ularitide and Postoperative-Complications

Ularitide is a member of the natriuretic peptide family which is presumably synthesized in the kidney. In physiological experiments a correlation between Ularitide excretion and natriuresis has been found. Ularitide infusions and bolus injections in animals initiated profound diuresis and natriuresis as the most prominent effects. On the basis of findings in in-vitro and in-vivo experiments, Ularitide was used in clinical trials, and the results indicate that it could be a promising new drug to prevent and treat acute renal failure in patients after cardiac surgery and organ transplantation.

Topics: Acute Kidney Injury; Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Clinical Trials as Topic; Diuretics; Humans; Kidney; Molecular Sequence Data; Muscle Proteins; Peptide Fragments; Postoperative Complications; Receptors, Atrial Natriuretic Factor; Second Messenger Systems; Transplantation; Vasodilator Agents

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.

Topics: Abdomen; Acute Kidney Injury; Adult; Aged; Atrial Natriuretic Factor; Critical Care; Diuretics; Dopamine; Double-Blind Method; Drug Therapy, Combination; Female; Furosemide; Humans; Kidney Function Tests; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Prospective Studies; Renal Replacement Therapy; Treatment Failure

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.

Topics: Acute Kidney Injury; Adult; Aged; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Diuretics; Double-Blind Method; Humans; Middle Aged; Peptide Fragments; Postoperative Complications; Treatment Outcome

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.

Topics: Acute Kidney Injury; Adult; Aged; Atrial Natriuretic Factor; Diuresis; Diuretics; Double-Blind Method; Female; Humans; Kidney Function Tests; Liver Transplantation; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Renal Dialysis

Acute renal failure (ARF) is a serious complication following cardiac surgery. This first controlled study was undertaken to verify, if Urodilatin (URO) infusion can revert incipient oliguric ARF after cardiac surgery. We conducted a randomized, double blind trial comparing 7 URO (20 ng/kg/min) with 7 placebo patients. Inclusion criterion was oliguria/anuria (< 0.5 ml/kg/hour) refractory to conventional treatment including administration of dopamine and furosemide. No patient in the URO treated group, but 6 patients in the placebo group had to be hemofiltered or hemodialyzed (p < 0.005) during the 7 day treatment period. In the URO group all 7 patients demonstrated a rapid recovery of diuresis after 2 - 8 hours of treatment that persisted throughout the treatment period. In contrast, placebo treated patients remained oliguric. Serum creatinine (SC) decreased in URO treated patients. No adverse effects were observed during URO administration. After termination of URO, 2 patients underwent hemodialysis for elevated blood urea nitrogen (BUN) values. In the postoperative follow-up period of 60 days, 4 out of 7 placebo treated patients died while still on hemodialysis. In contrast, all URO patients survived. URO is an effective drug to reverse oliguric ARF following cardiac surgery. Prolonged renal failure and renal replacement therapy can be avoided.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anuria; Atrial Natriuretic Factor; Cardiac Surgical Procedures; Diuretics; Dopamine; Double-Blind Method; Female; Furosemide; Humans; Male; Middle Aged; Oliguria; Patient Selection; Peptide Fragments; Postoperative Complications; Prospective Studies; Renal Dialysis

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.

Topics: Animals; Atrial Natriuretic Factor; Diet, Sodium-Restricted; Endothelins; Homeostasis; Hypertension, Renal; Kidney; Kidney Transplantation; Male; Nephrectomy; Peptide Fragments; Postoperative Complications; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Sodium Chloride, Dietary

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Diuresis; Heart Transplantation; Humans; Liver Transplantation; Natriuresis; Peptide Fragments; Pilot Projects; Postoperative Complications