Christiane M. Erley

Massive pulmonary embolism: percutaneous emergency treatment by pigtail rotation catheter.

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.

Microalbuminuria in essential hypertension. Reduction by different antihypertensive drugs.

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)

Plasma clearance of iodine contrast media as a measure of glomerular filtration rate in critically ill patients.

ObjectiveThe selection of the optimal method for assessing renal function relies on the accuracy of the technique. Plasma clearance of nonradioactive iodine contrast media (i.e., iohexol or iopromide) has been suggested as a reliable alternative to the renal clearance of inulin for estimating glomerular filtration rate (GFR). The accuracy of this method when used with critically ill patients displaying different levels of renal function in an intensive care unit (ICU) has not, until now, been examined. DesignThe accuracy of double- and multiple-point iohexol or iopromide plasma clearances was compared with that of already established techniques for measuring GFR (creatinine clearance, formula clearance by Cockcroft and Gault) and with that of inulin clearance, which is regarded as the gold standard for the measurement of GFR. PatientsValues were obtained from 31 ICU patients who exhibited a wide range of renal function (serum creatinine: 0.6–6.7 mg/dL). MeasurementsInulin clearance was performed using the constant-infusion technique. Creatinine clearance was determined from 24-hr urine samples. The clearance formula was calculated according to Cockcroft and Gault’s formula. Iohexol or iopromide were applied as a single intravenous dose, and blood samples were taken up to 6 hrs after the injection. Iodine concentrations were determined by radiographic fluorescence. ResultsPlasma clearance of iohexol/iopromide measured after the single injection of contrast media and that of the conventional inulin clearance was almost identical (y = 0.971x + 7.65, r2 = .96; n = 31). Two-point clearance of iohexol/iopromide (double sampling technique) was as reliable as the three-point clearance (three-slope-intercept method, y = 0.995x + 0.62, r2 = .999; n = 18). With respect to inulin clearance, GFR measurements determined by creatinine clearance or according to the formula given by Cockcroft and Gault revealed errors that increased proportionally (y = 1.03x, r2 = .88; n = 27; and y = 0.93x, r2 = .62; n = 31, respectively). It could also be shown that the accuracy of GFR measurements involving plasma clearance of iohexol was not greatly affected by the degree of renal insufficiency or the route by which contrast media were applied. ConclusionThese findings indicate that the determination of plasma clearance of iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used for estimating GFR in ICU patients with normal renal function or even different degrees of renal insufficiency.

Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients : a prospective analysis

The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45±15 years). We performed a captopril test with 25 mg captopril (n=25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin-converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n=23) and color-coded duplex ultrasonography of the transplant kidney vessels (n=24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS.

Reduction of proteinuria; combined effects of receptor blockade and low dose angiotensin-converting enzyme inhibition.

Objective Angiotensin-converting enzyme inhibitors (ACEI) show an antiproteinuric and thus nephroprotective effect in patients suffering from glomerulonephritis. Angiotensin II-receptor-antagonists (AT1RA) are also efficacious in reducing proteinuria. The study was performed to investigate the antiproteinuric effect of AT1RA candesartan in patients diagnosed with chronic glomerulonephritis by biopsy, and who were already being treated with an ACEI. Methods A total of 12 patients with a persistent proteinuria of at least 1 g/day who were already being treated with an ACEI for more than 3 months were included. The study was performed using a double-blind, placebo-controlled and randomized method with two treatment periods of 8 weeks (placebo or candesartan 8 mg/day) and a wash-out period of 4 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin- and PAH-clearances at the beginning and the end of each treatment period. Results Proteinuria significantly decreased from 2 ± 0.4 g/day to 1.3 ± 0.3 g/day (P < 0.05) with the addition of candesartan treatment, whereas it remained unchanged (from 1.8 ± 0.3 g/day to 1.9 ± 0.3 g/day) under placebo. GFR (candesartan: from 66 ± 13 to 58 ± 11 ml/min per 1.73 m2, placebo: from 64 ± 11 to 62 ± 13 ml/min per 1.73 m2) and ERPF (candesartan: from 329 ± 44 to 304 ± 37 ml/min per 1.73 m2, placebo: from 362 ± 48 to 315 ± 46 ml/min per 1.73 m2) did not alter significantly after 8 weeks of treatment. The addition of candesartan treatment significantly reduced systolic blood pressure (from 129 ± 3 to 123 ± 2 mmHg, P < 0.05) and diastolic blood pressure (from 79 ± 2 to 76 ± 2 mmHg, P < 0.05) compared with placebo (systolic: 128 ± 3 to 127 ± 3 mmHg, diastolic: 79 ± 2 to 79 ± 2 mmHg). Conclusion Candesartan promotes a complementary antiproteinuric and a small antihypertensive effect after a treatment period of 8 weeks in patients with chronic glomerulonephritis when given in conjunction with an ACEI. Renal hemodynamics did not vary significantly.

The selective adenosine A1 receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency.

Several studies have recently suggested a principal role of adenosine in the pathogenesis of radiocontrast media-induced nephropathy. In the present experiments, we therefore investigated the renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective adenosine A1 receptor antagonist, on radiocontrast media-induced nephropathy in the model of the N-pi-nitro-L-arginine methyl ester (L-NAME) hypertensive, chronic nitric oxide (NO)-depleted rat. Chronic NO depletion was induced by pretreatment with L-NAME, 50 mg/ml, added to drinking water for 8 weeks. Clearance experiments were performed in anesthetized rats and glomerular filtration rate was assessed prior to and following the application of high osmolar radiocontrast media (sodium diatrizoate, 3 ml/kg, i.v.) or an equivalent volume of isoosmolar mannitol to examine the role of hyperosmolarity in radiocontrast media-induced nephropathy. Subgroups received KW-3902 (0.1 mg/kg, i.v.), 20 min prior to radiocontrast media administration. Age-matched, untreated rats served as controls. Radiocontrast media application induced a significant decline in glomerular filtration rate in L-NAME hypertensive animals, whereas no effects were observed in control rats. KW-3902 fully prevented the drop in glomerular filtration rate in response to radiocontrast media in L-NAME hypertensive rats. No renal hemodynamic alterations were observed in mannitol-infused animals. The present experiments demonstrate that the decrease in glomerular filtration rate following radiocontrast media occurred independently of the osmotic load, and that KW-3902 effectively prevented the radiocontrast media-induced deterioration in renal function. KW-3902 may be especially beneficial in patients at high risk for developing acute renal failure following radiocontrast media application or in patients in which extracellular fluid volume expansion is limited by clinical conditions such as congestive heart failure.

Comparative Pharmacokinetics and Pharmacodynamics of Loop Diuretics in Renal Failure

Loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride and calcium in all stages of renal failure, and their potency is directly correlated with these excretory activities. Tubular secretion of loop diuretics in renal failure is impaired both by reduced renal blood flow and by reduced activity of the tubular carrier system. For these reasons, high concentrations of diuretics in the peritubular capillaries are necessary to guarantee delivery of sufficient drug to their site of action in the ascending limb of the loop of Henle. Piretanide and furosemide have a constant extrarenal elimination and thus accumulate in renal failure. Decreased renal excretion of bumetanide is compensated by hepatic elimination and hence bumetanide does not accumulate. Elimination of torasemide is also independent of its renal excretion. Thus in renal failure, torasemide is the only loop diuretic in which the plasma concentration is strictly dose dependent. Loop diuretics follow a number of different metabolic pathways, but this may not be clinically relevant.

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 patients 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.

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.

Posttransplant renal artery stenosis--outpatient intraarterial DSA versus color aided duplex Doppler sonography.

A prospective trial was conducted to assess the accuracy of color aided duplex Doppler (CADD) sonography to rule out transplant renal artery stenosis (TRAS) and to determine feasibility and safety of intraarterial digital subtraction angiography (DSA) in hypertensive renal allograft recipients on an outpatient basis. All patients were hypertensive (n = 18, mean age: 42 +/- 11 years) and underwent CADD and an i.a. DSA with 4F catheters. There was a 4 hour rest post DSA. Duplex Doppler measurements of maximum velocity were obtained. Absolute values of > or = 100 cm/s were considered indicative to suspect TRAS. DSA revealed severe TRAS in 4 patients (22%). The stenoses were located near the iliorenal anastomosis (n = 2) and at the bifurcation of the renal artery (n = 2). Duplex Doppler classified twelve (67%) renal artery pedicles normal (maximum velocity: 79 +/- 23 cm/s). TRAS was suspected in 6 patients with a maximum velocity of 159 +/- 48 cm/s (P < 0.01). False positive CADD diagnoses were due to tortuous graft vessels and a postbiopsy arteriovenous fistula. Sensitivity of CADD was 100%, specificity 86%. There were no DSA related complications. No impairment of graft function occurred. CADD allows renal angiography to be reserved to clarify an inconclusive ultrasound study and for definite diagnosis of angiomorphology and lesion classification. Intraarterial DSA of renal grafts in outpatients may be performed without an increased risk of procedure-related complications.