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 order to study the role of the renin-angiotensin system in patients with diabetic nephropathy, renin release and the juxtaglomerular apparatus were studied in 17 diabetic patients with proteinuria and in 23 without proteinuria; 8 normal subjects were used for conctrls. Despite hypertension and marked arteriosclerosis, plasma renin activity (supine posture) was normal; however, the renin response to salt restriction and upright posture was less in the diabetic patients with proteinuria than in the controls. Renal renin content, determined at autopsy, was also normal. Examination of the juxtaglomerular apparatus in the diabetic patients with proteinuria revealed hyalinization of the afferent and efferent arterioles in most of the glomeruli and various degrees of destruction of the juxtaglomerular cells. The findings suggest that renin production is not increased in diabetic patients with proteinuria plus marked vascular damage, and that the renin-angiotensin system in patients with diabetic nephropathy apparently does not play an important role in the exacerbation of hypertension or the degree of vascular damage.
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PMID:Renin and the juxtaglomerular apparatus in diabetic nephropathy. 61 49

Postural changes in plasma renin activity were studied in three groups of age and duration-matched male diabetics (potent, impotent and with postural hypotension) and in non-diabetic control subjects. Those diabetic subjects with postural hypotension due to automatic neuropathy had no increase in plasma renin activity to the erect posture whereas both the potent and impotent groups had similar plasma renin activity responses to the control subjects. There was a significant inverse correlation between the rise in plasma renin activity on standing and the postural drop in blood pressure (r = 0.476, P less than 0.01) but no correlation with other tests of autonomic reflex function such as the Valsalva manoeuvre and blood pressure response to sustained handgrip. The results suggested that the lesion responsible for the postural hypotension is in the efferent sympathetic pathway. However, neuropathy per se did not wholly explain the decreased postural plasma renin activity response. Diabetic nephropathy, with involvement of cells of juxtaglomerular apparatus, may also be implicated.
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PMID:Plasma renin activity in diabetic autonomic neuropathy. 97

Plasma renin activity (PRA) was determined in 48 patients with diabetes mellitus in sodium balance on a 10-20 mEq. Na diet. Nine were normotensive (group I), 11 11 were hypertensive without diabetic nephropathy (group III). Results were compared with those in 16 normal subjects and 49 nondiabetic patients with essential hypertension in similar Na balance. Mean supine PRA did not differ significantly among groups I and II, normal subjects, and patients with essential hypertension. Group III diabetics had a supine PRA of 2.4 +/- 0.4 ng./ml./hr. (x +/- S.E.M.), significantly lower than the other diabetic groups (P less than 0.005) and normal subjects (P less than 0.05). Upright PRA was 12.8 +/- 2.2 in group I diabetics, similar to that in normal subjects (13.3 +/- 2.3), and 8.1 +/- 1.4 in group II diabetics, similar to that in essential hypertensives (6.8 +/- 0.8). In group III diabetics, upright PRA was 4.0 +/- 0.5, significantly lower than that in any other group. These results suggest that (1) PRA is normal in normotensive diabetics, (2) upright PRA in diabetics with hypertension but no nephropathy is similar to that in essential hypertension, and (3) patients with diabetes, hypertension, and nephropathy have "low renin hypertension," explaining the virtual absence of malignant hypertension in this group. Although the major mechanism for this low PRA may be volume expansion, indicating the need for potent diuretics, other mechanisms include hyalinization of the afferent arteriole, decreased cathecholamine stimulation of renin release, and inadequate conversion of prorenin to renin.
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PMID:Plasma renin activity and hypertension in diabetes mellitus. 97 6

Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy.
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PMID:Big renin: identification, chemical properties and clinical implications. 125 3

Angiotensin-converting enzyme (ACE) inhibitors act by lowering the level of angiotensin II. The therapeutic benefits of these drugs and their potential side-effects therefore result from suppression of the physiological effects of angiotensin II. It is rational to prescribe an ACE inhibitor when the renin-angiotensin system is activated, as in renin-dependent essential hypertension, malignant hypertension and hypertension associated with heart failure. The beneficial effects of ACE inhibitor must be weighed against the special risks of renovascular hypertension: risk of renal artery thrombosis in case of unilateral stenosis and risk of renal failure if the stenosis is bilateral or affects a solitary kidney. In some situations the renin-angiotensin system is not directly involved in hypertension but may play a local haemodynamic role, as in some cases of primary or diabetic nephropathy. In such case the ACE inhibitors are thought to exert a protective effect. ACE inhibitors were reputed to be less effective in the elderly than in younger patients, but we now know that they can be prescribed with equal success in both instances to reduce peripheral resistance and improve regional blood flow as well as arterial compliance. Finally, ACE inhibitors can be prescribed, albeit with limited effectiveness, when the renin-angiotensin system is not activated, as in low renin hypertension and idiopathic hyperaldosteronism due to adrenal hyperplasia. They are ineffective in case of Conn's adenoma and contra-indicated in pregnant women.
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PMID:[For which hypertensive patient should angiotensin-converting enzyme inhibitor be prescribed or forbidden?]. 129 38

Angiotensin converting enzyme (ACE) inhibition has shown promising results in diabetic nephropathy, but long-term results on survival are not available. In a cohort of patients receiving antihypertensive treatment predominantly consisting of beta blockers in combination with diuretics, support for an improved survival has been presented. Addition of ACE inhibition to such a combination treatment may be favorable both due to the suggested renoprotective effects of ACE inhibitors and because diuretics activate the renin-angiotensin system. In 10 insulin-dependent diabetic patients with early diabetic nephropathy [urinary albumin excretion rate (UAE) less than 100o micrograms/min], who were receiving continuous therapy with metoprolol and bendroflumethiazide, a double-blind crossover study with four months addition of ramipril 5 mg (Ramace) and placebo was conducted. UAE (radioimmunoassay) and fractional albumin excretion were significantly reduced after the four months of ramipril administration [UAE: 114.1 x/divided by 1.3 (geometric mean x/divided by confidence factor] versus 174.6 x/divided by 1.2 micrograms/min, 2P less than 0.005). Renal plasma flow (clearance of 131I-hippuran) tended to increase [497 +/- 25 (mean +/- SE) vs. 464 +/- 28 ml/min/1.73 m2, 2P = 0.08], while GFR (125I-iothalamate) stayed unchanged (121 +/- 8 vs. 120 +/- 9 ml/min/1.73 m2). Mean arterial pressure during clearance studies fell moderately (95 +/- 3 vs. 101 +/- 1 mm Hg, 2P less than 0.05) and renal resistance was decreased (2P less than 0.03). ACE activity was suppressed in all patients. Twenty-four-hour ambulatory blood pressure measurements were not significantly different after the two periods (daytime averages: 91 +/- 2 vs. 93 +/- 2, nighttime 80 +/- 2 vs. 84 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ACE inhibition supplementary to beta blockers and diuretics in early diabetic nephropathy. 135 49

The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation.
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PMID:Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. 145 59

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

This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and its presence in extrarenal, as well as renal, tissues. Intriguing changes in plasma prorenin have been reported after treatment with antihypertensive and other drugs, following various physiological stimuli, and in pathophysiological states such as Wilms' tumor, Bartter's syndrome, and diabetic nephropathy. Lately, very high prorenin concentrations have been found in human and animal ocular fluid, ovarian follicular fluid, and in association with angiogenesis and microangiopathy. High circulating prorenin concentrations and fulminant hypertension have been reported in rats harbouring the mouse Ren-2 gene. However, what prorenin does in all these extrarenal fluids, tissues, and conditions is not well understood. Among the reasons for this lack of understanding are the difficulties in measuring prorenin and in establishing good animal models. We have not answered the critical question as to whether prorenin itself is bioactive like a hormone, and if so, what its action(s) might be. Nor have we established the main alternative, i.e., whether the function of prorenin is indirect, through renin--angiotensin, be it in the circulation or in the extrarenal tissues. This Symposium provides only partial methodological advances and answers, but we hope it will stimulate the breakthrough work needed to supply more complete answers.
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PMID:Activation and function of prorenin: different viewpoints. 175 30

The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng.ml-1.h-1, and so did serum potassium (from 4.57 to 4.83 mEq.1-1). Serum aldosterone fell from 161 to 70.9 pgm.ml-1 and from 27.3 to 15.3 micrograms.24 h-1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile.
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PMID:Effects of captopril on diabetic nephropathy in hypertensive women. 176 Oct 66


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