UMLS:C0011881 - FACTA Search

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

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.
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PMID:Optimizing antihypertensive therapy in patients with diabetic nephropathy. 985 27

Angiotensin II plays a pivotal role in the development of diabetic nephropathy, but it remains controversial as to the best approach to effectively block the actions of this hormone in the kidney. The aim of the present study was to explore the effects of long-term treatment (8 months) with a combination of an angiotensin type 1 (AT1) receptor antagonist, irbesartan (15 mg/kg per day), and an angiotensin-converting enzyme (ACE) inhibitor, captopril (100 mg/kg per day), in diabetic spontaneously hypertensive rats. Captopril treatment reduced blood pressure (163+/-3 mmHg versus diabetic 201+/-3 mmHg), but not albumin excretion rate (43.8x//1.3 mg/day versus diabetic 46.8x//1.4 mg/day). Irbesartan treatment was associated with a similar reduction in blood pressure (173+/-3 mmHg) to captopril, and albumin excretion rate was reduced (14x//1.5 mg/day). The combination of irbesartan and captopril induced further reductions in blood pressure (140+/-3 mmHg) and albumin excretion rates (4.0x//1.5 mg/day). Gene expression of transforming growth factor beta-1 was reduced by all treatments to a similar level as assessed by in situ hybridization. These results demonstrate the additive hypotensive and anti-albuminuric effects of an ACE inhibitor and an AT1 receptor, suggesting that combination therapy is an approach not only more effective at reducing blood pressure, but also at retarding the development of diabetic nephropathy.
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PMID:Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats. 1135 73

Blood pressure reduction is the most significant factor in delaying onset and progression of renal disease. Blockade of the renin-angiotensin system (RAS) using angiotensin-converting enzyme inhibitors (ACEIs) delays renal disease progression. More recently, agents that block the RAS by preventing angiotensin II from binding to its subtype 1 receptor (ARBs) have been developed in an effort to prevent deleterious consequences of pathologic levels of angiotensin II and to reduce the adverse effects of RAS blockade associated with ACEIs. Human studies with a variety of ARBs have clearly demonstrated the antihypertensive and antiproteinuric efficacy of these agents in patients with progressive renal diseases. Moreover, the effects of ARBs are similar or identical to those of ACEIs. Ongoing long-term clinical trials are designed to determine whether ARBs also preserve renal function similar to ACEIs. Specifically, the role of ARBs in patients with hypertension and type 2 diabetes is being evaluated in 3 large trials, including Appropriate Blood Pressure Control in Diabetes-Part 2 With Valsartan, the Losartan Renal Protection Study, and the Irbesartan Diabetic Nephropathy Trial. Definitive evidence of the long-term protective effects of ARBs in chronic progressive renal disease is expected from these important studies.
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PMID:Angiotensin II subtype 1 receptor blockers and renal function. 1142 96

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
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PMID:Hypertension and diabetes: the scope of the problem. 1146 14

Nephropathy associated with type 2 diabetes mellitus is a rising cause of end-stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy.
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PMID:[Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials]. 1176 85

The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies--the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL)--were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme--that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy.
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PMID:Type 2 diabetes: RENAAL and IDNT--the emergence of new treatment options. 1182 41

The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.
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PMID:Angiotensin II receptor blockers for the treatment of hypertension. 1182 17

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
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PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT(1)) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was approximately 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT(1) antagonists. These clinical trials suggest that there may be a class renoprotective action with AT(1) antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT(1) antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.
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PMID:Class benefits of AT(1) antagonists in Type 2 diabetes with nephropathy. 1199 40

Despite intense investigation and clinical attention, many challenges remain in the management of the hypertensive patient. It is clear that hypertension remains inadequately controlled worldwide, with the control rate in the United States approximating 27%. Furthermore, several recent studies have underscored that it is frequently difficult to attain control at goal blood pressure (BP) with monotherapy and that adequate control of hypertension based on the newer more intensified BP goals necessitates multiple drug therapy. Indeed, in the recently published landmark trials of angiotensin I receptor antagonists, including the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL), multiple antihypertensive drugs were required to attain goal. A pivotal class of drug required to comprise this regimen is the calcium antagonists. For example, in RENAAL, 78% of patients randomized to losartan required add-on therapy with a calcium antagonist. Calcium antagonists are an important and often necessary component of this multiple drug regimen.
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PMID:Recent landmark clinical trials: how do they modify the therapeutic paradigm? 1212 Oct 10

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