NDT Advance Access originally published online on November 28, 2006
Nephrology Dialysis Transplantation 2007 22(4):1269-1270; doi:10.1093/ndt/gfl697
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Human Urotensin II in the plasma of anephric subjects
Email: townsend{at}mail.med.upenn.eduSir,
Human urotensin II (UII), perhaps the most potent mammalian vasoconstrictor known, is thought to be produced by the kidneys. The urotensins are a family of vasoactive peptides first isolated from various fish species over 20 years ago. Homologous peptides have been isolated in numerous species including frogs, rodents, pigs, primates and humans. It has been demonstrated in-vitro that human UII is between 8- and 110-fold more potent than endothelin-1 as a vasoconstrictor, and is the most potent mammalian vasoconstrictor known. The precise metabolic pathway(s) of urotensin metabolism is unknown, though high density of UII and its receptor have been demonstrated in mouse and monkey kidneys [1] and human kidneys, [2] and is thus thought to be synthesized, secreted and cleared by the kidneys [3,4,5]. Also, some researchers have reported higher blood values of UII in patients with kidney disease as well as with hypertension. These reports have stimulated interest in a possible aetiological role of UII in kidney disease and hypertension in people with kidney disease; consequently we sought to determine whether plasma concentrations of UII are detectable in subjects with end-stage renal disease (ESRD) on dialysis, and in particular in surgically anephric subjects.
Thirty-one ESRD subjects undergoing routine haemodialysis were enrolled, including two surgically anephric subjects (i.e. both patients had bilateral nephrectomy at least 6 months prior to enrolment). Blood samples were obtained for UII before initiation of a mid-week dialysis session. UII concentrations were measured in unextracted plasma by radioimmunoassay using human UII-specific monoclonal antibody at GlaxoSmithKline laboratories (NA). The mean UII was compared between anephric and non-anephric subjects with a paired Students’ t-test, using JMP IN statistical software version 4 (SAS Institute, Carey, NC, USA).
The study was approved the Institutional Review Boards of the University of Pennsylvania and Gambro Healthcare. Written informed consent was obtained from all subjects. Data was stored in a password-protected laptop computer using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA).
Concentrations of UII were present (and higher) in the two surgically anephric subjects (20 216 and 21 555 pg/ml, mean = 20 886 pg/ml) compared with the other 29 subjects (16 039 ± 769 pg/ml) though these differences were not statistically significant.
Our findings of measurable (and perhaps elevated) concentrations of UII in anephric subjects are inconsistent with the conclusion that the kidneys are the primary source for production of UII. The high density of UII and its receptor in renal tissues suggest that UII is metabolically active in the kidney even though it is produced in sites outside of the kidneys.
Conflict of interest statement. The authors report the following financial conflicts of interests: R.R.T. is a speaker for BMS, Merck and Pfizer and has grant support from Novartis, Sankyo and DMV–international. TD and NA are employees and stockholders of GlaxoSmithKline.
1Department of Medicine, Renal
Electrolyte and
Hypertension Division
University of Pennsylvania
School of Medicine
Philadelphia
2GlaxoSmithKline
King of Prussia, PA
References
- Elshourbagy NA, Douglas SA, Shabon U, et al. (2003) Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey. Brit J Pharmacol 136:9–22.[Web of Science]
- Shenouda A, Douglas SA, Ohlstein EH, Giaid A. (2002) Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma. J Histochem Cytochem 50:885–889.
[Abstract/Free Full Text] - Ames RS, Sarau HM, Chambers JK, et al. (1999) Human urotensin II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature 401:282–286.[CrossRef][Medline]
- Matsushita M, Shichiri M, Imai T, et al. (2001) Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues. J Hypertens 19:2185–2190.[CrossRef][Web of Science][Medline]
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[Abstract/Free Full Text]
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