Professional Documents
Culture Documents
Spring 2020
NEPHROLO GY
UPDATE
Growing Expertise in Complement-
Mediated Kidney Diseases
I n a laboratory at Washington diseases recur in the allograft and can lead
University School of Medicine, transplant to loss of the precious kidney. Atypical HUS,
nephrologist Anuja Java, MD, is working TMA and C3G have a high risk of recur-
on identifying and treating rare kidney rence after a kidney transplant.
diseases. What she’s focused on are comple- “Knowing the underlying etiology
ment-mediated diseases that include atyp- allows us to use prophylactic treatment in
ical hemolytic uremic syndrome (aHUS), some cases, monitor for disease recurrence
thrombotic microangiopathy (TMA) and closely and initiate treatment early
C3 glomerulopathy. in others,” Java says. “Biopsies can confirm
“The prevalence is low, maybe two the presence of blood vessel damage or
or three people per million for aHUS, for blood clots within the kidneys, which can
example,” says Java. “But I believe the be a hallmark of TMA. Our suspicions are
prevalence may be low because these raised when we see that, so we order genetic
diseases are not widely recognized.” testing to assess if the problem could be a Anuja Java, MD, along with lab technician Zheng Hu,
She is building upon breakthrough im- genetically-mediated disease.” manufactures novel gene mutations in her lab to define
treatment options for complement-mediated diseases.
munology research conducted at the School Importantly, patients who developed
of Medicine over the past 40 years by her kidney failure due to pregnancy-associated “We now have more than 75 people in
research mentor and now collaborator, TMA or another secondary TMA whose our database for which we have identified
rheumatologist John Atkinson, MD. “We evolution was unusually aggressive should their specific gene variant,” says Java. “If
are both excited about the field of comple- also be evaluated for genetic causes. this work wasn’t accomplished, they might
ment immunology,” Java says. “He is an Genetic variants can be identified in have undergone a kidney transplant but
expert in the role of the complement system about 60 percent of cases, but most are then, later, have recurrence of disease in
in infectious, autoimmune and inflamma- characterized as of “uncertain significance,” the transplanted kidney and be diagnosed
tory diseases, such as lupus and age-related “likely pathogenic,” or “likely benign.” with kidney failure again.”
macular degeneration. In our collaborative When that occurs, Java turns to her lab, Her timing in identifying these vari-
research, we have been looking at gene actually manufacturing those specific gene ants comes at a time when there is now an
mutations and deficient proteins along the mutations to confirm a patient’s individual FDA-approved drug, eculizumab, to treat
complement pathway that predispose indi- diagnosis and define treatment options kidney patients with specific gene muta-
viduals to rare kidney diseases.” — in other words, personalized medicine tions who are diagnosed with aHUS. In
A former fellow in WU’s transplant for these rare diseases. The manufacturing addition, there are multiple drugs in the
nephrology program, Java was particularly of these complement mutations and Java’s pipeline for other complement-mediated
interested in complement immunology and work to conduct functional testing on the kidney diseases, includes C3G and IgA
how genetic mutations along the comple- expressed protein is not done regularly nephropathy.
ment pathway could impact the success or anywhere else in the United States. As a re- Java now is leading a new and grow-
failure of kidney transplants. sult of her translational and transformative ing program on complement-mediated
When evaluating patients for trans- research, patients from across the country
plant, it is critical to know the underlying are being referred to Java. continued on page 3
cause of their kidney failure since certain
Thank You! Dr. Arvind and Ms. Dipika Garg Dr. John Mellas
Ms. Judith A. Douglas Dr. Didier Portilla
The Division of Nephrology thanks the
Mr. & Mrs. Joel and Susan Allen Mr. & Mrs. Terrance Dwaine
following individuals who have generous-
Mr. & Mrs. Martin E. Jaffe and Karen Lee Sell
ly donated to our division from October
Dr. Richard M. Mazey Dr. Thomas Ralph Pohlman
2019 through February 2020:
Ms. Patricia M. McKevitt
Support the Division Washington University in St. Louis You may also contact Rachel A. Hartmann
Office of Medical Alumni and Development directly at 314-935-9715 or by email at
of Nephrology rachel_hartmann@wustl.edu if you are
Attn: Rachel A. Hartmann
If you would like to support our research 7425 Forsyth Blvd. considering supporting the Division
and teaching mission or contribute to the Campus Box 1247 through appreciated stocks, deferred
Division of Nephrology’s programs and St. Louis, MO 63105 giving, beneficiary plans or other assets.
services, please send your contribution to:
Administrative Office Consultations & On the web: Nephrology Fellowship Tingting Li, MD, MSCI Nephrology
Division of Appointments: Website: Steven Cheng, MD Associate Program Transplant Fellowship
Nephrology Patient Appointments nephrology.wustl.edu Program Director Director, Research & Rowena Delos Santos,
314-362-7603 stcheng@wustl.edu Career Development MD
Washington Twitter: tingli@wustl.edu
University Patient referrals twitter.com/ Seth Goldberg, MD Director
School of Medicine 800-867-3627 WUNephrology Associate Program Frank O’Brien, MD delossantos@wustl.edu
Director, Service & Associate Program
Campus Box 8126 Facebook: Director, Conferences
600 South Euclid Ave. www.facebook.com/ Assessment
sgolber@wustl.edu & Curriculum
St. Louis, MO 63110 WUSTL/Nephrology Development
Phone: 314-362-8232 fobrien@wustl.edu
Fax: 314-362-8237
2
Fellowship Notes
By Tingting Li, MD, MSCI, and myself, recently added Frank O’Brien, (and profiled in the last newsletter), I
Association Program MD as an associate program director to will explore elective options tailored
Director, Nephrology
oversee the educational curriculum. toward fellows’ interests and provide
Fellowship Program
Steven remains the program director, fellows with institutional and outside
handling administration and policy. Seth resources to support their professional
oversees clinical rotations and fellow growth. I will also develop a wellness cur-
competency assessment. Frank, who has riculum for fellows to ensure that
developed peritoneal and hemodialysis they have the optimal learning environ-
Expanded curricula for our trainees, steps into the ment and work-life balance.
larger role of supervising fellowship cur- The expansion of the program lead-
Leadership Team riculum development and revamping the ership reflects our ongoing commitment
In a move to enhance the educational educational conferences. to fellowship education, well-being, and
experience and to increase career devel- I will continue my role as the Associate career development. We are proud of our
opment and mentoring opportunities for Program Director of Clinical Research and standing as one of the premier nephrology
our nephrology fellows, the Fellowship Career development, providing guidance fellowship programs in the country and
Program has once again expanded its and mentorship to the fellows. In addition we will continue to strive to provide an
leadership team. The team, which included to the annual career development retreat, unparalleled training experience.
Steven Cheng, MD, Seth Goldberg, MD, which was launched successfully last year
4
Program Spotlight
Demand is High for Interventional
insertion and exchange,” he says. “We also are aware of the center as a “first call”
Nephrology Services offer accessory vein obliteration to assist option when access issues arise.
After opening a new interventional with maturation and cannulation.”
nephrology clinic last spring in west Davis, who has been an intervention-
St. Louis County, the Division has seen al nephrology specialist for more than 15
rapid growth in the demand for services. years both here and in Ohio, says there are
“We’ve seen 300 percent growth over several reasons for the demand for services.
the first year,” says James Davis, MD, FACP, First, he says, former WU nephrology
FASN, who oversees the clinic. “It’s been fellow Steve Bander, MD, who heads the
amazing to see the referrals grow so quickly.” St. Luke’s Vascular Access Center, has been
The clinic is a joint partnership with very supportive of Davis joining the team,
St. Luke’s Vascular Access Center. Davis which offers 24/7 treatment for patients
focuses specifically on fistula and graft with central venous catheter complications.
care. “We provide maturation assistance “I have the flexibility to see patients every
for immature AVF, angioplasty and day and get them cared for quickly,”
thrombectomy of grafts and fistula and all Davis explains. He also points out that the
manner of dialysis catheter care, including Division has ensured that physicians James Davis, MD
New Renal Services Clinic kidney stones, glomerulonephritis as well as University dialysis unit in north county
for Veterans hypertension, will be seen in the clinic. as well as offer inpatient renal services
“Our hope is that this clinic will at Christian Hospital and Barnes-Jewish
The Division of Nephrology has started a
decrease the drive time and wait times for West County Hospital.
new renal diseases clinic at the Veterans
veterans who live in north county and who “Both inpatient and outpatient renal
Affairs outpatient facility in north St. Louis
need these critical services,” she says. services have experienced growth within the
county. Manasa Metireddy, MD, who is
Metireddy, who joined the Division in past year and we anticipate the new veterans’
now part-time faculty with the VA, will
fall 2018, is part of the Division’s communi- clinic to do the same,” Metireddy says. “It’s
head the new clinic. Veterans with various
ty-based faculty practice. She and James all about placing services closer to patients’
conditions such as chronic kidney disease,
Davis, MD, oversee the Washington home and making access more convenient.”
Another Record Year for transplants last year — 319 transplants! talks for those who are already waiting for
Kidney Transplants! That’s an increase from 241 transplants an organ,” he says. “When patients are told
performed in 2018. that a living donor transplant will give them
With the 8th largest organ transplant center
“The jump in the number of trans- a better quality organ while also prevent-
in the nation, the Washington University
plants is due primarily to increased referrals ing them from waiting several years for a
and Barnes-Jewish Hospital Transplant
as a result of strong collaborations with the kidney, many of them reach out to more
Center logged a record number of kidney
referring nephrologoists, extensive outreach relatives and friends in the quest for
319 efforts, and the increased utilization of a donor.”
kidneys donated after cardiac death Last year, the team performed 73 living
254 (DCD),” Says Tarek Alhamad, MD, medical transplants, up from 55 the previous year.
229 239 238
222
241 director of Kidney and Combined Kidney/ Living donor evaluations also increased,
217 211
220 Pancreas Transplantation. from 356 in 2018 to 408 last year. Murad
Transplant nephrologist Haris Murad, notes, “While our transplant numbers
120 114 114 MD, who joined the team in mid-2019, also are increasing, the fact that close to half a
99 99 98
83 92 94 80 notes that better patient education efforts million patients are on dialysis means we
103
75 67 55 66 83 94 74 resulted in an increase in the number of pa- still have a lot more to achieve in terms of
69
53
40 41 39 tients undergoing living donor transplants. finding kidney donations. We have almost
29 35 35 29 29 36 30
“This was achieved through more robust 800 patients still on our own waiting list
2011 2013 2015 2017 2019 counseling of patients who are seen in the right now and receive more than 1,700 refer-
Kidney Liver Lung Heart pre-transplant clinics as well as educational rals annually to our program.”
$3 Million NIH Grant Awarded for Cilia Research of ciliary motors along the ciliary axoneme.
How this occurs, however, is not understood,
A four-year, $3.14 million RO1 renewal grant and genetic lung diseases such as primary impeding the development of therapeutic
from the National Heart, Lung, and Blood ciliary dyskinesis (PCD), among others. strategies. The researchers are investigating
Institute (NHLBI) grant has been awarded The current research effort focuses on how ciliary motor components are directed
to three prominent Washington University how genetic defects in cilia function result in from the cell body into the cilia and then to
researchers to study the “Regulation of PCD, lung infection and the development of specific sites along the ciliary axoneme. “Just
Motile Cilia Assembly in Lung Disease.” chronic lung disease. Researchers have found as movement through a city requires multiple
Principal investigators include Moe that these gene mutations result in defective modes of transportation, certain proteins
Mahjoub, PhD, Assistant Professor of production, transport, or proper placement must be moved from the cytoplasm to the
Medicine (Division of Nephrology), Cell basal bodies and into cilia using defined ve-
Biology and Physiology; Susan Dutcher, hicles and routes,” say the investigators. “We
PhD, Professor of Genetics, Cell Biology are expanding our previous research to de-
and Physiology; and Steven Brody, MD, the fine how these proteins are delivered to their
Dorothy R. and Hubert C. Moog Professor of appropriate addresses within each cilium and
Pulmonary Medicine. The three, all collab- how disease-causing mutations impact these
orators in the Washington University Cilia key trafficking steps.”
Group, collectively and individually research
the mechanisms and causes of ciliopathies, Cilia research PIs include Steven Brody, MD,
which include polycystic kidney disease Susan Dutcher, PhD, and Moe MahJoub, PhD.
Department of Defense Grant Focal Segmental Glomeruloscle- The ultimate goal, says Chen, is
Awarded to Chen rosis (FSGS). FSGS is the most to develop a new class of drugs —
common primary glomerulopa- podocyte ER calcium stabilizers —
Ying “Maggie” Chen, MD, PhD, has been thy leading to renal failure to treat FSGS. While it is known that
awarded a $1.8 million grant from the U.S. and disproportionately affects podocyte ER stress plays an import-
Department of Defense for her study, “De- African-Americans, a highly ant role in the pathogenesis of FSGS,
velopment of Novel Podocyte Endoplasmic represented population among there is no treatment option current-
Reticulum (ER) Calcium Stabilizers to Treat military personnel and veterans. Maggie Chen, MD, PhD ly available that targets podocyte ER.
6
Faculty News and Awards
Vijayan Inducted Into Shreveport, La. While working in Miner’s Nursing. Koester-Wiedemann is responsi-
Alpha Omega Alpha lab, Funk helped to develop a non-invasive, ble for clinical coverage of in-center
novel method that uses hair follicles to hemodialysis, home dialysis, and the
Anitha Vijayan,
diagnose X-linked Alport syndrome. The chronic kidney disease patient population.
MD, professor of
inherited disease is characterized by a The award, given during the 40th Annual
medicine in the
progressive loss in kidney function and Dialysis Conference this past February,
Division of
hearing as well as eye abnormalities. is named in honor of Barbara Prowant,
Nephrology, has
a renowned nephrology nurse and founder
been elected to
Delos Santos Chairs AST Conflicts of the conference, which was established in
Alpha Omega
of Interest Committee 1981 as the world’s largest multidisciplinary
Alpha, the national
conference on dialysis.
medical honor society. “AOA stands for Rowena Delos
excellence in academic scholarship, Santos, MD, takes
over as chair of
President-Elect Miner Chairs ASMB
leadership and professionalism,” Vijayan
says. “I am passionate about providing the Conflicts of Biennial Meeting in St. Louis
exemplary patient care and educating the Interest (COI) Make plans to come to St. Louis for the
next generation of physicians, and I am Committee of the 2020 biennial meeting of the American
privileged to be doing both at an outstand- American Society Society for Matrix Biology (ASMB). Chair
ing institution. I am truly honored that my of Transplantation of the meeting will be Jeffrey Miner, PhD,
work is recognized in this way.” Vijayan was (AST) in June 2020. Delos Santos, who FASN, who also will become president of
nominated for the honor by Division Chief is director of the Division’s Transplant the organization in 2021. “ASMB’s 2020
Benjamin Humphreys, MD, PhD, and Nephrology Fellowship, has served as meeting, “The Matrix in Focus: Matrix,
Victoria Fraser, MD, chair of Washington co-chair of the COI committee since last Cells, and Interactions in Health, Disease,
University’s Department of Medicine. year. The committee reviews all disclosures Aging, and Regeneration”, will bring togeth-
of potential conflicts of interest made by er matrix biologists from around the world
Steven Funk, PhD Joins Division AST speakers, moderators and planning to share knowledge and foster collabora-
committee members. tions regarding extracellular matrix biology
Instructor of
in order to improve human health,” notes
medicine Steven
Lifetime Achievement Award in Miner. “Defects in the extracellular matrix
Funk, PhD, is the
Nephrology Nursing can impact all tissues. This is especially
newest faculty
true in the kidney, where genetic defects in
member in the Lisa Koester- collagen IV cause Alport syndrome, and
Division. Funk Wiedemann, ANP, dysregulated matrix production causes
previously served CNN-NP, was renal fibrosis.” The organization anticipates
as a post-doctoral awarded the more than 350 extracellular matrix biolo-
research fellow in the laboratory of Jeffrey Barbara Prowant gists to attend the meeting, which will be
Miner, PhD. He earned his doctoral degree Lifetime Achieve- held at the Hyatt Regency, St. Louis Arch.
in cell biology and anatomy from Louisiana ment Award in
State University Health Sciences Center in Nephrology
Tennis, Anyone? Dharnidharka, who also is a member needed less space.” He re-discovered the
of the Board of Directors of the North sport after coming to St. Louis and began
Vikas Dharnidharka, MD, Chief of Pediat- American Pediatric Renal Trials and Collab- playing weekly in the St. Louis Table Tennis
ric Nephrology, can serve up a fun time, for orative Studies (NAPRTCS) organization, League. “When I discovered the league here,
sure! Last summer, he won two 4th place grew up playing table tennis in India. “It was I was able to get better because I’m playing
ribbons in his age category at the National so crowded there, that most indoor sports against people of all ages and all levels, so
Senior Games Table Tennis Tournament in were easier to play than outdoor sports. You my game really improved.”
Albuquerque, New Mexico.
“There are a lot of ways to relieve
stress,” he says. “Table tennis I’m good at.
Games involve skill, and there is physical
exercise. It takes you away and gives you
a life outside of work, too. I like all of
that. It’s fun!”
Dharnidharka placed 4th in both the
men’s double and mixed double matches
at the National Games. He is garnering
quite the streak — Last year, he won three
medals at St. Louis Senior Olympics Table
Tennis Tournament: a gold medal in mixed
doubles, a silver in men’s doubles, and a
bronze in singles. At the same tournament
in 2018, he won a gold medal in the singles
match and a silver medal in men’s doubles.
Now, his wins in 2019 may qualify him for
the 2021 National Games. Vikas Dharnidharka, MD, at the National Senior Games Table Tennis Tournament.