Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
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PMID:A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy. 135 Sep 91

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.
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PMID:Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury. 136 94

Hypertension is often seen in Type 1 and Type 2 diabetic patients, particularly in those with nephropathy, and the progression of diabetic nephropathy is closely related to blood pressure elevation. Thus, the effects of antihypertensive drugs on kidney function and insulin sensitivity in diabetic patients are of great clinical importance. Successful antihypertensive treatment has been shown to slow the progression of diabetic nephropathy. Several results from short term studies have suggested that angiotensin converting enzyme (ACE) inhibitors may be advantageous over other conventional antihypertensive agents in reducing albuminuria in both hypertensive and normotensive diabetics with microalbuminuria or persistent proteinuria. However, the decline in glomerular filtration rate during ACE inhibitor treatment is comparable to that during effective treatment with conventional antihypertensive drugs in hypertensive Type 1 diabetic patients with overt nephropathy. Whether ACE inhibitors possess a specific effect in preventing the development of diabetic nephropathy remains to be seen in properly designed long term studies. Although calcium antagonists may preserve kidney function or possess a renoprotective effect in hypertensive Type 2 diabetics with nephropathy, firm evidence supporting this contention seems to be lacking and also requires long term evaluation. Increasing attention is being directed toward the effect of antihypertensive drugs on insulin sensitivity in diabetic patients: ACE inhibitors and alpha 1-adrenoceptor blocking agents have been shown to improve this sensitivity. Despite the widespread involvement of calcium in hormone secretion and action, calcium antagonists appear to have little effects on the glucoregulatory and calcium-regulatory hormones within the drug dosages used in clinical practice. Several clinical variables, such as the presence or absence of hypertension, overt nephropathy and microalbuminuria, or a combination of variables should be accounted for when evaluating critically the cumulative data on the effects of antihypertensive drugs on kidney function and albuminuria in the variety of diabetic patient groups. Understanding the pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs will be of clinical importance in diabetic patients with advanced nephropathy (glomerular filtration rate of less than 30 ml/min) and/or other complications, such as impaired gastric motility or gastroparesis, and will thereby lead to a more rational management of hypertension in those patients.
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PMID:Recent advances in pharmacological management of hypertension in diabetic patients with nephropathy. Effects of antihypertensive drugs on kidney function and insulin sensitivity. 137 14

Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over one-quarter of all end-stage renal disease. Systemic/glomerular hypertension plays a role in the initiation and progression of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of glomerular hypertension may be the crucial factor involved. Human studies suggest that ACE inhibitors postpone the progression to clinical overt diabetic nephropathy in normotensive diabetic patients with persistent microalbuminuria. ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal insufficiency in hypertensive diabetics with overt nephropathy. No treatment modality other than antihypertensive treatment has yet been proven to be effective in protecting renal function in diabetic nephropathy. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate between 50 and 77% 10 years after the onset of proteinuria. Effective antihypertensive treatment has reduced the cumulative death rate to 15-20% 10 years after the onset of nephropathy.
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PMID:Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus. 138 60

Diabetes mellitus has become the leading cause of ESRF in the United States. Patients with diabetic nephropathy suffer high cardiovascular morbidity and mortality. Because only 40% of diabetic patients eventually develop diabetic kidney disease, it may be possible to devise primary prevention measures targeted at the subset of patients at risk. Recently, a predisposition to hypertension, a family history of diabetic nephropathy, and a family history of CVD disease each have been associated independently with the development of diabetic renal complication in IDDM. Risk factors for macrovascular damage, including raised arterial BP, dyslipidemia, and insulin resistance, can be detected early in the course of progression to diabetic nephropathy. These risk indicators recently have been shown to be already present at the stage of normoalbuminuria in those patients who eventually will progress to microalbuminuria. Treatment of established renal disease can only delay the onset of ESRF, and lowering of microalbuminuria has been shown to retard the onset of persistent proteinuria. However, no study to date has demonstrated prevention of renal disease in these patients. The ultimate aim should, therefore, be the prevention of the transition from normoalbuminuria to microalbuminuria in individuals who are at higher risk of diabetic renal disease and CVD.
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PMID:Diabetic nephropathy. Future avenue. 139 18

The number of glomeruli per kidney in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients was estimated by an unbiased stereological method: the fractionator. No significant differences were observed between Type 1 and Type 2 diabetic patients without severe diabetic glomerulopathy and non-diabetic patients. Diabetic patients with proteinuria who were in the early stages of diabetic nephropathy also had a normal number of glomeruli. On the other hand, a subgroup classified as Type 1 diabetic patients with severe diabetic glomerulopathy had significantly less glomeruli compared with Type 1 diabetic patients with mild or no glomerulopathy. A probable explanation is that Type 1 diabetic patients lose glomeruli in relation to the progression of diabetic glomerulopathy. A more theoretical alternative is, however, that development of diabetic glomerulopathy is facilitated by a low number of glomeruli.
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PMID:The number of glomeruli in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. 139 79

All diabetic patients should be screened for early signs of diabetic nephropathy, because it is a prognostic factor in the disease. The albusure test (AT), a latex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor for microalbuminuria, a reliable early marker of diabetic nephropathy.
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PMID:Utility of the latex agglutination nephelometric immunoassay (Albusure Test) in screening for microalbuminuria in patients with diabetes mellitus. 139 21

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients. 142 58

One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. Urinary albumin excretion was measured as the albumin:creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18-2.67; p < 0.01); the relative risk of microalbuminuria (UA/UC > 3.0 mg/mmol) associated with expression of HLA-A2 was 2.52 (95 per cent CI 1.11-5.73; p < 0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p < 0.01) and expression of the HLA-A2 antigen (p < 0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC > 45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroalbuminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p < 0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure.
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PMID:The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria. 144 47

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a nondiabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of beta-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of beta 2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein beta 2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.
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PMID:Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat. 145 Oct 36


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