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

Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of Rsal digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies.
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PMID:Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus. 145 65

Angiotensin II plays an important role in the kidney by regulating renal flow, glomerular filtration rate, mesangial cell function, and sodium reabsorption. Blockade of the renin-angiotensin system has powerful effects on kidney function. Studies in animal models of renal failure suggest that converting enzyme inhibitors slow down the inevitable progression of the renal failure. This could be in part due to their effect on reducing glomerular pressure or by reducing glomerular hypertrophy. In patients with malignant hypertension, diabetic nephropathy, and other causes of renal failure, preliminary evidence suggests that lowering the blood pressure with angiotensin-converting enzyme (ACE) inhibitors may possibly carry some other benefits compared with other blood pressure lowering regimens. However, single drug therapy is rarely sufficient to control blood pressure in these patients. Further properly controlled randomized trials should give a clear indication of whether any particular class of drug has any advantage in slowing down the progressive renal impairment for a given lowering of blood pressure. In patients with renovascular hypertension ACE inhibitors are effective drugs in lowering blood pressure. However, in certain settings they may cause a reversible decline in renal function.
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PMID:Blood pressure, angiotensin-converting enzyme (ACE) inhibitors, and the kidney. 158 Feb 76

The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity. 193 64

Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.
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PMID:Angiotensin carboxypeptidase activity in urine from normal subjects and patients with kidney damage. 201 86

We measured plasma- and extracellular fluid volume (125I-albumin, 51Cr-EDTA), plasma concentrations of renin, angiotensin I and II, aldosterone and atrial natriuretic peptide by radio-immunoassays in insulin-dependent diabetic (IDDM) patients with (n=28) and without (n=11) nephropathy and in 14 normal control subjects matched for sex and age. Glomerular filtration rate (GFR) (ml/min/1.73 m2, single intravenous bolus 51Cr-EDTA technique) was within normal range in all nephropathic patients; 107 (range 78-134). Mean arterial blood pressure (mmHg) was elevated 102 +/- 13 (+/- S.D.) compared to the diabetic and normal control group, 92 +/- 8 and 87 +/- 5, respectively (p less than 0.01). Plasma volume was identical in all three groups while extracellular volume (1/1.73 m2) was expanded in nephropathic patients, 14.5 +/- 1.5 vs 13.1 +/- 0.9 and 12.4 +/- 1.3 in the diabetic and non-diabetic control groups, respectively (p less than 0.05). A significant correlation between extracellular fluid volume and mean arterial blood pressure was found (n=53, r=0.49, p less than 0.001). Active renin was significantly increased in patients with diabetic nephropathy compared with the normal control subjects, while all the remaining hormones were about the same in the three groups. Our study suggests that fluid retention plays a dominant role in the initiation and maintenance of arterial blood pressure elevation early in the course of diabetic nephropathy.
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PMID:On the pathogenesis of arterial blood pressure elevation early in the course of diabetic nephropathy. 253 16

Diabetic nephropathy is characterized by persistent albuminuria, a decline in glomerular filtration rate (GFR) and elevated blood pressure. About 40% of all insulin-dependent diabetic patients will develop nephropathy, thus increasing their morbidity and mortality. The effect of early aggressive antihypertensive treatment with metoprolol, frusemide or thiazide in insulin-dependent diabetic patients with nephropathy has shown a significant reduction in albuminuria and in the rate of decline in the GFR (from 0.94 to 0.29 and 0.10 ml/min per month over 72 months of antihypertensive treatment). The effect of angiotensin converting enzyme (ACE) inhibition on kidney function in diabetic nephropathy showed that the GFR is not dependent on angiotensin II (Ang II), and that ACE inhibition diminished albuminuria, probably by lowering glomerular hypertension. In conclusion, antihypertensive treatment with ACE inhibitors or beta-blockers combined with a diuretic protects kidney function and reduces albuminuria in diabetic nephropathy. Angiotensin converting enzyme inhibitors can be considered as first-line drugs for hypertensive patients with diabetic nephropathy.
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PMID:The effect of beta-blockade and angiotensin converting enzyme inhibition on kidney function in diabetic nephropathy. 257 61

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.
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PMID:Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. 309 Nov 64

Roughly 40% of all diabetic patients, whether insulin dependent or not, develop persistent albuminuria (over 300 mg/24 hr), a decrease in the glomerular filtration rate, and elevated blood pressure, ie, diabetic nephropathy. Diabetic nephropathy is the single most important cause of end stage renal disease in the Western world, and accounts for over a quarter of all end stage renal disease. It also is a major cause of the increased morbidity and mortality seen in diabetic patients; for example, the cost of end stage renal care in the United States currently exceeds +1.8 billion per year for diabetic nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease. An impaired nocturnal decline in blood pressure is more prevalent in patients with diabetic nephropathy and autonomic neuropathy, and may contribute to the enhanced cardiovascular morbidity found in such patients. Moreover, raised blood pressure accelerates both the development and progression of diabetic nephropathy in insulin-dependent and non-insulin-dependent diabetes. The relationship between arterial blood pressure and diabetic nephropathy thus seems to be a complex one: nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. Effective blood pressure reduction reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium antagonists and the diabetic hypertensive patient. 850 35

Classically, the renin-angiotensin system (RAS) in diabetes was thought to be suppressed, and relatively unimportant in the regulation of hemodynamics and the development of complications. However, studies of pharmacologic interruption of the RAS with angiotensin converting enzyme (ACE) inhibition have implicated the RAS in the progression of diabetic nephropathy. Preliminary evidence also suggests a beneficial effect of angiotensin II receptor antagonists. The relative roles of the systemic versus intrarenal RAS in this process are under active investigation. Though plasma renin is generally low, there may be subtle changes in angiotensin (Ang) II metabolism that sustain relatively higher plasma Ang II levels. Furthermore, the intrarenal RAS may not be suppressed. Renal renin levels tend to be disproportionately elevated, as compared to plasma values. Renal Ang II levels are normal, and renal mRNAs for RAS components have been variable. In general, lack of intrarenal RAS suppression (despite plasma volume and increased exchangeable sodium) may indicate inappropriate activity of the local tissue RAS, and act as a proximate cause of the systemic RAS suppression. Ang II-mediated injury may occur via stimulation of sclerosing mediators, and there is evidence that hyperglycemia acts synergistically with Ang II to promote cellular injury. Together, these recent investigations lend further support to the notion that the RAS plays an important role in diabetic nephropathy, and are helping to shed light on the mechanisms of progressive renal injury.
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PMID:Role of local and systemic angiotensin in diabetic renal disease. 940 35

ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
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PMID:Angiotensin-converting enzyme inhibitors. 957 53


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