Cited by 194 publications

(159 citation statements)

References 48 publications

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“…The improvement of BP control by using antihypertensive agents, such as ACE inhibitors or ARBs, has also been reported in previous studies (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). A significant increase in the prescription of ARBs was observed in 2003 compared with 1996 in RD patients.…”

Section: Discussionsupporting

confidence: 73%

“…Several studies have suggested that the combined treatment with ACE inhibitors and ARBs may be more renoprotective than treatment with either agent alone (12,(20)(21)(22)24), and, indeed, in some RD patients, the combination of ACE inhibitors and ARBs was also prescribed in the present study. The improvement of BP control by using antihypertensive agents, such as ACE inhibitors or ARBs, has also been reported in previous studies (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 75%

“…Based on the findings obtained from the large-scale clinical trials (5,7), recent guidelines for the management of hypertension, such as JNC VI, JNC 7, WHO/ISH 1999, ESH-ESC 2003 and Japanese Society of Hypertension (JSH) 2004 recommend strict BP control in RD (8)(9)(10)(11). Moreover, the development of newer classes of antihypertensive drugs, such as angiotensin II receptor blockers (ARBs), has had a beneficial influence on the management of hypertension with RD (2,3,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Thus, the aim of the present study was to assess the current status of BP control in hypertensive patients with RD, and whether BP control improved during the period between 1996 and 2003, i.e., before and after the introduction of recent hypertension guidelines.…”

Section: Introductionmentioning

confidence: 99%

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Improvement of Blood Pressure Control in Hypertensive Patients with Renal Diseases

et al. 2007

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Improvement of Blood Pressure Control in Hypertensive Patients with Renal Diseases

et al. 2007

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“…The addition of ARB induced a mean reduction in albuminuria of 37% and a reduction in 24-h BP of 8 mmHg SBP (P ϭ 0.11) and 5 mmHg DBP (P Ͻ 0.01). Similar results were reported by the same author in type 1 diabetes in a randomized, double-blind, crossover trial of 18 patients who had albuminuria Ͼ300 mg/24 h and received 8 wk of placebo, 20 mg of benazepril, or 80 mg of valsartan and the combination (20 mg ϩ 80 mg) in a random order (29). Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo.…”

Section: Combined Treatment With Acei and Arbsupporting

confidence: 82%

Dual Blockade of the Renin-Angiotensin System in the Progression of Renal Disease

Fernández-Juárez¹,

Barrio²,

Vinuesa³

et al. 2006

Journal of the American Society of Nephrology

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There is clear evidence that pharmacologic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows the progression of renal disease in diabetic and nondiabetic nephropathies, a beneficial effect that is not related to BP control. Some patients exhibit a significant beneficial response, whereas others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove useful. ARB produces a complete blockade of the RAS. Several studies have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone. A recent study also demonstrated that this more marked antiproteinuric effect is associated with less progression of renal disease in primary nondiabetic nephropathies despite a similar effect on BP. Until now, there has not been any reference to a beneficial effect on progression of the dual blockade in type 2 diabetic nephropathy, which is the most frequent cause of ESRD. A multicenter, prospective, open, active-controlled, and parallel-group trial was designed to compare the effects of an ACE inhibitor versus an ARB or its combination on renal disease progression, proteinuria, and cardiovascular events in type 2 diabetic nephropathy. S ingle-nephron hyperfiltration hypothesis, put forward by Brenner more than 20 yr ago, helped to explain the inexorable decline in renal function that is observed in chronic renal disease once the initial insult has disappeared. Angiotensin II is responsible for the increase in glomerular hydraulic capillary pressure by means of increasing systemic BP along with vasoconstriction of the efferent arteriole, thereby increasing filtration pressure in glomerular capillary walls. In experimental rat models with renal disease, a decrease of similar magnitude in systemic BP can be achieved either with angiotensin-converting enzyme inhibitors (ACEI) or with a combination of diuretics, reserpine and hydralazine, although only in those who are treated with ACEI is a reduction in glomerular capillary pressure and in progression of renal disease observed (1). J Am Soc NephrolBesides these hemodynamic changes, many other experimental models of renal damage that result in severe proteinuria (e.g., nephrosis by adriamycin or immune-complex glomerulonephritis [2,3]) have implicated angiotensin as a mediator in most of the inflammatory mechanisms that are involved in the progression of chronic renal disease. In proteinuric nephropathies, protein trafficking through proximal tubular cells, besides damaging this tubular segment, stimulates the production of NF-B, in part induced by angiotensin (4). NF-B is present in all cellular types and plays a crucial role in inflammation and apoptosis. In experimental models of nephritis, activation of NF-B results i...

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“…All strategies reduce proteinuria compared with single-agent therapy (5)(6)(7)(8)(9)(10)(11), but hyperkalemia is a risk (12,13). Regimens including an ACE inhibitor and ARB or either drug and DRI are not recommended not only because of the risk of hyperkalemia but also because of renal failure and hypotension, which were seen in large clinical trials (14,15).…”

Section: Introductionmentioning

confidence: 99%

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

Buren

Adams‐Huet

Nguyen³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation.Design, setting, participants, & measurements In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models.Results Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P,0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P,0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study.Conclusion Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of extrarenal potassium homeostasis will provide an opportunity to use this drug more safely in patients with diabetic nephropathy as well as other patient populations.

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Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Cited by 194 publications

References 48 publications

Improvement of Blood Pressure Control in Hypertensive Patients with Renal Diseases

Improvement of Blood Pressure Control in Hypertensive Patients with Renal Diseases

Dual Blockade of the Renin-Angiotensin System in the Progression of Renal Disease

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

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