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.

Sequences associated with the mouse Smu switch region are important for immunoglobulin heavy chain transgene expression in B cell development.

Analyses of H-chain transgenes have indicated that sequences situated between the mu intronic enhancer and the Cmu exons are important for mu gene expression. We have analyzed several variant mu transgenes and find that a sequence element located within or just upstream of Smu is important for mu transgene expression in both immature and mature B cells. This Smu -associated element appears to be required for functional mu expression in small, resting pre-B cells but not in proliferating pre-B cells. Our results also indicate that this element is responsible for previously reported differential transgene expression in resting and activated/proliferating mature B cells. However, our studies of knockout mice show that deletion of the Smu -associated element from the endogenous IgH locus does not alter early B cell maturation. This indicates that other elements within the H-chain locus can replace the function of the Smu -associated element at least to the mature B cell stage. Surprisingly, we also find that Smu deletion in the IgH locus does not affect levels of the sterile germ-line mu transcripts that are involved in B cell class switching, even though S-region sequences have been indicated to be important for the production of analogous germ-line transcripts for other isotypes.

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.

[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.

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.

[Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors]. / Renale Hämodynamik und Proteinurie bei chronischer Glomerulonephritis unter Behandlung mit beta-Rezeptorenblockern oder ACE-Hemmern.

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.

Does L-arginine alter proteinuria and renal hemodynamics in patients with chronic glomerulonephritis and hypertension?

Endogenous nitric oxide (EDRF) plays an important role in the regulation of systemic and renal blood pressure by an alteration of vascular tone. To assess the effect of L-arginine (160 mumol/min i.v. for 3 hours), the precursor of EDRF, on blood pressure, protein-excretion and renal function (GFR = glomerular filtration rate, RPF = renal plasma flow) we performed a prospective, double blind, placebo controlled study. 18 patients with chronic glomerulonephritis (51.3 +/- 11.5 years), renal insufficiency (GFR < 65 ml/min) and hypertension were investigated for changes in GFR and RPF by continuous inulin- and PAH-clearances and for changes in permselectivity by determination of protein-excretion. L-arginine infusion results in a reduction of proteinuria (p < 0.05, t-test). There is no significant effect on renal hemodynamics and mean arterial pressure (MAP). Comparing the excretion of the endogenous proteins, only albuminuria is decreased significantly (p < 0.01), whereas IgG-excretion is reduced slightly (p < 0.05). This can be considered as an indicator of a special influence on the mesangial cells or the basement membrane of the glomerulum itself by EDRF. In conclusion L-arginine reduces protein-excretion without significant alterations in renal hemodynamics and so might prevent a decline in renal failure.