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Background. Radiographic contrast media (CM) application causes a decline in renal function, especially in patients with pre-existing renal dysfunction. In addition to hydration, several vasodilating substances have been evaluated for their ability to prevent renal damage after CM application. In a prospective, double-blind, placebo-controlled study we investigated the effect of the oral administration of theophylline, an adenosine receptor antagonist, on changes in renal haemodynamics and tubular injury induced by CM in well hydrated patients with mild-to-moderate renal insufficiency. [ABSTRACT FROM PUBLISHER]

Background: The endothelial nitric oxide (NO) system plays a central role in regulating vascular tone. Endothelial dysfunction has been closely linked to reduced activity in the NO system. Tetrahydrobiopterin (BH4) is an essential cofactor of all NO synthase isoforms., Methods: We examined the effects of BH4 on the NO system assessed by measurement of serum cGMP levels and NO breakdown products (NOx) in 12 healthy volunteers., Results: Application of a total of 19 mg/kg BH4 intravenously (i.v.) over 3 hours led to a dose-dependent increase in serum cGMP concentrations from a median 3.3 nM (interquartile range [IQR] 1.1-5.6) to 5.7 nM (IQR 2.4-13.3, p=0.008) and NOx from a median 49.3 microM (IQR 39.8-56.6) to 59.7 microM (39.6-85.5) (p=0.058). Systemic and renal hemodynamics measured by inulin and p-aminohippuric acid (PAH) clearance remained unchanged. Plasma renin activity was significantly increased (2.0 [IQR 1.0-2.8] to 2.3 ng AngI/mL per hour [IQR 1.7-4.0], p=0.045), whereas aldosterone, erythropoietin and B-type natriuretic peptide levels did not change. In a second study, oral BH4 given over 3 days (800 mg/day) similarly increased serum cGMP and ameliorated the depressive effects of the NO synthase inhibitor L-NAME (1.5 mg/kg i.v.) on the glomerular filtration rate., Conclusions: Application of BH4 in high doses is safe and enhances formation of cGMP, pointing to increased bioavailability of NO.

Background: To determine whether gadolinium-based contrast media (CM) could be used safely for angiographies in patients with renal dysfunction we investigated renal function after gadobutrol exposure and compared the results with standard iodinated CM (iohexol) in a randomized clinical study., Methods: Twenty-one patients (aged 67+/-11 years, nine female and 12 male) with severely impaired renal function [mean serum creatinine 3.2+/-1.3 mg/dl, mean glomerular filtration rate (GFR) 31+/-16 ml/min/1.73 m(2)] who needed to have angiography because of severe peripheral vascular disease, renal artery stenosis or aortic aneurysms were randomized to receive in a blinded manner either gadobutrol (Gadovist 1.0 mmol/ml) or iohexol (Omnipaque 350) as contrast agents. GFR was measured by CM clearance (Renalyzer) at baseline and 48 h after CM administration. The primary end point was the mean change of GFR from baseline at 48 h, the secondary one the incidence of CM-induced acute renal failure, defined as a decrease in GFR of >50% from baseline within 48 h of CM administration., Results: In the gadobutrol group (n = 10) we observed a statistically significant decrease in GFR of 10.6+/-13.8 ml/min/1.73 m(2) within 48 h after CM administration (P<0.05, paired t test). The incidence of CM-induced ARF amounted to 50%. In comparison, the iohexol group (n = 11) also showed a statistically significant GFR reduction of 8.7+/-8.8 ml/min/1.73 m(2) (P<0.05, paired t test), and of ARF by 45%. The percentile of differences of GFR decreases between the two groups was not significant (P = 0.70). No patient demonstrated other adverse effects of gadobutrol or iohexol administration, apart from GFR reduction. Despite the decline in GFR, no patient required haemodialysis in the 10 following days., Conclusions: In our study, gadolinium-based angiography showed no benefit over iohexol angiography with respect to preventing GFR reduction in patients with severely impaired renal function.

The present experiments were designed to assess the renal functional response to alterations in nitric oxide formation in animals with different forms of nephropathy. To address this issue, the effects of Nomega-nitro-L-arginine methyl ester (L-NAME) or L-arginine were assessed in animal models exhibiting arterial hypertension due to chronic nitric oxide inhibition (L-NAME, 50 mg/l in drinking water for 12 weeks) or diabetes mellitus (streptozotocin, 60 mg/kg IP). Vehicle-treated, age-matched animals served as controls. Following 12 weeks of pretreatment, mean arterial pressure (MAP), renal hemodynamics, urinary albumin, and electrolyte excretion were determined in standard clearance experiments prior to and following infusion of L-NAME (50 microg/kg/min), l-arginine (5 mg/kg/min), or saline vehicle. In control animals, L-NAME resulted in an increase in MAP and renal vascular resistance and a decline in glomerular filtration rate and renal plasma flow, as expected. L-arginine had no effect on renal hemodynamics. In nitric oxide-depleted hypertensive animals, L-NAME had no additional effect on MAP or renal hemodynamics. Infusion of L-arginine reduced elevated MAP but did not reverse changes in renal hemodynamics. Diabetic rats demonstrated glomerular hyperfiltration and proteinuria. No significant changes in MAP or renal hemodynamics were observed following infusion of L-NAME or L-arginine, respectively. However, L-NAME increased urinary albumin excretion in the absence of hemodynamic changes. The effects of nitric oxide on vascular tone were shown to be dependent on the vascular bed and the underlying disease. Variations in local nitric oxide formation and susceptibility may account for the differential response of the systemic and renal vasculature and contribute to the degree of renal functional impairment observed in different systemic diseases.

Objectives: This study was designed to assess the feasibility, efficacy and safety of mechanical fragmentation of pulmonary emboli using a new rotational pigtail catheter system., Background: Acute massive pulmonary embolism associated with right ventricular dysfunction is frequently lethal, despite high-dose thrombolytic therapy. Adjunctive catheter fragmentation may prevent a fatal outcome., Methods: In 20 patients (age 58.9+/-10.5 years) with severe hemodynamic impairment, massive pulmonary emboli were fragmented by mechanical action of the rotating pigtail. Fifteen patients received thrombolysis after embolus fragmentation or no thrombolysis at all (noninterference group)., Results: Prefragmentation pulmonary arterial occlusion was 68.6 +/- 11.3% for both lungs. Pulmonary placement and navigation of the fragmentation catheter was easy and rapid. Fragmentation time was 17+/-8 min. The noninterference group showed a decrease pre- to postfragmentation of shock index from 1.28+/-0.53 to 0.95+/-0.38 (p = 0.011), mean pulmonary artery pressure from 31+/-5.7 to 28+/-7.5 mm Hg (p = 0.02) and a recanalization by fragmentation of 32.9+/-11.8% (mean angiographic score per treated lung from 7.4 to 5.0). Overall mortality was 20%., Conclusions: Fragmentation by pigtail rotation catheter provided for a rapid and safe improvement of the hemodynamic situation and an average recanalization of about one-third of the pulmonary embolic occlusion. The method appears useful especially in high-risk patients threatened by right ventricular failure, to accelerate thrombolysis, and as a minimal-invasive alternative to surgical embolectomy.

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

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.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of four different antihypertensive drugs (the Ca(2+)-channel blocker felodipine, the beta-blocker metoprolol, the angiotensin converting enzyme inhibitor ramipril, and the alpha-blocking agent doxazosin) on microalbuminuria and renal hemodynamics were evaluated in a double-blind, crossover study in 17 patients (10 women, seven men, aged 39 +/- 14 years) with mild-to-moderate essential arterial hypertension and microalbuminuria. Patients were studied after a 2-week placebo phase preceded by 2 weeks off all medication and after 12 weeks of treatment with each drug. Between each drug treatment, there was another 14-day placebo washout period. At the end of the study, we performed two additional 2-week placebo periods. After each placebo and treatment period, we measured albumin excretion during a 3-day collecting period. Renal hemodynamics were assessed by clearance techniques (inulin and p-aminohippurate clearance) at the end of the first and last placebo periods and after each treatment period. All drugs reduced mean arterial pressure and microalbuminuria to a similar and statistically significant (p < 0.05) extent (mean arterial pressure: placebo phase, 116 +/- 5 mm Hg; felodipine, 101 +/- 4 mm Hg; metoprolol, 101 +/- 5 mm Hg; ramipril, 101 +/- 4 mm Hg; doxazosin, 102 +/- 5 mm Hg; urinary albumin excretion: placebo phase, 46 +/- 50 mg/day; felodipine, 18 +/- 23 mg/day; metoprolol, 14 +/- 12 mg/day; ramipril, 16 +/- 16 mg/day; doxazosin, 14 +/- 14 mg/day). Mean arterial pressure levels and urinary albumin excretion returned to baseline after the last placebo period (110 +/- 6 mm Hg and 40 +/- 46 mg/day, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of a nonselective beta-adrenergic blocking drug with beta-2 agonist activity (dilevalol 200 mg) on proteinuria and renal hemodynamics were evaluated in a double-blind crossover study versus an ACE inhibitor (enalapril 5 mg) in eight patients with glomerulonephritis, moderate renal function impairment and proteinuria greater than 1 g/24 hr. Patients were studied after a one week placebo phase while off all other medications, except steroids in a few cases, and after three weeks of treatment. A 10-day placebo washout perod was included between the various drug treatments. During each period renal hemodynamics were measured by clearance techniques, and urinary protein excretion as well as fractional clearance of albumin and IgG were determined. Both drugs reduced mean arterial pressure and proteinuria to a similar extent [mean arterial pressure: placebo 108 +/- 13 mm Hg; dilevalol 103 +/- 11 mm Hg (P less than 0.05); enalapril 103 +/- 12 mm Hg (P less than 0.05); protein excretion: placebo 5.1 +/- 4.2 g/day; dilevalol 3.3 +/- 3.0 g/day (P less than 0.05); enalapril 2.8 +/- 2.8 g/day (P less than 0.05)]. The antiproteinuric effect was greater with enalapril than dilevalol. Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR. Enalapril did not significantly lower the GFR (inulin clearance during enalapril 66.8 +/- 23 ml/min/1.73 m2) and the reduction of proteinuria did not correlate with the lowering of the GFR.(ABSTRACT TRUNCATED AT 250 WORDS)