Improved estimation of GFR by serum cystatin C in patients undergoing cardiac catheterization.

Clinical assessment of glomerular filtration rate (GFR) mainly relies on single determinations of serum creatinine (crea) which is commonly insensitive to mild renal dysfunction. Serum cystatin C (cysC) has been proposed as an alternative endogenous marker of GFR showing higher correlation to standard clearance methods such as inulin or iohexol clearance. We compared serum crea and cysC levels in n=127 patients undergoing cardiac catheterization. The clearance of the iodinated contrast dye iopromide served as reference method for GFR. Serum cysC was determined by a particle-enhanced immunonephelometric method. CysC showed higher non-parametric correlation (r=0.805) to the iopromide clearance compared to crea (r=0.652) and to the estimated GFR according to the Cockcroft-Gault formula (r=0.690), which underestimated true GFR systematically. Receiver operating curves revealed a greater area-under-the-curve (AUC) for cysC (0.957 vs. 0.801, p<0.05). At a cut-off level of >1.3 mg/l cysC exhibited an 88% sensitivity and a 96% specificity for detecting renal dysfunction which was defined as an iopromide clearance less than 80 ml/min/1.73 m2; best values for crea were 63% for sensitivity and 80% for specificity at a cut-off of >1.2 mg/dl. In conclusion, cysC detected reduced GFR more reliably and at an earlier stage in patients undergoing cardiac catheterization allowing a better identification of patients with renal dysfunction and those at risk for contrast damage.

What is the best hydration regimen to prevent contrast media-induced nephrotoxicity?

BACKGROUND: Hydration is a commonly used method to prevent the decline in GFR after contrast media (CM) application. So far, there have been no controlled, randomized trials investigating the most effective route of fluid administration. METHODS: Thirty-nine patients with normal renal function (65 +/- 9 years, serum creatinine 0.9 +/- 0.2 mg/dl, GFR = 110 +/- 31 ml/min/1.73 m2) receiving at least 80 ml of low-osmolality CM during an angiographic procedure were randomized to one of the following hydration regimens: Group 1: volume expansion with 300 ml saline during CM administration (n = 20, serum creatinine 0.8 +/- 0.1 mg/dl, GFR 119 +/- 27 ml/min/1.73 m2); Group 2: intravenous administration of at least 2,000 ml saline within 12 h before and after CM application (n = 19, serum creatinine 0.9 +/- 0.2 mg/dl, GFR 101 +/- 32 ml/min/1.73 m2). GFR was measured by CM clearance (Renalyzer) at baseline and 48 hours after CM administration. The primary end point was the mean change in the GFR after 48 hours, the secondary one was the incidence of CM-induced nephropathy (CMIN), defined as a decrease in GFR of more than 50% from the baseline GFR within 48 hours. RESULTS: Patients of group 1 showed a significantly (p < 0.05) higher decline in GFR (delta GFR 34.6 +/- 25.7 ml/min/1.73 m2) compared to patients receiving the intravenous prehydration regimen (delta GFR 18.3 +/- 25.0 ml/min/1.73 m2). The incidence of CMIN was lower in prehydrated patients (5.3%) compared to the other group (15%). CONCLUSION: In patients with normal renal function, intravenous prehydration seems to be a very effective and feasible method to prevent the decline in GFR after contrast media exposure. Volume expansion given only during the CM exposure appears not to be sufficient enough to prevent renal damage.

[Treatment of glomerulonephritis]. / Therapie der Glomerulonephritis.

The treatment of primary glomerulonephritis is a complex matter because of an unclear clinical picture. Glomerulonephritis may emerge as acute nephritis, nephrotic syndrome or minor proteinuria or hematuria. The symptomatic treatment may be derived from the clinical status; immunosuppressive therapy has to be substantiated by renal biopsy in order to offer the best choice to the patient.Rapid-progressive glomerulonephritis must be treated aggressively, as early as possible, to prevent chronic renal failure. Nephrotic syndrome should be treated symptomatically. Immunosuppressants are indicated according to the histological picture and accompanying clinical risk factors for progressive renal disease, which have to be evaluated before treatment. This paper gives the current strategies for treating primary glomerulonephritis.

Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone--a randomized pilot trial (the PROMPT Study). Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis.

PURPOSE: To evaluate the combination of a platelet glycoprotein IIb/IIIa complex receptor inhibitor and urokinase for treatment of recent (

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

OBJECTIVE: The 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. DESIGN: The 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. PATIENTS: Values were obtained from 31 ICU patients who exhibited a wide range of renal function (serum creatinine: 0.6-6.7 mg/dL). MEASUREMENTS: Inulin 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. RESULTS: Plasma 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. CONCLUSION: These 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.

[Endovascular therapy of renal artery stenosis: technical results with the Palmaz-Corinthian stent]. / Endovaskuläre Therapie der Nierenarterienstenose: Technische Ergebnisse mit dem Palmaz-Corinthian-Stent.

OBJECTIVE: To evaluate the technical performance and delivery characteristics of the Palmaz-Corinthian stent for endovascular therapy of atherosclerotic renovascular disease. METHODS: 61 patients underwent implantation of 76 Palmaz-Corinthian (PC) stents in 72 arteries. 50 original PC and 26 PC stents with the modified IQ-design were employed. The indications comprised primary stenting of ostial (n = 49) or truncal (n = 1) stenosis or occlusion (n = 3), and selective stenting following complicated (dissection, n = 4) or unsuccessful (n = 8) angioplasty. The remaining stents were placed in patients with recurrent stenosis (n = 5) or acute aortic dissection (n = 2) involving the renal artery. Mean severity and length of stenosis were 81.3% and 9.8 mm, respectively. 39 lesions were rated eccentric or calcified. Data on technical success, complication rate, delivery characteristics and ease of placement compared to standard renal stents were retrieved from a prospective multicenter registry. RESULTS: Stent delivery was successful in all patients, major complications were not reported. Stent placement was suboptimal in 7 of 72 cases: 4 stents were located too distally in the renal artery, necessitating proximal coaxial overstenting in 2 cases. The distal part of the stenosis was incompletely covered and the orifice of a segmental branch inappropriately overstented in one case each. One stent was dislodged from the balloon, resulting in stent protrusion in the aortic lumen. Significant residual stenosis after stenting was not observed. Overall stent deliverability, trackability and potential repositioning inside the stenosis were rated positive, radio-opacity was rated superior for the IQ design. CONCLUSION: Technical performance and delivery characteristics of the Palmaz-Corinthian stent have been significantly improved compared to the Palmaz design, allowing mostly correct placement in renal artery stenoses with a low complication rate.

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.

[Contrast media-induced kidney failure cannot be prevented by hemodialysis]. / Kontrastmittelinduziertes Nierenversagen lässt sich durch Hämodialyse nicht verhindern.

BACKGROUND AND OBJECTIVE: Radiographic contrast media (CM) administration causes a decline in renal function, especially in patients with pre-existing renal impairment. The value of CM removement by dialysis to prevent radiocontrast-induced nephropathy (RCIN) has not been established yet. The present study was designed to investigate the influence of haemodialysis on renal function in patients with preexisting renal failure receiving CM for various purposes. PATIENTS AND METHODS: 15 patients with reduced renal function (mean serum creatinine concentration 2.7 +/- 0.2 mg/dl) were randomly assigned to receive either haemodialysis for 2-3 hours, started as early as possible after administration of CM (106 +/- 25 minutes), or conservative treatment. Serum creatinine and iodine concentrations were measured over 5 days. RESULTS: The percentile creatinine increase on days 2 and 3 after CM application was higher in the dialysed group. The rate of RCIN (defined as a serum creatinine increase of greater than or equal to 0.5 mg/dl within 48 h after administration of CM) was significantly higher in the dialysed group (43% in the haemodialysis group and 13% in the group on conservative treatment, respectively). Iodine concentration declined earlier in the dialysed group. CONCLUSION: Our data indicate that haemodialysis performed within two hours after CM application did not prevent the occurrence or the outcome of RCIN in patients with renal failure. In some patients haemodialysis even seems to have worse effects regarding the development of RCIN.

[Consequences of intravascular contrast media on kidney function-- risk and prevention]. / Auswirkungen einer intravasalen Röntgenkontrastmittelgabe auf die Nierenfunktion--Risiken und Prävention.

The use of iodinated contrast media (CM) continues to be a common cause of hospital-acquired acute renal failure (ARF) and its development increases the in-hospital mortality significantly. 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, alternative contrast media and "prophylactic hemodialysis".

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.

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.

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.

Local administration of ramiprilat is less effective than oral ramipril in preventing restenosis after balloon angioplasty in an animal model.

PURPOSE: To test the hypothesis that local administration of angiotensin converting enzyme (ACE) inhibitor via a microporous balloon catheter would be more effective than oral administration of ACE inhibitor in preventing neointima formation after balloon angioplasty. MATERIALS AND METHODS: Neointima formation was induced by balloon denudation followed by 0.5% cholesterol diet in 29 New Zealand White rabbits. Directly after denudation, local administration of 1.8 mg of ramiprilat (n = 7) or saline (n = 7) with a microporous balloon catheter at a pressure of 3 atm was performed. Both groups additionally received ramipril orally (1 mg/d). Seven animals were treated exclusively with oral ramipril. The control group was fed a 0.5% cholesterol diet and given no medication (n = 8). Six weeks after intervention, the animals were killed and morphometric and immunohistologic analyses were performed. RESULTS: Oral administration of ramipril resulted in a significant reduction of placque area (-66%, P < .05). Oral and local administration of the ACE inhibitor was followed by a nonsignificant reduction of the neointimal area (-17%). Local administration of saline combined with oral ramipril failed to prevent neointimal formation (reduction of 6%, NS). CONCLUSION: Oral administration of ramipril resulted in a significant reduction of neointimal proliferation in New Zealand White rabbits. The possible benefit of an additional administration of local ramiprilat was diminished by an excessive neointimal hyperplasia, which was most likely caused by the inherent vessel trauma with use of the microporous balloon catheter.

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.

Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.

The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.

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.