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

Diabetes mellitus and arterial hypertension are the leading causes of end-stage renal disease in industrialized countries. Although attention has focused on renal disease and insulin-dependent diabetes mellitus (type 1 diabetes), a silent epidemic of renal disease caused by type 2, noninsulin-dependent diabetes mellitus is rapidly developing. The course of renal function is heterogeneous in type 2 diabetic patients and reflects heterogeneous patterns of renal lesions. A subset of patients with microalbuminuria and proteinuria is characterized by the typical diabetic glomerulopathy usually observed in type 1 diabetic patients, with altered albumin excretion rate (AER), for example, glomerular basement membrane thickening and mesangial fractional volume expansion. These patients also have diabetic retinopathy and rapidly lose renal function despite tight blood pressure control. In contrast, a second subset of type 2 diabetic patients has normal or near-normal patterns of glomerular structure, despite abnormalities of AER comparable to those of the patients with diabetic glomerulopathy. Thus abnormalities of AER have a different renal prognostic value depending on the underlying renal structure. The patients with worse clinical prognosis and typical diabetic glomerulopathy also have diabetic retinopathy, whereas those with a better course of renal function quite often have no diabetic retinopathy. Several findings, albeit not unanimous, suggest that HbA1c levels above 7.5 to 8.0 % are closely associated with a rapid decay of renal function in type 2 diabetes. Tight blood pressure control plays a further important role in determining the progression of renal a damage in type 2 diabetes mellitus. Convincing evidence has been provided that drugs capable of inhibiting the renin-angiotensin hormonal system are quite effective in preventing and delaying the evolution of renal damage in both type 1 and 2 diabetes. Equally strong data support the view that other antihypertensive compounds such as beta-blockers and calcium antagonists also delay the progression of renal damage in diabetes mellitus. Whatever the drug used to treat hypertension, the majority of the authors conclude that blood pressure levels should be maintained below 130/85 mmHg in diabetic patients. While it is well established that uncontrolled diabetes underlies the development of diabetic nephropathy, newer evidence suggests that genetically determined susceptibility to hyperglycemia-caused glomerular injury is also necessary. More information on this issue will help to design new therapeutical approaches to treat hypertension and renal complications in type 2 diabetes.
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PMID:Hypertension and renal complications in type 2 diabetes. 1622 1

Lipoprotein glomerulopathy (LPG) is a unique entity of renal lipidosis characterized by peculiar histopathologic characteristics of lipoprotein thrombi and an abnormal plasma lipoprotein profile resembling type III hyperlipoproteinemia, with a marked increase in serum apolipoprotein E (apoE) concentrations. At present, 65 cases have been reported worldwide, although most patients are found in Japan and east Asian countries. Recently, we identified 4 types of novel apoE mutations associated with LPG. In particular, a mutation designated apoE Sendai, in which arginine 145 is substituted with proline, occurs in the majority of Japanese patients. The virus-mediated transduction of apoE Sendai resulting in the development of LPG in apoE-deficient mice confirms the etiologic role of apoE mutation in LPG. Conversely, experimental graft-versus-host disease induced in Fc receptor gamma-chain-deficient mice showed LPG-like lesions in glomeruli without apoE mutations. Considered together, we believe that intrinsic factors in the kidney also contribute to the induction of LPG. Today, apoE and related lipid abnormalities are reported to have an important role in the development of various renal diseases, eg, diabetic nephropathy and immunoglobulin A nephropathy. In this article, we review clinical and histopathologic features of LPG, describe the etiologic role of apoE variants and intrinsic renal factors, and discuss the impact of LPG on mechanisms of other renal diseases.
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PMID:Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. 1643 Dec 49

Diabetes is the most common cause of ESRD in Western countries. This article describes the impact of glycemic control in the various stages of the disease and considers the impact of tight glycemic control on the development and progression of diabetic nephropathy (DN). The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetic Study have demonstrated in type 1 and type 2 diabetes that intensive glycemic control significantly reduces the risk for development of microalbuminuria. Although observational studies suggest an impact of glycemia also on the progression of DN, fewer data are available on the impact of improved metabolic control in secondary prevention. The long-term follow-up of the patients who participated in the Diabetes Control and Complications Trial (Epidemiology of Diabetes Interventions and Complications Study) demonstrated a sustained effect of previous tight glycemic control on both development and progression of DN. Finally, long-term normoglycemia, achieved by pancreas transplantation, is able not only to prevent the development of early diabetic glomerulopathy in kidney transplant recipients but also to halt progression and induce regression of the established diabetic renal lesions in nonuremic patients. Taken together, these studies strongly demonstrate that improvement in glucose control is the most important therapeutic approach in primary prevention. Tight glycemic control also is important in slowing progression of DN, and if blood glucose is normalized, then regression of DN can be achieved. Therefore, a target of glycated hemoglobin levels <7% should be recommended in all patients with diabetes.
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PMID:Renal protection in diabetes: role of glycemic control. 1656 55

The incidence of end-stage renal failure has increased in Italy from 70-80 to 120 per 1x10(6). About 20-30% of patients with diabetes develop nephropathy, usually within 20-25 yrs after disease onset. Diet plays an essential role in the therapy of diabetic nephropathy. A well planned diabetic diet with intensive glycemic control can significantly reduce the risk of microalbuminuria development, and moderate protein restriction reduces hyperfiltration and intraglomerular pressure, and retards the progression of diabetic glomerulopathy. Various studies have shown a positive effect of diet with a protein intake of approximately 0.8 g/kg(-1)/day(-1) in patients with overt nephropathy, with a further restriction to 0.6 g/kg(-1)/day(-1) when the glomerular filtration rate begins to fall. Extra protein intake should counterbalance massive proteinuric losses.
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PMID:[Nutrition in diabetic nephropathy]. 1663 99

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.
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PMID:Renal disease in obesity: the need for greater attention. 1682 23

Differential solute clearances were used to examine the effects of enalapril on glomerular barrier function in 16 proteinuria patients with diabetic glomerulopathy. In these patients, a 90-day course of enalapril reduced arterial pressure without lowering renal plasma flow or glomerular filtration rate. Glomerular clearances of dextrans of broad size distribution (28 to 60 A) were lowered significantly. Theoretical analysis of the dextran clearance profiles revealed that enalapril shifted glomerular pore size distribution to a smaller size. This change in barrier size selectivity was associated with a reduction in fractional albumin and immunoglobulin G clearances during enalapril therapy; urinary protein excretion tended to decrease in parallel. These results indicate that converting enzyme inhibition diminishes glomerular permeability to proteins in diabetic nephropathy by enhancing barrier size selectivity. Because enalapril therapy did not alter the renal plasma flow rate or glomerular filtration rate, these results further suggest that the primary action of enalapril may be to modulate the intrinsic membrane properties of the glomerular barrier.
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PMID:Converting enzyme inhibition and glomerular size selectivity in diabetic nephropathy. 1698 68

Glomerular injury plays a pivotal role in the development of diabetic nephropathy. To elucidate molecular mechanisms underlying diabetic glomerulopathy, we compared glomerular gene expression profiles of db/db mice with those of db/m control mice at a normoalbuminuric stage characterized by hyperglycemia and at an early stage of diabetic nephropathy with elevated albuminuria, using cDNA microarray. In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress. Podocyte structure-related genes, actinin 4alpha and dystroglycan 1 (DG1), were also significantly upregulated at an early stage. The alteration in the expression of these genes was confirmed by quantitative RT-PCR. Through pioglitazone treatment, gene expression of ephrin B2, Pod-1, actinin 4alpha, and DG1, as well as that of oxidative stress and lipid metabolism, was restored concomitant with attenuation of albuminuria. In addition, HIF-1alpha protein expression was partially attenuated by pioglitazone. These results suggest that not only metabolic alteration and oxidative stress, but also the alteration of gene expression related to glomerulogenesis and podocyte structure, may be involved in the pathogenesis of early diabetic glomerulopathy in type 2 diabetes.
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PMID:Altered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone. 1700 39

The obesity epidemic has reached nephrology in the form of increasing numbers of patients with chronic kidney disease (CKD) caused by obesity-related metabolic disorders, IgA nephropathy, stone disease, and a unique glomerulopathy now known as obesity-related glomerulopathy (ORG). Obesity has been identified as an independent risk factor for CKD, and patients with central adiposity or high waist-to-hip ratios appear to have the highest risk. The metabolic syndrome is a risk factor for albuminuria and CKD, and studies now show that the risk of CKD increases with increased numbers of components of the metabolic syndrome. Obesity is not just a bystander or accelerator of other kidney diseases, but has unique histopathologic characteristics that can cause progressive kidney disease. ORG may accompany and worsen IgA nephropathy, urate nephropathy, and possibly even diabetic nephropathy. The origins of obesity-related kidney disease can be traced to insufficient glomerular complement from birth, and low birth weight may be an important precursor to obesity and its many comorbidities. Intervention strategies may need to target prenatal care through the elderly to combat this problematic epidemic.
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PMID:Epidemiology of obesity and chronic kidney disease. 1704 19

Epidemiological studies have proven that obesity is a significant risk factor for type 2 diabetes. Long-term progression of diabetes leads to various microvascular complications, of which diabetic nephropathy has become of increasing importance, and is the main cause of end-stage renal failure in occidental countries. Microalbuminuria is the first marker of incipient diabetic nephropathy, an early stage glomerulopathy which can progress to renal failure and which historically has been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. We report a severely obese diabetic patient on treatment for diabetic nephropathy with ACE-inhibitors and poor results, which resolved after Roux-en-Y gastric bypass.
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PMID:Resolution of early stage diabetic nephropathy in an obese diabetic patient after gastric bypass. 1705 53

Obesity and being overweight are risk factors for kidney diseases. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 ml/min/1.73 m(2)) is related to the increasing number of components of the metabolic syndrome; that is, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol level and hypertension. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise) or eventually by antiobesity medication or bariatric surgery. Rimonabant, a new antiobesity medication, showed beneficial potential effect in treating clusters of metabolic syndrome, which may ultimately suggest potential benefit in treating obesity-related glomerulopathy.
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PMID:Rimonabant as a potential new treatment for an emerging epidemic of obesity-related glomerulopathy? 1706 18


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