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

Diabetic nephropathy is the most serious problem among current issues in nephrology, as 40% of the cases of end-stage renal disease are due to this entity. The close relationship between type 2 diabetes and hypertension makes the problem even more severe. The knowledge of the intrarenal effects of angiotensin II and the greater effect of angiotensin converting enzyme inhibitors (ACEI) on reducing albuminuria suggested in the past a trend toward preferable use of these drugs in diabetic nephropathy. The first relevant clinical trials yielded rather poor conclusions because of lack of blind randomization and short duration. Subsequent double-blind studies with adequate numbers of patients and sufficient duration underlined the importance of blood pressure (BP) control as well as the rather poor response of diabetic nephropathy to any treatment. In most of these studies, the changes in albuminuria or microalbuminuria were a substitute end point for the renal function. Three clinical trials using angiotensin II receptor blockers (ARB), planned specifically to monitor the progression of renal damage, have been recently published. They showed better renal protection by ARB, as compared with placebo or calcium channel blockers (CCB), beyond or independently of the BP reduction. Nevertheless, these recent trials, like the previous ones with similar results, invariably demonstrate slightly better control of BP in the groups of the active drug. Another issue is that the vast majority of the patients need so many nonstudy drugs to keep their pressure under control, that the isolation of advantageous effects of certain drugs seems unrealistic.
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PMID:Diabetic nephropathy and antihypertensive treatment: what are the lessons from clinical trials? 1287 77

Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide. Until recently, it was thought that once a patient developed overt proteinuria, diabetic nephropathy was irreversible and inevitably progressed to ESRD. However, the reversal of lesions caused by diabetic nephropathy (e.g., glomerular basement membrane thickening and mesangial matrix increase) has been demonstrated in a series of patients who underwent a pancreas transplantation 10 years prior to the reversal. Remission of nephrotic range proteinuria has also been reported in some patients with type 1 diabetes from the Collaborative Study Group during a median follow-up of 3 years of angiotensin-converting enzyme (ACE) inhibitor administration; no deterioration of renal function was observed in these patients. Remission and regression in nephropathy of type 1 diabetes patients have also been reported when blood pressure was controlled aggressively. Recent clinical trials have demonstrated that angiotensin II receptor blocker (ARB) preserved renal function and slowed the progression of nephropathy to ESRD in patients with type 2 diabetes. Since many patients with type 2 diabetes manifest with a metabolic syndrome, multifactorial intensive treatment is necessary; such treatment includes behavior modifications, dietary intervention, exercise, and smoking cessation. In this population, pharmacological therapy targeting hyperglycemia, hypertension (including ARB/ACE inhibitor), and hyperlipidemia in cases of type 2 diabetes is also necessary.
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PMID:Remission and regression of diabetic nephropathy. 1292 17

Candesartan shows beneficial end-organ effects in the kidney. Some of these appear to be related not to the reduction in systemic blood pressure induced by candesartan, but to its blockage of intrarenal angiotensin II type I (AT1) receptors. Initial studies have shown that renal vascular resistance was reduced in patients with hypertension receiving candesartan, and urinary albumin excretion was reduced in patients with type 2 diabetes mellitus and concomitant microalbuminuria or proteinuria. These findings, together with the results of recently published large randomized studies involving diabetic patients with hypertension treated with other angiotensin II receptor blockers, indicate that this class of drugs is beneficial in preventing the development or progression of diabetic nephropathy. This review summarizes the large body of findings related to these renoprotective effects and reported during experimental and clinical research on candesartan for the treatment of diabetic nephropathy.
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PMID:Candesartan: nephroprotective effects and treatment of diabetic nephropathy. 1294 96

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group ( P = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (-11% and -38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan.
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PMID:Treatment of diabetic nephropathy with angiotensin II receptor antagonist. 1458 37

The incidence of diabetes as cause of end-stage renal failure (ESRF) has significantly increased, and will continue to grow during the next few years. Moreover, diabetic nephropathy is associated with elevated cardiovascular morbidity and mortality. These guidelines focus on the possible intervention strategies to prevent and treat ESRF in diabetic patients. In normoalbuminuric patients, glycated haemoglobin levels less than and equal to 7.5% is mandatory for reducing the risk of incipient nephropathy. Furthermore, blood pressure levels < 130/80 mmHg are strongly recommended. In microalbuminuric patients, glycated hemoglobin levels below 7.5% and blood pressure levels below 130/80 mmHg (120/70-75 mmHg in patients < 50 years) are recommended. Moreover, there is evidence that inhibition of the rennin-angiotensin-aldosterone system, either by angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin II receptor antagonists (AIIRA) is able to reduce the incidence of overt nephropathy, regardless of blood pressure levels. Current guidelines recommed ACE-I as the first-choice drug in type 1 diabetes, while both ACE-I and AAIRA are considered first-choice therapy in type 2 diabetes. In proteinuric patients it is uncertain whether glycemic control affects the progression of nephropathy, which in turn is dramatically influenced by blood pressure. Optimal blood pressure levels are below 130/80 mmHg (120/70-75 mmHg in patients < 50 years). In type 1 diabetes there is consensus on the renoprotective role of ACE-1. In type 2 diabetes, two recent trials demonstrated that AIIRA are more effective than conventional therapy or calcium channel blockers in slowing down the progression of nephropathy. ACE-I are indeed recommended as first-choice drugs in type 1 diabetes while AIIRA are the first-choice agents for ESRF prevention in type 2 diabetes. Dialysis treatment should be started as soon as the creatinine clearance is reduced to about 10-15 mL/min. The choice of dialysis schedule should be individualized according to clinical and adequacy criteria (CAPD weekly Kt/V > or = 2 and single HD session Kt/V > or = 1.5). Simultaneous pancreas-kidney transplantation should be the first-choice therapeutic option in type 1 diabetes, while renal transplantation has been demonstrated to significantly improve the prognosis of type 2 diabetes patients with ESRF.
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PMID:[Guidelines for diagnosis and therapy of diabetic nephropathy]. 1466 6

Olmesartan is an angiotensin II receptor antagonist indicated for the treatment of essential hypertension. Angiotensin II is an important hormonal effector and end-product of the renin-angiotensin system. When it binds to its endogenous receptor sites, it causes widespread vasoconstriction and a subsequent increase in blood pressure. Olmesartan works by selectively binding to AT(1) against the pathophysiologic events leading to diabetic nephropathy and cardiovascular morbidity/mortality. This end-organ protection is independent of olmesartan's blood pressure lowering properties and is therefore thought to be mediated by different mechanisms. In summary, olmesartan has an efficacy profile superior to other available antihypertensive agents, with a tolerability profile comparable to that of placebo. In addition, the convenience of its once-daily dosing means that olmesartan should be considered not only as an alternative, but also as a first-line treatment for patients with mild to severe essential hypertension. Thus, olmesartan appears to be a very promising new therapy for the treatment of hypertension.
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PMID:Olmesartan, an AT1-selective antihypertensive agent. 1466 30

Hypertension, impaired renal function, and proteinuria are commonly associated to the presence of diabetes. They play a major role in the development of cardiovascular and renal damage. Effective antihypertensive treatment reduces the progression of diabetic nephropathy and improves cardiovascular prognosis. Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic patients. Achieving BP targets represents the most important determinant of cardiovascular and renal protection. However, it has been suggested that specific classes of antihypertensive drugs may exert additional organ protection beyond their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone system has been shown to convey greater renal and cardiovascular protection compared with other classes of drugs. In particular, studies focusing on renal end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor blockers prevent the progression from microalbuminuria to clinical proteinuria in type 2 diabetes, but angiotensin blockers provide better renoprotection in patients with overt nephropathy. Regarding cardiovascular protection, several studies (but not all) have shown that ACEI exert a protective effect on diabetic patients. Recently, interesting results in favor of angiotensin receptor blockers have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that to achieve maximal renal and cardiovascular protection, most diabetic patients require integrated therapeutic intervention, including not only several antihypertensive drugs, but statins and antiplatelet therapy as well.
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PMID:Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment. 1468 64

Nephropathy is the main cause of morbidity and mortality in patients with type 1 diabetes and, in adults, persistent microalbuminuria is the best marker of the consequent risk for its development. In the pediatric population, puberty represents the most important risk factor for the development of microangiopathic complications, although it is not necessarily associated with the progression to frank proteinuria. As many as 50% of subjects may revert to normoalbuminuria. Hypertension is a further risk factor and may accelerate the progression of micro- and macrovascular complications. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce renal damage by one or more mechanisms independent of their antihypertensive effects--hence they represent the drug of choice for the treatment of diabetic nephropathy. However, as angiotensin II receptor antagonists are more specific, they may become the obvious treatment choice in the near future. There is no consensus as to who should be treated and when treatment with renoprotective drugs should begin in the pediatric population, due to the lack of a clear definition of the natural history of microalbuminuria in this age group. In this review some models and controversial aspects of this issue are presented and discussed.
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PMID:Treatment of hypertension and microalbuminuria in children and adolescents with type 1 diabetes mellitus. 1501 66

The activity of the renin-angiotensin-aldosterone system (RAAS) is elevated both in the circulation and in the renal tissue of diabetic and nondiabetic nephropathies. The increased RAAS activity plays an important role in the hemodynamic and nonhemodynamic pathogenetic mechanisms involved in kidney disease. Previous studies have demonstrated that albuminuria is not only a marker of glomerular lesions, but also a progression promoter, and finally a powerful predictor of the long-term beneficial effect of blood pressure-lowering therapy. Randomized crossover and parallel blind studies in patients with diabetic nephropathy have demonstrated that angiotensin II receptor blockers (ARB) induce favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by angiotensin-converting enzyme (ACE) inhibition. Studies have revealed the optimal renoprotective dose for some ARBs; however, additional dose titration studies are urgently needed to obtain the maximum benefit of this valuable new class of compounds. The combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy. In addition, dual RAAS blockade is safe and well tolerated. Impaired autoregulation of glomerular filtration rate (GFR); demonstrated with some blood pressure-lowering agents implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension depending of the level of blood pressure. ARB does not interfere with GFR autoregulation in hypertensive diabetic patients. In contrast to previous observational studies with ACE inhibition, long-term treatment with ARB has similar beneficial renoprotective effect on progression of diabetic kidney disease in hypertensive diabetic patients with ACE II and DD genotypes. ARB can prevent/delay development of diabetic nephropathy independently of its beneficial blood pressure-lowering effect in patients with type 2 diabetes and microalbuminuria. Recently, two landmark studies led to the following conclusion: "Losartan and Irbesartan conferred significant renal benefit in patients with type 2 diabetes and nephropathy. This protection is independent of the reduction in blood pressure it causes. The ARB is generally safe and well tolerated." A recent metaanalysis indicates that ARBs reduce cardiovascular events mainly because of reduction in first hospitalization for congestive heart failure in hypertensive type 2 diabetic patients with albuminuria. The studies mentioned here suggest that ARB represents a beneficial treatment of hypertension and proteinuria in incipient and overt diabetic nephropathy.
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PMID:Angiotensin receptor blockers in diabetic nephropathy: renal and cardiovascular end points. 1501 27

VEGF expressed in glomerular podocytes, is known to increase vascular permeability to macromolecules. Angiotensin II can stimulate the release of VEGF, and the protective effects of angiotensin II antagonist against diabetic glomerular injury suggest that the angiotensin II-induced VEGF is an important pathogenetic mechanism in the development of proteinuria during diabetic nephropathy although this mechanism is not fully understood. In this study, the changes of VEGF expression was examined in the experimental diabetic nephropathy to determine whether these changes were modified by renoprotective intervention by blockers of angiotensin II receptors. The streptozotocin- induced diabetic rats were treated with L-158,809, a blocker of angiotensin II receptors, for 12 weeks. Age-matched rats with L-158,809 served as controls. RT-PCR and immunohistochemistry were used to assess and quantify gene and protein expression of VEGF. A progressive increase in urinary protein excretion was observed in diabetic rats. Glomerular VEGF expression was significantly higher in diabetic rats than in the control groups, with a significant reduction in glomerular VEGF expression and proteinuria in L-158,809- treated diabetic rats. VEGF mRNA was also significantly higher in diabetic kidneys than in the control groups, with a significant reduction in VEGF mRNA in L-158,809-treated diabetic kidneys. These results demonstrates that VEGF expression is significantly increased in diabetic podocytes, and angiotensin II receptor antagonist attenuated these changes in VEGF expression and prevented the development of proteinuria in vivo. Attenuation of increased VEGF expression in podocytes could contribute to the renoprotective effects of angiotensin II receptor antagonists in diabetic nephropathy.
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PMID:Angiotensin II receptor blocker attenuates overexpression of vascular endothelial growth factor in diabetic podocytes. 1503 73

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