[Iodinated contrast agent-induced nephropathy]. / Mit jodhaltigen Kontrastmitteln induzierte Nephropathie.

Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management.A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.).

Concomitant drugs with exposure to contrast media.

The increasing number of radiological procedures performed in old patients with high co-morbidity may be one of the problems physicians have to deal with when regarding the increasing number of acute renal failures. A key question when addressing the patients scheduled to receive iodinated contrast media (CM) is which concomitant medications prescribed to the patient are potentially harmful or helpful in terms of the risk of contrast-induced nephropathy. This overview summarizes the knowledge of concomitant medications in the setting of CM application and gives suggestion for prescription. In general, due to the unique (yet not fully understood and of high complexity) mechanism of renal damage proposed for a variety of nephrotoxic drugs including CM, physicians should carefully monitor patients' renal function and hydration status whenever concomitant nephrototoxic drugs are used. Recommendations are to monitor kidney function with more sensitive measurements of glomerular filtration rate (i.e. cystatin C).

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.

Renin producing neuroendocrine pancreatic carcinoma--a case report and review of the literature.

A 44 year old male patient presented with severe hypertension. The diagnostic work-up revealed elevated levels of plasma renin activity (about 10 times the upper limit of normal) in the presence of normal plasma aldosterone levels and serum potassium concentrations. Renovascular disease was excluded by angiography. Selective renal vein sampling did not show any renin gradient. CT-scans of the abdomen demonstrated normal morphology of the kidneys and adrenals but revealed a big mass in the pancreatic corpus and tail with infiltration of the splenic vein and the presence of enlarged local lymph nodes. The endocrine nature of the pancreatic mass was further supported by a positive octreotide scintigraphy scan. Surgical removal of the tumor by left sided pancreatectomy combined with splenectomy resulted in rapid normalization of elevated renin concentrations as well as blood pressure. Histological examination of the tumor tissue revealed the presence of a neuroendocrine pancreatic carcinoma. Highly (x 70) elevated renin levels were detected by radioimmunoassay in the tumor tissue. To our knowledge this is the first renin-producing neuroendocrine pancreatic carcinoma described in the literature. The present paper describes the case in detail and reviews the available literature on clinical symptomatology, diagnosis and treatment of renin-producing tumors.

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".

Immunoadsorption onto protein A induces remission in severe systemic lupus erythematosus.

BACKGROUND: Reduction of pathological autoantibodies and circulating immune complexes can be useful in the treatment of autoimmune disease. Plasmapheresis has been shown to reduce autoantibody levels in systemic lupus erythematosus (SLE), but its effect on patients' outcome was not better compared with conventional immunosuppression in the past. AIM OF THE STUDY: Immunoadsorption as a selective extracorporeal immunoglobulin elimination technique was evaluated as rescue therapy in patients suffering from SLE. METHODS: Eight patients with severe, therapy-resistant SLE underwent immunoadsorption onto protein A sepharose without concomitant immunosuppressants. RESULTS: Remission of the disease was achieved in seven patients. Therapy had to be stopped in one patient because of side-effects. The best results were obtained when immunoadsorption was carried out daily, without supplementary intravenous immunoglobulin therapy. Oral cyclophosphamide for 3-6 months during follow-up was used to suppress relapse. Autoantibodies and circulating immune complexes were effectively eliminated regardless of their IgG subclass. CONCLUSION: Immunoadsorption onto protein A might be used as an extracorporeal treatment option in SLE when other therapies are ineffective.

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.