P
diabetes to have abnormally acidic
BETES HAVE HIGHLY ACIDIC
urine, and what urinary factors pro-
URINE, A METABOLIC FEA-
tect diabetic patients who do not
TURE THAT EXPLAINS THEIR
form uric acid stones,” said Dr. Mary
GREATER RISK FOR DEVELOPING
Ann Cameron, the paper’s lead
URIC-ACID KIDNEY STONES,
author and an assistant professor of
RESEARCHERS AT UT SOUTH-
internal medicine.
WESTERN MEDICAL CENTER HAVE
FOUND.
Their study, published recently
Obesity and a diet rich in animal
protein are associated with abnor-
Kidney Stones
EOPLE WITH TYPE 2 DIA-
may play a role.”
Dr. Khashayar
Sakhaee, senior
author of the
study, chief of
mineral metabolism and
BeautiControl
mally acidic urine. In earlier studies,
Cosmetics Inc. Professorship in
in the Journal of the American Society
UT Southwestern researchers also
Mineral Metabolism and
concluded that uric-acid stones are
Osteoporosis, said: “Our group at
pares the urinary biochemical char-
associated with insulin resistance
UT Southwestern was the first to
acteristics of type 2 diabetics with
and type 2 diabetes.
determine that the more overweight
Individuals with type 2 diabetes,
But when researchers in this latest study accounted for these com-
a person is the more likely he or she
is to form uric-acid kidney stones.”
also called non-insulin dependent
ponents, type 2 diabetics continued
diabetes mellitus, are at increased
to have more acidic urine levels
the United States live with diabetes,
risk for developing kidney stones in
when compared to non-diabetics.
a chronic disease that affects the
general, and have a particular risk
These findings suggest that other
body’s ability to produce or respond
for uric acid stones. The mecha-
factors associated with type 2 dia-
to insulin. It can lead to life-threat-
nisms for this greater risk were pre-
betes or insulin resistance account
ening illness, including heart disease
viously not well understood.
for the overly acidic urine in this
and stroke.
This new study demonstrates
that the propensity for type 2 dia-
population.
“Diet intake and obesity, those
More than 18 million people in
Uric-acid stones are more difficult to diagnose than other types of
betics to develop uric acid stones is
two factors alone, don’t explain
stones because they don’t show up
elevated because their urine is high-
the whole picture,” said Dr. Naim
on regular abdominal X-rays, often
ly acidic.
Maalouf, a study author and assis-
delaying the diagnosis and leading
tant professor of internal medicine.
to the continued growth of the
“So, other unrecognized factors
stone, Dr. Sakhaee said.
“Our next step is to find out
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VOL. 13, NO. 1, SPRING 2007
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holder of the
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those of normal volunteers.
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Type 2 diabetics’ acidity heightens risk for kidney stones
Clinic earns service in excellence awards ★ ★ ★ ★ ★
EBI MOSES BROKE HER HIP
D
WHILE ON A SKI VACATION
★
MORE THAN A DECADE AGO.
During surgery to repair the fracture, her bones shattered. Doctors
didn’t know why.
Five years ago, she sought the
expertise of UT Southwestern Medical
Center specialists at the Mineral
Metabolism Clinic at the Charles
and Jane Pak Center for Mineral
Metabolism and Clinical Research.
She visited with Dr. Clarita
Odvina, the medical director for
the clinic.
“That’s when I found out that I
had osteoporosis,” Mrs. Moses said.
Since then, her condition has
improved. Mrs. Moses no longer
suffers from osteoporosis. Instead,
she has been diagnosed with
osteopenia, a condition that refers
– Dr. Clarita Odvina and patient Debi Moses
to having low bone density.
The Friends of Mineral Metabolism
News is a publication of the Charles
and Jane Pak Center for Mineral
Metabolism and Clinical Research of
UT Southwestern Medical Center.
Director . . . . . . . . . . Dr. Orson Moe
Editor . . . . . . . . Amanda Siegfried
Writer . . . . . . . . . . . .. . Connie Piloto
Designer . . . . . . . . Yolanda Fuentes
Photographer . . . . . David Gresham
UT Southwestern is an equal
opportunity institution.
The Charles and Jane Pak
Center for Mineral Metabolism
and Clinical Research
5323 Harry Hines Blvd.
Dallas, Texas 75390-8885
Address service requested
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Continued on page 5
New generation of investigators leads the way
WO UT SOUTHWESTERN
T
at UT Southwestern. Now, both
director of the center and holder
MEDICAL CENTER FACULTY
have accepted jobs as assistant pro-
of the Charles Pak Distinguished
MEMBERS ARE LEADING THE
fessors in the mineral metabolism
Chair in Mineral Metabolism and
NEXT GENERATION OF PATIENT-
division of the internal medicine
the Donald W. Seldin Professorship
Dr. Moe’s Perspective . . . . . . . . . 2
ORIENTED RESEARCH AT THE
department.
in Clinical Investigation.
Profiles . . . . . . . . . . . . . . . . 3 , 6
CHARLES AND JANE PAK CENTER
“I witnessed the growth of both
“Both Dr. Maalouf and
WHAT’S INSIDE
Osteoporosis Q & A . . . . . . . . . . 4
FOR MINERAL METABOLISM AND
Dr. Maalouf and Dr. Cameron as
Dr. Cameron exemplify the triple
Calcium and kidney stones . . . . . 7
CLINICAL RESEARCH.
trainees and was most impressed
excellence in academic medicine
Topamax and kidney stones . . . . 8
with their high standards of patient
as clinicians, teachers and
OJ and kidney stones. . . . . . . . . 9
Ann Cameron started out as fellows
care and medical research. We are
researchers. There is no doubt that
News you can use . . . . . . . . . . . 10
and spent several years of their
most fortunate to retain them
our patient population will benefit
Acidic urine and kidney stones . . 12
postdoctoral fellowships doing
here at the Charles and Jane Pak
tremendously from their care.”
research in mineral metabolism
Center,” said Dr. Orson Moe,
Drs. Naim Maalouf and Mary
Continued on page 3
Dr. Moe’s Perspective
D
FRIENDS:
The research on uric-acid stones cov-
As a new year begins, the
ered in this newsletter is an example
transition of Winter to
where the UT Southwestern mineral
EAR
Spring provides a backdrop to reflect
group has led, and continues to lead,
on the strong commitment our
the entire front of progress. This
Center has to the tripartite mission of
work also was inspired by patients
patient care, education and research.
in our practice over the years.
These three activities are not inde-
DR. ORSON W. MOE
Our faculty and staff are commit-
The Charles and Jane Pak
Center for Mineral Metabolism
and Clinical Research
at Baylor College of Medicine in
Houston. She came to UT Southwestern in 2002 as a fellow to specialize in nephrology.
She became a faculty member in
A S S O C I AT E D FA C U LT Y
October and has dual appointments
Orson W. Moe, M.D., director
in the divisions of mineral metabolism and nephrology.
pendent but are intimately woven.
ted to fulfill the missions of patient
Beverley Adams-Huet, M.S.
Patient care is of paramount
care, teaching and research. We will
Peter P. Antich, Ph.D.
importance and it precedes all other
strive to further improve our practice,
Mary Ann Cameron, M.D.
National Kidney Foundation fellow-
endeavors. In this tertiary referral
take education to higher grounds and
Weidong Geng, M.D., Ph.D.
ship grant to support her research
center, we often get the most chal-
train more physicians and scientists,
Ming-Chang Hu, M.D., Ph.D.
into how uric acid kidney stones
lenging cases that have baffled other
and conduct clinical and basic
Chou-Long Huang, M.D., Ph.D.
develop.
physicians. As stated on the cover of
research of the highest quality
Naim Maalouf, M.D.
the newsletter, our clinic has enjoyed
possible. All these activities stem
Clarita V. Odvina, M.D.
UT Southwestern researchers chosen
the honor of Service in Excellence
from patients, and it is our duty
Orhan K. Oz, M.D., Ph.D.
as the first group of young investi-
Team Awards, which reflect the high-
to bring the outcome back to the
Margaret S. Pearle, M.D., Ph.D.
gators to participate in the Clinical
est patient satisfaction. I cannot over-
benefit of the patients. We are
Craig D. Rubin, M.D.
Scholars Program.
state how gratifying that is. In addi-
most grateful for the support of our
Khashayar Sakhaee, M.D.
tion to deriving satisfaction out of
patients and donors who share our
Lidia Szczepaniak, Ph.D.
spends 75 percent of her time in an
seeing our patients get better, our
views and we look forward to serving
Joseph E. Zerwekh, Ph.D.
intense three-year educational and
physicians often use these cases as
and working with our Friends of
Charles Y.C. Pak, M.D., former director
training program to prepare her for a
teaching materials as well as starting
Mineral Metabolism.
points to launch research projects.
As a fellow, she received a
In 2005, she was one of 12
lism and witnessed some of them
commence their own careers elsewhere. It is rewarding to see that
O R S O N W. M O E , M . D .
they will spread the knowledge and
DIRECTOR OF THE CHARLES AND JANE PAK
philosophy from our center. We are
CENTER FOR MINERAL METABOLISM AND
fortunate to retain Drs. Maalouf and
CLINICAL RESEARCH
Alireza Atef-Zafarmand, M.D.
INVESTIGATORS
Olivier Bonny, M.D., Ph.D.
Continued from page 1
■
■
■
The Mineral Metabolism Clinic
specializes in various mineral metabo-
sions and duties in the years ahead.
lism diseases such as osteoporosis,
osteomalacia, Paget’s disease, hyper-
moving steadily forward. The study
parathyroidism, acid base bone metab-
on kidney-stone risk in patients
olism, nephrolithiasis, kidney-stone
taking Topamax is an example of
disease and prevention, and calcium
research that came straight out of
disorders.
Patients are seen on a referral basis.
national and international meetings
Please have your primary care physi-
in mineral research in the past year,
cian contact our clinic at 214-645-2870
I felt great pride and satisfaction to
to schedule an appointment with one
see our faculty poised in pivotal posi-
of our specialists.
tions in the research community.
The Mineral Metabolism Clinic is
located in the James W. Aston
Ambulatory Care Center at 5303 Harry
Hines Blvd., Dallas.
career as an independent clinical
investigator.
Her research interests include
Cameron, who will share our mis-
the clinic. As I participated in
– Drs. Mary Ann Cameron and Naim Maalouf
Damaris Vega, M.D.
trained specialists in mineral metabo-
Numerous research projects are
As a clinical scholar, Dr. Cameron
FELLOWS
On the teaching front, we have
2
degree and completed her residency
dependent diabetes mellitus.
“The studies on kidney stones in
studying the effects of insulin resistance on renal physiology, specifically
patients with type 2 diabetes is where
on the development of acidic urine
Dr. Moe also said: “It is unlikely that
I started,” Dr. Maalouf said. “It was
and uric acid stones, as well as
our trainees will encounter better
a good way for me to bridge the
hypertension.
teachers. I am looking forward to see-
research between endocrinology
ing both of them evolve into medical
researchers of international stature.”
Dr. Maalouf received his medical
degree from the American University
and mineral metabolism.”
In addition to studies on kidney
stones, Dr. Maalouf is interested in
osteoporosis research. He has pub-
Dr. Cameron also sees patients at
the Mineral Metabolism Clinic at the
Aston Center and supervises fellows
during their rotations in nephrology.
“I have performed patient orient-
of Beirut. He completed a residency
lished research in several journals
ed research over the past three years
in internal medicine at Emory
and recently received a five-year,
in the Center for Mineral Metabolism.
University.
$500,000 grant from the National
It has been an excellent experience
Institutes of Health to study the
that allows me to study the patho-
2001 as a fellow in endocrinology
mechanism by which high-protein
physiology of kidney stones with the
and spent his first year treating
diets increase the risk of bone loss
goal of providing new treatment
patients with diabetes and other
and stone formation.
options,” Dr. Cameron said. “I enjoy
He joined UT Southwestern in
Dr. Maalouf also sees patients
working with our volunteers whose
with kidney stones and osteoporosis
interest and dedication is essential
relationship between body weight
at the Mineral Metabolism Clinic in
for these studies, as well as with our
and uric acid kidney stones, which
the James W. Aston Ambulatory
supportive staff. I look forward to
are prevalent in individuals with type
Care Center.
developing and performing future
endocrine problems.
As a researcher, he has studied the
2 diabetes, also called non-insulin
Dr. Cameron earned her medical
studies at the center.”
3
Osteoporosis is increasingly becoming a man’s disease, too
STEOPOROSIS IS COMMONLY
O
THOUGHT OF AS A WOMAN’S
A pack of
Pak Awards
Several employees in the
HEALTH PROBLEM, BUT IT IS
Charles and Jane Pak Center for
Osteoporosis
INCREASINGLY BECOMING A
MAN’S HEALTH ISSUE, TOO.
Although it strikes more women
than men – of the 10 million
Americans estimated to have osteoporosis, 8 million of them are women
and 2 million are men – the disease
is more likely to go undiagnosed in
men.
Dr. Khashayar Sakhaee, chief of
the division of mineral metabolism, a
member of the Charles and Jane Pak
Center for Mineral Metabolism and
Clinical Research, and holder of the
BeautiControl Cosmetics Inc. Profes-
Mineral Metabolism and Clinical
Osteoporosis, discusses the disease
and offers some recommendations.
Q: WHY IS OSTEOPOROSIS LESS
and she has not had any additional
“If you know you have this,
about it,” said Mrs. Moses. “And
Awards. The Pak awards are given
there is no one else I’d go see for
twice each year in recognition of
treatment.”
Many other patients share
maintain excellence in all aspects
Mrs. Moses’ respect and affection for
of the center’s operations.
the doctors and staff at the Mineral
The most recent winners,
recognized in November 2006,
OUR PRIORITY.
WHEN WE
fractures.
with the Charles and Jane Pak
outstanding efforts to achieve and
“TAKING CARE OF PATIENTS IS
It is less severe than osteoporosis
there’s no reason not to be proactive
RECEIVE COMPLIMENTS FROM
OUR PATIENTS, IT ABSOLUTELY
REAFFIRMS OUR COMMITMENT
TO SERVE THEM.”
Metabolism Clinic.
Since 2004, the clinic has received
are: Kathy Hill, a research asso-
four Service in Excellence Team
ciate; and Mary “Kitty” Jackson,
Awards from UT Southwestern
a cook in the General Clinical
recognizing excellence in patient
Research Center.
satisfaction.
UT Southwestern randomly sur-
– DR. CLARITA ODVINA
six months for follow-up exams.
“Some patients have been with us
winners are: Beverly Kemp,
veys patients about their experience
since the start and they have watched
clinical staff supervisor; Paulette
at all campus clinics. In order to be
the clinic grow,” Mrs. Jackson said.
Padalino, research scientist, and;
recognized for excellence, the clinics
Trevor Henderson, technical
must receive a score in the 90th
the Center for Mineral Metabolism
support specialist.
percentile.
and Clinical Research at UT South-
“Taking care of patients is our
COMMON IN MEN THAN IN
Dr. Charles Y.C. Pak established
western in the early 1970s. In 2004,
WOMEN AND HOW DOES IT
priority,” Dr. Odvina said. “When
the center was renamed to honor
DIFFER BETWEEN THE SEXES?
we receive compliments from our
his decades of contributions to the
patients, it absolutely reaffirms our
medical center.
– Dr. Khashayar Sakhaee
Dr. Sakhaee: Men generally have
■
larger and stronger bones than
as well as to check the level of calci-
Q: WHAT IS THE TREATMENT
women. They also don’t experience
um in the patient’s urine, which is an
AND WHAT CAN MEN DO TO TRY
the hormonal changes that women
indicator of bone loss.
TO PREVENT OR LIVE WITH
do after menopause. The pattern of
It begins later in life and advances
■
■
“THE TWO MOST CRITICAL
OSTEOPOROSIS?
bone loss is also different in men:
ELEMENTS OF A GOOD CLINICAL
Q: WHO SHOULD BE TESTED?
Dr. Sakhaee: Lifestyle modifications
such as abstinence from smoking,
more slowly.
Dr. Sakhaee: Men with a history of
moderate alcohol intake, regular
fractures and long-term users of
physical exercise and specific atten-
Q: HOW IS OSTEOPOROSIS
certain medications, such as steroids
tion to underlying conditions are
DIAGNOSED? WHAT TYPE OF
used to treat asthma or arthritis, anti-
important. Adequate calcium intake
TESTS SHOULD BE DONE?
convulsants and certain cancer treat-
is essential. In general, men aged 30
ments, should be evaluated. Those
to 50 should take 1,000 milligrams of
Dr. Sakhaee: Bone mineral density
with a family history of osteoporosis,
calcium daily and 1,200 milligrams
measurement is the first step in the
chronic gastrointestinal or liver
after age 50. Vitamin D is also impor-
diagnosis of osteoporosis in men, just
diseases, and renal impairment
tant. In men 50 to 70 years old, 400
as it is in women. If the patient’s
should also be tested, as should
to 800 international units (IU) of
bone mineral density is found to be
smokers and excessive alcohol users.
vitamin D may be sufficient, but the
significantly below young normal
dose should increase after age 70.
mean, the next step would be to
An annual bone mineral density
measure blood levels of testosterone,
analysis and blood and urine tests
vitamin D and parathyroid hormone,
are also good ways to try to prevent
the disease.
4
Continued from page 1
Research were honored in 2006
The May 2006 Pak Award
sorship in Mineral Metabolism and
CLINIC
commitment to serve them.”
Metabolism Clinic and coordinates
the clinic staff includes two nurses,
the activities of the National Insti-
a medical office assistant, a clerical
tutes of Health-funded General
assistant and two bone-density
Clinical Research Center.
technicians.
“Many patients suffer with kidney
PRACTICE ARE OUTSTANDING
MEDICAL EXPERTISE AND PASSIONATE
DEDICATION TO PATIENT CARE.
ONE WITHOUT THE OTHER WILL
a good clinical practice are outstanding medical expertise and passionate
before they come here, after no one
dedication to patient care. One with-
had been able to help them,” said
out the other will simply not suffice,”
Kimberly Jackson, the clinic’s nursing
said Dr. Orson Moe, director of the
supervisor. “Once they get here, they
Charles and Jane Pak Center for
know that whatever condition or
Mineral Metabolism and Clinical
ailment they have, it will be taken
Research and holder of the Charles
care of.”
Pak Distinguished Chair in Mineral
Metabolism and Donald W. Seldin
research nurse, said many patients
Professorship in Clinical
are long-term visitors to the clinic
Investigation.
and have established relationships
– DR. ORSON MOE,
DIRECTOR OF THE CHARLES AND JANE PAK
CENTER FOR MINERAL METABOLISM
AND CLINICAL RESEARCH
“The two most critical elements of
stones or osteoporosis for years
Mrs. Jackson, who is also a
SIMPLY NOT SUFFICE.”
The Center oversees the Mineral
In addition to the physicians,
“The experience of Mrs. Moses
with their doctors. Those patients
exemplifies both features at the
include Mrs. Moses, who has given
Mineral Metabolism Clinic. I
up skiing but remains physically
congratulate the staff of our clinic
active. She visits Dr. Odvina every
for their performance and I am proud
to be their associate,” he added.
5
Brinkley retires after more than three decades
patient groups being
Medical Center in 1972 and hired
evaluated.
Ms. Brinkley in 1973. He was one of
the UT Southwestern faculty mem-
I
bers utilizing the National Institutes
STONES SHOULD NOT TAKE EXTRA
ensure they prepare the
of Health-funded General Clinical
CALCIUM ON THEIR OWN AS SUG-
foods by following strict
Research Center. He later established
GESTED BY PREVIOUS RESEARCH,
guidelines so that the
the Center for Mineral Metabolism
BUT SHOULD CHECK WITH THEIR
research diets don’t inter-
and Clinical Research, under which
DOCTORS TO DETERMINE THE
fere with what investiga-
the GCRC operates. The Center for
DIETARY GUIDELINES THAT WORK
tors are trying to deter-
Mineral Metabolism and Clinical
BEST FOR THEM, RESEARCHERS AT
mine when testing medica-
Research was named in Dr. Pak’s
UT SOUTHWESTERN MEDICAL
tions or treatments.
honor in 2004.
CENTER HAVE FOUND.
Urinary calcium – the amount of
calcium in a person’s urine – is an
important contributing factor in the
formation of both types of kidney
stones. Earlier studies had downplayed the significance of calcium
when compared to the levels of
oxalate in urine, and even encouraged kidney stone patients to increase their dietary intake of calcium.
“We often see patients who tell us
they have been advised to take more
calcium; however, that could be a
dangerous recommendation for some
individuals,” said Dr. Margaret Pearle,
professor of urology and holder of
the Dr. Ralph C. Smith Distinguished
Chair in Urologic Education at
UT Southwestern. She and her colleagues published their findings
about calcium in two studies in
Kidney International and the Journal of
Urology.
“While we want to be cautious in
members hired by Dr. Pak who have
Ms. Brinkley’s career, I
spent the rest of their medical careers
came in rather late in the
working for him.
picture. Ms. Brinkley was
“We all developed good working
publishing in medical jour-
relationships over time,” Ms. Brinkley
nals with Dr. Pak while I
said. “I’m the only dietitian, but I
was still in medical school,” said Dr.
don’t feel isolated from the rest of
Orson Moe, director of the Charles
the unit – the nurses, the people that
HEN LINDA BRINKLEY
W
and Jane Pak Center for Mineral
work in the lab, the administrators.
STARTED WORKING AS A
Metabolism and Clinical Research
We’re all part of the same team and
RESEARCH DIETITIAN AT
and holder of the Charles Pak Distin-
that’s the only way to get anything
THE GENERAL CLINICAL RESEARCH
guished Chair in Mineral Metabolism
done – through teamwork.”
CENTER (GCRC) IN 1973, DIETS FOR
and Donald W. Seldin Professorship
RESEARCH SUBJECTS WERE CALCU-
in Clinical Investigation.
A CALCULATOR.
“Ms. Brinkley is an integral part
of the history of our center. It is no
When Ms. Brinkley first started,
the GCRC and her research kitchen
were still under construction.
“We were doing things piecemeal
exaggeration when I state that
in temporary facilities and we were
day to determine the proper diets
Ms. Brinkley’s contribution to our
spread out all over the place,”
for Dr. Charles Y.C. Pak’s research
center and to mineral metabolism
Ms. Brinkley recalled.
subjects or those of his investigators.
research in general has been signifi-
Some days, it would take half a
The opening of the center is one
cant over the years. There are few
of the highlights of her career, she
with a few computer keystrokes, in
individuals in this field who have
said. The center’s first federal grant
a quarter of the time.
such in-depth knowledge of dietetics.
renewal allowed her to achieve a
Nowadays, diets are calculated
Her departure will be missed by the
personal goal – the purchase of her
dietitian, is no longer doing those
faculty, the staff and the patient
first home.
calculations or serving as the “resi-
subjects.”
But Ms. Brinkley, a registered
dent historian.” After more than
Ms. Brinkley received a bachelor’s
degree from North Texas State
buy my house,” Ms. Brinkley said.
University in 1965 and completed a
“I wanted to make sure that I had
dietetic internship at the Medical
a job.”
Ms. Brinkley said. “I really enjoy
College of Virginia in Richmond.
A native Texan, she returned to
BRINKLEY
“I waited five years, until the
she retired in February.
“The hardest thing is leaving
CIUM PHOSPHATE KIDNEY
center’s first grant was renewed, to
three decades in the department,
the people that I work with,”
Continued from page 6
For example, when she first started,
sites in Texas and Georgia to visit
and archives. She also enjoys photo-
has enjoyed watching the Charles
time,” Ms. Brinkley said. “New inves-
graphy.
tigators, new studies, new things to
learn.”
Metabolism and Clinical Research and
with them.
Hospital as a clinical dietitian. She
the GCRC grow into world-renowned
Dr. Pak arrived at UT Southwestern
“The thing that kept me going all
She and her mother have traveled
to Arkansas, Tennessee and various
GCRC. Now, for many studies, the
ed working at Parkland Memorial
obtain accurate data from the
tional needs of patients.
researching her family tree.
graveyards, libraries, courthouses
other pretty well over the years.”
Woman’s University.
protocols and dealing with the nutri-
something new going on all the
and Jane Pak Center for Mineral
develop diets so that they can
dietetics, the action of implementing
these years is that there is always
Dallas after her internship and start-
also took graduate courses at Texas
formation in earlier studies because a
different “stability constant,” or
mathematical formula, was used to
calculate urinary saturation of calcium oxalate, with results showing
that less attention should be focused
on calcium. Researchers at
UT Southwestern, however, used a
newer, lower stability constant, today
regarded as the “gold standard” in
the industry, yielding data that pointed to calcium’s more essential role.
Dr. Charles Y.C. Pak, former
director of the Charles and Jane Pak
Center for Mineral Metabolism and
Clinical Research, urges patients to
seek their physician’s advice before
deciding whether to limit or increase
calcium in their diets.
“For the patient, the message of
these studies is that the recommendation for calcium intake cannot be
generalized because the effect of
calcium intake on stone formation
depends on the type of stone, oxalate
intake, presence of stones and the
efficiency of calcium absorption from
the bowel,” Dr. Pak said.
“Our future challenge is to understand various factors that modify the
effect of calcium restriction on urinary calcium and stone-forming
propensity, and to determine how
best to use diet and drugs to control
high urinary calcium and stone formation.”
living in the inpatient facility of the
them and we’ve gotten to know each
Ms. Brinkley has helped investigators
asking anyone to restrict calcium
intake because of the risk of bone
disease, we also realize that urinary
calcium has about the same influence
as urinary oxalate in calcium oxalate
stone formation, and we may want to
recommend calcium restriction in
patients who have moderately to
severely elevated intestinal calcium
absorption and urinary calcium
levels,” she said.
The same is true for patients with
calcium phosphate stones, said
Beverley Adams-Huet, a faculty associate in internal medicine and a
biostatistician in UT Southwestern’s
General Clinical Research Center
(GCRC).
“Our research shows that the
level of urinary calcium also has an
important influence in the formation
of calcium phosphate stones,” she
said. “Both of these studies offer
supportive evidence that people with
calcium phosphate stones may need
to carefully monitor their calcium
dietary intake.”
The most common type of kidney
stone contains calcium in combination with either oxalate or phosphate, with calcium oxalate stones
accounting for about 60 percent and
calcium phosphate about 20 percent
of kidney stones.
Calcium was not regarded as
important as oxalate in kidney-stone
research patients would spend weeks
Through the years, Ms. Brinkley
foods are packaged and sent home
As a research dietitian,
6
Ms. Brinkley is one of several staff
the time course of
CALCIUM OXALATE OR CAL-
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“When viewed in
LATED WITH A PENCIL, PAPER AND
NDIVIDUALS WITH EITHER
she oversees the cooks to
In the research kitchen,
– Linda Brinkley
Calcium intake a factor in formation of kidney stones
In 1981, Ms. Brinkley became the
And she’s excited about the new
research centers. She has also wit-
administrative manager of the GCRC,
adventures that retirement will bring.
nessed the field of dietetics evolve.
but she returned to her previous post
Ms. Brinkley developed an interest
Continued on page 7
after seven years because she missed
“I like to take pictures, which goes
along with the genealogy and the
traveling,” Ms. Brinkley said. “I have
enough hobbies to last me for the
next 30 years.”
in genealogy several years ago and is
7
Drug for migraines and seizures increases risk of kidney stones
OPIRAMATE (TOPAMAX), A
DAILY GLASS OF ORANGE
T
A
AND MIGRAINE HEADACHES, CAN
STONES BETTER THAN OTHER
INCREASE THE PROPENSITY OF
CITRUS FRUIT JUICES SUCH AS
CALCIUM PHOSPHATE KIDNEY
LEMONADE, A RESEARCHER AT
STONES, RESEARCHERS AT
UT SOUTHWESTERN MEDICAL
UT SOUTHWESTERN MEDICAL
CENTER HAS DISCOVERED.
The study, published in the
DRUG COMMONLY PRE-
JUICE CAN HELP PREVENT
SCRIBED TO TREAT SEIZURES
THE RECURRENCE OF KIDNEY
CENTER HAVE FOUND.
A study – the largest cross-sectional
examination of how long-term use of
topiramate affects kidney-stone formation – was published recently in
the American Journal of Kidney Diseases.
Several case reports have described an association between topira-
– Drs. Khashayar Sakhaee and Dion Graybeal
mate and the development of kidney
stones, but this complication had not
been well recognized and physicians
The study comprised two phases.
that form in the kidneys from sub-
have not informed patients about the
Thirty-two individuals already being
stances excreted in the urine. When
risk, the UT Southwestern researchers
treated with topiramate and 50 nor-
waste materials in urine do not dis-
said. More important, the mecha-
mal volunteers were enrolled in a
solve completely, microscopic parti-
nism of stone formation was largely
cross-sectional study in which their
cles begin to form and, over time,
unknown previously.
blood and urine were tested for
grow into kidney stones.
“The wide-spread and escalating
kidney-stone risk. A short-term study
Before this study, the rate of kid-
use of topiramate emphasizes the
also was conducted in seven individ-
ney-stone formation with topiramate
importance of considering the long-
uals to assess stone risk before and
was reported as 1.5 percent. The low
term impact of this drug on kidney-
three months after taking topiramate.
incidence rate may be an underesti-
stone formation,” said Dr. Khashayar
All patients were evaluated at
mation due to the short length of
Sakhaee, senior author of the study,
UT Southwestern’s General Clinical
observation and the lack of ongoing
chief of mineral metabolism at
Research Center.
kidney-stone surveillance and data
collection for this drug, Dr. Sakhaee
UT Southwestern and holder of the
Researchers found that taking
BeautiControl Cosmetics Inc. Profes-
topiramate on a long-term basis, or
sorship in Mineral Metabolism and
for about one year, caused systemic
Osteoporosis.
metabolic acidosis – a buildup of
the occurrence of kidney stones with
excessive acid in the blood – as a
long-term topiramate treatment,”
suffer from migraines, with women
result of the inability of the kidney
Dr. Sakhaee said. “Studies are needed
being affected three times more often
to excrete acid. Topiramate use also
to explore optimal measures to pre-
than men, according to the National
increased the urine pH and lowered
vent kidney-stone formation with
Headache Foundation.
urine citrate, an important inhibitor
topiramate use.”
More than 29 million Americans
“Topiramate is probably one of
the most commonly prescribed and
of kidney-stone formation.
“These changes increase the pro-
said.
“There is a legitimate concern for
Other UT Southwestern researchers
contributing to the study were
most effective neurological medica-
pensity to form calcium phosphate
Drs. Orson Moe, director of the
tions right now,” said Dr. Dion
stones,” Dr. Sakhaee said.
Charles and Jane Pak Center for
Graybeal, assistant professor of neurology and a study author.
In the short-term study, urinary
Mineral Metabolism and Clinical
calcium and oxalate – a chemical
Research, Naim Maalouf, assistant
professor of internal medicine, and
calcium and is found in most cal-
Brian J. Welch, a postdoctoral fellow
is to develop a way to block the
cium stones – did not significantly
in internal medicine.
development of kidney stones for
change in people taking topiramate.
topiramate users.
Kidney stones are solid deposits
The research was supported by the
National Institutes of Health.
Clinical Journal of the American Society
of Nephrology, indicates that although
many people assume that all citrus
fruit juices help prevent the formation of kidney stones, not all have
the same effect.
Medically managing recurrent
kidney stones requires dietary and
lifestyle changes as well as treatment
such as the addition of potassium
citrate, which has been shown to
lower the rate of new stone formation in patients with kidney stones.
But some patients can’t tolerate
potassium citrate because of gastrointestinal side effects, said Dr. Clarita
Odvina, associate professor of internal medicine at the Charles and Jane
Pak Center for Mineral Metabolism
and Clinical Research and the study’s
lead author. In those cases, dietary
sources of citrate – such as orange
juice – may be considered as an
alternative to pharmacological drugs.
“Orange juice could potentially
play an important role in the management of kidney-stone disease and
may be considered an option for
patients who are intolerant of potassium citrate,” Dr. Odvina said.
All citrus juices contain citrate, a
negatively charged form of citric acid
that gives a sour taste to citrus fruits.
Researchers compared orange juice
and lemonade – juices with comparable citrate contents – and found
that the components that accompany the citrate can alter the effectiveness of the juice in decreasing
the risk of developing new kidney
stones.
Kidney stones develop when the
urine is too concentrated, causing
minerals and other chemicals in the
urine to bind together. Over time,
these crystals combine and grow into
a stone.
In the UT Southwestern study,
13 volunteers – some with a history
of kidney stones and some without –
underwent three phases, each lasting
one week. Chosen in random order,
the phases included: a distilled water
or control phase; an orange juice
phase; and a lemonade phase. There
was a three-week interval between
phases.
During each phase, volunteers
drank 13 ounces of orange juice,
lemonade or distilled water three
times a day with meals. They also
maintained a low-calcium, lowoxalate diet. Urine and blood samples
were taken at intervals during
each phase. The study was done at
UT Southwestern’s General Clinical
Research Center.
Orange juice, researchers found,
boosted the levels of citrate in the
urine and reduced the crystallization
of uric acid and calcium oxalate – the
most frequently found ingredient in
kidney stones.
But lemonade did not increase the
levels of citrate, an important acid
neutralizer and inhibitor of kidneystone formation.
“One reason might be the different constituents of various beverages,” Dr. Odvina said.
For instance, the citrate in orange
and grapefruit juice is accompanied
by a potassium ion, which has a
negative electronic charge, while the
citrate in lemonade and cranberry
juice is accompanied by a hydrogen
ion, which has a positive charge. Ions
of hydrogen, but not potassium,
counteract the beneficial effects of
the high citrate content.
“There is an absolute need to
consider the accompanying positive
charge [of hydrogen ions] whenever
one assesses the citrate content of a
diet,” Dr. Odvina said.
“ORANGE JUICE
COULD POTENTIALLY
PLAY AN IMPORTANT
ROLE IN THE MANAGEMENT OF KIDNEYSTONE DISEASE.”
– DR. CLARITA ODVINA
Orange
Juice
compound that binds strongly with
at UT Southwestern say the next step
Dr. Graybeal and other researchers
8
OJ is better than lemonade at keeping kidney stones away
9
danc
ng
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■ ■ ■ ■ ■
determining how the kidney han-
renowned expert in osteoporosis
dles calcium.
and a professor of medicine at
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their balance. The best exercises for
formerly a resident in internal medi-
the bones are weight-bearing activi-
cine at Wayne State University in
ties such as walking, dancing, jog-
Michigan, began a postdoctoral fel-
ging, hiking, tennis or stair climbing.
lowship in nephrology at UT South-
Dr. Damaris Vega, who received
her medical degree in 2002 from
Ponce School of Medicine in Puerto
Rico and completed a residency in
internal medicine at UT Southwestern, has started a postdoctoral
fellowship in mineral metabolism.
Dr. Vega will assist Dr. Khashayar
Sakhaee in his studies comparing
potassium citrate and citric acid supplements for patients being treated
with topiramate, a drug commonly
prescribed for the treatment of
seizures and migraine headaches.
conference room. Ask your friends to join. Membership is renewable
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western in 2004 and in mineral
preserve bone mass and strengthen
metabolism in 2005. Currently, he is
muscles, which improves balance and
working with Dr. Khashayar Sakhaee
can prevent falls,” said Dr. Naim
and Dr. Orson Moe on several
Maalouf, assistant professor of
projects, including the investigation
internal medicine.
of post-renal transplant hyperphos-
If you’ve been sedentary for any
phaturia and different techniques
Consider an endowment-naming opportunity:
length of time, be sure to consult
for measuring gastrointestinal calci-
with your doctor before starting an
um absorption.
Please consider one of the following levels of named endowment to
exercise program.
support the Charles and Jane Pak Center for Mineral Metabolism and
■
Clinical Research at UT Southwestern Medical Center. (Designation by
Kidney stones – painful, but
M.D. and Ph.D. from the University
name is contingent upon approval by the UT System Board of Regents.)
perhaps preventable
of Lausanne in Switzerland. After
ENDOWMENT LEVEL
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in internal medicine and nephrolo-
covery in a 7,000-year-old Egyptian
gy, he has joined the laboratory of
mummy shows they have been with
Dr. Orson Moe to conduct basic
us since ancient times.
research in regulation of calcium
handling by the kidney. Dr. Bonny
exacerbate kidney stones, which can
has received grant support from the
contain a variety of substances, most
Swiss National Science Foundation
commonly calcium and uric acid.
and the National Kidney Founda-
Dr. Orson Moe, director of the
For a particular type of disease, such as osteoporosis, stone disease
Charles and Jane Pak Center for
or bone disease.
Mineral Metabolism and Clinical
treatment methods for osteoporosis
as part of the Lillian B. Clark Lecture
Series in Mineral Metabolism.
■
Three staff members joined the
Charles and Jane Pak Center for
Mineral Metabolism and Clinical
Research since July. Gail Cook is a
senior administrative assistant,
Amy Fitts is an administrative
assistant and Miranda King is a
clinical research coordinator.
■
Researchers in the biotechnology
program within the Charles and
Jane Pak Center for Mineral Metabolism and Clinical Research are
involved in a collaborative study
with the Henry Ford Hospital in
Detroit to measure bone quality by
using ultrasound. This non-invasive
technique has the potential to safely
measure cortical and trabecular bone
strength.
Roy Peterson, who came to work
for Dr. Charles Y.C. Pak in 1973,
retired in June 2006. Mr. Peterson’s
main duties were to coordinate
and monitor clinical studies for
the Center for Mineral Metabolism
and Clinical Research. Since his
retirement, Mr. Peterson has been
returning to work one day a week
to attend meetings and work on
special projects for Dr. Pak. He also
continues to monitor some studies.
tion. He studies a protein in the
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■
DISTINGUISHED CHAIR
completing his postgraduate training
more painful disorders and their dis-
Modern lifestyles, however, can
UT Southwestern to discuss new
■
Dr. Olivier Bonny received his
Kidney stones are one of life’s
Dr. David Baylink, a world-
Loma Linda University, visited
Dr. Alireza Atef-Zafarmand,
“Exercise helps to increase or
Sponsor members are recognized on a permanent plaque in the main
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exchange which has major roles in
Exercise can help people with
osteoporosis stay fit and improve
$10,000 OR MORE
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NOTES
kidney called the sodium-calcium
The best bones are those that
Research, said there are ways to
prevent kidney stones from forming.
In general, drink up to 12 full
Consider a space-naming opportunity:
glasses of water daily to help dilute
Please consider one of the following space-naming opportunities
or flush away substances that form
in support of the Charles and Jane Pak Center for Mineral
stones, he said. Also, avoid excessive
Metabolism and Clinical Research at UT Southwestern Medical
protein intake to reduce the risk.
Center. (Designation by name is contingent upon approval by
Dr. Moe said signs of a possible
kidney stone include extreme pain
the UT System Board of Regents.)
in the back or side that will not go
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