Beginning with the cell and ending with the body as a whole, this session will explore how the hormones
(vasopressin) and systems (kidney) that regulate body water balance affect a wide range of processes.
The session can be broken down into two distinct parts. First, the session will describe the current
state of knowledge about how challenges to water balance impact cell signaling and intracellular
processes, metabolic pathways, and kidney function. Second, the session will take a practical, wholebody approach by exploring the epidemiology of water intake and disease, the use of urinary hydration
biomarkers to assess adequate intake, and the size of the population currently at risk for insufficient
water consumption.
Lawrence E. Armstrong, Ph.D, FACSM,
Professor at the University of Connecticut, USA, in the Human Performance
Laboratory, with joint appointments in the Nutritional Sciences Department
and the Department of Physiology & Neurobiology.
He presently teaches undergraduate and graduate courses in Exercise Metabolism, Thermal Physiology,
Scientific Presentations, and Physiological Responses to Stressful Environments. His research interests include
the effects of mild dehydration with water replacement on cognitive performance (men and women), fluid status
during pregnancy and lactation, water-salt balance during exercise in hot environments, thirst, human temperature
regulation, hydration biomarkers, physiological effects of caffeine, and dietary interventions such as low salt diets. He serves as an Editorial
Review Board Member of three peer-reviewed journals. He has authored/coauthored over 200 scientific articles and published the book
Performing in Extreme Environments in 2000. He has edited two books : Exertional Heat Illnesses (2003) and ACSM’s Research Methods (2016).
He formerly held the position of Physiologist at the Research Institute of Environmental Medicine, Natick, MA. Dr Armstrong is a present member
of the Danone Research Scientific Advisory Board in France and a past member of the U.S. National Research Council, Institute of Medicine,
Committee on Military Nutrition Research. He now serves as the 2015-2016 President of the American College of Sports Medicine.
Water and Electrolyte Homeostasis
Section
Chair : Lawrence Armstrong
University of Connecticut, USA
Cell physiology and water balance
Florian Lang,
Physiological Institute,
University of Tübingen,
Germany - 10:30 AM - 10:50 AM
Water, vasopressin and the kidney
Lise Bankir,
INSERM, Unité 1138,
The Cordeliers Research center,
France - 10:50 AM - 11:10 AM
Dehydration-induced renal injury :
a fructokinase-mediated disease ?
Miguel Lanaspa Garcia,
Medicine, University of Colorado Anschutz
Medical Campus, USA - 11:10 AM - 11:30 AM
Vasopressin from regulator to disease
predictor
Olle Melander,
Clinical Research Center, Lund University,
Sweden - 11:30 AM - 11:50 AM
Defining and assessing hydration through
relevant biomarkers
Erica Perrier, Danone Nutricia Research,
France - 11:50 AM - 12:10 PM
PhD, CSCS,
Danone Nutricia
Research, France
Erica Perrier earned her MS and PhD in Exercise and Sport Science
from Oregon State University, and is a Certified Strength and
Conditioning Specialist with a background in sports performance and
exercise physiology. Erica currently manages projects investigating
the complex physiological relationships between fluid intake and
hydration balance, in order to understand the mechanisms and
consequences of fluid balance regulation. Prior to joining Danone
Nutricia Research, Erica held adjunct faculty appointments at
Clark College, the University of Western States, and Oregon State
University, where she taught undergraduate and graduate courses
in exercise science, cardiovascular physiology, sports performance
enhancement, health and nutrition. She is a former NCAA Division-I
athlete, earning Academic All-American and Phi Beta Kappa honors
while earning her BS from Duke University (summa cum laude).
Her background in sports performance is complemented by
experience as a clinical exercise physiologist, specializing in
cardiovascular stress testing and aerobic performance.
She has authored publications in the fields of hydration
assessment, sports performance, and sports nutrition.
Danone Nutricia
Research is
happy to support
this session
Defining and assessing hydration through
relevant biomarkers
From intracellular processes and cell volume regulation,
to the role of vasopressin as a modulator of cardiometabolic disease,
to the importance of water intake for kidney health, there is evidence
for the importance of water for normal physiological function.
Drinking more water has been suggested as a simple action that
can contribute to improved health and wellness ; however, water
needs are variable. Further, research focused on collecting detailed,
accurate, and thorough fluid intake data is scarce, and quantifying
the dose-response effect of water on health is even more limited.
Thus, a real question remains around how much water is optimal
for health. Some evidence can be obtained by examining differences
between otherwise healthy individuals whose habitual, ad libitum
drinking habits differ, and by identifying physiological changes in
low-volume drinkers who increase their water intake. Aside from
obvious differences in urinary volume and concentration, a growing
body of evidence is emerging that links differences in fluid intake
with small, but biologically significant, differences in vasopressin
(copeptin), glomerular filtration rate, and metabolic markers.
Combined, these pieces of the puzzle begin to form a picture of
how much water intake should be considered adequate for health.
Finally, if adequate water intake can play a role in maintaining
health, how can we tell if we are drinking enough ? Urine output
is easily-measured, and can take into account differences in daily
physical activity, climate, dietary solute load, and other factors that
influence daily water needs. Reasonable targets will be proposed for
urine osmolality (500 mOsm/kg), specific gravity, and color that may
be used by researchers, clinicians, and even individuals as simple
indicators of optimal hydration.
SYMPOSIUM :
Hydration
Physiology :
From Cells to
Systems and
Clinical Health
Outcomes
agence neocom
Erica T.
Perrier,
Water is known to be essential for a wide variety of physiological functions. Recent evidence suggests
that water intake above the amount necessary to replace losses may be beneficial for long term health.
Specifically, recent studies have highlighted a relationship between water intake, urine output and
recurrent kidney stone disease, chronic kidney disease, and impaired glucose regulation. However,
relatively little attention has been paid to how challenges to water balance impact underlying,
fundamental processes, including cell signaling, metabolism, and kidney function.
Water and Electrolyte
Homeostasis Section
Monday, April 4, 2016 • 10:30 AM - 12:30 PM
Convention Center, Room 22 • SAN DIEGO
Florian
Lang,
MD,
Physiological
Institute, University
of Tübingen, Germany
Florian Lang has studied medicine in Munich and Glasgow.
Since 1992 he is professor and chairman of the Department of
Physiology at the Eberhard-Karls-University Tübingen, Germany.
Prior appointments, sabbaticals, guest & visiting professorships
include Mayo Clinic, Yale University, University of Innsbruck,
University of Naples, Kitasato University School of Medicine and
Kyoto Prefectural University of Medicine. Research activities include
properties, regulation and significance of channels and transporters,
role of transport in regulation of excitability, cell metabolism,
migration, cell proliferation, suicidal cell death and its impact on
epithelial transport, platelet activation, cardiac and renal function.
Major scientific topics include eryptosis, the suicidal erythrocyte
death, mechanisms and significance of cell volume regulation,
physiological and pathophysiological significance of serum &
glucocorticoid inducible kinase, as well as pathophysiology of
mineral metabolism and tissue calcification. He has been the most
frequently cited physiologist in Europe. He was President of the
German Physiological Society and President of the German Society
of Nephrology. He was awarded several honours including the Anton
v. Eiselsberg-Award of the Austrian Medical Association, the award
of the City of Innsbruck, the Volhard Award of the German Society of
Nephrology, the award of the Austrian Society of Nephrology,
honorary membership of the Rumanian Society of Nephrology,
International Medal of the (American) National Kidney Foundation,
Membership of the German Academy of Natural Sciences Leopoldina,
Borrelli Medal from the University of Naples, Honorary doctorate
from the University of Heraklion, Volhard Medal of the German
Society of Nephrology, and honorary professorship of the Harbin
Medical University.
Cell physiology and water balance
Obvious requirements for cell survival include avoidance of
excessive cell volume alterations. As most cell membranes are
highly permeable for water, cell volume constancy requires osmotic
equilibrium between cytosol and extracellular fluid. Following
swelling, cells decrease intracellular osmolarity by release of
ions through activation of K+ channels and/or anion channels,
KCl-cotransport, or parallel activation of K+/H+ exchange and Cl-/
HCO3- exchange. Following shrinkage cells accumulate ions through
activation of Na+,K+, 2Cl- cotransport, Na+/H+ exchange in parallel
to Cl-/HCO3- exchange, or Na+ channels. The Na+ taken up during
cell shrinkage is extruded by the Na+/K+ ATPase in exchange for K+,
i.e. cells accumulate eventually KCl. Shrunken cells further increase
cellular osmolarity by accumulation of the organic osmolytes sorbitol
and glycerophosphorylcholine through altered metabolism.
Cell shrinkage further stimulates degradation of proteins to free
amino acids and degradation of glycogen to lactate. Upon cell
shrinkage, the organic osmolytes myoinositol, betaine, taurine,
and amino acids are accumulated by Na+ coupled uptake from
extracellular space. Cell volume regulatory mechanisms are
controlled by kinases (e.g. SPAK, OSR1 and SGK1) and transcription
factors (e.g. NFAT5). Cell volume regulatory mechanisms are
challenged by alterations of extracellular osmolarity, transport,
metabolism, hormones, transmitters, drugs, cell proliferation
and apoptotic cell death. Cell shrinkage following insufficient
water intake upregulates SGK1 and NFAT5 which in turn influence
a wide variety of cellular functions and thus contribute to the
pathophysiology of hypertension, obesity, diabetes, thrombosis,
stroke, inflammation, tumor growth, fibrosing disease, infertility,
tissue calcification and ageing.
Lise Bankir
Ph. D,
INSERM,
Unité 1138,
The Cordeliers
Research Center
Lise Bankir is Directeur de Recherche Emeritus at INSERM,
Centre de Recherche des Cordeliers, Paris, France.
She graduated in Paris and got her Master and Ph.D. in the
University of Paris-Sorbonne. Most of her carreer has been devoted
to experimental and applied research in renal physiology and
pathophysiology. She initially got interested in the anatomical and
functional adaptations of the kidney that allow mammals to excrete
electrolytes and soluble metabolic endproducts in a concentrated
urine. She and her group studied the consequences on the kidney
of the sustained action of the antidiuretic hormone vasopressin or
of a protein-rich diet that imposes on the kidney a more intense
concentrating activity. These experimental studies revealed that
the long term action of vasopressin on the kidney, besides its
advantageous effects on water economy, has adverse consequences
on the incidence and/or progression of chronic kidney disease,
diabetic nephropathy and hypertension. Several studies are now
confirming this pathophysiologic link in humans.
Lise Bankir has published over 150 original papers and invited
reviews in peer-reviewed journals, and written several book chapters.
She is a member of several national and international Societies of
Nephrology and Biology. In 2011, she received the Berliner
Award from the American Physiological Society and the Collery
Award from the French National Academy of Medecine.
Water, vasopressin and the kidney
One of the major functions of the kidney is to excrete the soluble
end-products of the metabolism and the electrolytes ingested daily,
so as to keep the body in steady state. Most of the time,
the kidney concentrates these organic and mineral solutes in a
relatively low volume of urine that is hyperosmotic to plasma. Urine
concentration depends on the action of the antidiuretic hormone
vasopressin, that allows water reabsorption from the tubular fluid in
the collecting ducts. Vasopressin is a small peptidic hormone with a
short half life. The main stimulus for its secretion is a rise in plasma
osmolality, usually resulting from a modest water deficit.
The intensity of urine concentration differs widely among individuals
(200 to 1 200 mosm/kg H2O in 24h urine). All solutes are not
concentrated equally. Sodium is often less concentrated in urine than
in plasma. In contrast, the nitrogen end-products, i.e.,
urea (the most abundant solute in urine), ammonia and uric acid
are markedly concentrated in urine compared to their relatively low
concentration in plasma. Together, thirst and vasopressin adapt
fluid intake and excretion to create the best compromise between
efficient water conservation and efficient excretion of soluble wastes.
However, reducing the amount of fluid carrying away these solutes
also reduces the efficiency of their excretion. The price to pay for
a better water conservation (and low urine flow rate), is a rise in
glomerular filtration rate that partially compensates for the lesser
efficiency in the excretion of organic solutes. In the long run,
this hyperfiltration may induce or aggravate glomerular,
tubular and interstitial damage, as demonstrated in several animal
models and suspected in humans.
Miguel
Lanaspa
Garcia
Ph. D, DMV,
Medicine,
University of Colorado
Anschutz Medical Campus, USA
Miguel A. Lanaspa (DVM, PhD) is an Assistant Professor of Medicine at
the University of Colorado. His research focuses in two main areas of
interest, the role of fructose and other sugars in the development and
progression of metabolic syndrome and kidney disease ; and the effect
of hypertonicity and dehydration in the progression of chronic kidney
disease (CKD), in particular in the new epidemic of non traditional
CKD occurring in Central America and other parts of the globe
known as Mesoamerican Nephropathy. He holds a K01 and an R03
award from the National Institutes of health (NIH) on the deleterious
role of endogenously produced sugars in different models of acute
kidney injury (AKI) including ischemia-reperfusion and induced
by hyperosmolar radiocontrast agents and recently, he received
two R01 awards on studies characterizing the effects of fructose
blockade in hereditary fructose intolerance as well as on the role of
non-caloric dietary salt in promoting leptin resistance, hypertension,
metabolic syndrome and kidney disease. His studies, funded also by
the Departments of Defense (DOD) and Veteran Affairs (VA) as well
as La Isla Foundation try to ascertain the crosstalk between sugar
and osmolality in dehydrating states in the regulation of vasopressin
production, secretion and interaction with V1a, V1b and V2 receptors
during the progression of kidney disease and metabolic diseases.
Potential molecular mechanisms taking
place in the pathogenesis of Mesoamerican
Nephropathy
Traditionally, the main risk factors in chronic kidney disease (CKD)
are diabetes and hypertension. However, they do not account for
all cases suggesting that other important yet unknown factors
may be key deleterious players in its pathogenesis. We have shown
that excessive consumption and metabolism of sugars, especially
fructose, cause acute kidney injury and accelerate CKD in a
mechanism exacerbated by dehydration and mediated by the
anti-diuretic hormone, vasopressin. This observation could be
particularly important for understanding the pathogenesis of
Mesoamerican Nephropathy (MeN) a non-traditional form of CKD
affecting sugarcane workers in hot areas of Central America.
MeN is associated with high mortality – affected regions are known
as widow islands- and severely affect the socioeconomy of countries
that rely on sugar production. In our lab, we aimed to mimic in mice
the environmental conditions of sugarcane workers to understand
the pathophysiology of the disease. These environmental factors
include hydration state, sugar consumption, severity of manual
labor, temperature and humidity. Based on our data, we propose
that three mechanisms take place in the pathogenesis of MeN,
dehydration coupled with heat leading to exacerbated vasopressin
response further amplified by re-hydration with sugar-containing
beverages, activation of the polyol pathway in kidney cortex leading
to endogenous fructose production and metabolism and urinary
acidification in which uric acid induces an inflammatory response.
Based on these observations, therapeutic approaches to prevent the
progression of MeN should include improved hydration policies aimed
to increase water intake and reduce vasopressin release, reduce
the amount of sugar in hydration packages, employment of specific
inhibitors of fructose metabolism and reduction in workload and
exposure to heat of these workers.
Olle
Melander
Ph. D, MD,
Clinical Research
Center, Lund
University, Sweden
Olle Melander (MD, PhD) is professor of Internal Medicine at Lund
University and consultant at the Department of Internal Medicine,
Skåne University Hospital, Malmö, Sweden. His research is
focused on improvement of cardiovascular risk stratification and
identification of potentially life style and drug modifiable mechanisms
behind diabetes and cardiovascular disease. Melander is author of
372 international original scientific publications and according to
”Web of Science” he has 20272 citations, (19510 citations if
self-citations are excluded) with an h-index = 63. He holds a
European Research Council Consolidator grant (15 million euros),
partly funding the studies that will be presented and has been
awarded the “Peter Slight Award” (10 000 euros) in 2010 by the
European Society of Hypertension for “his contributions to prediction
and prevention of cardiovascular disease” and the Fernstrom award
(100 000 SEK) of Lund University 2013.
Vasopressin, from regulator to
disease predictor for diabetes and
cardiometabolic risk
The links between early endocrine disturbances and the development
of diabetes and cardiovascular disease (cardiometabolic disease),
are incompletely understood. Animal models have implicated
a role of altered activity of both vasopressin receptor 1A (AVPR1A)
and 1B (AVPR1B) in development of insulin resistance and diabetes.
Here, data will be presented showing that high fasting plasma
level of vasopressin in humans (measured with a stable
fragment of the vasopressin precursor hormone called “copeptin”)
independently predicts the development of a phenotype resembling
a mild form of Cushing´s syndrome. In the healthy population with
normal glycemia (n = 4 700) high copeptin (top quartile) strongly
predicts increased risk of new-onset diabetes during 13 years of
follow-up. Despite a strong correlation between copeptin and fasting
glucose already at the baseline, the top quartile of copeptin denoted
a 3-4 fold increase of the risk of future diabetes development after
adjustment for all diabetes risk factors at baseline, including levels
of glycemia. Apart from being associated with predisposition to
diabetes, high copeptin is linked to increased risk of abdominal
obesity, insulin resistance, hypertension, microalbuinuria and
reduced kidney function, i.e. metabolic syndrome features also
seen in patients with Cushing´s syndrome, suggesting a mediating
role of pituitary AVPR1B. In rats, chronically high levels of
vasopressin (however still within the physiological range)
deteriorated glucose tolerance, an effect partially reversible by
AVPR1A blockade, whereas chronically low levels of vasopressin,
achieved by hydration, was associated with improvement of insulin
resistance and protection from high fat diet induced liver steatosis.
In ongoing studies we are testing if hydration may beneficially affect
glucose tolerance and cardiometabolic risk in humans.
In summary and conclusion, there is firm evidence that high level
of copeptin predicts development of diabetes and diabetes-related
cardiovascular disease. As animal studies support a causal link
between level of vasopressin and cardiometabolic phenotypes,
reduction of vasopressin secretion by increased water-intake
at the population level appears as a very promising and safe
candidate for prevention of cardiometabolic diseases.