Efficacy of low-dose continuous infusion of alpha-human atrial natriuretic peptide (hANP) during cardiac surgery: possibility of postoperative left ventricular remodeling effect. Efficacy of continuous low-dose human atrial natriuretic peptide given from the beginning of cardiopulmonary bypass for thoracic aortic surgery. Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study. Effects of atrial natriuretic peptide in clinical acute renal failure. Synthetic human alpha-atrial natriuretic peptide improves the management of postoperative hypertension and renal dysfunction after the repair of abdominal aortic aneurysm. Efficacy of continuous low-dose hANP administration in patients undergoing emergent coronary artery bypass grafting for acute coronary syndrome. Effects of intraoperative administration of atrial natriuretic peptide. Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. [Urodilatin (INN: ularitide). A new peptide in the treatment of acute kidney failure following liver transplantation]. Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation. Therapeutic use of the natriuretic peptide ularitide in acute renal failure. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Prevention of renal impairment by continuous infusion of human atrial natriuretic peptide after liver transplantation. Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group. Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group. Urodilatin (INN:ularitide) as a new drug for the therapy of acute renal failure following cardiac surgery. Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery--a randomized controlled trial. Effects of atrial natriuretic peptide versus mannitol on renal blood flow during radiocontrast infusion in chronic renal failure.
The aim of the present study was to evaluate the efficacy of alpha-human atrial natriuretic peptide (hANP) in cardiac surgery under cardiopulmonary bypass (CPB).
                A prospective randomized study was conducted with 150 patients who underwent scheduled coronary artery bypass grafting to compare a group of patients receiving 0.02 microg x kg(-1) x min(-1) of hANP from the initiation of CPB with a group not receiving hANP. Hemodynamics, levels of atrial and brain natriuretic peptides (BNP), angiotensin-II and aldosterone, renin activity, and left ventricular (LV) function were examined. The hANP group showed significantly lower renin activity and lower levels of angiotensin-II and aldosterone during the early postoperative period, compared with the non-hANP group. The incidence of postoperative ventricular arrhythmia and the postoperative peak level of creatine kinase-MB were significantly lower in the hANP group. BNP at 1 month after surgery and measures of LV function were also significantly lower in the hANP group.
                Low-dose continuous infusion of hANP during cardiac surgery not only had a compensatory effect for the imperfections of CPB during the early postoperative period but also an inhibitory effect on postoperative LV remodeling and a reduction in ischemia/reperfusion injury. hANP should be part of the postoperative care for cardiac surgery. Cardiac surgery performed under cardiopulmonary bypass (CPB) causes abnormalities of the renin-angiotensin-aldosterone system, resulting in decreased urine output and an accumulation of water in the third space. We studied the efficacy of continuous low-dose human atrial natriuretic peptide (hANP) in patients undergoing thoracic aortic surgery.
                We divided 40 patients undergoing thoracic aortic surgery into two groups: the hANP group, which received 0.02 microg/kg per minute of hANP and the non-hANP group, which did not. The hemodynamics, urine output, intensive care unit (ICU) and hospital stay, bleeding volume, homologous blood transfusion volume, furosemide dose, corrected KCl volume, and postoperative respiratory, hepatic, and renal function were compared in the two groups.
                The urine output during CPB and from CPB weaning to return to ICU was significantly better in the hANP group. The bleeding volume, homologous blood transfusion volume, furosemide dose, and corrected KCl volume were all significantly less in the hANP group.
                These findings support the consensus that hANP exerts its diuretic effects to their full potential when administered continuously at low doses during thoracic aortic surgery. We found it to be effective for postoperative hemostasis and for preventing ischemic reperfusion injury. Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation. Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation. The present study reports the first prospective randomized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation. Seventy consecutive recipients of primary liver transplants were included in the study following randomization, and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period. The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production. However, the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2, whereas this observation was not made in the placebo group. Furthermore, less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either (urodilatin group 4, vs. placebo group 6 and 22 for both groups, respectively). Side effects of the urodilatin therapy were not detected. The prophylactic low-dose urodilatin administration resulted in a trend towards amelioration of the renal function, but did not result in significant differences between the two experimental groups. Further studies, using higher doses, will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation. Fifty-three consenting patients meeting clinical and urine composition criteria for established intrinsic ARF were assigned to two treatment groups. Group I patients were treated with human atrial natriuretic peptide (ANP) with or without diuretics. Groups II patients were treated with or without diuretics and with no ANP. Age, sex, etiology of ARF, entry serum creatinines (SCr) (Group I, 5.3 +/- 1.8; Group II, 5.1 +/- 2.1 mg/dl) and creatinine clearances (CCr) (Group I, 9.9 +/- 2.1; Group II, 9.2 +/- 2.1 ml/min) were similar. Thirty patients received ANP [0.20 micrograms/kg/min i.v. x 24 hr (N = 20) or 0.08 micrograms/kg/min i.a. x 8 hr (N = 10)] and furosemide, 0.5 mg/kg/hr x 24 hr or mannitol, 12.5 g every six hours x 4, or no diuretic; 23 Group II patients received diuretics as above or no diuretic in a similar distribution to Group I. CCr (verified with simultaneous inulin clearances x 12, r = 0.93, P < 0.001) increased significantly by eight hours of ANP treatment to 17.1 +/- 3.2 ml/min and by 24 hours after discontinuing ANP to 21.0 +/- 4.4 ml/min (both P < 0.05). There was no corresponding increase in CCr in Group II. Dialysis was required in 23% of Group I and in 52% of Group II patients (different at P < 0.05). Mortality rates of 17% for Group I and 35% for Group II were not significantly different (P = 0.11). It is concluded that parenteral ANP increases CCr and reduces need for dialysis in patients with established intrinsic ARF. Delayed hypertension (HT) and renal dysfunction (RD) are observed after aortic operations accompanied by infra-renal aortic cross-clamping (AXC). Atrial natriuretic peptide (ANP) has effects on vasodilation and renal protection, and we examined the hypothesis that synthetic human alpha-ANP (hANP) improves the postoperative management for abdominal aortic aneurysm (AAA).
                Fifty patients undergoing elective aneurysmectomy for infrarenal-AAA between 1998 and 2001 (M:F = 43:7, mean age 70.5 +/- 7.7 years) were randomly allocated to one of 2 groups; Group H (n = 24) received hANP immediately after operation (initial dose: 0.025 microg/kg/min), and Group C (n = 26) served as a control group.
                All patients in Group C required nicardipine hydrochloride (4.41 +/- 1.68 mg/h) for prevention of postoperative HT, whereas only 6 patients in Group H required the increase in hANP dose due to HT (P < 0.0001). Maximum hANP dose was 0.035 +/- 0.019 microg/kg/min. Group H showed significantly smaller furosemide dosage in the initial 3 days (H vs. C; 9.2 +/- 11.0 vs. 58.8 +/- 41.5 mg, P < 0.0001), significantly lower peak-Crn (H vs. C; 1.16 +/- 0.53 vs. 2.58 +/- 1.42 mg/dL, P < 0.0001), and significantly lower plasma renin-activity (7.09 +/- 2.38 vs. 11.52 +/- 4.89 ng/mL/h, P = 0.0002) and aldosterone (51.6 +/- 12.7 vs. 81.2 +/- 34.2 pg/mL, P = 0.0002) on the first postoperative day than Group C did.
                These results imply that renin-angiotensin system may play a role in the incidence of postoperative HT and RD, and suggest that hANP infusion is a simple, reliable, and effective method for management during the immediate period after AAA operations. Low-dose continuous human atrial natriuretic peptide (hANP) administration during cardiac surgery has been reported on previously. In the present study, the efficacy of the therapy during emergent coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) is investigated.
                One hundred and twenty-four patients patients undergoing emergent CABG for ACS were divided into 2 groups; a group receiving administration of hANP (hANP group) and a group not receiving hANP infusion (non-hANP group). The postoperative peak levels of creatine kinase-MB were significantly lower in the hANP group as compared with those in the non-hANP group. The incidence of postoperative arrhythmias was also significantly lower in the hANP group as compared with that in the non-hANP group. The postoperative brain natriuretic peptide was significantly lower in the hANP group as compared with that in the non-hANP group until 1 year after the operation. The free-rate of cardiac events after the operation was also significantly higher in the hANP group as compared with that in the non-hANP group.
                It is therefore considered that hANP might not only be effective for overcoming some major shortcomings of cardiopulmonary bypass, but also might be effective to attenuate ischemia-reperfusion injury, protect the myocardium, have an anti-arrhythmic effect, and suppress left ventricular remodeling. Biological activity of endogenous atrial natriuretic peptide (ANP) may decrease during cardiopulmonary bypass. To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass, we conducted a prospective randomized study.
                Eighteen patients undergoing mitral valve surgery were randomized to receive either ANP treatment (ANP group; n = 9) or no ANP treatment (control group; n = 9). Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours (0.05 microg x kg(-1) x min(-1)). Plasma ANP, brain natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels, hemodynamic variables and renal function were assessed perioperatively.
                Administration of ANP increased plasma cyclic guanosine monophosphate levels, urine output and fractional sodium excretion, and decreased preload, afterload and plasma brain natriuretic peptide levels significantly (p < 0.05). Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels (r = 0.95, p = 0.0001), correlated with fractional sodium excretion (r = 0.53, p = 0.02), and correlated inversely with systemic vascular resistance (r = -0.54, p = 0.02).
                Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels. The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass. We evaluated the effects of human atrial natriuretic peptide (hANP) during cardiopulmonary bypass (CPB).
                Forty patients undergoing coronary artery bypass grafting were investigated. A group of patients given hANP for 24 hours from the start of CPB (hANP group) was compared with a non-hANP group. Parameters examined were hemodynamics, urine volume, dosage of furosemide, respiratory index, pleural effusion, ANP, cyclic guanosine monophosphate, renin activity (renin), angiotensin-II, aldosterone, and glomerular filtration rate.
                Central venous pressure, systemic vascular resistance index, and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group. The hANP group showed significantly higher levels of ANP, cyclic guanosine monophosphate, glomerular filtration rate, and respiratory index, and significantly lower levels of renin, angiotensin-II, aldosterone, and pleural effusion, as compared with the non-hANP group. The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group.
                hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance, suppressing the renin-angiotensin-aldosterone system, and exerting a strong diuretic effect. Acute renal failure (ARF) is a serious complication following liver transplantation. Many therapeutic regimens have been used so far but with limited success. Urodilatin (URO) is a new member of the atrial natriuretic peptide (ANP) family. When administered intravenously, URO induces strong diuresis and natriuresis with tolerable hemodynamic side effects. Preliminary non-controlled clinical studies demonstrate beneficial effects using URO as a therapeutic agent in patients suffering from ARF following heart and liver transplantation (HTx, LTx). These results prompted us to initiate this first controlled clinical trial to investigate whether URO infusion can improve renal function in patients with emerging ARF following LTx.
                We initiated a randomized, double-blind, placebo-controlled study comparing five patients receiving i.v. URO infusion (20 ng/kg bw/min) with four placebo patients after informed consent was obtained. Optional inclusion criteria were oliguria/anuria ( < 0.5 ml/kg/h), refractory to conventional treatment including administration of furosemide and dopamine, increase of serum creatinine to a least 200% of preoperative values, and BUN levels > or = 25 mmol/l. The primary parameters for efficacy was the frequency of hemodialysis/hemofiltration.
                The frequency of hemodialysis/hemofiltration during URO or placebo infusion was significantly reduced (P = 0.03) in the URO-treated patients in comparison with placebo. BUN levels did not differ between two groups, but serum creatinine levels were consistently lower in the URO group. Diuresis tended to be stronger in the URO group, maintaining high levels despite a significant reduction in the administration of furosemide in comparison with placebo.
                We conclude that URO seems to be a new approach for the treatment of therapy-resistant postoperative ARF following LTx. Acute renal failure is associated with significant morbidity and mortality rates. Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery. Human atrial natriuretic peptide (h-ANP) is a potent endogenous natriuretic and diuretic substance. Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure. We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure.
                A prospective, double-blind, randomized, placebo-controlled study.
                Cardiothoracic intensive care units of two tertiary care centers.
                Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support.
                The patients were randomized to receive a continuous infusion of either recombinant h-ANP (50 ng.kg(-1).min(-1)) or placebo when serum creatinine increased by >50% from baseline. The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis.
                The primary outcome variable was dialysis on or before day 21 after the start of treatment. Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance. Twenty-nine patients were assigned h-ANP and 30 placebo. Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group needed dialysis before or at day 21 (hazard ratio, 0.28; 95% confidence interval, 0.10-0.73; p =.009). Eight (28%) patients in the h-ANP group compared with 17 (57%) in the placebo group suffered from the combined end point dialysis or death before or at day 21 (hazard ratio, 0.35; 95% confidence interval, 0.14-0.82; p =.017). h-ANP improved creatinine clearance in contrast to placebo (p =.040).
                Infusion of h-ANP at a rate of 50 ng.kg(-1).min(-1) enhances renal excretory function, decreases the probability of dialysis, and improves dialysis-free survival in early, ischemic acute renal dysfunction after complicated cardiac surgery. Acute renal failure is a serious problem following heart transplantation. In first uncontrolled clinical trials, Urodilatin revealed beneficial effects in the prophylaxis and therapy of acute renal failure following heart and liver transplantation. Here, we present the first randomized, placebo-controlled, double-blind study on 24 patients following heart transplantation to investigate whether prophylactic i.v. Urodilatin infusion can prevent acute renal failure requiring renal replacement therapy. Postoperative drug management was characterized by intravenous application of high furosemide, cyclosporine, and vancomycin doses. Urodilatin infusion was started postoperatively with a dose of 40 ng / kg bw / min for 6 days. 6 of the 12 patients in the Urodilatin group and 6 of the 12 patients in the placebo group had a stable diuresis (3 - 4 l / day) during the study period of 6 days. In contrast, the remaining 6 patients of each group developed oliguria / anuria and required subsequent hemofiltration / hemodialysis. Cumulative duration of hemofiltration (88 +/- 7.39 hours in the placebo treated patients versus 44 +/- 5.35 hours in the Urodilatin treated patients, p < 0. 05) as well as frequency of hemodialysis (3.0 +/- 0.49 times in the placebo group vs 1.2 +/- 0.29 times in the Urodilatin group, p < 0. 05) were significantly reduced using Urodilatin. Mean arterial blood pressure was stable during the Urodilatin infusion period and was not different to that observed in placebo patients. We conclude that Urodilatin does not reduce the incidence of acute renal failure and the subsequent requirement for hemofiltration / hemodialysis in our patient population, but seems to reduce the duration of hemofiltration and frequency of hemodialysis compared to the placebo group. Ularitide is a member of the natriuretic peptide family. This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide. Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously. Its main action sites are the glomerulum, inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate, and the tubular system inhibiting Na(+)-reabsorption. In initial uncontrolled clinical trials, this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure.
                We conducted a double-blind, placebo-controlled, multicenter, dose-finding trial recruiting 176 patients randomized into 4 different Ularitide doses groups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5. The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours.
                The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)).
                In summary, the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol. Further prospective clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure. Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus. Acute renal failure occurring immediately after liver transplantation and requiring hemodialysis is a major problem resulting in a poor prognosis. We investigated the efficacy of human atrial natriuretic peptide, which has potent natriuretic effects and unique protective effects for glomeruli in preventing acute renal failure after liver transplantation.
                Thirty-seven patients who underwent live donor liver transplantation with model for end-stage liver disease scores greater than 15 were the subjects of the study. Subjects were prospectively randomized into two groups: patients that received synthetic human atrial natriuretic peptide infusion (Group H: n=19) and those that received conventional diuretics, furosemide and potassium canrenoate (Group C: n=18). The peri- and postoperative changes in hemodynamic status and renal function were compared between the two groups.
                There were no statistical differences in the changes in hemodynamic status between groups. Hemodialysis was required after liver transplantation in nine patients, two in Group H and seven in Group C (P=0.04). Postoperative creatinine clearance was higher in Group H (P=0.03). Aldosterone level was suppressed in group H (P=0.006).
                Continuous infusion of synthetic human atrial natriuretic peptide might be effective for preventing acute renal failure requiring hemodialysis after liver transplantation. Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality. Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide.
                We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis. The patients received a 24-hour intravenous infusion of either anaritide (0.2 microgram per kilogram of body weight per minute) or placebo. The primary end point was dialysis-free survival for 21 days after treatment. Other end points included the need for dialysis, changes in the serum creatinine concentration, and mortality.
                The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group (P = 0.35). In the prospectively defined subgroup of 120 patients with oliguria (urinary output, < 400 ml per day), dialysis-free survival was 8 percent in the placebo group (5 of 60 patients) and 27 percent in the anaritide group (16 of 60 patients, P = 0.008). Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most. Conversely, among the 378 patients without oliguria, dialysis-free survival was 59 percent in the placebo group (116 of 195 patients) and 48 percent in the anaritide group (88 of 183 patients, P = 0.03).
                The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis. 1. Acute renal failure is a severe complication following major cardiac surgery. 2. The effects of urodilatin were evaluated in a randomized, double-blind trial in patients suffering from incipient acute renal failure following cardiac surgery. 3. In the urodilatin group (n = 7) acute renal failure was reverted, whereas in the placebo group (n = 7) six patients had to be haemofiltered or haemodialysed (P < 0.005). 4. Urodilatin induced a rapid onset of diuresis in contrast to placebo-treated patients, who remained oliguric. 5. In the placebo group four of seven patients died while still on haemodialysis (mortality rate 57.1%) during a postoperative follow-up period of 60 days, while all patients treated with urodilatin survived. 6. On the basis of these results it would appear that urodilatin is an effective drug for the treatment of incipient oliguric acute renal failure following cardiac surgery and for avoiding haemodialysis/haemofiltration. Acute renal failure after major abdominal surgery is a severe complication in critically ill patients in intensive care units (ICU). The aim of the study was to investigate the effect of urodilatin on the peak value and course of serum creatinine in patients with acute renal insufficiency after major abdominal surgery and the necessity of apparatus-based renal replacement treatment. Furthermore, the incidence and nature of adverse events under urodilatin was documented. In a prospective randomized double-blind placebo-controlled study, 12 critically ill patients after major abdominal surgery with acute renal failure in an intensive care unit (ICU) received 20 ng/kg b.w./min urodilatin (ularitide, INN) or placebo in addition to the standard diuretic therapy or low-dose dopamine (2.5 micrograms/kg b.w./min) and furosemide (1000 mg/24 hr) for a minimum of 96 hours. All patients received mechanical ventilation. Both groups had similar serum creatinine values on the day before the onset of urodilatin/placebo infusion (2.80 +/- 0.24 mg/dl, 2.93 +/- 0.48 mg/dl). Peak serum creatinine was lower in the urodilatin group (4.65 +/- 0.57 mg/dl) compared to vehicle treatment (5.78 +/- 1.58 mg/dl), although the difference did not reach statistical significance (P = 0.148). The total number of hemodialyses due to oligo-/anuria and/or hyperkalemia was the same in both groups during the study. In 4 patients of the placebo group, diuresis was reduced to anuria, whereas only 1 of the patients treated with urodilatin became anuric. No hemodynamic side effects or adverse events due to urodilatin were observed. This clinical study under double blind conditions revealed that the addition of urodilatin to the standard diuretic therapy of low-dose dopamine and furosemide failed to improve renal function in patients with established acute renal failure and that urodilatin did not eliminate the need for apparatus-based renal replacement treatment. This study was performed to investigate the effects of atrial natriuretic peptide (ANP) and mannitol on renal blood flow (RBF) and radiocontrast-induced nephropathy (RCIN) in human subjects with chronic renal failure. ANP preserves glomerular filtration rate or RBF (or both) in severe animal models of acute renal failure. Radiocontrast is known to substantially decrease RBF and can induce acute renal failure. Twenty consecutive patients with chronic renal failure (60% with diabetes) were randomized in a prospective, double-blind fashion to receive either ANP (50 micrograms bolus, then 1 microgram/min infusion) or mannitol (15% at 100 ml/hr) for 2 hours before and during cardiac catheterization with diatrizoate. Baseline serum creatinine level (ANP 2.4 +/- 0.7 mg/dl, mannitol 2.5 +/- 0.8 mg/dl), medications, and quantity of radiocontrast were similar in both groups. Direct measurements of RBF were made with thermodilution catheters placed in the left renal vein. RBF rose significantly (p less than 0.05), to 198% of baseline at 15 minutes and 166% of baseline at 65 minutes in the group receiving ANP and remained stable in the group receiving mannitol. ANP levels rose significantly from baseline at 5, 15, 65 and 120 minutes in both groups (p less than 0.05). Acute renal failure defined as a 0.5 mg/dl rise of creatinine within 24 hours of cardiac catheterization, developed only in patients with diabetes mellitus and was similar in both experimental groups (ANP, 50%; mannitol, 30%). Only patients with diabetes mellitus responded with an increase in RBF after a 5-minute infusion of either ANP or mannitol (diabetes, 165% +/- 28% baseline; no diabetes, 96% +/- 8% baseline) (p less than 0.05). In conclusion, RBF was maintained or increased despite administration of radiocontrast, a documented renal vasoconstrictor. Patients with diabetes mellitus had a renal vasodilatory response to drug infusion. Acute renal failure occurred to a similar extent in both groups. Plasma ANP levels rose significantly in both groups. Mannitol may induce ANP release, thus contributing to mannitol's renal effects.