Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:[For which hypertensive patient should angiotensin-converting enzyme inhibitor be prescribed or forbidden?]. 129 38

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.
 ...
PMID:Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus. 138 60

Angiotensin-converting enzyme (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/- 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure.
 ...
PMID:Captopril acutely lowers albuminuria in normotensive patients with diabetic nephropathy. 146 82

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
 ...
PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy.
 ...
PMID:Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. 283 66

Hypertension in patients with diabetes mellitus increases the risk of both macrovascular and microvascular complications. Such microvascular complications as diabetic nephropathy and retinopathy are accelerated in the presence of arterial hypertension. Evidence suggests that the complications of diabetes mellitus begin early in the course of the disorder as manifested by microalbuminuria and increased vascular reactivity. These findings are accompanied by changes in the renin-angiotensin-aldosterone system including reductions in plasma renin activity. These changes could be secondary to volume expansion that may be a direct consequence of elevated blood glucose, suggesting that the metabolic disorder in diabetes contributes to the etiology of hypertension in these patients. Adequate treatment of hypertension is crucial to the prevention of complications; however, many antihypertensive agents have limited usefulness in diabetes mainly because of their unfavorable side effects. Diuretics lower blood pressure in hypertensive diabetics, but their metabolic effects are especially undesirable in this population. beta-Blockers alter glucose and lipid metabolism in diabetic patients and reduce regional blood flow. Central acting agents and alpha-blockers are often associated with orthostatic hypotension, sexual dysfunction, and central nervous system side effects. Angiotensin-converting enzyme inhibitors (ACEIs) such as captopril effectively lower blood pressure in diabetic patients and have few unwanted effects. They may improve metabolic control and have favorable effects on glucose metabolism. The ACEIs also produce improved regional hemodynamics which may lead to the improvement in or prevention of the progression of diabetic nephropathy.
 ...
PMID:Management of hypertension in the patient with diabetes mellitus. Focus on the use of angiotensin-converting enzyme inhibitors. 305 49

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce urinary albumin excretion (UAE) in diabetic patients. Animal studies have shown that, besides diminishing the glomerular capillary pressure, ACE inhibitors might reduce albuminuria by influencing glomerular charge selectivity through glomerular preservation of heparan sulphate proteoglycan. In humans, an indirect measurement of glomerular charge selectivity can be obtained by calculating the glomerular charge selectivity index (SI), a clearance ratio of IgG/IgG4, two identically sized but differently charged molecules. The aim of the present study was to evaluate the effect of ACE inhibition on charge selectivity by comparing SI in type I (insulin-dependent) diabetic patients with microalbuminuria after 6 years of treatment either with or without captopril. Thirty-five of 45 patients participating in a prospective randomized study evaluating the effect of captopril in preventing the development of diabetic nephropathy were included in the present study, 17 being treated with captopril, 18 left as untreated controls. The selectivity index was calculated after measuring s-IgG, u-IgG, s-IgG4, and u-IgG4. The results demonstrated a higher selectivity index in the captopril-treated group [1.21 (0.51-1.94) median (range)] compared to the control group [0.94 (0.31-1.87)], however, the difference was not statistically significant (p = 0.16). A negative correlation between the selectivity index and UAE was demonstrated in the captopril-treated group (r = -0.77; p = 0.0004), whereas the correlation in the control group did not reach statistical significance (r = -0.3; p = 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Possible effect of angiotensin-converting enzyme inhibition on glomerular charge selectivity. 754 79

The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Angiotensin-converting enzyme inhibition in diabetic nephropathy: ten years' experience. 761 Dec 76

Antihypertensive treatment has been shown to slow down the decline in glomerular filtration rate (GFR) with time. This has been most extensively studied in patients with diabetic nephropathy and, to some extent, with other forms of renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. This important aspect of antihypertensive treatment has not been studied previously in patients with essential hypertension. Preliminary results regarding the effects of two different antihypertensive therapies on the loss of GFR with time, determined with 51Cr-EDTA clearance after 6, 12, and 24 months of treatment, are presented here. The GFR was assessed in a prospective, randomized, double-blind trial in 257 patients with essential hypertension. All had a normal renal function, and none had diabetes mellitus or glucosuria. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering the systolic blood pressure. However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure after 6, 12, and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months, the reduction in GFR was 1.0 (cilazapril) vs. 4.0 (atenolol) ml/min x 1.73 m2 (p < 0.01). After 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2 (p < 0.05) and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2 (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of angiotensin-converting enzyme inhibition versus conventional antihypertensive therapy on the glomerular filtration rate. 761 4

In addition to factors such as protein intake or hyperlipidemia, hypertension contributes to the progressive deterioration of renal function in experimental animal models of renal disease, and has a prominent role in the imbalance of intrarenal hemodynamics. Reduction of arterial pressure was shown to alter the course of human chronic renal disease. In patients with diabetic as well as nondiabetic nephropathy, the lowering of proteinuria by angiotensin-converting enzyme inhibitors is greater than that observed with other antihypertensive drugs and appears to be independent of blood pressure control alone, whereas albuminuria may be unaffected or worsened during nifedipine treatment. Angiotensin-converting enzyme inhibitors may afford better protection than conventional treatment at various stages of diabetic nephropathy and prevent the evolution from incipient to overt nephropathy. In patients with nondiabetic renal disease, no unequivocal evidence exists for such a protective effect. In renal transplant recipients receiving cyclosporine, converting enzyme inhibitors and calcium antagonists are equally effective in the control of hypertension and both leave unaltered the glomerular filtration rate. It remains to be demonstrated, using adequate study designs, whether a particular class of agent is superior to another in patients with chronic renal disease.
 ...
PMID:Angiotensin-converting enzyme inhibitors versus calcium antagonists in the progression of renal diseases. 781 39


1 2 3 4 5 6 7 8 Next >>