Eikelis, Nina

Hennebry, Sarah C.

Lambert, Gavin W.

Schlaich, Markus P.

Elsevier - Publisher Connector 

the clinical signiﬁcance of this change at this time remains
unknown.
Drs Shamseddin and Gupta suggest that further studies are
required before we ‘substitute MMF/CNI with the MMF/SRL
regimen’. We would agree that no immunosuppressive
regimen is right for everyone. We believe that, given the
similarity of results from the STN experience in the United
States and the results of the CONCEPT3 study conducted in
France, these two regimens, for at least the ﬁrst 2 years post-
transplant, were therapeutically equivalent, albeit with a
different side effect proﬁle. What will be important is
longitudinal follow-up of these two studies in order to
validate the durability of these 2-year observations. As with
any form of chronic immunosuppression, there is a learning
curve that takes many years. Fortunately, given the results of
studies such as CONCEPT and STN, we have a better picture
as to how best to incorporate the use of mammalian target of
rapamycin inhibitors during the ﬁrst 2 years post-transplan-
tation. We thank Drs Shamseddin and Gupta for their critical
comments.
1. Shamseddin KM, Gupta A. Sirolimus: not so sparing in the Spare-the-
Nephron trial. Kidney Int 2011; 79: 1379.
2. Weir MR, Mulgaonkar S, Chan L et al. Mycophenolate mofetil-based
immunosuppression with sirolimus in renal transplantation: a
randomized, controlled Spare-the-Nephron trial. Kidney Int 2011; 79:
897–907.
3. Lebranchu Y, Thierry A, Toupance O et al. Efficacy on renal function
of early conversion from cyclosporine to sirolimus 3 months after
renal transplantation: CONCEPT study. Am J Transplant 2009; 9:
1115–1123.
Matthew R. Weir1
1Division of Nephrology, University of Maryland School of Medicine,
Baltimore, Maryland, USA
Correspondence: Matthew R. Weir, Division of Nephrology, University of
Maryland School of Medicine, N3W143 Nephrology, UMMS, Baltimore,
Maryland 21201, USA. E-mail: mweir@medicine.umaryland.edu
Kidney International (2011) 79, 1379–1380; doi:10.1038/ki.2011.89
Does renalase degrade
catecholamines?
To the Editor: Wu et al.1 recently reported that renalase
deﬁciency alone is associated with hypertension and suscept-
ibility to ischemic myocardial damage. They contend that
renalase’s cardioprotective effects are mediated by its ability to
metabolize catecholamines. The hypothesis that renalase could
degrade catecholamines was ﬁrst proposed given its moderate
sequence homology to monoamine oxidases.2 However, it is
our opinion that no concrete evidence exists in the literature
to directly support this hypothesis. Wu et al.1 refer to the
publication2 that ﬁrst observed potential catecholamine-
degrading activity for renalase. However, the methodology
employed to arrive at this observation has been questioned.3
Furthermore, the rate of catecholamine degradation was
thought to be too low to be ascribed to enzymatic activity.3
Recently, Pandini et al.4 showed that structurally sound
recombinant renalase did not metabolize catecholamines.
The renalase-deﬁcient mice studied by Wu et al.1 were
generated from C5BL/6 mice. Nucleotide sequences encoding
renalase in wild type (C57BL/6) published at Ensembl and
NCBI do not encode proteins with ﬂavin adenosine
dinucleotide or nicotinamide adenine dinucleotide-binding
sites. Our own sequencing of renalase transcripts
from various mouse strains demonstrates that renalase in
these animals is shorter than rat and human renalase and
does not contain the N-terminal ﬂavin adenosine dinucleo-
tide-binding site characterized by a GxGxxG motif, as
described by Wu et al.1 It would have been informative for
the authors to provide a sequence alignment of C5BL/6
renalase and human renalase to illustrate this point. It is
difﬁcult to comprehend how renalase normally functions in
mice if the protein does not possess this supposedly essential
active site.
Although renalase may well have an important physiolo-
gical role in the context of hypertension and cardio-renal
disease, this appears unlikely to be mediated by degradation
of catecholamines.
1. Wu Y, Xu J, Velazquez H et al. Renalase deficiency aggravates ischemic
myocardial damage. Kidney Int 2011; 79: 853–860.
2. Xu J, Li G, Wang P et al. Renalase is a novel, soluble monoamine oxidase
that regulates cardiac function and blood pressure. J Clin Invest 2005; 115:
1275–1280.
3. Boomsma F, Tipton KF. Renalase, a catecholamine-metabolising enzyme?
J Neural Transm 2007; 114: 775–776.
4. Pandini V, Ciriello F, Tedeschi G et al. Synthesis of human renalase1 in
Escherichia coli and its purification as a FAD-containing holoprotein.
Protein Expr Purif 2010; 72: 244–253.
Nina Eikelis1, Sarah C. Hennebry1,
Gavin W. Lambert1 and Markus P. Schlaich1
1Neurovascular Hypertension and Kidney Disease, Baker IDI Heart and
Diabetes Research Institute, Melbourne, Victoria, Australia
Correspondence: Nina Eikelis, Neurovascular Hypertension and Kidney
Disease, Baker IDI Heart and Diabetes Research Institute, PO Box 6492,
St Kilda Road Central, Melbourne, Victoria 3008, Australia.
E-mail: nina.eikelis@bakeridi.edu.au
Kidney International (2011) 79, 1380; doi:10.1038/ki.2011.90
The Author Replies: Eikelis et al.1 suggest that the cardiac
and hypertensive phenotype of the renalase knockout (KO)
mouse2 is unlikely to be mediated by renalase’s ability to
metabolize catecholamines, and also question the notion that
renalase metabolizes catecholamines.
The renalase KO was maintained on a mixed background
(129Sv/J and C5BL/6) as detailed in the Materials and
Methods section. Sequence analysis of 129Sv/J genomic DNA
revealed the presence of the N-terminal ﬂavin adenine
dinucleotide-binding site of renalase. Additionally, comple-
mentary DNA sequence from NOD (EMBL-Bank:
AK170321.1) and Kunming (EMBL-Bank: DQ788834.1)
mouse strains conﬁrm the presence of the ﬂavin adenine
1380 Kidney International (2011) 79, 1379–1382
l e t te r to the ed i to r


Does renalase degrade catecholamines? 

file:///data/remote/core/dit/data/elsevier/pdf/158/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDA4NTI1MzgxNTU0NzU2eA==.pdf

Does renalase degrade catecholamines?

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector