Blood pressure reduction is necessary for the reduction of proteinuria in diabetic nephropathy--comparison of different antihypertensive agents.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
C M Erley
Publications and source records attributed to C M Erley.
Protective effects of endothelin antagonists in chronic renal failure.
The present study suggests that ET-1 is involved in the pathogenesis of uraemic cardiac hypertrophy and in the progression of renal failure in rats with subtotal nephrectomy examined after an intermediate period of 12 weeks of renal failure. Furthermore, proteinuria is reduced by the selective ETA receptor antagonist more than by the unselective ETAB receptor antagonist, without reducing the blood pressure. ET receptor blockade might preserve renal function by reduction of protein excretion. In addition, ET receptor antagonists influence the aldosterone system. In our animal studies, the medication was well tolerated. Our study results provide a possible therapeutic approach using ET receptor antagonists for cardiac hypertrophy and renal protein excretion by blockade of endogenous ET-1. Further human studies are needed to show whether this protection of the heart and kidney might influence the survival and life expectancy of patients suffering from chronic renal failure, of patients on dialysis or after kidney transplantation.
Animals↗
Platelet glycoprotein IIb/IIIa receptor antagonist used in conjunction with thrombolysis for peripheral arterial thrombosis.
OBJECTIVE: This feasibility study was designed to evaluate the therapeutic potential of intraarterial urokinase combined with abciximab, an IV platelet glycoprotein IIb/IIIa receptor antagonist, in peripheral arterial thrombosis. CONCLUSION: The administration of a highly potent glycoprotein IIb/IIIa inhibitor in conjunction with intraarterial fibrinolysis was safe in 14 patients. One distal embolization and no major bleeding occurred. The primary success rate was 100%. Treatment times ranged from 50 min to 8 hr. We found a reocclusion rate of 7% (1/14) at intermediate follow-up.
Abciximab↗
Images in clinical medicine. Floating right atrial thrombus and massive pulmonary embolism.
Explore the source record for details and available documents.
Electrocardiography↗
A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine.
OBJECTIVE: A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage. Equally high blood pressure without symptoms is called a hypertensive crisis. Patients with hypertensive crisis or emergency need prompt, effective, and specific therapy and a controlled reduction of blood pressure. METHODS: We performed a randomized, double-blind multi-centre study, to compare the safety, efficacy and tolerability of an intravenous (i.v.) infusion of two dihydropyridine calcium channel blockers (either nifedipine or felodipine) in 122 patients, of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis, who had not reacted adequately (diastolic blood pressure <115 mmHg) to 5 mg of nifedipine PO. RESULTS: Both drugs lowered blood pressure adequately in more than 90% of the patients and were well tolerated. Only one patient had to be withdrawn, because of an excessive decrease in blood pressure. CONCLUSION: Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV. Felodipine is easier to handle because of its lack of light sensitivity.
Administration, Oral↗
Gd-enhanced 3D phase-contrast MR angiography and dynamic perfusion imaging in the diagnosis of renal artery stenosis.
The objective of this study was to investigate the role of contrast enhancement using a three-dimensional (3D) phase-contrast (PC) magnetic resonance (MR) sequence (3D PC-MRA) and to assess the value of a dynamic MR perfusion study of the kidneys to determine the hemodynamic relevance of unilateral renal artery stenosis (RAS). Seventeen patients with unilateral RAS were examined on a standard 1.0 T imaging system using a phase shift and magnitude sensitive 3D PC sequence (TR=160 ms, TE=9 ms, venc. 30 cm/s). Following the initial pre-contrast 3D PC-MRA a dynamic first pass perfusion study was performed using a Turbo-FLASH 2D sequence (TR=4.5 ms, TE=2.2 ms, TI=400 ms) after bolus injection of 0.15 mmol gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)/kg body weight. The 3D PC-MRA was then repeated during infusion of 0.15 mmol Gd-DTPA/kg body weight. Evaluation by three independent readers was based on maximum intensity projection images. Source images were rendered on request. Signal intensity (SI) over time curves of the renal cortex were obtained from the dynamic perfusion study and analyzed for maximum signal enhancement as well as temporal relationship to the aortic SI curve. Results from 3D PC-MRA revealed a sensitivity (pre-/post-contrast) of 100%/89%, specificity of 76%/63%, positive predictive value of 80%/69 %, negative predictive value of 90%/78%, and accuracy of 85%/75% (p=0.07). Interobserver agreement was kappa=0.61/kappa=0.47 (pre/post Gd-DTPA), respectively. Increased signal-to-noise was present in all segments of the renal arteries post contrast (p=0.0003). This came along with image degradation due to aliasing and elevated SI of venous flow that partially obscured the renal arteries. Dynamic SI curves showed a significantly decreased maximum SI in RAS (p=0.01-0.001). A temporal delay of cortical signal intensity enhancement could not be confirmed in this setting. Gd-enhanced 3D PC-MRA did not yield a superior diagnostic value in the diagnosis of RAS compared to pre-contrast measurements. Dynamic perfusion imaging of the kidneys, in combination with 3D PC-MRA, can contribute additional information in suspected unilateral RAS.
Aged↗
Immunoglobulin and circulating immune complex kinetics during immunoadsorption onto protein A sepharose.
Immunoadsorption onto protein A sepharose can be applied to eliminate immunoglobulins, autoantibodies and circulating immune complexes from the circulation. In vivo kinetic studies showed that all IgG subclasses are removed from the patient's plasma although IgG3 elimination is variable and dependent on the presence of other immunoglobulins. IgG elimination half time was 4.8 days during intermittent and 2.9 days for daily therapy in the absence of immunosuppression. Autoantibodies and immune complexes can be cleared effectively but administration of intravenous immunoglobulins should be avoided because of competition for protein A binding sites. Redistribution/ denovo synthesis (half time 2.1-8.8 d for IgG 1-4) occurred in the absence of immunosuppression.
Antigen-Antibody Complex↗
Adenosine and extracellular volume in radiocontrast media-induced nephropathy.
Renal hemodynamic changes could play a key role in radiocontrast media-induced nephropathy (RCIN), although the pathophysiological mechanisms are unclear. We investigated the role of adenosine in RCIN caused by sodium diatrizoate (Urografin, 3 ml/kg) in nitro-L-Arg methyl ester (L-NAME)-hypertensive rats in different hydration states [eight weeks of L-NAME (50 mg/liter) in drinking water; high or low sodium intake for the last two weeks]. In clearance experiments under thiobutabarbital anesthesia in these previously mentioned animals, glomerular filtration rate (GFR), renal blood flow (RBF), and mean arterial pressure (MAP) were measured in the presence or absence of the adenosine A1-receptor antagonist 8-cyclopropyl-1,3-dipropylxanthine (DPCPX, 100 microg/kg bolus plus 10 microg/kg/hr). DPCPX or pretreatment did not change control hemodynamics. Contrast medium caused GFR and RBF to fall significantly in volume-depleted rats (from 0.29 +/- 0.02 to 0.21 +/- 0.02 ml/min/100 g and 5.4 +/- 0.3 to 4.0 +/- 0.4 ml/min, respectively) without change in MAP. In volume-expanded rats, changes were not significant (0.25 +/- 0.01 to 0.24 +/- 0.02 ml/min/100 g and 5.6 +/- 0.3 to 5.3 +/- 0.4 ml/min, respectively). In the volume-depleted rats, changes were prevented by DPCPX (0.27 +/- 0.02 to 0.24 +/- 0.02 ml/min/100 g and 4.8 +/- 0.1 to 5.0 +/- 0.1 ml/min, respectively). The acute hemodynamic effects elicited by contrast medium in L-NAME hypertensive rats thus can be prevented by volume expansion. Adenosine, via A1-receptors, contributes to the adverse effects of contrast media.
Acute Kidney Injury↗
Endothelin-1 and endothelin-3 levels in different types of glomerulonephritis.
There is evidence that an activated renal endothelin (ET) system is involved in development of glomerulosclerosis. However it is still unknown if different ETs are involved in the pathogenesis of various types of glomerulonephritis (GN). This study characterized ET-1 and ET-3 levels in patients suffering from chronic GN. We performed a prospective study to evaluate the ET-1 and ET-3 levels in 19 patients with biopsy-proven GN, including four minimal-change nephropathies (MCN), six perimembraneous GN (PM-GN), and nine mesangioproliferative GN (MP-GN). Twelve healthy subjects matched for age and sex served as controls. ET-1 and ET-3 were measured in plasma (p) and in urine [spontaneous urine (sp.urine) and urine over 24 h (24-h urine)] using a specific radioimmunoassay. Patients and controls were compared using the Wilcoxon rank-sum test. In MCN, ET-1 levels were enhanced in sp. urine (p = 0.03) and 24-h urine (p = 0.01), whereas ET-3 levels did not differ from controls. In comparison, in PM-GN we found an increased ET-3 level in 24-h urine (p = 0.004). In MP-GN, ET-3 levels were also elevated in p (p = 0.0002) and urine specimens (sp. urine p = 0.05; 24-h urine p = 0.03). No positive correlation to C3 or C4 complement fractions was found. Age, blood pressure or renal function did not correlate with ET-1 or ET-3 levels. In MP-GN and PM-GN, ET-3 is elevated whereas ET-1 is not. In contrast ET-1 is increased in MC-GN. These data indicate an important role for the ET-1 and ET-3 systems in the pathophysiology of different forms of GN. This is significant with regard to an early preservation of renal function at the onset of GN by the use of selective ET antagonists.
Adult↗
[Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors].
BACKGROUND AND OBJECTIVE: In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function. Treatment regimens which reduce proteinuria and hypertension improve prognosis. The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest. PATIENTS AND METHODS: The studied cohort consisted of 11 patients with CGN, hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks, doubly blinded and randomized according to a "Latin-square design": Celiprolol (beta-1-antagonist, beta-2-agonist, 200 mg/d), Atenolol (selective beta-1-antagonist, 50 mg/d), Ramipril (ACE-inhibitor, 2.5 mg/d) and placebo. There was a two-week wash-out phase between each of the four treatment phases. At the end of each treatment phase glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-amino-hippuric acid (PAH) clearance. Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase. During this period blood pressures were measured with a continuous 24-hour blood pressure monitor. RESULTS: Mean arterial blood pressure (MAP) was significantly reduced, compared with placebo, by all three antihypertensives (108 +/- 9 mm Hg with placebo, 98 +/- 12 mg Hg with atenolol, 101 +/- 11 mm Hg with celiprolol and 98 +/- 8 mm Hg with ramipril; P < 0.01). Celiprolol produced a significant rise In ERPF (322 +/- 109 ml/min with placebo, 391 +/- 110 ml/min with celiprolol: P < 0.05). GFR was slightly, but not significantly, reduced by celiprolol and atenolol. Filtration fraction remained unchanged with atenolol and celiprolol, while it was slightly, but not significantly, reduced with ramipril. Compared with the placebo, all three drugs significantly reduced proteinuria (P < 0.05): 1.8 +/- 1.3 g/24 h with placebo, 1.2 +/- 1.2 g/24 h with atenolol, 1.2 +/- 1.1 g/24 h with celiprolol and 1.4 +/- 1.4 g/24 h with ramipril. CONCLUSION: These data indicate that, in addition to ACE inhibitors, the new generation of beta-receptor blockers in particular, because of their vasodilator action, favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension.
Adrenergic beta-Antagonists↗
[The adjuvant use of the monoclonal antibody c7E3 Fab in peripheral arterial thrombolysis].
Thrombolysis of arterial occlusions has limitations, e.g. it requires extensive time for thrombolysis, occlusions may be resistant to lysis, and the rate of reocclusions may be high. c7E3 Fab inhibits platelet aggregation by binding to the GPIIb/IIIa receptor on platelets. Experimentally, this monoclonal antibody has been shown to decrease, the time required for lysis, and to prevent reocclusion. This is the first report on the adjunctive use of c7E3 Fab in peripheral arterial occlusions in humans. Three patients with occlusion of the iliac or femoropopliteal artery were treated with c7E3 Fab (bolus injection of 0.25 mg/kg KG + i.v.-application 12 micrograms/min for 12 h). In addition, the patients received urokinase (100,000 IU bolus + 100,000 IU/h). Heparin (5,000 IU bolus + 1,000 IU/h) and acetylsalicylate (100 mg/day/p.o.). Occlusion length ranged between 6-40 cm. Therapy was successful in all patients. During the follow-up period (4-6 months) no reocclusion occurred. There were no serious side effects like major bleeding or thrombocytopenia. We conclude that the applied doses appear safe. Even the time required for thrombolysis was short, a conclusion in respect of a significant reduction of the time required for lysis can be drawn only after further controlled studies.
Abciximab↗
Prevention of radiocontrast-induced nephropathy by adenosine antagonists in rats with chronic nitric oxide deficiency.
To evaluate therapeutic options for the prevention of radiocontrast media (RCM)-induced nephropathy, a model was developed in which rats received NG-nitro-L-arginine methyl ester (L-NAME) for 10 wk in order to inhibit nitric oxide (NO) synthetase. This study tests the hypothesis that infusion of an adenosine antagonist before RCM application may avoid the vasoconstrictive response in NO-depleted rats. Rats received L-NAME for 10 wk orally (50 mg/L drinking water) to achieve NO depletion. Renal function was determined by [3H]inulin clearance for analysis of the GFR and by flowmetry for assessing renal blood flow (RBF). After a control clearance period (baseline clearance period), the renal response to RCM application (sodium diatrizoate, 2 ml/kg body wt) was measured two times every 30 min starting 30 min after RCM application (clearance periods 1 and 2). L-NAME rats and control rats received two adenosine antagonists. The nonselective adenosine antagonist theophylline was given as an initial bolus of 50 mumol/kg body wt within 10 min, followed by continuous infusion of 100 mumol/kg body wt per h, and the specific adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was given as a bolus of 100 micrograms/kg body wt before RCM application. Results were compared with vehicle infusion. In the control group, no significant change of GFR or RBF could be detected after application of RCM with or without prior infusion of DPCPX or theophylline. In L-NAME rats, RBF decreased significantly after RCM application (baseline, 5.6 +/- 0.2 ml/min; first clearance period, 4.6 +/- 0.3 ml/min [P < 0.05]; second clearance period, 4.3 +/- 0.3 [P < 0.01]). GFR was also reduced in L-NAME rats without previous infusion of theophylline or DPCPX (baseline, 0.95 +/- 0.1 ml/min; first clearance period, 0.83 +/- 0.1 ml/min; second clearance period, 0.69 +/- 0.1 ml/min [P = 0.058]). Prior treatment with either theophylline or DPCPX resulted in complete protection against a decline of RBF and GFR induced by RCM in L-NAME rats. Rats with chronic NO blockade showed a significant increase of the renal vasoconstrictive effect of contrast media. Application of L-NAME in rats seems to constitute a suitable animal model to study the pathophysiology of radiocontrast media-induced nephropathy. In this animal model, administration of adenosine antagonists prevented the decline of GFR and RBF.
Acute Kidney Injury↗
[Contrast media-associated nephropathy--pathogenesis and prevention].
Contrast media-associated nephrotoxicity continues to be a relevant cause of acute renal failure, especially in patients with pre-existing renal insufficiency. Alterations in renal hemodynamics and direct tubular toxicity by contrast media are the primary factors believed to be responsible for contrast media-associated nephrotoxicity. We review recent insights into the pathogenesis of this complication and summarize prophylactic strategies focussing on hydration, vasoactive pharmacological agents, and prophylactic hemodialysis'.
Acute Kidney Injury↗
[Diuretic therapy in chronic kidney failure].
Explore the source record for details and available documents.
Diuretics↗
Randomized controlled trial of ACE-inhibitors and beta-blockers with and without vasodilating activity in chronic glomerulonephritis.
A prospective double-blind, randomized study was conducted to compare the effects of the beta 1 antagonist, beta 2 agonist celiprolol (200 mg daily) on renal hemodynamics and protein excretion with those of the beta 1 antagonist atenolol (50 mg daily), the ACE-inhibitor ramipril (2.5 mg daily), and placebo in 11 patients with proteinuria > 400 mg/24 h due to chronic glomerulonephritis. All 4 substances were given in a double-blind, randomized manner according to a latin-square design over a period of 4 weeks with a wash-out period of 2 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and PAH clearance. Proteinuria was assessed by urine sampling at the end of each treatment period. Mean arterial pressure (MAP) was reduced significantly (p < 0.01) by all 3 drugs compared to placebo (108 +/- 9 mmHg placebo, 98 +/- 12 mmHg atenolol, 101 +/- 11 mmHg celiprolol, and 98 +/- 8 mmHg ramipril). Celiprolol induced a significant increase in ERPF compared to placebo (322 +/- 109 ml/min under placebo versus 391 +/- 110 ml/min under celiprolol, p < 0.05). GFR was slightly but insignificantly increased under atenolol and celiprolol. Filtration fraction (FF) remained unchanged in case of atenolol and celiprolol treatment and was slightly but not significantly reduced by ramipril. Proteinuria was significantly (p < 0.05) reduced compared to placebo by all 3 drugs (1.8 +/- 1.3 g/24 h under placebo, 1.2 +/- 1.2 g/24 h under atenolol, 1.2 +/- 1.1 g/24 h under celiprolol, and 1.4 +/- 1.4 g/24 h under ramipril). These data demonstrate that new beta-blocking agents show favorable effects on proteinuria and renal blood flow in patients with chronic glomerulonephritis and arterial hypertension. This may be attributed to their vasodilating properties.
Adrenergic beta-1 Receptor Antagonists↗
Subpressor doses of angiotensin II do not increase albumin excretion in humans.
The objective of our study was to evaluate the effects of subpressor doses of angiotensin II and mild physical stress on renal hemodynamics and urinary albumin excretion (UAE) in a group of young patients with essential hypertension compared to normotensive subjects. Eleven patients (26 +/- 6 years) and ten healthy control persons (25 +/- 2 years) were enrolled in the study. Secondary forms of hypertension had been excluded. Angiotensin II was infused at a dose of 0.3 and 1.0 ng/kg/min and physical stress testing was done with a cycle ergometer (50 W at 10 min for hypertensives, 100 W at 10 min for normotensives). Renal hemodynamics were assessed by clearance techniques (continuous insulin and p-aminohippurate clearance). Mean arterial pressure (MAP) and UAE were significantly higher in the hypertensive group than in normotensive control persons at any time of measurement. There was no significant increase in MAP or UAE under angiotensin II infusion either in the hypertensive group or in the normotensive group. MAP increased significantly under physical stress in the normotensive group only (83 +/- 7 mmHg baseline vs. 108 +/- mmHg during physical stress, p < 0.05). Angiotensin II infusion resulted in a significant change concerning renal hemodynamics in the hypertensive group only. The filtration fraction increased (18 +/- 3% baseline vs. 25 +/- 7% under infusion of 1.0 ng/kg/min angiotensin II, p < 0.05) due to a decline in ERPF and an increase in GFR in the hypertensive group. The amount of UAE correlated with the magnitude of the MAP in both groups. No correlation was found between renal hemodynamic parameters and the UAE. A significant correlation was found between the norepinephrine levels and the UAE in the control group. We could not demonstrate an albuminuric effect of subpressor doses of angiotensin II in normotensive or hypertensive subjects despite its well known effects on renal hemodynamics with an increase of the filtration fraction. These data provide evidence against a predominant role of angiotensin II and renal hemodynamics concerning the elevated urinary albumin excretion in young patients with arterial hypertension.
Adult↗
[Nephropathy due to contrast media. Its pathogenesis and prevention].
Explore the source record for details and available documents.
Contrast Media↗
Effect of continuous hemodiafiltration on IL-6, TNF-alpha, C3a, and TCC in patients with SIRS/septic shock using two different membranes.
Explore the source record for details and available documents.
Adolescent↗