Axelsson, J.

Lindholm, B.

Stenvinkel, P.

Elsevier - Publisher Connector 

independent from glomerular filtration rates is of consider-
able interest, as elevated resistin levels in various other
disorders have been associated with both inflammation as
well as malnutrition.3–5
Taking into account that inflammation has been closely
related to malnutrition and in particular to protein–energy
malnutrition,6 one may assume that there is a relationship
between inflammation, plasma resistin levels, and protein
malnutrition in hemodialysis patients and in patients with
chronic kidney disease that is yet to be clarified.
1. Axelsson J, Bergsten A, Qureshi AR et al. Elevated resistin levels in chronic
kidney disease are associated with decreased glomerular filtration rate
and inflammation, but not with insulin resistance. Kidney Int 2006; 69:
596–604.
2. Filippidis G, Liakopoulos V, Mertens PR et al. Resistin serum levels are
increased but not correlated with insulin resistance in chronic
hemodialysis patients. Blood Purif 2005; 23: 421–428.
3. Karmiris K, Koutroubakis IE, Xidakis C et al. Circulating levels of leptin,
adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm
Bowel Dis 2006; 12: 100–105.
4. Housova J, Wilczek H, Haluzik MM et al. Adipocyte-derived hormones in
heroin addicts: the influence of methadone maintenance treatment.
Physiol Res 2005; 54: 73–78.
5. Bahr MJ, Ockenga J, Boker KH et al. Elevated resistin levels in cirrhosis are
associated with the proinflammatory state and altered hepatic glucose
metabolism, but not with insulin resistance. Am J Physiol Endocrinol
Metab 2006 (in press, doi:10.1152/ajpendo.00291.2005).
6. Sauerwein RW, Mulder JA, Mulder L et al. Inflammatory mediators in
children with protein–energy malnutrition. Am J Clin Nutr 1997; 65:
1534–1539.
V Liakopoulos1, PR Mertens2, T Eleftheriadis1, G Koukoulis3
and I Stefanidis1
1Department of Nephrology, University of Thessalia School of Medicine,
Larissa, Greece; 2Department of Nephrology and Immunology, University
Hospital Aachen, Aachen, Germany and 3Department of Endocrinology,
University of Thessalia School of Medicine, Larissa, Greece
Correspondence: I Stefanidis, Department of Nephrology, University of
Thessalia School of Medicine, Mezourlo Hill, Larissa 41110, Greece.
E-mail: stefanid@med.uth.gr
Response to ‘Resistin letters’
Kidney International (2006) 70, 1372. doi:10.1038/sj.ki.5001602
We thank Fagerberg et al. for their contribution to the
growing body of evidence refuting a causative relationship
between the protein resistin and insulin resistance in
man.1 Indeed, resistin was first described as found in
inflammatory zone (FIZZ)-1, indicating its structural
similarity to several other proinflammatory cytokines.2
Indeed, resistin is expressed mainly in immunocompetent
cells such as leukocytes, and not in adipocytes as had
previously been thought.3,4
Given the fact that even a mild renal function
impairment is associated with a chronic low-grade
inflammation5 and a markedly increased risk of cardio-
vascular death, it is not surprising that the patients in the
study of Fagerberg et al. displayed increased resistin levels
that were also correlated with serum creatinine, C-reactive
protein, and leukocyte counts.
Taken together, we believe that this study further
underscores the relationship between decreasing renal
function and increased risks of inflammation and cardio-
vascular disease. Resistin is one part of this complex, where
we are still looking for a unifying mechanism and an
effective therapy.
1. Arner P. Resistin: yet another adipokine tells us that men are not mice.
Diabetologia 2005; 48: 2203–2205.
2. Holcomb IN, Kabakoff RC, Chan B et al. FIZZ1, a novel cysteine-rich
secreted protein associated with pulmonary inflammation, defines a new
gene family. EMBO J 2000; 19: 4046–4055.
3. Patel L, Buckels AC, Kinghorn IJ et al. Resistin is expressed in human
macrophages and directly regulated by PPAR gamma activators. Biochem
Biophys Res Commun 2003; 300: 472–476.
4. Sopasakis VR, Nagaev I, Smith U. Cytokine release from adipose tissue of
nonobese individuals. Int J Obes (London) 2005; 29: 1144–1147.
5. Fried L, Solomon C, Shlipak M et al. Inflammatory and prothrombotic
markers and the progression of renal disease in elderly individuals. J Am
Soc Nephrol 2004; 15: 3184–3191.
J Axelsson1, B Lindholm1 and P Stenvinkel1
1Department of Renal Medicine, Karolinska Institute, K56 Karolinska
University Hospital at Huddinge, Stockholm, Sweden
Correspondence: J Axelsson, Department of Renal Medicine, Karolinska
Institute, K56 Karolinska University Hospital at Huddinge, Stockholm 141 86,
Sweden. E-mail: jonas.axelsson@ki.se
Enlightenment on liver lanthanum
exposure
Kidney International (2006) 70, 1372–1373. doi:10.1038/sj.ki.5001636
To the Editor: Tissue lanthanum concentrations in the paper
by Slatopolsky et al.1 are similar to our own and others’
findings,2 but have been interpreted very differently.
Comparisons with ‘untreated’ controls are used to highlight
‘marked’ and ‘striking’ increases in deposition in nephrecto-
mized rats, including a 98-fold increase in liver concentra-
tion. When the appropriate comparator is used (lanthanum-
treated rats with normal renal function), there is no statistical
increase in bone and kidney concentrations in the uremic
animals, and only two- to three-fold higher liver concentra-
tions after 15 weeks of treatment. This is entirely consistent
with the absence of any effect of renal failure on systemic
lanthanum exposure3 and a small (two- to three-fold)
increase in first-pass liver exposure, as reported recently for
this uremic model.2 Although tissue concentrations increased
over time (termed ‘progressive accumulation’), their study
was too short to fully reflect the tissue kinetics of lanthanum,
and longer-term studies suggest achievement of steady-state
conditions (Figure 1). Although a maximal dose of
lanthanum (3% (w/w) of diet, 15–22 times the human dose
of 3 g/day)1 was administered for as long as practicable in a
nephrectomized model (limited by death owing to renal
failure), lanthanum concentrations were still only at trace
levels (o3 p.p.m.). As the natural liver concentrations of
other lysosomally transported metals such as iron and copper
are up to 2007 and 55 p.p.m., respectively,4 there would
1372 Kidney International (2006) 70, 1371–1384
l e t t e r t o t h e e d i t o r


Response to ‘Resistin letters’ 

file:///data/remote/core/dit/data/elsevier/pdf/b1c/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDA4NTI1MzgxNTUyMDk1NA==.pdf

Response to ‘Resistin letters’

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector