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

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased. Besides the link between albuminuria (nephropathy) and atherosclerosis in coronary arteries, albuminuria is also a predictor of microangiopathy in other organs than the kidneys. The annual incidence of proliferative retinopathy in early nephropathy is 10-15% compared to only 1% in patients without nephropathy. Also signs of cardiomyopathy have been demonstrated in early nephropathy. Further we have described markers of universal endothelial damage in these patients, and we hypothesize that albuminuria not only is a predictor of renal disease but also of widespread vascular disease. Long-term improvement of metabolic control by use of insulin infusion pumps and early antihypertensive treatment seem to stop the further progression of early diabetic nephropathy and to significantly improve the prognosis of clinical nephropathy.
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PMID:Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients. 149 Jun 95

Late complications of diabetes mellitus include a variety of clinical pictures, mainly related to the involvement of the arterial wall both of large vessels (macroangiopathy) and small vessels (microangiopathy), and of the peripheral nervous system (neuropathy). Their presence in almost all types of diabetes indicates that there is a common pathogenetic mechanism, which can be substantially identified in high blood glucose levels and related alterations. Hyperglycemia, in fact, leads to some metabolic abnormalities, i.e. non-enzymatic glycosylation of proteins and polyol pathway activity; moreover it can negatively affect the pattern of some hormones, especially GH and sex steroids, and normal rheological and clotting properties of blood. These abnormalities, confirmed by experimental models, play a key role in the development of late diabetic complications. However some evidence indicates that a genetic background may predispose to their development or protect from their onset. The two main forms of diabetic retinopathy, non-proliferative and proliferative, show an incidence which increases with age and duration of diabetes, reaching 100% when diabetes lasts for more than 20 years. The risk of blindness, which is very high for the proliferative form, has been dramatically reduced by laser-photocoagulation. Diabetic nephropathy affects a lesser number of diabetics but, after a silent or preclinical stage, leads to renal failure and subsequent replacement therapy. Strict metabolic control in the silent stage and later rigid anti-hypertensive treatment can prevent or retard the evolution of this complication. A close association has been observed between diabetes and hypertension, which can directly affect the onset and evolution of diabetic nephropathy, probably through a common genetic mechanism. Diabetic neuropathy has a wide variety of clinical manifestations, at somatic, autonomic and central levels and can greatly modify the quality and expectancy of life. However, the major cause of death in diabetic subjects is large vessel disease or macroangiopathy, which is similar to non-diabetic atherosclerosis regarding the main histopathological and clinical manifestations but has a much higher prevalence and severity. Finally, a specific cardiomyopathy has also been described in diabetes mellitus and can account for the high rate of heart failure observed in these patients.
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PMID:The late complications of diabetes mellitus. 174 48

Atherosclerotic vascular disease is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. The frequent coexistence in these patients of microangiopathy and coronary artery disease was observed more than 30 years ago and later verified in large epidemiological studies. Thus, the subgroup (30-40%) of patients who develop clinical nephropathy, also are at extremely high risk of early cardiovascular death. A number of established cardiovascular risk factors are present not only in advanced clinical nephropathy but also in its earliest stages. These include elevated blood pressure, atherogenic changes in the plasma concentrations of lipids and lipoproteins, elevated plasma levels of fibrinogen and probably hyperreactivity of platelets. However, it seems unlikely that these risk factors fully explain the excess cardiovascular morbidity and mortality in insulin-dependent diabetic patients with clinical nephropathy. Patients with slightly elevated urinary albumin excretion are at increased risk of developing not only clinical nephropathy and coronary heart disease but also proliferative retinopathy and cardiomyopathy. We have, therefore, hypothesised that elevated urinary albumin excretion is a marker of generalized disease in the vascular wall of small and large blood vessels. Findings of elevated transcapillary escape rate of albumin, elevated plasma concentration of von Willebrand factor and impaired fibrinolytic capacity in early diabetic nephropathy have supported this hypothesis. However, the initial pathophysiological mechanisms involved are still hypothetical and largely unknown. During recent years the incidence of clinical nephropathy has declined and the prognosis of insulin-dependent diabetic patients has improved. Whether intervention directed against the often clustered cardiovascular risk factors will further improve the prognosis in proteinuric patients is suggested but still unknown. However, the key question is still, why is the vascular wall, in small and large blood vessels, vulnerable in some but not all diabetic patients? In the future more studies of the initial pathophysiological mechanisms involved in this vulnerability are needed.
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PMID:Albuminuria--a marker of renal and generalized vascular disease in insulin-dependent diabetes mellitus. 206 Mar 21

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.
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PMID:[ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation]. 896 87

Insulin-dependent diabetic patients with increased urinary albumin excretion are characterized by elevated blood pressure and declining kidney function. In addition, such patients have a high risk of atherosclerotic vascular disease, proliferative retinopathy, and cardiomyopathy, suggesting that albuminuria is a marker of widespread vascular dysfunction. Increased transport of macromolecules across the vascular wall, elevated plasma levels of von Willebrand factor, and impaired fibrinolytic capacity have been demonstrated in albuminuric patients. The cause of this vascular vulnerability in susceptible patients is unknown, but increasing evidence has suggested that loss of the proteoglycan heparan sulfate in the vasculature may explain the widespread nature of the disease. Heparan sulfate is important for the glomerular endothelial cell and basement membrane charge densities, the anticoagulant properties of the vessel wall, and the growth regulation of intimal smooth muscle cells. Recent studies have shown that heparin increases the biosynthesis of heparan sulfate in endothelial cell cultures and prevents the characteristic glomerular basement membrane thickening when given to diabetic rats. Moreover, heparin has been shown to reduce albuminuria in patients with incipient diabetic nephropathy. Although increasing evidence supports the hypothesis that loss of heparan sulfate may play a pathophysiological role in the development of diabetic vascular complications, there are still many unresolved problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?
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PMID:Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan. 928 8

Angiotensin-II (ANG-II) is a potent endocrine and paracrine hormone that functions in humans through two distinct G-protein-coupled transmembrane receptor subtypes (AT-1 and AT-2). ANG-II is found in nearly all tissues of the body including the brain, heart, kidneys, gonads, and gastrointestinal tract. Just as it is found in nearly every organ system of the body, so is it involved in an array of physiologic processes from fetal development to blood pressure control. ANG-II regulates blood pressure by controlling sodium reabsorption in the proximal tubule, altering the glomerular filtration rate and renal blood flow, and by modifying the production and release of aldosterone in the adrenal gland. Additionally, ANG-II is involved in several pathologic processes including the development of hypertension, cardiomyopathy, atherosclerosis, and diabetic nephropathy. It is able to exert influences in these widely varying processes by working together with multiple different second messenger systems including the MAP kinase pathway, nitric oxide production, and phospholipase C and D, and several arachidonic acid metabolites. This paper is a review of the current knowledge of ANG-II and its receptors in health and disease.
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PMID:Action of angiotensin receptor subtypes on the renal tubules and vasculature: implications for volume homeostasis and atherosclerosis. 993 Mar 75

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K(+)-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K(+)-ATPase activity was strongly related to blood C-peptide levels in non-insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene. A polymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K(+)-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K(+)-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K(+)-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K(+)-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K(+)-ATPase activity. This impairment in Na+,K(+)-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetes-induced decrease in Na+,K(+)-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K(+)-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K(+)-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K(+)-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications.
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PMID:C-peptide, Na+,K(+)-ATPase, and diabetes. 1519 70

Despite recent advances, cardiovascular disease continues to be the leading cause of death among patients with diabetes. Diabetes-related heart disease makes up the majority of the cardiovascular morbidity and mortality and this clinical entity results from synergistic interaction amongst various overlapping mechanisms. Diabetes-related heart disease is characterised by a propensity to develop premature, diffuse atherosclerotic disease, structural and functional abnormalities of the microvasculature, autonomic dysfunction and intrinsic myocardial dysfunction (the so-called diabetic 'cardiomyopathy'), all of which are exacerbated by hypertension and diabetic nephropathy. The renin-angiotensin-aldosterone system possesses various autocrine and paracrine effects which drive most of the pathophysiological mechanisms in diabetes-related heart disease. This review aims to describe the expanding role of the renin-angiotensin-aldosterone system, the complex entity of diabetes-related heart disease and the (emerging) evidence for specific inhibition of the renin-angiotensin-aldosterone system in diabetes.
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PMID:Diabetes, the renin-angiotensin system and heart disease. 1532 Aug 46

A 65-year-old man was admitted to our hospital for high fever and severe left shoulder pain. He was initiated on maintenance hemodialysis for end-stage renal failure caused by diabetic nephropathy 9 years previously. On admission, the serum CRP level was 29.3 mg/d/l and the white blood cell count was 29,000/mm3. Bacterial examination of blood and spinal fluid revealed MRSA colonization. On the 6th hospital day, a giant negative T wave in the V2-6 leads of an electrocardiogram asymptomatically appeared. Ultracardiogram revealed apical systolic paradoxical centrifugal motion. None of the cardiogenic enzymes, such as creatine kinase, lactate dehydrogenase and glutamic oxaloacetic transaminase was elevated. Cardiac thallium-201-chloride (201Tl-Cl) and I-123 beta-metyl iodophenyl-pentadecanoic acid (123I-BMIPP) scintigraphy revealed a decreased accumulation of isotopes in the apex. From these findings, we diagnosed Takotsubo cardiomyopathy induced by MRSA meningitis. Vancomycin was administrated and the inflammatory signs decreased. On the 46th hospital day, tetraplegia and respiratory suppression occurred. A cervical spinal magnetic resonance image revealed cervical spondylodiscitis and cervical epidural abscess, which compressed the medulla oblongata. Surgical spinal decompression and drainage of the abscess were performed. The giant negative T wave in the electrocardiogram improved after the operation. Two months after the operation, cardiac 201Tl-Cl scintigraphy revealed improvement in the accumulation of isotopes in the apex. Takotsubo cardiomyopathy is secondary cardiomyopathy presenting with apical systolic paradoxical centrifugal motion without coronary stenotic disease. It has been reported to be induced by severe mental stress or intracranial disease. In the present patient, it was predicted that stress on the central nerve system caused by the MRSA meningitis and the cervical epidural abscess induced the Takotsubo cardiomyopathy.
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PMID:[Takotsubo cardiomyopathy thought to be induced by MRSA meningitis and cervical epidural abscess in a maintenance-hemodialysis patient: case report]. 1677 1

Chronic diabetes mellitus is associated with various complications such as retinopathy, neuropathy, nephropathy, cardiomyopathy, vasculopathy, dermatopathy and encephalopathy. Nephropathy is one of the major complications of diabetes mellitus, and the morbidity and mortality due to diabetic nephropathy is constantly progressing in industrialized nations. No satisfactory therapeutic option is currently available to treat patients with nephropathy except for fewer agents like angiotensin converting enzyme inhibitors, angiotensin AT(1) receptor blockers and few antioxidants, which have been shown to improve the function of diabetic kidney to some extent. Thus, tremendous efforts are being made to explore promising therapeutic interventions to treat diabetic nephropathy. This review discussed various presently employed and recently developed pharmacological interventions to treat diabetic nephropathy and to improve the function of diabetic kidney. In addition, the recently identified potential target sites involved in the pathogenesis of diabetic nephropathy have been delineated.
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PMID:Recent advances in pharmacotherapy for diabetic nephropathy: current perspectives and future directions. 1942 82


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