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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

Through an integrative understanding of cardiovascular pathophysiologic characteristics at the multiorgan level, significant achievements in cardiovascular therapeutics have been achieved and enabled the rationale design and development of drugs such as the angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). In this article, we present a detailed review of the physiologic features of the renin-angiotensin-aldosterone system (RAAS), ACE inhibitors and ARB clinical pharmacologic characteristics, and specific diseases in which they are considered to be the standard of the care as supported by important clinical trial data. It is envisioned that an updated and detailed understanding of ACE inhibitors and ARBs will facilitate their successful use in the treatment of heart failure, myocardial infarction, hypertension, renal failure, and diabetic nephropathy.
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PMID:The clinical use of angiotensin-converting enzyme inhibitors. 1558 52

Diabetic nephropathy is the number one cause of endstage renal disease in the United States. Blood pressure is most important in delaying the progression of renal disease in persons with diabetes and, agents that block the renin angiotensin system (RAS) should be the primary agents used to achieve blood pressure reduction. There is debate regarding which method of RAS blockade should be used as primary therapy in persons with diabetes. There are not significant differences between angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) with regard to renal outcomes. Consideration of the enormously high rates of cardiovascular disease (CVD) in persons with diabetes and renal disease is the primary factor in choosing agents for blood pressure reduction. The ACE inhibitors and ARBs have been shown to reduce cardiovascular events in persons with diabetes and, there are recent comparable trials between the 2 classes. Some studies and meta-analyses show ACE inhibitors as being superior with regard to cardioprotection. In our nephrology clinic, we find that patients who presented on an ACE inhibitor had significantly lower CVD than those on ARBs (49.2% vs 70.1% prevalence of CVD, ACE inhibitor vs ARB respectively, P=.042). We conclude that ACE inhibitors should be strongly considered as the primary method of RAS inhibition in persons with diabetes.
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PMID:Therapeutic controversies in hypertension management: angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers in diabetic nephropathy? ACE inhibitors. 1572 89

High blood pressure plays a key role in the progression of renal failure. Hypertension is a common presentation of kidney disease and an almost invariable accompaniment of renal failure. Hypertension is also a major contributor to cardiovascular disease, the major cause of morbidity and mortality in renal failure. Hypertension is both cause and consequence of renal failure, but the precise nature and prevalence of hypertensive nephrosclerosis as a cause of renal failure remains controversial. There is strong evidence that hypertension accelerates the progression of experimental renal disease and that control of blood pressure is effective in preventing this progression. Hypertension, both accelerated and "benign" (a misnomer), has long been recognised as a poor prognostic feature in human renal disease and more recently in renal allograft survival. Blood pressure control is very effective in retarding renal disease progression. There are compelling indications for angiotensin-converting enzyme inhibitors in both non-diabetic and type 1 diabetic nephropathies, and for angiotensin receptor blockers in type 2 diabetic nephropathy. Most patients will require combination drug therapy to control blood pressure and reduce both progression of renal failure and the associated cardiovascular morbidity and mortality.
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PMID:Progression of renal failure -- the role of hypertension. 1572 14

Diabetic nephropathy (DN) is characterized by glomerulopathy and tubulointerstitial expansion followed by renal fibrosis. Angiotensin II (Ang II) and connective tissue growth factor (CTGF) are involved in the pathogenesis of DN, while Janus kinase 2 (JAK2) is important in advanced glycation end-product (AGE)-induced effects in renal interstitial (NRK-49F) fibroblasts. Thus, we studied the role of Ang II, CTGF, and JAK2 in AGE-induced effects in NRK-49F cells. We found that AGE (150 microg/ml) increased mitogenesis and type I collagen production at 7 days while Ang II (10(-7)M) increased mitogenesis and type I collagen production at 3 days. We also found that AGE (150 microg/ml) increased angiotensinogen protein at 2 days, which was attenuated by AG-490 (a JAK2 inhibitor). AGE (150 microg/ml) increased CTGF mRNA and protein expression at 3 and 5 days, respectively. Ang II (10(-7)M) increased CTGF mRNA and protein expression at 1 and 2 days, respectively, which were attenuated by AG-490. Moreover, losartan (a type I angiotensin receptor blocker) and captopril (an angiotensin converting enzyme inhibitor) attenuated AGE-induced CTGF mRNA/protein expression while attenuating AGE-induced mitogenesis and type I collagen production. AG-490 and CTGF antisense (but not sense) oligodeoxynucleotide (ODN) attenuated Ang II (10(-7)M) and AGE-induced mitogenesis and type I collagen production at 3 and 7 days, respectively. We concluded that AGE (150 microg/ml)-induced mitogenesis and type I collagen production are dependent on the Ang II-JAK2-CTGF pathway in NRK-49F cells. Moreover, Ang II-induced mitogenesis and type I collagen production are dependent on the JAK2-CTGF pathway.
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PMID:Advanced glycation end-product-induced mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cells. 1577 Jun 49

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. 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 to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.
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PMID:The reno-protective effect of the dual blockade of the renin angiotensin system (RAS). 1585 85

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action. Fixed-dose combinations of an ARB and low-dose hydrochlorothiazide provide a convenient and effective treatment option for patients who do not achieve blood pressure targets on monotherapy, without compromising the placebo-like tolerability of ARBs. In Europe, fixed-dose combinations with hydrochlorothiazide currently are available for the ARBs candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. Recently, a number of studies have focused on the use of ARBs in monotherapy and in combination therapy, in conditions including congestive heart failure, post-myocardial infarction management, hypertension with cardiovascular risk factors, and diabetic and non-diabetic nephropathy. Evidence from these studies suggests a beneficial role beyond the antihypertensive effect of these therapies in providing protection against cardiovascular, renovascular, and cerebrovascular events.
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PMID:Angiotensin II receptor antagonists alone and combined with hydrochlorothiazide: potential benefits beyond the antihypertensive effect. 1590 Dec 5

Type 2 diabetes is reaching epidemic proportions throughout the world, representing the most common cause of ESRD. Early identification of renal impairment associated with diabetes and initiation of renoprotective therapy are imperative. High BP, dyslipidemia, long duration of diabetes, and poor glycemic control are important risk factors; their modification, renal function monitoring, and combined therapies are the current integrated approaches to treat patients with diabetic kidney disease. Strong evidence suggests that achieving target BP goals via inhibition of the renin-angiotensin-aldosterone system confers significant renal protection for diabetic patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers lower BP and reduce both the progression of renal damage and adverse cardiovascular events; some important renoprotective actions seem to be independent of the antihypertensive effect. Stringent quality of glycemic control is another key point to prevent onset of nephropathy or slow its progression. Evidence from basic research and clinical trials indicates that hypolipidemic drugs, mainly statins, contribute to modulate the progression of renal damage in diabetes; their use should be considered in any patient with diabetes. Smoking cessation may slow nephropathy progression; given the additional health benefits of stopping smoking, this advice is an important part of the strategy of diabetic nephropathy treatment and prevention. In conclusion, a target-driven, long-term, intensified intervention aimed at multiple risk factors should be recommended in patients with diabetes to preserve their kidney function.
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PMID:Antihypertensive treatment and multifactorial approach for renal protection in diabetes. 1593 27

Since recent studies demonstrated an impaired outcome after percutaneous coronary interventions (PCI) in patients with chronic renal failure but did not address the aetiology of renal failure, we now analysed the outcome of patients with diabetic nephropathy in 721 consecutive patients undergoing PCI. Diabetic nephropathy was present in 37 patients (5.1%), and diabetes alone in 126 patients (17.5%); 178 patients (24.7%) suffered from renal insufficiency of other causes; the other 380 patients (52.7%) were used as controls. Although angiographic success rates were similar in the subgroups (94-97%), 30-day and long-term mortality after 4 years was significantly higher in patients with diabetic nephropathy (8.1 and 27%, respectively) than in diabetics (1.6 and 8.7%, respectively), patients with renal insufficiency (3.9 and 16.8%, respectively), or controls (2.4 and 5.0%, respectively, each p<0.001, log-rank test). Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a marked decrease in 2-year mortality in patients with diabetic nephropathy (19.4 vs. 33.3%, respectively, p=0.02, log-rank test).
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PMID:Diabetic nephropathy, percutaneous coronary interventions, and blockade of the renin-angiotensin system. 1594 80

Increasing number of diabetic patients develop different stages of renal failure. However, often an inappropriate parameter, the serum creatinine is measured as a marker of glomerular function. Calculated glomerular filtration rate or endogenous creatinine clearance are suggested to be used for the estimation of the glomerular function. Important structures preventing proteinuria in the kidney are glomerular basement membrane, podocytes and proximal tubular cells. In diabetes mellitus loss of nephrin of podocytes can play a role in the development of microalbuminuria, and podocyte desquamation may result in the progression to proteinuria. In diabetes mellitus there is an increased formation of advanced glycation endproducts (AGE), of which the only elimination organ is the kidney. The AGE induce proteinuria and atherosclerosis. Therefore, in diabetes mellitus a vicious circle develops due to proteinuria, nephron loss and accumulation of AGE, which play a role in the initiation and progression of diabetic nephropathy and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers having antiproteinuric effect may decrease the risk of diabetic nephropathy and atherosclerosis. Improvement of carbohydrate metabolism with a consequential decrease in the formation of AGE is an important contributor to the prevention and treatment of diabetic nephropathy and atherosclerosis.
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PMID:Prevention and treatment of diabetic nephropathy. 1595 73


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