Burnett, John C

Cataliotti, Alessandro

Grande, Joseph P

Heublein, Denise M

Martin, Fernando L

McKie, Paul M

Rule, Andrew D

Sangaralingham, Jeson S

BMC Pharmacology

English

PubMed

Jeson S Sangaralingham

Denise M Heublein

Joseph P Grande

Alessandro Cataliotti

Andrew D Rule

Paul M McKie

Fernando L Martin

John C Burnett

Springer - Publisher Connector

POSTER PRESENTATION Open Access
C-Type natriuretic peptide: a potential urinary
biomarker for renal remodeling and fibrosis
during aging
Jeson S Sangaralingham1*, Denise M Heublein1, Joseph P Grande3, Alessandro Cataliotti1, Andrew D Rule2,
Paul M McKie1, Fernando L Martin1, John C Burnett Jr1
From 5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications
Halle, Germany. 24-26 June 2011
Background
Renal aging is characterized by structural changes in the
kidney, including fibrosis, which are often accompanied
by reduced glomerular filtration rate (GFR) and elevated
urinary protein excretion (UPE) that likely contributes
to increased risk of kidney failure, cardiovascular disease
and mortality in the elderly. Importantly a recent study,
using biopsy in healthy kidney donors across six decades
of life, demonstrated the presence of preclinical age-
related nephropathy which was otherwise undetectable
using conventional clinical tests including GFR and
UPE. Although, there are a number of biomarkers for
renal disease and injury, there are few which target early
renal remodeling prior to the onset of symptoms during
natural aging. C-type natriuretic peptide (CNP) is highly
expressed in renal cells, is potently anti-fibrotic, inhibits
renal mesangial matrix accumulation and may play a
role in podocyte-glomerular basement membrane
(GBM) integrity. Since aging is associated with altered
renal structure and function that may contribute to the
development of kidney and heart failure, we sought to
determine if CNP might serve as a urinary biomarker
for global renal remodeling as a compensatory renal
response to injury induced by aging.
Objective
The objective of this study was to determine urinary
CNP excretion in normal aging Fischer rats and its rela-
tionship to renal structure and function. We hypothe-
sized that an increase in urinary CNP excretion will
parallel increases in renal fibrosis and GBM thickening,
which importantly, will precede an elevation in protei-
nuria in the aging kidney.
Methods
Studies were performed in 2, 11 and 20 month old male
Fischer rats (equivalent to human aging from childhood
to the 6th decade of life; n=8-10/group). Blood pressure
(BP) UPE, GFR, urinary CNP was measured. Kidneys
harvested for histologic and electron microscopic analy-
sis. Mean±SE, +P<0.05 vs 2 months, † P<0.05 vs 11
months.
Results
Aging from 2 to 11 to 20 months was associated signifi-
cant ang progressive renal cortial (1±0.3 vs 8±2* vs 17
±1* † %) and medullary (4±0.8 vs 11±1* vs 17±1* † %)
fibrosis, as well as GBM thickening (120±13 vs 305±12*
vs 535±20*† nm). Further, electron microscopy revealed
progressive mesangial matrix accumulation at 11 and 20
months, along with focal effacement of visceral epithelial
cell foot processes of the podocyte at 20 months. Impor-
tantly, urinary CNP excretion significantly increased at
11 months, which was associated with early non-patho-
logical renal fibrosis and glomerular remodeling as
described, and remained elevated at 20 months (64±4 vs
110±vs 103±pg/day). BP and UPE were mildly but sig-
nificantly elevated at 20 months (90±1 vs 90±2 vs 100
±3*† mmHG and 8.1±0.6 vs 8.2±0.4 vs 20±3*† mg/day,
respectively). Further, GFR decreased at 11 months and
was sustained at 20 months (3.52±0.29 vs 2.55±0.37 vs
2.83±0.30 ml/min/kg).* Correspondence: sangaralingham.jeson@mayo.edu
1Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo
Clinic, Rochester, Minnesota 55905, USA
Full list of author information is available at the end of the article
Sangaralingham et al. BMC Pharmacology 2011, 11(Suppl 1):P60
http://www.biomedcentral.com/1471-2210/11/S1/P60
© 2011 Sangaralingham et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Conclusion
We report for the first time that a significant increase in
urinary CNP excretion during aging is strongly associa-
tion with global renal fibrosis and GBM thickening,
which occurred prior to the onset of significant protei-
nuria or BP elevation. Further studies are warranted to
explore the idea that urinary CNP may serve as a sensi-
tive urinary biomarker to detect the presence of precli-
nical renal structural remodeling and/or impairment,
particularly during aging, to facilitate early diagnosis and
intervention to reduce the burden of chronic kidney
disease.
Author details
1Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo
Clinic, Rochester, Minnesota 55905, USA. 2Division of Nephrology and
Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota
55905, USA. 3Department of Laboratory Medicine and Pathology, Mayo
Clinic, Rochester, Minnesota 55905, USA.
Published: 1 August 2011
doi:10.1186/1471-2210-11-S1-P60
Cite this article as: Sangaralingham et al.: C-Type natriuretic peptide: a
potential urinary biomarker for renal remodeling and fibrosis during
aging. BMC Pharmacology 2011 11(Suppl 1):P60.
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C-Type natriuretic peptide: a potential urinary biomarker for renal remodeling and fibrosis during aging

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C-Type natriuretic peptide: a potential urinary biomarker for renal remodeling and fibrosis during aging

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