Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial hypertension increase progression of late diabetic complications. Renin-angiotensin-aldosterone system plays an important role in the regulation of arterial pressure. The aim of the study was the assessment of plasma renin activity (PRA) and aldosterone (aldo) in type I euglycaemic diabetic patients on intensive insulin treatment without autonomic neuropathy. 30 type I diabetic patients (including 11 with nephropathy defined as urinary albumin excretion > 30 mg/24 h and 19 without albuminuria) were admitted into the trial. Mean age 31.9 + 1.4 years, duration time of disease was 9.1 + 1.5 years, HbA1c level 7.6 + 0.25%; GFR 124.7 + 3.9 ml/min/1.73 m2 (135.8 + 5.1 in subgroup with nephropathy and 118.2 + 5.08 in non-nephropathic group). Blood samples were taken during normal sodium intake (120 mmol/24 h) after 0.5 h supine. PRA was significantly lower in type I diabetics vs control (0.27 + 0.04, 0.61 + 0.09 pmol/l/s respectively-p < 0.005). PRA was significantly lower both in nephropathic and non-nephropathic diabetic group vs control (respectively 0.22 + 0.06 and 0.31 + 0.05-p < 0.05). Aldo in diabetic patients and in subgroups with and without nephropathy was significantly lower vs controls (respectively 173 + 12.9, 165.1 + 14.4, 182.1 + 18.8 and 257.1 + 24.1 pmol/l; p < 0.01, p < 0.05). Significant differences in hormonal changes between diabetic patients with and without nephropathy were not found. Basing upon the results we conclude that in euglycemic intensively insulin treated type I diabetic patients without neuropathy presented decreased level of PRA and aldo. Early stage of diabetic nephropathy does not influence the examined hormones level.
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PMID:[Activity of the renin-angiotensin-aldosterone system in euglycemic type I diabetic patients on intensive insulin treatment without diabetic neuropathy]. 859 57

Renin angiotensin(RA) system is deeply involved in the pathophysiological conditions of essential hypertension. To inhibit RA system is supposed to be induced cardiovascular protective effect. ACEIs and ARBs are used as first choice of drugs in the treatment of hypertension. Clinical evidence shows that ACEIs have protective effects on heart, kidney and brain. Several large clinical trials suggest that ARBs have also protective effects on heart and diabetic nephropathy. Furthermore, recent study has demonstrated that an ARB prevents more cardiovascular morbidity and death than a beta blocker and is better tolerated in hypertensive patients with left ventricular hypertrophy. Now accumulated evidence indicates that ARBs are useful drugs in the treatment of hypertension.
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PMID:[Clinical application of ARB and ACEI]. 1239 95

The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.
J Renin Angiotensin Aldosterone Syst 2002 Dec
PMID:Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes. 1258 66

Blockade of the effects of angiotensin II (Ang II) by using an angiotensin-converting enzyme (ACE) inhibitor has been proven to be of value in Type 1 diabetic nephropathy and in non-diabetic renal disease. Evidence in favour of Ang II blockade in Type 2 diabetic patients with renal damage is still lacking for ACE inhibitors (ACE-Is), while recent data indicate that angiotensin receptor blockers (ARBs) could be the drugs of choice in this situation. On the other hand, renal damage from the onset of disease is accompanied by a very significant increment in global cardiovascular risk. This fact, as well as that of simultaneous renal and cardiovascular protection, have to be considered for drug selection. In this sense, ACE-Is have been shown to be the drugs of choice when secondary cardiovascular prevention is required, while the evidence in primary prevention in hypertensive patients has been shown with losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. All these facts led to the conclusion that both ACE-Is and ARBs can be considered when both renal and cardiovascular protection are aimed for in Type 2 diabetic patients.
J Renin Angiotensin Aldosterone Syst 2003 Jun
PMID:ACE inhibition or angiotensin receptor blockade: which should we use in diabetic patients? 1280 88

Renin-angiotensin system (RAS) inhibitors are effective in reducing renal disease progression in early diabetic nephropathy, but they provide imperfect protection at a later stage. Due to the pivotal role of transforming growth factor-beta (TGF-beta) in the pathogenesis of diabetic kidney disease, this study tested the effect of simultaneously interrupting TGF-beta and angiotensin II on disease progression in diabetic rats with overt nephropathy. Diabetes was induced by streptozotocin injection in uninephrectomized rats. Diabetic rats received murine (1D11) or human (CAT-192) anti-TGF-beta monoclonal antibodies alone or in combination with lisinopril, 13C4 irrelevant murine antibody, saline or lisinopril from month 4 (when animals had proteinuria) to month 8. Normal animals served as controls. Systolic BP increase was controlled by single treatments and even more by the combined therapies. 1D11 and lisinopril kept proteinuria at levels numerically lower than irrelevant antibody and saline, while CAT-192 was ineffective. The addition of either TGF-beta antibody to lisinopril normalized proteinuria. Consistent results were obtained for glomerulosclerosis and tubular damage, which were abrogated by the combined therapy. Interstitial volume expansion and infiltration of lymphocytes/macrophages were limited by 1D11 and lisinopril and further reduced by their combination. The increase of type III collagen in the renal interstitium was partially attenuated by 1D11 and lisinopril while normalized by their combination. It is concluded that anti-TGF-beta antibody when added to a background of chronic angiotensin-converting enzyme (ACE) inhibition fully arrests proteinuria and renal injury of overt diabetic nephropathy, providing a novel route to therapy and remission of disease for diabetic patients who do not respond to RAS inhibition.
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PMID:Add-on anti-TGF-beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat. 1281 41

It was analyzed the forms of renin produced by a mouse immortalized mesangial cell line (MIC) and their ability to generate angiotensin II (AII). The synthesis, localization and secretion of renin and AII by MIC were evaluated under conditions of normal (10 mM) or high (30 mM) glucose concentration. Two major bands of 35 kDa and 70 kDa were observed in SDS-PAGE. The amino-terminal sequencing revealed the presence of prorenin and renin in these bands with higher homology with the submaxillary gland form of renin. Renin and AII were detected in cell lysate and in culture medium, indicating that MIC synthesize and secrete these peptides. Renin was localized in the cytoplasm while AII was seen predominantly inside the nucleus. High glucose induced an increase in the synthesis and secretion of renin and AII. Results suggest that MIC produce AII and a renin form similar to the submandibular. Intracellular AII may be directed at the nucleus and/or be secreted, indicating that AII may directly influences gene expression in these cells. The mechanisms of synthesis and secretion of renin and AII are potentially modified by high glucose concentration, suggesting a possible role of AII produced by mesangial cells in diabetic nephropathy.
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PMID:Renin similar to the submaxillary gland form is expressed in mouse mesangial cells: subcellular localization and all generation under control and glucose-stimulated conditions. 1463 Nov 42

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.
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PMID:The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study. 1567 11

Diabetic nephropathy is a major cause of diabetes- related morbidity and mortality; however the clinical course of the disease and the renal prognosis is highly variable among individuals. The current review will discuss the genetic influence on the development of end stage renal disease (ESRD) in diabetic patients and potential improvements to the current treatment strategy to slow the loss of kidney function in these patients. In this first part, the growing evidence that glucose-induced activation of the intra-renal and systemic renin-angiotensin systems plays an essential role in processes leading to destruction of renal function is summarised. Genetic variations, especially the angiotensin-converting enzyme (ACE)/ID polymorphisms in the gene coding for ACE, are involved in activation of the renin-angiotensin system and seem to influence the clinical course of diabetic nephropathy during treatment with ACE inhibitors. In addition, this polymorphism may interact with other polymorphisms within the renin-angiotensin system, leading to high risk of ESRD. As new genetic approaches and methods develop, further understanding of diabetic nephropathy will evolve and genotyping will help prevent ESRD in diabetic patients.
J Renin Angiotensin Aldosterone Syst 2005 Mar
PMID:Preventing end stage renal disease in diabetic patients--genetic aspect (part I). 1608 46

Diabetic nephropathy is a major cause of diabetes related morbidity and mortality. The first part of the current review was published in the last issue of this journal and discussed the important role of the renin-angiotensin system (RAS) in diabetic nephropathy and the genetic influence on development of endstage renal disease (ESRD) in diabetic patients. This second part of the review focus on the potential improvement of the current treatment strategy to slow down the loss of kidney function using dual blockade of the RAS with both ACE-inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs). Substantial evidence from short-term studies using surrogate endpoints indicates a beneficial impact of dual blockade of the RAS, not obtainable with single agent blockade alone, both in diabetic and non-diabetic renal disease. This conclusion has been confirmed and extended in a longterm trial with regard to prevention of ESRD in non-diabetic renal disease. Results indicate that dual blockade of the RAS may further slow down, but not arrest progressive loss of renal function. However, studies defining the optimal dose of ACE-I / ARBs without additional adverse effects are essential to ensure relevant comparison with dual blockade therapy. Trials using primary renal endpoints in diabetic nephropathy are still needed, and will finally establish the role of dual blockade of the RAS in a clinical setting.
J Renin Angiotensin Aldosterone Syst 2005 Sep
PMID:Preventing end-stage renal disease in diabetic patients - dual blockade of the renin-angiotensin system (Part II). 1647 Apr 84

The initial stages of diabetic nephropathy are characterized by glomerular hyperfiltration and hypertension, processes that have been linked to initiation and progression of renal disease. Renin angiotensin system (RAS) blockade is commonly used to modify the hyperfiltration state and delay progression of renal disease. Despite this therapy, many patients progress to ESRD, suggesting heterogeneity in the response to RAS modulation. The role of the RAS in the hyperfiltration state in adolescents with uncomplicated type 1 diabetes was examined, segregated on the basis of the presence of hyperfiltration. Baseline renal hemodynamic function was characterized in 22 patients. Eleven patients exhibited glomerular hyperfiltration (GFR>or=135 ml/min), and in the remaining 11 patients, the GFR was <130 ml/min. Renal hemodynamic function was assessed in response to a graded angiotensin II (AngII) infusion during euglycemic conditions and again after 21 d of angiotensin-converting enzyme (ACE) inhibition with enalapril. AngII infusion under euglycemic conditions resulted in a significant decline in GFR and renal plasma flow in the hyperfiltration group but not in the normofiltration group. After ACE inhibition, GFR fell but did not normalize in the hyperfiltration group; the normofiltration group showed no change. These data show significant differences in renal hemodynamic function between hyperfiltering and normofiltering adolescents with type 1 diabetes at baseline, after AngII infusion and ACE inhibition. The response to ACE inhibition and AngII in hyperfiltering patients suggests that vasodilation may complement RAS activation in causing the hyperfiltration state. The interaction between glomerular vasoconstrictors and vasodilators requires examination in future studies.
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PMID:Impact of renin angiotensin system modulation on the hyperfiltration state in type 1 diabetes. 1667 13


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