Therapeutic use of the natriuretic peptide ularitide in acute renal failure.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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)). INTERPRETATION: 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.

Ularitide: from renal natriuretic peptide to clinical trials.

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.

Searching for information on chemical substances in selected biomedical bibliographic databases.

A method was developed which allows effective searching for information on chemical substances in databases. Several searches for chemicals in bibliographic databases were carried out to analyse the method of indexing chemical names. The recall rates of documents were compared to evaluate information resources as well as searching strategies. Recall rates of documents searched with the CAS Nos. were compared to those searched with substance name. It turned out that searching for substances is most specific and fastest with CAS Nos. They should always be used whenever possible. However, this is not sufficient in many BDs, making an additional search using chemical names necessary. Specific search options that have to be considered for each database are reported.