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

Total serum homocysteine (tHcy) has been shown to predict de novo and recurrent cardiovascular events in many studies. However, results in diabetic populations with minimal nephropathy are mixed. The independent relationship between tHcy and arteriosclerotic outcomes and congestive heart failure (CHF) events in a population with high cardiovascular risk and diabetic nephropathy was examined. A total of 1575 individuals were enrolled in the international Irbesartan Diabetic Nephropathy Trial (IDNT) and followed for 2.6 yr. All participants had baseline diabetic nephropathy, overt proteinuria, and hypertension and were recruited between 1996 and 1999. A total of 492 total arteriosclerotic outcomes (primary outcome) and 317 CHF events (secondary outcome) were tallied. Established cardiovascular risk factors were highly prevalent, as were high tHcy levels (quintiles [microM]: first 4.5 to 11; second >11 to 13; third >13 to 15; fourth >15 to 19; fifth >19). No association between tHcy and arteriosclerotic outcomes was observed in a univariate model or after adjustment for study randomization and established cardiovascular risk factors. The strongest outcome predictor was the presence of baseline cardiovascular disease, followed by an inverse relationship to diastolic BP. The significant univariate association between tHcy and CHF events disappeared when serum creatinine alone was added to the model. These findings question the utility of tHcy in predicting de novo or recurrent cardiovascular events in individuals with diabetic nephropathy. Further studies are needed to confirm whether these negative results apply to other populations with heavy cardiovascular risk burdens. Previous positive findings can potentially be explained through tHcy's role as a sensitive surrogate marker for kidney disease, itself a recognized cardiovascular risk factor.
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PMID:Total plasma homocysteine and arteriosclerotic outcomes in type 2 diabetes with nephropathy. 1616 14

Despite the well-documented effect of irbesartan, an angiotensin AT1 receptor antagonist, on diabetic nephropathy, its effect on mortality related to multiple metabolic risk factors is unknown. To address this question, obese fa/fa Zucker rats were submitted to a 13-month treatment by irbesartan (30 mg/kg/day p.o.). Vehicle-treated obese fa/fa Zucker rats exhibited an important mortality (72%), which was markedly reduced by irbesartan (22%, P<0.05). Mortality in control lean fa/+ rats attained 12%. Irbesartan diminished the elevation in urinary protein excretion, plasma creatinine and urea nitrogen levels, and reduced the extent of glomerular and tubulo-interstitial lesions together with a reduction of urinary monocyte chemoattractant protein-1 excretion in fa/fa Zucker rats. Irbesartan treatment prevented the rise in plasma total cholesterol, triglycerides and glucose levels, and partially corrected low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio in fa/fa Zucker rats. Therefore, prolonged irbesartan treatment preserves renal function and metabolic profile, and substantially increases survival in obese fa/fa Zucker rats.
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PMID:Long-term blockade of angiotensin AT1 receptors increases survival of obese Zucker rats. 1651 82

There is a rising incidence and prevalence of ESRD as a result of diabetes, with poor outcome and growing costs. Recently, two large trials, the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL), showed that angiotensin receptor blockers (ARB) are more effective than traditional antihypertensive therapies at reducing progression toward ESRD in hypertensive patients with type 2 diabetes and overt nephropathy, regardless of changes in BP. The results of these two trials were used to compare the costs of ARB with those of renal replacement therapy (dialysis and renal transplantation) in an effort to establish whether ARB are cost-saving because they delay ESRD. Two different pharmacoeconomic approaches were used. With regard to the RENAAL trial, the number of ESRD days on losartan therapy as compared with the number of ESRD days on standard antihypertensive therapy was calculated, and the difference between the two was combined with the costs of ESRD. In the IDNT trial, Markov models were applied to assess the economic impact of irbesartan and to extrapolate future clinical and cost outcomes. Several economic analyses were performed in the United States and in European countries. Applying pharmacoeconomic models showed that treatment with ARB was associated with a greater improvement in life expectancy and lower total costs compared with amlodipine and standard antihypertensive therapy. Therefore, treating patients with type 2 diabetes, nephropathy, and hypertension with ARB is life- and cost-saving compared with traditional antihypertensive therapy.
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PMID:Economic evaluation of angiotensin receptor blockers in type 2 diabetes, hypertension, and nephropathy. 1656 46

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.
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PMID:Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making. 1676 1

Angiotensin II antagonists (AIIAs) were introduced to treat hypertension about 10 years ago. During this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. They are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. Cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) and Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). Their blood pressure independent protective effect is also mentioned by the blockade of AT1 receptor. As a class AIIs have a tolerability profile similar to placebo.
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PMID:Angiotensin II antagonists: clinical experience in the treatment of hypertension, prevention of cardiovascular outcomes and renal protection in diabetic nephropathy and proteinuria. 1676 99

The objective of the study was to determine the impact of irbesartan treatment on life expectancy (LE), costs and progression to end-stage renal disease (ESRD) in hypertensive type 2 diabetes patients. A peer-reviewed and published Markov model was used to simulate progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, ESRD and all-cause mortality in hypertensive patients with type 2 diabetes. Three treatment strategies were evaluated: (i) 'control' regimen of conventional antihypertensive therapy (excluding angiotensin-converting enzyme inhibitors, angiotensin-2-receptor antagonists and dihydropyridine calcium-channel blockers), (ii) 'early irbesartan' 300 mg daily and (iii) 'late irbesartan' 300 mg daily (started when overt nephropathy developed). Transition probabilities determining nephropathy progression were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial and other published sources. Outcomes were projected over 25 years. The mean +/- SD cumulative incidence of ESRD was reduced by 8.8% +/- 0.6 and 12.4% +/- 0.7 in patients treated with early irbesartan compared with late irbesartan and control respectively. Early irbesartan treatment improved undiscounted LE by 1.38 +/- 0.08 years (discounted: 0.81 +/- 0.04 years) compared with late irbesartan and 1.41 +/- 0.08 years (discounted: 0.83 +/- 0.04 years) compared with control. Early irbesartan treatment was projected to save (mean +/- SD) pounds 2310 +/- 327 and pounds 3801 +/- 327 over patient lifetimes compared with late irbesartan and control respectively. Irbesartan treatment is predicted to improve survival and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria compared with 'control'. Early irbesartan treatment is more effective than late irbesartan. Irbesartan is a valuable treatment option in this patient group in a UK setting.
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PMID:Irbesartan treatment of patients with type 2 diabetes, hypertension and renal disease: a UK health economics analysis. 1787 49

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.
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PMID:The value of irbesartan in the management of hypertension. 1960

Renin-angiotensin system (RAS) plays a central role in the development and progression of diabetic nephropathy. Further, there is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) axis also contributes to diabetic nephropathy. However, the pathophysiological crosstalk between the RAS and AGE-RAGE system in tubular cell injury, which is more important than glomerulopathy in terms of renal prognosis in diabetic nephropathy, remains unknown. In this study, we examined whether and how irbesartan, an angiotensin II type 1 receptor blocker (ARB), inhibited the AGE-induced tubular cell apotptosis and damage in vitro. Gene expression was analyzed by quantitative real-time reverse transcription-polymerase chain reactions. Intracellular formation of reactive oxygen species (ROS) was measured with dihydroethidium staining. Apoptosis levels were evaluated for DNA fragments with an enzyme-linked immunosorbent assay kit and for caspase-3 activity. Irbesartan inhibited the AGE-induced up-regulation of RAGE mRNA levels and subsequently reduced ROS generation in human proximal tubular cells. AGEs induced apoptosis and increased inflammatory, thrombogenic and fibrogenic gene expressions in tubular cells, which were also blocked by the treatment with irbesartan. Our present data suggest that there exists a crosstalk between the RAS and AGE-RAGE system in tubular cell apoptosis and damage. Blockade of the RAS by irbesartan may play a protective role against tubular injury in diabetes by attenuating the deleterious effects of AGEs via down-regulation of RAGE.
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PMID:Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression. 1963 64

The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.
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PMID:Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria. 1976 96

Diabetic nephropathy is a leading cause of renal failure requiring replacement therapy. Diabetic nephropathy is typically characterized by persistent microalbuminuria progressing to nephrotic syndrome, a progressive decline in glomerular filtration rate, and hypertension. Diabetic nephropathy prevention strategies may involve early angiotensin-converting enzyme (ACE) inhibitor treatment and the control of diabetes to reduce glomerular hypertension and hyperfiltration. Treatment strategies include the use of ACE inhibitors or angiotensin receptor blockers (ARBs), and cholesterol-lowering agents. Early intervention is key to the prevention of more severe renal outcomes. Although intensive and early control of blood pressure (BP) is key to renoprotection, the class of antihypertensive has an important bearing on outcome. There is evidence for the efficacy of ARBs in preventing the progression from microalbuminuria to overt nephropathy (urine protein excretion >500 mg/day) from the IRbesartan in patients with diabetes and MicroAlbuminuria (IRMA 2) Study using irbesartan and the INcideNt to OVert: Angiotensin II receptor blocker, Telmisartan, Investigation On type 2 diabetic Nephropathy (INNOVATION) Study using telmisartan. For the management of overt nephropathy, the findings of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) demonstrate that losartan and irbesartan, respectively, reduce the time to doubling of serum creatinine levels and development of end-stage renal disease.
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PMID:Slowing the progression of kidney disease in patients with diabetes. 2040 36


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