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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 (DN) is the leading cause of end stage renal disease (ESRD). Although the pathogenesis of DN is multifactorial, local inflammatory stress may result from both the metabolic and hemodynamic derangements observed in DN. Inflammatory markers such as Interleukin-18 and Tumor Necrosis Factor (TNF)-alpha are increased in the serum of patients with diabetes and DN. This occurs at a very early stage of disease, and correlates with the degree of albuminuria. Recent data suggest that standard pharmacologic interventions for DN, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, may have anti-inflammatory properties that are independent of their hemodynamic effect. Although inflammation is traditionally thought of as a process resulting in macrophage infiltration, current scientific progress has lead to the novel idea that even cells distant from the blood stream, such as podocytes, can produce cytokines and can express molecules that are part of the co-stimulatory pathway. A strong translational research effort is currently aimed at defining the role of such molecules in cells other than lymphocytes and macrophages. Experimental animal models have recently provided evidence that some acute phase markers of inflammation such as intracellular cell adhesion molecule-1 (ICAM-1), TNF-alpha and Monocytes Chemoattractant Protein-1 (MCP-1) may have a causative role in the development of DN. Here, we review the current evidence supporting the role of inflammation in the early phases of clinical and experimental DN. A complete understanding of inflammatory pathways activated in DN may lead to the discovery of earlier and more reliable markers of DN than albuminuria and the identification of novel therapeutic targets.
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PMID:Role of inflammation in diabetic nephropathy. 1822 Jun 90

Diabetes is currently one of the leading causes of end-stage renal failure requiring renal replacement therapy in the Western World. About 15% to 20% of type 1 diabetic patients and 30% to 40% of type 2 diabetic patients will eventually develop end-stage renal failure. To prevent the development or progression of diabetic kidney disease, good glycaemic control remains the cornerstone in the management of diabetic patients. Beyond glycaemic control, other metabolic factors have been shown to be involved in the development of diabetic kidney disease, i.e. advanced glycation endproducts (AGEs) and the aldose reductase pathway. Furthermore, an adequate control of high blood pressure and treatment of microalbuminuria are major therapeutic targes. To achieve adequate blood pressure control, a combination therapy with different classes of antihypertensive agents is often necessary, especially including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Other vasoactive factors involved in diabetic nephropathy such as endothelin and nitric oxide will be covered briefly. Besides hyperglycaemia and high blood pressure, other risk factors have been identified in the development or progression of diabetic kidney disease: smoking, hyperlipidaemia, obesity and high protein intake. Their impact on renal function will be highlighted. Finally, recent research has also identified intracellular pathways such as the diacylglycerol-protein kinase C pathway and several growth factors, such as growth hormone, insulin-like growth factor, transforming growth factor-beta, vascular endothelial growth factor, and platelet derived growth factor as players in diabetic kidney disease.
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PMID:Novel insights in the treatment of diabetic nephropathy. 1822 60

Renin angiotensin system (RAS) worsens diabetic nephropathy (DN) by increasing oxidative stress. We compared the effect of three different RAS inhibitors: the angiotensin converting enzyme inhibitor Ramipril, the vasopeptidase inhibitor AVE7688 and the angiotensin receptor (AT1) antagonist Losartan on the formation of oxidative and carbonyl stress derived protein modifications in kidney from Zucker obese hyperglycemic rats (ZDFn Gm-fa/fa). Gas chromatography-mass spectrometry was used to measure representative markers of several protein oxidative pathways: direct oxidation [dinitrophenylhydrazine reactive carbonyls (DNP), glutamic (GSA), and aminoadipic (AASA) semialdehydes], mixed glyco- and lipoxidation [N(epsilon)-carboxyethyl-lysine (CEL) and N(epsilon)-(carboxymethyl)-lysine (CML)] and lipoxidation-[N(epsilon)-(malondialdehyde)-lysine-(MDAL)], as well as renal fatty acid composition. Urinary albumin (a marker of DN), DNP, GSA, and MDAL levels, were increased in all obese rats and were dose dependently decreased by AVE7688 whereas Ramipril and Losartan were less efficient. These results show that RAS inhibition improves DN at several levels, independently of its effects on blood pressure and glycemic control, via mechanisms depending of renal oxidative stress.
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PMID:Inhibition of renin angiotensin system decreases renal protein oxidative damage in diabetic rats. 1824 27

In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IGFBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.
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PMID:Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line. 1839 86

The inhibition of the renin-angiotensin system is one of the most commonly utilized ways to lower blood pressure in patients with arterial hypertension. Up till now, angiotensin-converting enzyme inhibitors as well as angiotensin receptor blockers are the established inhibitors of this system, and both classes are used in clinical routine. There is a wealth of information about those classes, which are known not only to lower blood pressure, but also to prevent end-organ damage and, ultimately, reduce mortality in patients. Direct renin inhibition was already targeted 30 years ago to inhibit the renin-angiotensin system, but low bioavailability and short duration of action of the first generations of renin inhibitors withheld their clinical success. With the new generation of non-peptide orally available renin inhibitors, a third substance to inhibit the renin-angiotensin system is on the market, and the prototype of this class, aliskiren, has now been tested in various clinical trials in arterial hypertension. We review the studies of aliskiren and discuss its current role in the contemporary treatment of arterial hypertension as well as the possible new fields of action for aliskiren in treating heart failure and diabetic nephropathy.
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PMID:Renin inhibitors, clinical experience. 1843 34

Risk factors such as hypertension or diabetes result in a continuum of renal damage. Without intervention, initial subclinical endothelial damage progresses to incipient disease, identified by microalbuminuria. Glomerular filtration rate declines, macroalbuminuria develops, and eventually end-stage renal disease (ESRD) emerges. Because of the interrelationship between cardiovascular and renal disease and their common pathophysiologies involving angiotensin II, many patients die of cardiovascular disease before renal replacement therapy is needed. Blood pressure control is key to renoprotection, but blood pressure-independent mechanisms are also implicated. Targeting the renin-angiotensin system (RAS) using angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) is a logical approach to managing all at-risk patients. In advanced nephropathy, therapy aims at retarding progression to ESRD. For incipient nephropathy, ideal therapy should bring about microalbuminuria regression. In patients at risk of renal damage, preventing early target-organ damage is essential. Although evidence of ACE inhibitor benefit is limited, data show that ARBs provide renoprotection throughout the continuum and that this may be related to their cardioprotective effects. More aggressive RAS targeting by combination blockade is under investigation. Telmisartan is an ARB that delays progression of incipient and overt diabetic nephropathy and brings about regression from microalbuminuria to normoalbuminuria in hypertensive and normotensive patients. The ultimate proof of benefit will come from the ONTARGET trial, which will evaluate the cardiovascular and renal protective effects of the combination of telmisartan and ramipril.
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PMID:Prospects for renovascular protection by more aggressive renin-angiotensin system control. 1844 82

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.
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PMID:Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. 2020 69

The number of Hispanic people in the United States with diagnosed diabetes mellitus is projected to increase by 107% by 2020. The author presents the case of a 62-year-old obese Hispanic man, with newly diagnosed type 2 diabetes mellitus (T2DM), diabetic peripheral neuropathy, background retinopathy, and diabetic nephropathy. The patient also had diagnosed hypertension, peripheral vascular disease, and hyperlipidemia. The treatment plan for this patient included the following medications: pioglitazone hydrochloride (a thiazolidinedione, 30 mg/d); irbesartan (an angiotensin receptor blocker, 150 mg/d titrated to 300 mg/d); hydrochlorothiazide (an antikaliuretic agent, 12.5 mg/d); and aspirin (325 mg/d). Sitagliptin phosphate (a dipeptidyl peptidase IV inhibitor, 50 mg/d) was added to the treatment regimen to improve glycemic control. Simvastatin (20 mg/d) and niacin (1 g/d) were used for lipid management. Therapy also included a low-protein diet and walking program. At 6-month follow-up, the patient showed substantial improvement in his glycosylated hemoglobin level, lipid profile, blood pressure, creatinine clearance rate, and urine albumin level. There were also improvements in his peripheral vascular disease and diabetic peripheral neuropathy. Furthermore, the patient demonstrated encouraging progress in diet and lifestyle modification and in mental attitude.
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PMID:Treating Hispanic patients for type 2 diabetes mellitus: special considerations. 1851 40

In current study, the effect of angiotensin receptor blocker Micardis on the localization and expression of aquaporin-2 (AQP2) was investigated in the renal medullary collecting duct of mice with diabetic nephropathy (DN). Mice were divided into three groups: normal group, DN group and Micardis-treated group. Six weeks after establishment of STZ-induced DN model in mice, the expression of AQP2 in renal medulla was detected measured by semiquantitative immunofluorescence histochemistry and Western blot techniques, and the localization of AQP2 by confocal immunofluorescence laser scanning microscopy. The results showed that the urinary osmolality was decreased in DN group as compared with normal group (2.39+/-0.11 vs 3.16+/-0.16, P<0.05). Although the localization of AQP2 on the renal medulla was unchanged, the expression of AQP2 was increased significantly in DN group as compared with normal group. Micardis could partly attenuate above changes. It was concluded that treatment with Micardis could partly rectify the abnormal expression of AQP2 in renal medulla of DN mice, which suggested that rennin-angiotensin system (RAS) is implicated in the pathogenesis of DN by regulating the expression of AQP2.
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PMID:Effect of Micardis on the expression of renal medulla aquaporin-2 in diabetic mice. 1856 21

Prorenin and renin bind to a 350-amino acid protein called the (pro)renin receptor, which is present on the surface and functions intracellularly. When the receptor's N terminus binds either prorenin or renin, intracellular signaling occurs via extracellular-regulated kinases, which can result in plasminogen activator inhibitor and transforming growth factor-beta production. Investigators have developed a novel decoy peptide, called the handle-region peptide (HRP), which obviates binding of prorenin to the receptor. HRP has successfully inhibited diabetic nephropathy in rats and in angiotensin receptor-deleted mice, and has blocked fibrosis in the hearts of spontaneously hypertensive rats. The same researchers developed a transgenic (pro)renin receptor-expressing rat with glomerulosclerosis that responded dramatically to HRP treatment. However, groups in Paris, Rotterdam, and Berlin have not been able to confirm the findings, and the precise role of the (pro)renin receptor remains imperfectly defined.
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PMID:Renin receptor blockade: a better strategy for renal protection than renin-angiotensin system inhibition? 1877 20


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