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.


RESULTS
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)).


CONCLUSIONS
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.
Lower Saxony Institute for Peptide Research Hannover, Germany. 106523.221@compuserve.com
M
M
Meyer
E
E
Pfarr
G
G
Schirmer
H J
HJ
Uberbacher
K
K
Schöpe
E
E
Böhm
T
T
Flüge
P
P
Mentz
P
P
Scigalla
W G
WG
Forssmann
D058186:Acute Kidney Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D001806:Blood Urea Nitrogen; D002318:Cardiovascular Diseases / Q000209:etiology; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017582:Renal Replacement Therapy; D013997:Time Factors
D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D003404:Creatinine