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

The pathogenesis of hypertension in diabetes type 1 and type 2 is different. Diabetic nephropathy is regarded as the most essential factor contributing to the development of hypertension in patients with diabetes mellitus type 1. Obesity, insulin resistance and hyperinsulinaemia are responsible for hypertension in diabetes mellitus type 2. In both types of diabetes, hypertension is involved in fast progress of diabetic renal disease. Antihypertensive treatment in diabetic patients should include: non-pharmacological interventions, drug-therapy, regular blood pressure monitoring, educational efforts. ACE-inhibitors, calcium antagonists, diuretics, beta-blockers, angiotensin II receptor antagonists and alpha 1-blockers are used as antihypertensive agents in diabetic patients. Neutral endopeptidase inhibitors are the new, promising therapeutic option.
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PMID:[Hypertension in patients with diabetes mellitus--selected pathogenetic and therapeutic aspects]. 1147 57

A prospective, randomized, three-armed, double-blind, placebo-controlled clinical trial has been completed in 210 sites worldwide to determine whether the angiotensin II receptor blocker irbesartan or the calcium channel blocker amlodipine has a renoprotective effect in patients with overt type 2 diabetic nephropathy. A total of 1,715 subjects randomized during a 3-year period were followed a minimum of 2 years. The goal for all treatment groups was to achieve equivalent blood pressure control, with the blinded study drug (irbesartan, amlodipine, or placebo) as primary therapy with additional antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, calcium antagonists, and angiotensin II receptor antagonists, to achieve seated systolic blood pressure less than 135 mm Hg and diastolic blood pressure less than 85 mm Hg. The primary outcome was the combined endpoint of time to doubling of entry serum creatinine, end-stage renal disease, or death. Secondary outcomes included fatal and nonfatal cardiovascular events. A Clinical Management Committee monitored the conduct of the study. An Outcome Confirmation Committee classified all study outcome events in blinded fashion. An external Data Safety Monitoring Committee monitored unblinded data for interim safety and efficacy analyses of the study. Eligibility criteria included informed consent, age 30 to 70 years, adult-onset diabetes, hypertension, urine protein excretion greater than 900 mg/24 hours, and serum creatinine values of 90 to 265 micromol/L in women and 110 to 265 micromol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive heart failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm Hg, and diastolic blood pressure, 85 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5 g/24 hours; serum creatinine, 150 +/- 53 micromol/L; serum potassium, 4.6 +/- 0.5 mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%. This large-scale international trial should help define the clinical course and standards of care for hypertensive adults with type 2 diabetes mellitus and nephropathy. Results available on May 19, 2001, will help in defining the current controversy of the risks and benefits of blockade of the renin-angiotensin system versus calcium channel blockade versus standard antihypertensive therapy in this large patient population.
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PMID:A clinical trial in type 2 diabetic nephropathy. 1157 53

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

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

In the field of cardiovascular pharmacology the year 2001 has been marked by the demonstration of the clinical significance of new anti-thrombotics and by the interesting results with anti-endothelins. Whereas the failure of oral antiGPIIb-IIIa has been confirmed, melagatran (an anti-thrombin administered orally) and pentasaccharide (a new subcutaneous anti-Xa) have proved their efficacy in the prevention of venous thromboembolic disease compared to low molecular weight heparins, with an acceptable incidence of unwanted effects. Anti-endothelins under development have variable mechanisms of action from one drug to another. Their efficacy in cardiac insufficiency, pulmonary artery hypertension and arterial hypertension is suggested by clinical studies investigating small population; a more important study in decompensated cardiac insufficiency has not however shown a reduction of the morbidity and mortality with one of these drugs. The clinical significance of angiotensin II receptor antagonists has been confirmed for the indications which they share with ACE inhibitors (cardiac insufficiency, prevention of diabetic nephropathy). However, there are not enough comparative trials for these indications between these two classes in order to draw conclusions about the equivalence or superiority of one or the other. Of help elsewhere has been a re-interpretation of the mode of action of arterial wall drugs, and the inflammatory theory of atherosclerosis, putting the accent for example on the reduction of C reactive protein with a statin, or on the anti-inflammatory effect of aspirin. However, one study has not shown any benefit in giving a short course of corticosteroids in unstable angina. A very prominent event in the year 2001 remains the withdrawal of cerivstatin due to fatal rhabdomyolysis. The consequences go far beyond this drug, as its withdrawal justifies a fresh examination of the risk-benefit ratio for all the statins, with the probable corollary of a halt in the escalation of prescriptions. In this context, the new ezetimibe-type cholesterol absorption inhibitors could be a future solution.
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PMID:[The best of 2001. Clinical pharmacology]. 1190 97

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

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

The DETAIL (diabetics exposed to telmisartan and enalapril) study will compare the long-term renal outcome of treatment with the angiotensin II receptor antagonist (ARA) telmisartan versus the angiotensin-converting enzyme (ACE) inhibitor enalapril in patients with mild-to-moderate hypertension and diabetic nephropathy. In short-term clinical studies, ACE inhibitors reduce microalbuminuria and, in the longer term, they are superior to conventional therapies in maintaining normal renal function. ARAs also appear to be renoprotective in diabetic animals. In this double-blind, parallel-group study, 252 patients with Type 2 diabetes and concurrent hypertension (mean seated systolic blood pressure < or = 180 mm Hg, on treatment seated diastolic blood pressure < or = 95 mm Hg) have been randomised to once-daily telmisartan 40 mg or enalapril 10 mg; doses are mandatorily titrated to 80 and 20 mg once daily, respectively, after 4 weeks. The primary endpoint will be the change from baseline in glomerular filtration rate (GFR) after 5 years of therapy, using the iohexol method and central laboratory analysis. The secondary endpoints to be evaluated will be: changes in GFR in relation to baseline after 1-4 years of therapy; percentage changes in albumin excretion rate after 1-5 years; and incidences of end-stage renal disease, cardiovascular events, all-cause mortality, and adverse events. The planned date for the completion of the study is 2005.
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PMID:Rationale and design of diabetics exposed to telmisartan and enalapril (DETAIL) study. 1201 88

To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or 0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug.
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PMID:Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes. 1204 43

Nephropathy is the main cause of morbidity and mortality in patients with Type 1 diabetes and persistent microalbuminuria is the best marker of the consequent risk for its development in adults. In the paediatric population, puberty has long been recognised as a major risk period for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. In fact, as many as 50% of subjects might revert to normoalbuminuria. Hypertension is a further risk factor and accelerates the progression of micro and macrovascular complications. There is evidence that angiotensin-converting enzyme inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects and they are the drug class of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific they might become the obvious treatment choice in the near future. There is no consensus on who should be treated with reno-protective drugs in the paediatric population, and when this should occur, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review controversial aspects of this issue are presented and discussed.
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PMID:New trends in the treatment of diabetic nephropathy in children. 1215 Jun 94


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