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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify the possible contribution of the abnormal polyol pathway to the development of diabetic nephropathy, the effect of aldose reductase inhibitor on renal function and morphology was examined in streptozotocin (STZ)-induced diabetic rats. Six months after STZ injection, glomerular filtration rate and renal plasma flow showed marked decline with significant increase in nuclear-free mesangial area (MA) and relative mesangial area (RMA; MA per glomerular area) in diabetic rats. Oral administration of an aldose reductase inhibitor, Epalrestat, prevented renal hypofunction and mesangial expansion in diabetic rats without influencing the levels of blood glucose. These results suggest that the abnormal polyol pathway in diabetic rats is closely related to the development of mesangial expansion, a morphologic representative of diabetic glomerulopathy, and renal hypofunction.
Diabetes Res Clin Pract 1994 Oct
PMID:The effect of an aldose reductase inhibitor (Epalrestat) on diabetic nephropathy in rats. 785 Dec 68

The key change in diabetic glomerulopathy is accumulation of extracellular material. Basement membrane thickening and matrix expansion develop concomitantly. In insulin-dependent diabetic patients persistent microalbuminuria is associated with an early stage of glomerulopathy. Albuminuria in non-insulin-dependent patients does not always reflect glomerulopathy. Renal and glomerular hypertrophy in the early stages of insulin-dependent diabetes mellitus is unlikely to play a dominant role in the development of glomerulopathy. Loss of capillary surface, closely associated with loss of glomerular function, is only partly explained by mesangial expansion--glomerular occlusion plays an important role. Possible mechanisms of albuminuria are qualitative changes of the basement membrane, eg, loss of proteoglycans and excess glycosylation; epithelial cell changes; new vessel formation; remodeling of glomerular structures; and impeded function of juxtaglomerular arterioles. The interplay among abnormalities in individual compartments of the diabetic kidney should be explored.
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PMID:Renal pathology in diabetes mellitus. 792 8

The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.
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PMID:[Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]. 800 9

A 24 year old male diagnosed of type II diabetes mellitus of 2 years of known clinical evolution discovered by an episode of hyperglycemic decompensation without ketoacidosis is presented. In the study of possible visceral involvement of the disease agenesis of the left kidney with compensating hypertrophy of the right kidney, increase of glomerular filtrate and proteinuria of 1.8 g/24 hours were observed. Renal histologic study demonstrated the existence of diffuse intercapillar glomerulosclerosis compatible with diabetic glomerulopathy. From these data and review of the literature the possibility of the greater risk of individuals with a single kidney to present nephropathy in the case of coexistence of associated diabetes mellitus.
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PMID:[Early diabetic nephropathy in a patient with agenesis of one kidney]. 833 23

Urinary tract infections rank first among the infections of patients with diabetes mellitus. They are encouraged by chronic hyperglycaemia and occur more frequently in diabetic women aged over 50 who suffer from disorders of the autonomic nervous system responsible for disturbances of bladder voiding. Another facilitating factor in younger women is pregnancy. Acute pyelonephritis is more dangerous than in non-diabetic populations, being often painless and therefore neglected. An unexplained blood glucose imbalance may be the only manifestation of acute pyelonephritis. In these patients, pyelonephritis is more frequently complicated by pyonephritis or papillary necrosis, both capable of threatening the patient's life or renal function. Moreover, since the diabetic kidney is exposed to a specific glomerulopathy with nephroangiosclerosis and interstitial lesions, all infections may aggravate these lesions, and they must be treated vigorously. Antibiotics may be less effective due to reduction of their tissue levels, and relapses, more frequent and resistant to treatment, may call for prophylactic treatment in certain patients. This is why urinary tract infections must be detected systematically and with a frequency which depends on the presence or absence of facilitating factors: female sex, age, neuropathy, mechanical causes and pregnancy. Using dipsticks that detect urinary leucocytes and nitrates makes detection easier and less costly.
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PMID:[Acute pyelonephritis in diabetic patients]. 837 19

Blood flow autoregulation is impaired in early diabetes mellitus, predisposing the renal microcirculation to injury. These hemodynamic changes have been strongly implicated in the development and progression of diabetic glomerulopathy. Blood flow autoregulation is predominantly a myogenic reflex which is strongly dependent on Ca2+ uptake by vascular smooth muscle cells (VSMC). Because impaired blood flow autoregulation may be responsive to glycemic control, the present study examined the effects of elevated extracellular glucose concentrations on basal, voltage sensitive and receptor operated Ca2+ uptake by VSMC. Confluent cultured rat VSMC were exposed to: (1) control medium (CM; 5 mM glucose); (2) high glucose medium (HGM; 10 to 30 mM glucose); or (3) osmotic control medium (OCM; glucose 5 mM + L-glucose 25 mM or mannitol 25 mM). A threshold glucose concentration of 15 mM markedly and maximally depressed basal Ca2+ uptake by VSMC (HGM 52% vs. CM). In addition, HGM significantly depressed voltage sensitive Ca2+ uptake by VSMC as determined by responses to BAY K 8644 (10(-7) M) or high extracellular [K+] (65 mM, HGM 50% vs. CM). HGM similarly depressed pressor hormone-stimulated Ca2+ uptake (AVP or Ang II 10(-7) M) by VSMC. The effects of HGM on Ca2+ uptake were time exposure dependent and reversible. Ca2+ uptake by VSMC in the presence of OCM did not differ from CM. Elevated extracellular glucose concentrations thus exert a direct and profound effect on basal, voltage sensitive and receptor operated Ca2+ uptake by VSMC. These observations may provide a biochemical basis for glucose-induced dysregulation of regional blood flow autoregulation in early diabetes mellitus.
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PMID:Effect of elevated extracellular glucose concentrations on transmembrane calcium ion fluxes in cultured rat VSMC. 839 16

Activity of renal meprin, a membrane-bound proteinase in the proximal tubule brush border, was measured in normal rats and in two disease groups: chronic puromycin aminonucleoside nephropathy for 12 weeks and streptozocin-induced diabetes for 6 months. Enzyme activity in kidney homogenates was assayed using azocasein as substrate. The mean activity of mephrin was 3.22 +/- 0.34 U/g kidney weight in normal rats. In diabetic animals, enzyme activity was 8.58 +/- 2.11 U/g kidney weight, P < 0.01. In contrast, meprin activity was decreased in rats with puromycin-induced glomerulopathy, 2.13 +/- 0.17 U/g kidney weight, P < 0.01. These findings indicate that meprin activity is elevated in experimental diabetes. Diminished activity of this luminal membrane enzyme in puromycin aminonucleoside nephropathy may contribute to renal injury in this disease model associated with massive urinary protein excretion.
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PMID:Meprin activity in rats with experimental renal disease. 841 99

A case of nephrotic syndrome in a 21-yr-old black man with secondary syphilis and diabetes mellitus is described. A renal biopsy was performed, which showed membranous glomerulopathy stage I associated with mesangial hyperplasia and mesangial deposits. The clinical course and the histologic findings, compatible with syphilitic nephropathy, are offered to remind internists (nephrologists) that sexually transmitted diseases, like syphilis or hepatitis B, in addition to human immunodeficiency virus, can have important renal manifestations.
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PMID:Secondary syphilis and the nephrotic syndrome. 843 46

The constant presence of albumin, as detected by common biochemical methods, in multiple urine samples of a patient, was first considered by Bright, in 1836, as a cardinal sign of renal disease ("clinical proteinuria"). Since then this view was widely adopted for studying the clinical evolution of the patients with diabetes mellitus, whose high risk to develop proteinuria and subsequently a progressive decline of renal function was well known. Thus the finding of "clinical proteinuria" by traditional, merely biochemical techniques, has been considered for more than one century as the opening event in the onset of diabetic nephropathy, and a distinctive sign of glomerulopathy in general. More recently, this view has been deeply criticized, mainly because it lies on the implicit assumption that the sensitivity limits of the biochemical tests for the detection of urinary protein concentrations (about 300 mg/dl), coincide with the ones that can distinguish non nephropathic from nephropathic patients (either diabetic or not). Indeed new techniques, that detect urinary proteins down to 1 microgram/ml, have shown that the upper limit of protein excretion in healthy people is well below the minimum concentration detectable by all the traditional tests. Therefore a new clinical entity, named "microproteinuria" has been defined, meaning the urinary excretion rate ranging between the "physiological" and the "clinical" proteinuria; its pathophysiologic, diagnostic and prognostic significance has been extensively evaluated in the last 20 years. Microproteinuria has been shown to represent a crucial event in the natural history of the diabetic nephropathy; in diabetic patients it is strictly related to the risk of future (months to years) development of overt nephropathy and chronic renal failure, and it may predict the risk of macroangiopathic complications. More recently new settings have been proposed for the study of microproteinuria, as an early and sensitive marker of cardiovascular diseases in hypertensive non diabetic patients and even in non hypertensive non diabetic elderly people. The role of microproteinuria in the diagnosis and follow-up of many non-diabetic glomerulopathies is a very interesting though still unexplored field.
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PMID:[Microalbuminuria: theoretical bases and new applications]. 846 3

The mechanisms of glomerular injury can be separated into nonimmunologically mediated glomerulonephritis (GN) such as diabetes, leading to glomerular hypertension and into immunologically mediated GN. The immunologically mediated GN may induce chronic glomerulopathy such as membranous GN or proliferative GN. The final pathway of these two types of GN is proteinuria and renal failure linked to glomerulosclerosis. In inflammatory GN, most of the mediators could be synthesized either by infiltrating cells or by resident glomerular cells. They include cytokines, lymphokines, complement activation, generation of superoxyde anions, arachidonic acid metabolites, and fibrin deposition. (a) We have investigated the interaction between isolated glomeruli and platelets and have demonstrated that lipidic and proteic extracts of glomeruli enhance thromboxane B2 platelet synthesis. This fact is related to the generation by isolated glomeruli of saturated fatty acids and tissue factor. (b) We investigated the interaction between rat isolated glomeruli and peritoneal macrophages. We have demonstrated that 12-HETE synthesized by isolated glomeruli induce macrophage prostaglandin synthesis which, in turn, inhibits the 12-HETE synthesis. (c) We have demonstrated, using human glomerular epithelial cells, that alpha-thrombin, the active form of thrombin, generated before fibrin formation, is able to induce cell proliferation and abolishes the profibrinolytic activity of these cells. In summary, the mechanisms of glomerular injury are complex, certainly acting by multiple pathways. So far, the mediators leading to proteinuria and renal failure after glomerular injury remain under investigation.
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PMID:Mechanisms of glomerular injury: overview and relation with hemostasis. 851 88


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