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)

In the Prague register of all adult diabetics by April 1, 1992 data on 1443 patients above 18 years with type 1 DM were recorded. In 42.2% of diabetics diabetic retinopathy was observed which is manifested most frequently after 11 to 15 years' persistence of diabetes. Proteinuria, the first sign of diabetic nephropathy, was found in 13.8% of the group, 5.4% of the diabetics are in the stage of renal insufficiency. Nephropathy is 3 to 4 times more frequent in diabetics with retinopathy. Peripheral neuropathy is found in 32.8% type 1 diabetics.
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PMID:[The Prague Diabetes Registry. 3. Retinopathies, nephropathies and neuropathies in type 1 diabetics. The Prague Diabetes Collective]. 840 14

The epithelial polyanion (podocalyxin) on the foot processes (pedicels) of podocytes plays a pivotal role in maintaining slit pore integrity and excluding proteins from the glomerular filtrate. Chromatographically purified recombinant sialidase from Vibrio cholerae, a corresponding heat-inactivated enzyme, truncated enzyme (missing the last 17 amino acids from the carboxyl terminus), and the sialidase from Salmonella typhimurium strain LT2 were inoculated intraperitoneally into mice, and the resultant renal alterations were documented by a variety of functional, morphologic, and histochemical techniques. Proteinuria and renal failure developed in a dose-dependent manner after a single inoculation of sialidase from Vibrio cholerae, but not with the corresponding heat-inactivated enzyme, truncated enzyme, or the sialidase from Salmonella typhimurium strain LT2. Biotinylated lectins of known sialyl linkage specificity demonstrated that Vibrio cholerae sialidase primarily removed alpha 2-->6-linked sialic acids from the glomerulus. Furthermore, the use of a poly-L-lysine cationic gold ultrastructural probe confirmed a transient loss of charge from the endothelium and epithelium of the glomerular filtration barrier. Loss of the epithelial polyanion was accompanied by the effacement of pedicels and the apparent formation of tight junctions between adjacent podocytes. The anionic charge returned to endothelial and epithelial sites within 2 days of sialidase inoculation, but the foot process loss remained. This animal model, in addition to providing an opportunity to study basic mechanisms of renal physiology, seems to mimic minimal change disease in children, diabetic nephropathy, and the renal effects of some bacterial infections.
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PMID:In vivo enzymatic removal of alpha 2-->6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury. 864 86

Proteinuria in diabetic nephropathy has been correlated with reduction in heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane. We have previously shown that the underlying mechanism probably involves reduction in the synthesis by glomerular epithelial cells. In this study we explored whether high glucose medium regulates basement membrane HSPG gene expression. Northern analysis demonstrated that rat glomerular epithelial cells in vitro constitutively express mRNA for basement membrane HSPG, similar to that observed in rat kidney glomerulus. RNase protection assay showed that incubation of glomerular epithelial cells with 30 mM glucose for 24 h and 7 days resulted in reduction in HSPG mRNA abundance. The decrease in mRNA abundance correlated with reduction in the synthesis of 35SO4-labeled basement membrane HSPG as measured by immunoprecipitation. Reduction in synthesis of HSPG could not be entirely accounted for by decrease in mRNA abundance, suggesting both transcriptional and posttranscriptional mechanisms may be involved in reduction of glomerular basement membrane HSPG synthesis by glomerular epithelial cells in diabetic nephropathy.
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PMID:Regulation of basement membrane heparan sulfate proteoglycan, perlecan, gene expression in glomerular epithelial cells by high glucose medium. 869 30

Diabetic nephropathy is the leading cause of end-stage renal failure in the developed world. Proteinuria ("macroalbuminuria" > 200 micrograms/min; or 300 mg/24 h) heralds a phase of established renal pathology with inexorable decline to end-stage renal disease, although its progression can be delayed by antihypertensive medication, in particular the angiotensin-converting enzyme inhibitors (ACEI). Control of blood pressure is vital; even if in the normal range, it is usually raised compared with that in nondiabetic control groups. Reducing blood pressure can lower the rate of decline of the glomerular filtration rate by 90%. Before established proteinuria there is a "microalbuminuric" (20-20 micrograms/min, or 30-300 mg/24 h) phase, and during this time preventive intervention may be effective. In so-called "normotensive" microalbuminuric subjects antihypertensive medications, in particular the ACEI, significantly reduce the progression to macroalbuminuria. Control of glycemia is important; recent evidence has shown that it is particularly important before the development of microalbuminuria; thereafter the role of glycemic control is not clear. Some researchers have suggested that protein restriction may be helpful, but more data are required. For the moment, improved glycemic control in the normoalbuminuric diabetic subjects and treatment with ACEI after the onset of microalbuminuria would seem appropriate in light of knowledge today. Furthermore, any level of hypertension is totally unacceptable and should be treated aggressively; the ACEI seem to be becoming the "agents of choice."
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PMID:Diabetic renal disease: microalbuminuria, implications and intervention. 871 37

1. Treatment with angiotensin converting enzyme (ACE) inhibitors ameliorates human and experimental diabetic nephropathy, possibly as a result of changes in angiotensin II (AngII) and/or bradykinin concentrations. However, ACE is an indiscriminate enzyme, which hydrolyses numerous vasoactive peptides at two catalytic sites that are thought to be substrate specific. AngI is cleaved at the C-terminal site, bradykinin at both the C- and N-terminal sites, while other substrates may be preferentially cleaved at the N-terminal site. Of the various ACE inhibitors, some (e.g. perindopril) bind preferentially to the C-terminal site while others (e.g. enalapril) bind to both. We compared the efficacy of perindopril and enalapril in the diabetic SHR to determine whether all the benefits of ACE inhibition derive from changes in the concentrations of C-terminal related substrates. 2. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg) in 14 week old SHR. Blood glucose was maintained at 4-8 mmol/L by daily ultralente insulin injection and rats were randomized to control, enalapril (10 mg/kg per day) or perindopril (4 mg/kg per day) groups. Blood pressure, creatinine clearance and urinary protein excretion were monitored for 3 months. 3. Blood pressure in both treatment groups was lower than in control (perindopril P < 0.0001; enalapril P < 0.0001). Levels were marginally higher in the perindopril group than the enalapril group, although this difference was significant only in the second month (P < 0.025). Creatinine clearance was significantly lower in the perindopril group (0.44 +/- 0.05 mL/min) than in either the control rats (0.85 +/- 0.11 mL/min; P < 0.001) or the enalapril-treated group (0.66 +/- 0.05 mL/min; P < 0.005). Proteinuria was also lower in this group (4.3 +/- 0.9 mg/24h) than in the enalapril-treated (11.3 +/- 5.8 mg/24h; P < 0.05) or control groups (32.1 +/- 4.5 mg/24h; P < 0.0005). 4. The difference in efficacy between perindopril and enalapril that we have observed suggests that the benefits of ACE inhibition derive from changes in the concentrations of peptides catalysed by the C-terminal rather than the N-terminal site.
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PMID:Differential efficacy of perindopril and enalapril in experimental diabetic nephropathy. 880 Jun

Although complications of diabetes are common among Southwest American Indians, little is known about diabetes and associated risk factors for nephropathy and cardiovascular disease in other genetically distinct tribes. We conducted a retrospective analysis of 665 diabetic patients at two Chippewa Indian reservations in northern Minnesota to evaluate the prevalence of risk factors for diabetic nephropathy and cardiovascular disease. In 79 patients, a more detailed study was carried out, including an assessment of renal function and urinary albumin excretion (UAE). The overall prevalences of proteinuria and hypertension were 47.9% and 62.6%, respectively. Proteinuria was observed more often in hypertensive than in non-hypertensive patients (55.2% vs 44.4%, p < 0.05), and in patients with diabetes for longer than 10 years (57% vs 40% for diabetes less than 10 years, p < 0.05). Although hypercholesterolemia (total cholesterol > or = 200 mg/dl) was observed in 54% of patients, there was no relationship between hypercholesterolemia and proteinuria. In the 79 patients studied in more detail, UAE was greater in hypertensive patients compared to non-hypertensive patients (606 +/- 15600 mg/24h vs 101 +/- 157 mg/24 h, p < 0.05), and in patients with diabetes for 10 years or longer compared to patients in the first decade of disease (748 +/- 1732 mg/24 h vs 96 +/- 171 mg/24 h, p < 0.05). Hypercholesterolemia and elevated LDL-cholesterol (> 130 mg/dl) were observed in 56% and 49% of patients, respectively, but were not associated with increased UAE. In contrast, hypertriglyceridemia (> 250 mg/dl) was associated with an elevated UAE (932 +/- 2150 mg/24 h vs 245 +/- 735 mg/24h, p < 0.05). Increased lipoprotein(a) was found in patients with overt albuminuria. In summary, the prevalence of risk factors for diabetic nephropathy and associated cardiovascular disease is high in Chippewa American Indians in northern Minnesota. Although detecting abnormal UAE may be useful in identifying high-risk patients who may benefit from early intervention, traditional risk factors such as hypercholesterolemia may not explain the risk associated with increased UAE.
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PMID:Risk factors for nephropathy and cardiovascular disease in diabetic Northern Minnesota American Indians. 886 85

Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria. Calcium channel blockers (CCBs) have variable effects on proteinuria; their long-term effects on progression of diabetic nephropathy are not known. The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus (NIDDM) by a degree comparable to ACE inhibitors, given similar levels of blood pressure control. To test this hypothesis we randomized 52 patients with NIDDM associated nephropathy and hypertension, mean age of 63 +/- 8 years, to either the ACE inhibitor, lisinopril (N = 18), nondihydropyridine CCBs (NDCCBs), verapamil SR (N = 8) or diltiazem SR (N = 10), or the beta blocker, atenolol (N = 16). Goal blood pressure was < or = 140/90 mm Hg. Patients were followed for a mean period of 63 +/- 7 months. The primary end point was change in creatinine clearance (CCr) slope in each group. There was no significant difference in mean arterial pressure reduction among the groups over the study period (P = 0.14). The mean rate of decline in CCr was greatest in the atenolol group (-3.48 ml/min/year/1.73 m2; P < 0.0001). There was no difference in the CCr slopes between lisinopril and NDCCBs groups (P = 0.36). Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups (P > 0.99). Therefore, in persons with renal insufficiency secondary to NIDDM, similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol. Moreover, this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria, findings not observed in the atenolol group.
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PMID:Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. 891 31

Diabetic nephropathy is the major cause of illness and premature death in people with diabetes, largely through accompanying cardiovascular disease and end-stage renal failure. Diabetic patients are several times as prone to kidney disease as nondiabetic people and the accumulative risk of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) is about 30%-50% after 25 years of disease. Diabetic nephropathy is a progressive disease that takes several years to develop, ending in chronic renal insufficiency. Proteinuria heralds the onset of diabetic nephropathy, and the worsening of proteinuria parallels the progression of renal disease. The main risk factors for the frequency, severity, and progression of diabetic nephropathy are the degree of hyperglycemia and associated metabolic disturbances, hypertension, protein overload, cigarette smoking, as well as the duration of diabetes. Interventional strategies for primary, secondary, and tertiary prevention of diabetic nephropathy therefore include meticulous glycemic control, appropriate treatment of associated lipid abnormalities, rigorous control of the blood pressure, reduction in dietary protein intake, in particular animal protein, and of fat intake, and stopping cigarette smoking. Randomized clinical trials indicate that antihypertensive therapy is beneficial in preventing and slowing down the progression of diabetic nephropathy. There is now increasing evidence that angiotensin-converting enzyme inhibitors and certain calcium antagonists produce a more beneficial effect on diabetic nephropathy in terms of reducing proteinuria and slowing the progression to diabetic renal failure. These drugs are attributed nephroprotective capacity beyond their blood pressure lowering capacity and initial clinical trials with combinations have revealed even additive protective effects on end organs.
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PMID:Prevention and slowing down the progression of the diabetic nephropathy through antihypertensive therapy. 910 97

Diabetic nephropathy is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. Proteinuria heralds the clinical nephropathy, and the worsening of proteinuria parallels the progression of renal disease towards chronic renal failure. A large body of evidence has accumulated that emphasizes the role of elevated blood pressure in the progression of renal disease, as well as the clear benefit of antihypertensive treatment. However, the choice of antihypertensive drug to protect renal function was less clear in the past. In earlier studies, a reduction in the rate of progressive renal failure in hypertensive subjects has been shown with diuretics, beta-blockers, and vasodilators. However, there is now increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some calcium antagonists produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive nephroprotective effects. Finally, ACE-inhibitors and calcium antagonists have no adverse effects on glycemic control or lipid levels and may even improve insulin sensitivity. This further promotes these antihypertensives to first-line drugs when treating subjects at risk of metabolic disorders or people with diabetes.
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PMID:Protecting the residual renal function: which drugs of choice? 923 93

Proteinuria is one of the bad prognostic indices in renal disease. This study compares the pattern of protein excretion in 10 patients with IgA nephropathy (IgAN), 10 patients with chronic glomerulonephritis approaching end-stage renal failure (ESRF) who still had proteinuria and 10 other patients with diabetic nephropathy (DN) with proteinuria but normal renal function. The pattern of proteinuria was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing (IEF) and assayed for orosomucoid, alpha-1-microglobulin, retinol-binding protein, lysozyme, beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase activity. Our data showed much similarity in the pattern of proteinuria between the DN and ESRF groups but significant differences with the IgAN group. The pattern of proteinuria in the IgAN group reflects glomerulonephritis whereas the similar pattern between the ESRF and DN groups may reflect hyperfiltration as well as tubular injury.
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PMID:Pattern of proteinuria in tubular injury and glomerular hyperfiltration. 939 12


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