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

It has been hypothesized that the renin-angiotensin system plays a pathophysiologic role in the renal hemodynamic abnormalities that occur in diabetes mellitus and thereby contributes to the development of diabetic nephropathy. In this study, the tissue-specific regulation of renin and angiotensinogen mRNA levels and the abundance of glomerular angiotensin II receptors were examined in male Sprague-Dawley rats (160 to 240 g) made diabetic with streptozotocin. One subgroup of diabetic rats remained untreated, whereas a second diabetic subgroup received twice-daily doses of insulin to ameliorate hyperglycemia. Animals were euthanized 2 wk after the induction of diabetes. Mean plasma glucose levels at the time of euthanasia were significantly elevated in the untreated diabetic animals when compared with controls or insulin-treated diabetic rats. Weight gain was similar in control and insulin-treated diabetic rats, whereas the untreated diabetic rats gained significantly less. Plasma renin concentration did not differ between control, diabetic, and insulin-treated diabetic groups. In the kidney, no significant differences were found in either angiotensinogen or renin mRNA levels in diabetic animals, whereas glomerular angiotensin II receptors were significantly less abundant in untreated rats as compared with control or insulin-treated diabetic subgroups. Angiotensinogen mRNA levels were significantly lower in the livers and adrenals of diabetic rats in comparison to those in controls and insulin-treated diabetic rats, whereas angiotensinogen mRNA levels in the brain remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat. 813 Mar 60

The factors that initiate chronic renal failure in patients with hypertension, diabetes mellitus, and chronic glomerular disease are largely unknown. The likely genetic contribution to ESRD, particularly in African Americans, suggests that linkage analysis may be useful to evaluate the role of candidate genes in the pathogenesis of chronic renal failure. The renin-angiotensin-aldosterone (RAA) axis has been intensively evaluated for its contribution to cardiovascular disease and nephropathy. This study tested for linkage between candidate genes in the RAA axis and chronic renal failure, using 85 African-American sibling pairs (from 65 families) concordant for ESRD. Angiotensinogen was selected because of the putative link between it and mild to moderate essential hypertension and nephrosclerosis; angiotensin-converting enzyme because of its possible contribution to diabetic nephropathy; and renin, the angiotensin II receptor, and kallikrein because of their roles in hypertension and renal perfusion. These candidate loci did not demonstrate linkage to either diabetic or nondiabetic renal disease in this study's collection of sibling pairs. These results suggest that polymorphisms at these RAA axis loci do not make major contributions to the pathogenesis of renal disease in African Americans.
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PMID:Linkage analysis between loci in the renin-angiotensin axis and end-stage renal disease in African Americans. 898 34

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
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PMID:Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. 1049 84

Prevalence of diabetic nephropathy is increasing. Understanding of pathogenesis and clinical picture helps to manage this disease. Recent data of the research of this disease support that the renin-angiotensin system plays a pivotal role in the pathogenesis. Hyperglycaemia activates the renin-angiotensin system and induces transforming growth factor-beta expression. These both lead to glomerulosclerosis and tubulointerstitial fibrosis. Diabetic nephropathy develops earlier and progress faster in patients with DD or ID genotypes of angiotensin-I-converting-enzyme gene. Angiotensinogen and type 1 angiotensin-II-receptor gene mutations may be also predisposing factors for diabetic nephropathy. All these factors can be responsible for the hyperfiltration, albuminuria, salt sensitivity, and hypertension, which are characteristic features of diabetic nephropathy. According to these, one can suppose that inhibitors of the renin-angiotensin system are effective in the prevention and treatment of this disease. Evidence of clinical studies suggests that angiotensin-I-converting-enzyme inhibitors in type 1 diabetes can prevent overt nephropathy, decrease proteinuria, inhibit the loss of the glomerular filtration and decelerate progression. Angiotensin-II-receptor blockers exert the same effect in type 2 diabetic patients, and presumably angiotensin-I-converting-enzyme inhibitors have similar activity in this group of patients. That is why, in the case of intolerance of one class of drugs, the other should be substituted. Combination therapy of angiotensin-I-converting-enzyme inhibitors with angiotensin-II-receptor blockers can be the choice of treatment in the future.
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PMID:[Role of the renin-angiotensin system in the pathogenesis, clinical picture and treatment of diabetic nephropathy]. 1272 86

Recent findings related to the renin-angiotensin system have provided a more elaborated understanding of the pathophysiology of hypertension and kidney diseases. These findings have led to unique concepts and issues regarding the intrarenal renin-angiotensin system. Angiotensinogen is the only known substrate for renin that is the rate-limiting enzyme of the renin-angiotensin system. Because the level of angiotensinogen in human beings is close to the Michaelis-Menten constant value for renin, changes in angiotensinogen levels can control the activity of the renin-angiotensin system, and its upregulation may lead to elevated angiotensin peptide levels and increases in blood pressure. Enhanced intrarenal angiotensinogen mRNA or protein levels or both have been observed in multiple models of hypertension including angiotensin II-dependent hypertensive rats, Dahl salt-sensitive hypertensive rats, and spontaneously hypertensive rats, as well as in kidney diseases including diabetic nephropathy, immunoglobulin A (IgA) nephropathy, and radiation nephropathy. Renal angiotensinogen is formed primarily in proximal tubular cells and is secreted into the tubular fluid. Urinary angiotensinogen excretion rates show a clear relationship to kidney angiotensin II contents and kidney angiotensinogen levels, suggesting that urinary angiotensinogen may serve as an index of the intrarenal renin-angiotensin system status. Establishment of concise and accurate methods to measure human angiotensinogen may allow clinical studies that would provide important information regarding the roles of intrarenal angiotensinogen in the development and progression of hypertension and kidney diseases.
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PMID:Young Scholars Award Lecture: Intratubular angiotensinogen in hypertension and kidney diseases. 1664 30

Increased generation of reactive oxygen species (ROS) leads to oxidative stress in diabetes. Catalase is a highly conserved heme-containing protein that reduces hydrogen peroxide to water and oxygen and is an important factor decreasing cellular injury owing to oxidative stress. Hyperglycemic conditions increase oxidative stress and angiotensinogen gene expression. Angiotensinogen conversion to angiotensin II leads to a furtherance in oxidative stress through increased generation of reactive oxygen species. In this study, we utilized mice transgenically overexpressing rat catalase in a kidney-specific manner to determine the impact on ROS, angiotensinogen and apoptotic gene expression in proximal tubule cells of diabetic animals. Proximal tubules isolated from wild-type and transgenic animals without or with streptozotocin-induced diabetes were incubated in low glucose media in the absence or presence of angiotensin II or in a high-glucose media. Our results show that the overexpression of catalase prevents the stimulation of ROS and angiotensinogen mRNA in tubules owing to elevated glucose or angiotensin II in vitro. Additionally, overexpression of catalase attenuated ROS generation, angiotensinogen and proapoptotic gene expression and apoptosis in the kidneys of diabetic mice in vivo. Our studies point to an important role of ROS in the pathophysiology of diabetic nephropathy.
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PMID:Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice. 1755 51

The autocrine and paracrine activation of the renin-angiotensin system (RAS) within cells of the kidney plays a role in the overall pathophysiology of the renal disease due to diabetes. In this study, we focus on components of the RAS in the podocyte as these cells are important in the pathogenesis of glomerulosclerosis and proteinuria. Immortalized mouse podocytes were exposed to media containing normal glucose (NG) or high glucose (HG) for in vitro studies. In vivo studies utilized kidney tissue obtained from rats treated for 3 months with streptozotocin to induce diabetes. Angiotensinogen (AGT) and the angiotensin II (AII) type 1 receptor mRNA and protein were significantly increased in the podocytes cultured under the high glucose conditions. Both angiotensins I and II levels were significantly higher in cell lysates and the conditioned media of cells grown in high glucose. There were no differences in renin activity, angiotensin-converting enzyme level, or AII type 2 receptor level. Glomerular AGT and AII type 1 receptor assessed by means of immunohistochemistry were increased in diabetic rats compared with the control rats. Other measured components of the RAS within the glomeruli were not different. We suggest that increased AGT, an attendant increase in AII and increased AII type 1 receptor in podocytes experiencing diabetic conditions play an important role in the pathogenesis of diabetic nephropathy.
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PMID:Activation of the renin-angiotensin system within podocytes in diabetes. 1736 Nov 12

Substantial evidence suggests that the intrarenal renin-angiotensin system (RAS) plays a role in the pathogenesis of diabetic nephropathy. Although the glomerular RAS is activated in the streptozotocin (STZ)-diabetic rat, the status of the glomerular RAS in the Zucker diabetic fatty (ZDF) rat, which is a commonly used genetic model of diabetes, is not known. Angiotensinogen (AGT), angiotensin II (Ang II), angiotensin converting enzyme (ACE), and angiotensin converting enzyme 2 (ACE2) were measured in glomeruli isolated from 4-week-old STZ-diabetic rats and 32-week-old ZDF rats. Glomerular injury was evaluated by histopathologic methods. Both STZ-diabetic and ZDF rats exhibited marked hyperglycemia and renal hypertrophy, but only ZDF rats demonstrated proteinuria and glomerulosclerosis. Glomerular AGT and Ang II levels were increased significantly in STZ-diabetic compared with nondiabetic control rats, accompanied by a reduction in ACE2 activity. In contrast, glomerular AGT, Ang II, and ACE2 were similar in ZDF rats and lean controls. ACE levels were not affected by diabetes in either diabetic model. In conclusion, the glomerular RAS is activated in the STZ diabetic rat but not in the ZDF rat despite a similar degree of hyperglycemia. The mechanism of nephropathy in the ZDF rat may involve factors other than hyperglycemia and RAS activation, such as hypertension and hyperlipidemia.
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PMID:Glomerular renin angiotensin system in streptozotocin diabetic and Zucker diabetic fatty rats. 1835 68

Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.
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PMID:Role of the renin angiotensin system in diabetic nephropathy. 2153 41

Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by multiple independent mechanisms. Angiotensinogen (AGT) is the only known substrate for renin that is a rate-limiting enzyme of the RAS. Recently, enhanced intrarenal AGT levels have been shown to reflect the intrarenal RAS status in hypertension, chronic glomerular disease and diabetic nephropathy. In this review, we focus on AGT expression of the diseased glomeruli in the progression of glomerular disease. An anti-glomerular basement membrane nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of AGT and Ang II. The addition of Ang II type 1 receptor blocker to CC-chemokine recaptor 2 antagonist markedly attenuated the induction of macrophage infiltration, AGT and Ang II, and reduced glomerular crescent formation. Next, the levels of glomerular AGT expression and marker of reactive oxygen species in Zucker diabetic fatty (ZDF) obese rats were higher than those in ZDF lean rats. Hydrogen peroxide (H(2)O(2)) induced an increase in the AGT expression in primary rat mesangial cells. Furthermore, the H(2)O(2)-induced upregulation of AGT was inhibited by a mitogen-activated protein kinase kinase and a c-Jun N-terminal kinase inhibitor. These data suggest the potential contribution of enhanced AGT expression in glomeruli to the intrarenal RAS activation for the development of glomerular disease.
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PMID:Angiotensinogen Expression Is Enhanced in the Progression of Glomerular Disease. 2224 11


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