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The Translational Research in Biomarker Endpoints and Applications in Kidney
Disease (TRIBE-AKD)


   
 * Home
   About Us Team
   
 * Projects
   Project Overview Ongoing TRIBE-AKI Deceased Donor Study Diabetic Kidney
   Disease Chronic Kidney Disease in Children Kidney Precision Medicine Project
   Completed ASSESS-AKI Acute Kidney Injury in Cirrhosis PRESERVE Trial
   
 * Resources
   Biorepository Biomarker Research Laboratory Instructional Videos Methodology
   Work for Biomarker Development
   
 * Career
   
 * News and Gallery

Chirag R. Parikh, M.D., PhD,
Director, Division of Nephrology
Ronald Peterson Professor of Medicine,
1830 E. Monument Street
4th Floor, Suite 416
Baltimore, MD 21287
Phone: (410) 955-5268
Fax: (410) 367-2258


My research group is dedicated to the application of laboratory and
preclinical-based discoveries to clinical studies in kidney disease and related
disorders. An overarching component of our mission is to advance the mechanistic
understanding of novel biomarkers and to enhance their clinical utility in
complex diseases. Our multidisciplinary team is comprised of talented physicians
and scientists committed to patient-oriented research and developing solutions
in clinical medicine and disease management in the community. Our group aims to
leverage our collective creativity, commitment, experiences, and skills to
improve the care of patients and communities.

I founded the Translational Research in Biomarker Endpoints and Applications in
Kidney Disease (TRIBE-AKD) consortium in 2005. This consortium has conducted
multicenter studies for efficient discovery and validation of novel biomarkers
of kidney diseases. Current clinical definitions of kidney disease are largely
based on serum creatinine, an imperfect measure that obscures much of the
heterogeneity in kidney diseases thereby impeding clinical management and drug
development. Work from the TRIBE-AKD group has dissected this heterogeneity in
kidney diseases through biomarkers of renal tubular injury, repair, and
inflammation.

The TRIBE-AKD group has developed assays for several kidney injury biomarkers
and amassed novel translational research methodologies for biomarker development
and assessing biomarker performance. We have assembled multicenter longitudinal
prospective cohorts for translational research studies across several clinical
settings of acute kidney injury and chronic kidney disease supported by a large
biosample repository with associated bioinformatic methods. Leveraging both our
biosample repository and bioinformatics, we are positioned to support all phases
of translational research and biomarker development. Our studies have advanced
clinical management in several settings such as; expand deceased donor kidney
transplantation by reducing discard of kidneys with acute kidney injury, refine
the clinical definitions of perioperative AKI and hepatorenal syndrome and
identify patients with rapid decline in kidney function in diabetic kidney
disease. Our studies have also advanced the regulatory approvals of kidney
injury biomarkers.

We have created a collaborative environment supported by a strong research
network and infrastructure. We actively seek the perspective of patients,
communities, and other fields of research. The group also seeks to recruit and
train students and young scientists to translate pathophysiological mechanisms
into clinical practice that can directly improve patient outcomes.



Johns Hopkins Team Collaborators

MEET THE JOHNS HOPKINS TEAM



Teresa Chen, MD, MHS

Dr. Chen is an Adjunct Assistant Professor in the Division of Nephrology at the
Johns Hopkins University School of Medicine and Associate Faculty at the Welch
Center for Prevention, Epidemiology, and Clinical Research in Baltimore, MD. She
received her undergraduate degree in Molecular, Cellular, and Developmental
Biology from Yale University, medical degree from the University of Texas Health
Science Center at Houston, and Master of Health Science degree in Clinical
Epidemiology from the Johns Hopkins Bloomberg School of Public Health. She
completed her Internal Medicine residency at Barnes-Jewish Hospital/Washington
University in St. Louis and Nephrology fellowship at The Johns Hopkins Hospital.
Dr. Chen’s research interests have primarily been directed towards better
understanding chronic kidney disease and its related complications. She was
recently awarded a mentored clinical scientist research career development grant
(K08) from the NIH/NIDDK to study the role of immune activation in chronic
kidney disease progression and the interactive effects of immune activation with
APOL1 risk variants.






Celia Pamela Corona Villalobos, MD, MS

Dr. Corona-Villalobos is a Research Associate of medicine at the Johns Hopkins
University School of Medicine. Her area of research expertise is diffuse
interstitial fibrosis. Dr. Corona-Villalobos has extensive experience in cross
sectional imaging and cardiovascular MRI using novel functional imaging
techniques. She has validated new methods for detailed functional and
morphologic imaging assessment. Her research interest in renal fibrosis has
grown over the last couple of years when she joined the Division of Nephrology.
She is currently dedicated to develop biomarkers of kidney injury to predict AKI
Onset and Progression in HIV and collaborating with the kidney precision
medicine project.

Dr. Corona-Villalobos earned her M.D. at Universidad Panamericana in Mexico
City. She completed her residency training in Mexico with honors and performed a
Clinical Research Fellowship in the Department of Radiology at Johns Hopkins.
She has published 38 original research papers, 10 review articles and 3 book
chapters. Dr. Corona-Villalobos has also been the recipient of numerous awards,
including the Trainee Research Prize from the RSNA Scientific Assembly and
Annual Meeting.






Steven Menez, MD, MHS

Dr. Menez is an Instructor of Medicine at the Johns Hopkins University School of
Medicine. After completing his undergraduate studies at Georgetown University,
he remained at Johns Hopkins for his medical school education, internal medicine
residency, and nephrology fellowship. During his fellowship training, he
completed a Master of Health Science degree at the Johns Hopkins Bloomberg
School of Public Health in clinical epidemiology. Since July 2019 he has been a
member of the faculty in the Division of Nephrology.














Yumeng Wen, MD

Yumeng received his medical degree at Peking University Health Science Center in
Beijing, China and completed his medical residency at the Icahn School of
Medicine at Mount Sinai in New York. He is currently a nephrology fellow at
Johns Hopkins School of Medicine. His research interests are non-invasive
approaches to evaluate tubular injury and long-term outcomes of acute kidney
injury.


















Wassim Obeid, PhD

Wassim is a Research Associate in the Division of Nephrology at Johns Hopkins
University.

He has experience in developing, optimizing, and validating assays for
biomarkers of kidney disease. Wassim received his BS in Chemistry from the
American University of Beirut, Lebanon and his PhD from Old Dominion University,
Norfolk, VA.






Heather Thiessen Philbrook, MMath

Heather is a Research Associate in the Division of Nephrology at Johns Hopkins
University. She is a biostatistician with extensive experience in the design and
analysis of multi-center observational studies and the evaluation of biomarkers
in translational research. She has co-authored over 100 publications.

She completed her training (BMath Statistics, MMath Biostatistics) at the
University of Waterloo, Canada.










David Hu, MS

David is a biostatistician in the Division of Nephrology at Johns Hopkins
University. He received his Master's degree with a concentration in
biostatistics from North Carolina State University. He has previously worked as
a biostatistician for the University of North Carolina at Chapel Hill, and as a
data analyst at the American Institutes for Research in Washington, DC.














Prakash Nadkarni, MD

Prakash M. Nadkarni, MD is a Health Informatician who focuses on problems of
databases, data analytics, natural language processing and machine learning. He
is an elected Fellow of the American College of Medical Informatics and has been
an Associate Editor of the Journal of the American Medical Informatics
Association since 2005.






Jack Bitzel, BS

Jack is a Computer Science graduate with an emphasis on data management. He
received his BS from the University of Maryland, Baltimore County where he also
studied and received a degree in Music Technology.






















Ashley Wang, BA

Ashley is a Research Assistant in the Division of Nephrology at the Johns
Hopkins School of Medicine. She earned her B.A. in Biophysics with a minor in
Space Science & Engineering from Johns Hopkins University in 2022.














Jen Hernandez, BS

Jen is a Research Assistant in the Division of Nephrology at Johns Hopkins
School of Medicine. She earned her B.S. in Molecular & Cellular Biology from
Johns Hopkins University in 2022 and is currently a Masters of Science student
in Biotechnology from Johns Hopkins Krieger School of Arts & Sciences.



















Serena D'Souza, PhD

Serena is a Research Associate in the Division of Nephrology at Johns Hopkins
University. She has experience in devising and testing assays/protocols for
rapid detection of disease biomarkers/metabolites. She has worked on developing
Point of Care (PoC)/ Point of Use (PoU) prototypes and devices. Serena received
her Ph.D. in Animal Biotechnology from Mangalore University at St Aloysius
College (Autonomous), Mangalore, India. She completed her Post-Doctoral
Fellowship at IIT Bombay, India in the field of healthcare and diagnostic
solutions and continued to work there as a Research Scientist in the same field.











FORMER TEAM



Lauren Bernard, MHS

Lauren is a former Research Assistant in the Division of Nephrology at Johns
Hopkins School of Medicine. She earned her B.A. in Public Health Studies with
secondary majors in History of Medicine and Natural Sciences from Johns Hopkins
University and a Masters of Health Science degree in Epidemiology from Johns
Hopkins Bloomberg School of Public Health.














Alan Xu, BS

Alan is a former Research Assistant in the Division of Nephrology at the Johns
Hopkins University School of Medicine. He earned his B.S. in Biomedical
Engineering from Johns Hopkins University.


















Yaqi Jia, MD, MPH

Yaqi received his medical degree from Peking University Health Science Center,
China and Master of Public Health degree from Emory University, Atlanta, GA.

Yaqi was previously a Research Associate in the Division of Nephrology at Johns
Hopkins University. He is an experienced biostatistician and has co-authored
over 20 publications.














Rubab Malik, BA

Rubab is a former Research Assistant in the Division of Nephrology at the Johns
Hopkins University School of Medicine and continues to work on kidney transplant
projects with us.

Rubab earned her B.A. in Biophysics from Johns Hopkins University. She is
currently a medical student at Johns Hopkins University School of Medicine.














Caroline Liu, MHS

Caroline is a former Research Assistant in the Division of Nephrology and
continues to work on kidney transplant-related projects.

Caroline earned a B.A. in Public Health Studies from Johns Hopkins University
and a Master of Health Science degree from the Johns Hopkins Bloomberg School of
Public Health. She is currently a medical student at Icahn School of Medicine at
Mount Sinai.










Richard Liu, MHS

Richard is a former Research Assistant in the Division of Nephrology at Johns
Hopkins University. Richard earned a B.S. in Biomedical Engineering from Johns
Hopkins University and a Masters of Health Science degree from the Johns Hopkins
Bloomberg School of Public Health. Richard is interested in the application of
omics in precision medicine, and is applying to medical school.














Crystal Chang, BS

Crystal is a former Research Assistant in the Division of Nephrology at the
Johns Hopkins University School of Medicine. She earned her B.S. in Molecular
and Cellular Biology and Psychology from Johns Hopkins University.























COLLABORATORS

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TRANSLATIONAL RESEARCH INVESTIGATING BIOMARKER ENDPOINTS (TRIBE) STUDY

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DECEASED DONOR STUDY

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OVERVIEW OF PROJECTS


The group currently has 8 main projects, both ongoing and complete in data
collection. Below you will find information regarding each of them. If you are
interested in learning more or would like to work with these studies, you can
explore their individual pages or contact us.




ONGOING STUDIES


Translational Research in Biomarker Endpoints Consortium (TRIBE-AKI)
This consortium aims to investigate novel biomarkers in the detection of early
AKI after major cardiac surgery Read More

Deceased-Donor Biomarker Study
The shortage of kidneys for transplantation is a major dilemma. Efforts have
been taken to expand the organ supply by using kidneys from deceased donors.
However, deceased donor kidneys often come with risk factors for allograft
dysfunction, such as older age and acute kidney injury. This project directly
addresses these problems by studying biomarkers in kidney transplantation and
their associations with allograft outcomes. Read More

Novel Serum and Urinary Biomarkers of Diabetic Kidney Disease
Type 2 diabetes is a major public health problem worldwide. Progressive chronic
kidney disease (CKD) in type 2 diabetes is associated with significant morbidity
and mortality. The primary goal of this project is to develop novel urine
biomarkers to better predict progressive CKD in diabetics. Read More

Chronic Kidney Disease in Children
Progression of chronic kidney disease (CKD) in children leads to end stage renal
disease (ESRD), which is associated with mortality rates 30-150 times higher
than in the general pediatric population. In this project, novel biomarkers of
kidney injury, inflammation, repair, and fibrosis will be combined with
traditional measures to facilitate risk prediction of CKD progression. Read More

Kidney Precision Medicine Project (KPMP)
In the hopes of discovering therapeutic targets for acute kidney injury, which
currently has no specific therapy, the NIH/NIDDK has created the Kidney
Precision Medicine Project consortium. Read More




COMPLETED STUDIES


The ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney
Injury (ASSESS-AKI) Network
The ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney
Injury (ASSESS-AKI) Network is an epidemiological study of long term outcomes
following episodes of AKI. Read More

Kidney Biomarkers and the Differential Diagnosis and Prognosis of AKI in
Patients with Cirrhosis
Renal dysfunction is a common complication in hospitalized patients with
cirrhosis. The diagnosis of Type 1 Hepatorenal syndrome (HRS) is one of
exclusion and cannot be made until other causes of renal failure, particularly
acute tubular necrosis (ATN), are ruled out. In this prospective multicenter
cohort study, we are determining the efficacy of biomarkers in correctly
identifying ATN in hospitalized patients with cirrhosis and renal dysfunction,
thereby facilitation the diagnosis of Type 1 HRS.
Read More

PRESERVE Trial (Sub-Study 578) Biomarker Collection and Analysis Among
Participants
The PRESERVE trial (Prevention of Serious Adverse Events Following Angiography)
is a multicenter VA Healthcare System study that is led by Steven Weisbord, MD,
MSc and Paul Palevsky, MD, of the Pittsburgh VA Healthcare System. This study
seeks to collect and analyze serum and urine biomarkers in high-risk patients
undergoing coronary and non-coronary angiography to enhance our understanding of
their role in the setting of CIAKI.
Read More


Back to Project Overview


AKI IN CIRRHOSIS


Renal dysfunction is a common complication in hospitalized patients with
cirrhosis. The diagnosis of Type 1 Hepatorenal syndrome (HRS) is one of
exclusion and cannot be made until other causes of renal failure, particularly
acute tubular necrosis (ATN), are ruled out. The treatment for ATN is solely
supportive via hemodialysis. Differentiating between Type 1 HRS and ATN may be
difficult and often takes several days, as traditionally-used distinguishing
common urinary parameters may be altered in advanced liver disease.
Additionally, it is challenging to differentiate patients who are at risk for
AKI progression early in the course of their disease. Crucial delays in
diagnosis impair the ability to begin early treatment which can lead to
increased morbidity and mortality. Research in both experimental animals and
humans has identified urine biomarkers that are capable of detecting renal
tubular injury, a prerequisite for ATN with high degrees of sensitivity and
specificity which also associate with AKI progression. In this prospective
multicenter cohort study, we enrolled ~200 patients from four major academic
medical centers with cirrhosis and renal dysfunction. Our mission is twofold –
(1) to determine the ability of urinary IL-18, NGAL, KIM-1, and L-FABP to
correctly differentiate between Type 1 HRS and ATN and (2) to evaluate the
association of these biomarkers with AKI progression and mortality to identify
high risk patients.


Belcher JM, Garcia-Tsao G, Sanyal AJ, Bhogal H, Lim JK, Ansari N, Coca SG,
Parikh CR; TRIBE-AKI Consortium. Association of AKI with mortality and
complications in hospitalized patients with cirrhosis. Hepatology 2013;
57(2):753-62.



FUNDING INFORMATION FOR THIS PROJECT

This study was supported by the NIH/NIDDK (1R21-DK078714, “Identifying Acute
Tubular Necrosis in Cirrhosis Patients with Renal Dysfunction”)




PUBMED

Acute Kidney Injury in Cirrhosis
Back to Project Overview


PRESERVE SUB-STUDY 578


Contrast-induced acute kidney injury (CIAKI) is a common form of iatrogenic
renal disease that is associated with serious, adverse, short- and long-term
outcomes. While certain risk factors for CIAKI (e.g., chronic kidney disease,
heart failure) are well known, our current capacity to accurately predict which
patients are going to develop CIAKI based on these factors is limited. This
results in the need to implement resource-intensive preventive care on a
widespread basis, rather than in the sub-group of patients at greatest risk.
Furthermore, the clinical diagnosis of CIAKI, which is based on small increments
in serum creatinine (SCr), is delayed by up to 2-5 days following contrast
administration because elevations in SCr reflect the functional effects of renal
injury rather than tubular cell damage itself. Identifying serum and/or urine
biomarkers that effectively stratify patients' risk fr CIAKI and diagnose its
incipient stages could help concentrate the use of preventive care in those
patients most likely to derive benefit and facilitate the provision of
supportive care early after renal injury in order to mitigate further tubular
damage and attenuate the risk for serious, adverse, longer-term outcomes.

The PRESERVE trial (Prevention of Serious Adverse Events Following Angiography)
has been funded by the Department of Veterans Affairs to conduct a multicenter,
randomized, clinical trial of high-risk patients with chronic kidney disease
undergoing angiography to compare the effectiveness of intravenous (IV) isotonic
sodium bicarbonate with IV isotonic sodium chloride and oral N- acetylcysteine
with oral placebo for the prevention of serious adverse outcomes (i.e., death,
need for dialysis, persistent decline in kidney function at 90 days) associated
with CIAKI. Dr. Parikh served on the Executive Committee for the trial which
oversaw study operations, the performance of participating medical centers, and
data quality. He leveraged the substantial resources committed to this large
trial to establish a biorepository of blood and urine samples collected from
study participants. This biorepository, which will be available as a common-use
resource for future investigation of putative and yet-to-be identified
biomarkers of CIAKI, will be used for the current proposal to address the
following specific aims:


 * Aim 1 - To assess whether serum and/or urine biomarkers measured prior to
   angiography are able to stratify the risk of developing: a) CIAKI and; b)
   serious, adverse, longer-term outcomes (90-day death, need for dialysis,
   persistent renal injury)
 * Aim 2 - To assess whether serum and/or urine biomarkers measured 4 hours
   following angiography: a) permit the early diagnosis of CIAKI and; b) are
   able to stratify the risk of developing serious, adverse, longer-term
   outcomes (90-day death, need for dialysis, persistent renal injury)
 * Aim 3 - To examine the effect of the clinical trial interventions (i.e., IV
   isotonic sodium bicarbonate and oral N-acetylcysteine) on serum and urine
   biomarkers 4 hours following angiography and their capacity to predict the
   development of: a) CIAKI and; b) serious, adverse, longer-term outcomes



FUNDING INFORMATION FOR THIS PROJECT

The PRESERVE Trial was supported by the U.S. Department of Veterans Affairs
Office of Research and Development, the National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Health and Medical Research
Council of Australia

ClinicalTrials.gov Identifier: NCT01467466



PUBMED

PRESERVE Trial
back to Project Overview


TRANSLATIONAL RESEARCH INVESTIGATING BIOMARKER ENDPOINTS (TRIBE)


The Translational Research Investigating Biomarker Endpoints (TRIBE) consortium
aims to improve the outcomes and safety of cardiac surgery. This multicenter
prospective observational study is sponsored by the National Heart, Lung, and
Blood Institute to investigate novel biomarkers in the detection of early AKI
after major cardiac surgery. The main objective of the study is to determine
whether the novel biomarkers can be used as diagnostic tests to improve
pre-operative and post-operative risk-stratification of acute kidney injury
(AKI). Nine North American sites are participating in this projects. Over 3,000
patients, both adult and children, undergoing cardiac surgery were enrolled.
Blood and urine specimens were collected preoperatively and daily during the
first 5 days of hospitalization. Some key results from this study are given
below:

 1. Kidney injury biomarkers peaked earlier than serum creatinine and were
    associated with AKI.
    
    Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S,
    Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski
    CD. Postoperative biomarkers predict acute kidney injury and poor outcomes
    after adult cardiac surgery. J Am Soc Nephrol 2011; 22(9): 1748-1757.

 2. Mortality Rates approx. 3 years after cardiac surgery increased
    monotonically by tertile of urinary biomarkers in the patients with and
    without AKI during index hospitalization. The mortality rate in the highest
    tertile of urinary biomarkers of kidney injury in those without clinical AKI
    approximated the mortality rate in the lowest tertile of biomarkers in those
    with clinical AKI (except for L-FABP).
    
    Coca,S.G.; Garg,A.X.; Thiessen-Philbrook,H.; Koyner,J.L.; Patel,U.D.;
    Krumholz,H.M.; Shlipak,M.G.; Parikh,C.R. Urinary Biomarkers of AKI and
    Mortality 3 Years after Cardiac Surgery. J Am Soc Nephrol 2014;
    25(5):1063-71.

 3. Clinical AKI at the time of cardiac surgery is indicative of concurrent
    cardiovascular stress rather than an independent renal pathway for long-term
    adverse cardiovascular events.
    
    Coca,S.G.; Garg,A.X.; Thiessen-Philbrook,H.; Koyner,J.L.; Patel,U.D.;
    Krumholz,H.M.; Shlipak,M.G.; Parikh,C.R. Urinary Biomarkers of AKI and
    Mortality 3 Years after Cardiac Surgery. J Am Soc Nephrol 2014;
    25(5):1063-71.

FUNDING INFORMATION FOR THIS PROJECT

The TRIBE-AKI Consortium is supported by the NIH/NHLBI (R01HL085757, “Novel
Biomarkers in Cardiac Surgery to Detect Acute Kidney Injury”)



PUBMED

Biomarker Consortium in Acute Kidney Injury (TRIBE-AKI)
Back to Project Overview


DECEASED-DONOR STUDY


The shortage of kidneys for transplantation is a major dilemma, which has driven
efforts to expand the organ supply by using kidneys from deceased donors;
however these have higher risk factors for allograft dysfunction. Greater use of
kidneys with uncertain quality and the lack of precise tools to measure kidney
quality during procurement have led to high organ discard rates and increasing
numbers of transplant recipients with allograft dysfunction. Without precise
methods to assess kidney quality, it is likely that some useful kidneys are
discarded and some low-quality kidneys are transplanted with potentially harmful
results. This project both directly addresses these problems and advances the
goals of a recent FDA conference statement by studying biomarkers of
ischemia-reperfusion injury in kidney transplant and their associations with
allograft outcomes.

This biomarker study is one of the largest, applied, translational research
studies in kidney transplantation. In collaboration with several organ
procurement organizations, urine was collected from 1,679 deceased donors at the
time of procurement along with samples of transport solution for every pumped
kidney. We have measured known injury biomarkers including IL-18, NGAL, KIM-1,
LFABP, and cystatin C, with further plans to measure biomarkers of chronic
kidney disease, such as uromodulin, albumin, and TGF-ß. We are evaluating rates
of delayed graft function and allograft failure in recipients of these kidneys
by linkage to the United Network for Organ Sharing database. We are also
collecting detailed recipient data about estimated glomerular filtration rate,
immunosuppression, acute rejection, and other complications for two years after
transplant via chart review at several participating transplant centers. Our
ultimate goals are to help maximize the allocation of viable kidneys, develop
therapies for ischemia-reperfusion injury, and improve recipient outcomes
through the study of noninvasive deceased-donor biomarkers at the time of
procurement. Some key results from this study are given below:





FUNDING INFORMATION FOR THIS PROJECT

The Deceased Donor Study is supported by the NIH/NIDDK (R01DK093770, “Novel
Kidney Injury Tools in Deceased Organ Donation to Predict Graft Outcome”)


PUBMED

Deceased Donor Study
Back to Project Overview


DIABETIC KIDNEY DISEASE


Chronic kidney disease (CKD) and end stage renal diseases (ESRD) represent an
enormous burden in the United States and worldwide. Diabetic kidney disease
(DKD) is the single largest cause of CKD and ESRD. DKD is progressive and few
therapies are able to alter its course. Currently, clinical risk assessment of
DKD depends upon measures of estimated GFR (eGFR) and glomerular injury
(albuminuria). However, these two markers fall short of providing sufficient
risk stratification for progression to advanced DKD, ESRD and cardiovascular
(CV) events. Development of prognostic biomarkers to identify patients with a
high risk of progression will aide future clinical trials by serving to enrich
the enrollment with patients with a higher event rate, thereby allowing for a
reduced sample size to detect an intervention with a given relative risk
reduction. Moreover, there is an urgent need to identify the subgroups of
patients that are most likely to drive benefit from various forms of intensive
therapy (predictive biomarkers) and to identify better surrogate endpoints. By
leveraging the data and stored blood and urine samples from three large clinical
trials in patients with type 2 diabetes (VA- NEPHRON-D, ACCORD, and Sun-MACRO),
we will measure blood and urine biomarkers from diverse pathways including
inflammatory, glomerular, tubule injury, and tubulointerstitial fibrosis
markers.

There are three principal aims of this project:

 * Aim 1 - To derive and validate biomarker panels for prognosis of renal
   endpoints (GFR progression and dialysis)
 * Aim 2 - To derive and validate biomarker panels for prognosis of
   cardiovascular events and death
 * Aim 3 - To test for effect modification by biomarkers to determine if there
   were sub-groups that demonstrated benefit with various interventions employed
   in the trials (specifically, dual renin angiotensin aldosterone blockade,
   intensive glycemic control, or lower systolic blood pressure targets)


FUNDING INFORMATION FOR THIS PROJECT

Funding for this project comes from the NIH/NIDDK (U01DK106962, “Leveraging
Clinical Trials of Diabetic Kidney Disease to Advance Biomarkers”) and utilizes
blood and urine samples from two large clinical trials: VA- NEPHRON-D and ACCORD

 * VA-NEPHRON-D (ClinicalTrials.gov Identifier: NCT00555217)
 * ACCORD (ClinicalTrials.gov Identifier: NCT00000620)


PUBMED

Diabetic Kidney Disease
Back to Project Overview


ASSESSMENT, SERIAL EVALUATION, AND SUBSEQUENT SEQUELAE IN ACUTE KIDNEY INJURY
(ASSESS-AKI)


The ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney
Injury (ASSESS-AKI) Network is an epidemiological study of long term outcomes
following episodes of AKI. The AKI Network includes the Clinical Research
Centers at Kaiser Permanente of Northern California, the Vanderbilt University -
Validation of Acute Lung Injury Biomarkers for Diagnosis (VALID) Study, the
Translational Research Investigating Biomarker End-Points (TRIBE) consortium
(Yale University, University of Cincinnati, University of London, Ontario,
McGill University, Montreal), and a Data Coordinating Center at Penn State
University. The overall goals of ASSESS-AKI are to make significant
contributions to the field of AKI in the five following areas:
 * Establishing a diverse prospective parallel, matched cohort of adults and
   children with and without AKI.
 * Characterizing the short-term and long-term natural history of AKI based on
   current serum creatinine-based criteria.
 * Evaluating the incremental utility of novel blood and urine biomarkers to
   refine the diagnosis and prognosis of AKI.
 * Developing a prognostic risk score that integrates patient characteristics
   and biomarkers to help inform providers and patients about the risks of
   adverse events after an episode of AKI.
 * Identifying the subset of high-risk patients with AKI who could be targeted
   for future interventional clinical trials to improve outcomes after an
   episode of AKI.

The ASSESS-AKI Study will address the following Specific Aims through the
initiation and follow-up of a long-term prospective cohort of patients with and
without evidence of having AKI:

Primary Aims

 * Aim 1 — To determine whether patients who survive an episode of AKI have a
   greater risk of developing chronic kidney disease or faster progression of
   pre-existing chronic kidney disease than hospitalized patients without AKI
   after accounting for pre-existing level of kidney function and potential
   confounders.
 * Aim 2 — To determine whether patients who suffer an episode of AKI have a
   higher risk of death, cardiovascular events, and other adverse events after
   hospital discharge than matched patients who did not suffer AKI during
   hospitalization, after accounting for pre-existing level of kidney function
   and potential confounders.


Secondary Aims

 * Aim 3 — To evaluate the incremental value of serial measurements of several
   different blood and urine biomarkers for predicting short- and long-term
   clinical outcomes after an episode of AKI currently defined using a serum
   creatinine-based criteria.
 * Aim 4 — To assess whether severity and type of the AKI episode and the
   presence of pre-existing chronic kidney disease influence long-term risks of
   loss of kidney function, death, and cardiovascular events in patients with
   AKI.
 * Aim 5 — To determine if patients who completely recover kidney function
   within three months of an episode of AKI have a lower risk of adverse events
   than those patients with AKI whose recovery is incomplete.
 * Aim 6 — To develop a risk score incorporating demographic features, clinical
   factors, and/or biomarkers that accurately predicts outcomes after an episode
   of AKI.

More information on the project can be found here

FUNDING INFORMATION FOR THIS PROJECT

The ASSESS AKI study is sponsored by the NIDDK (U01DK082185, “Progression of
Acute Kidney Injury to Chronic Kidney Disease”)



PUBMED

ASSESS-AKI
Back to Project Overview


CHRONIC KIDNEY DISEASE IN CHILDREN


We have several ongoing epidemiologic and translational research studies that
examine risk factors, early diagnosis and prognosis of kidney disease in
children. Several of these are multicenter studies done in collaboration with
Yale University, University of Cincinnati and academic centers in Canada. The
following protocols had children enrolled and are being followed longitudinally.
Data and samples from these studies are available for ancillary studies:


 * In TRIBE-AKI, over 300 children undergoing congenital cardiac surgery were
   enrolled during hospitalization and the cohort has been followed for seven
   years through phone calls, medical chart review and data linkages.
 * The Assessment, Serial Evaluation, and Subsequent Sequelae in AKI
   (ASSESS-AKI) cohort has annual in-person follow-up of over 100 children for
   five years.
 * We are also measuring urine and serum biomarkers of kidney injury,
   inflammation, repair, and fibrosis from the samples of the children enrolled
   in the CKD in Children (CKiD) cohort


Greenberg JH, Whitlock R, Zhang WR, Thiessen-Philbrook HR, Zappitelli M,
Devarajan P, Eikelboom J, Kavsak PA, Devereaux PJ, Shortt C, Garg AX, Parikh CR;
TRIBE-AKI Consortium. Interleukin-6 and interleukin-10 as acute kidney injury
biomarkers in pediatric cardiac surgery. Pediatr Nephrol 2015; 30(9):1519-27.



FUNDING INFORMATION FOR THIS PROJECT

The TRIBE-AKI Consortium is supported by the NIH/NHLBI (R01HL085757, “Novel
Biomarkers in Cardiac Surgery to Detect Acute Kidney Injury”) and the ASSESS AKI
study is sponsored by the NIDDK (U01DK082185, “Progression of Acute Kidney
Injury to Chronic Kidney Disease”)


PUBMED

Chronic Kidney Disease in Children
Back to Project Overview


KIDNEY PRECISION MEDICINE PROJECT (KPMP)


In the hopes of discovering therapeutic targets for acute kidney injury, which
currently has no specific therapy, the NIH/NIDDK (National Institute of Diabetes
and Digestive and Kidney Diseases) has created the Kidney Precision Medicine
Program (KPMP) consortium. The KPMP project is composed of recruitment sites,
tissue interrogation sites, and central hubs. Together, the project intends to
create a kidney tissue atlas, define disease subgroups, inform critical cells
and pathways, and identify targets for novel therapies through kidney biopsies
from participants with AKI or CKD. More information on the Kidney Precision
Medicine Project can be found on the NIDDK and KPMP website.






FUNDING INFORMATION FOR THIS PROJECT

Funding for this project comes from the NIH-NIDDK (UG3DK114866, "AKI Matched
Phenotype Linked Evaluation with Tissue")


BIOREPOSITORY


The TRIBE Biorepository System (TBS) facilitates global sharing of specimens
among investigators to facilitate research leading to treatments and cures for
complex clinical syndromes by improving researchers' access to human
biospecimens. The scope of the biorepository includes providing guidance and
support for all aspects of translational research studies that involve human
biospecimens. This incorporates practices for the collection, handling, and
processing of specimens, models and templates for informed consent, ethical and
legal guidelines for handling human subject material for research and treatment,
and links to related publications and protocols and other useful information.
The TBS objectives can be summarized as follows:
 * Acquire biospecimens for the TRIBE Biorepository System by supporting
   recruitment in translational research protocols
 * Store DNA, plasma, serum, perfusates, urine, and other human biospecimens for
   future analysis at optimal temperatures
 * Establish and maintain secured databases for data storage and sample
   inventory
 * Share stored biological specimens to interested investigators for research
 * Development and maintenance of a quality assurance program with continuous
   auditing and real time reporting


BIOMARKER RESEARCH LABORATORY


The TRIBE Biomarker Laboratory (TBL) promotes discovery and analysis of novel
biomarkers in human bio specimens for translational research studies. The
laboratory utilizes a variety of instrumentation for sample analysis including a
compound light microscope, IDEXX SediVue DX automated urine microscope, BioTek
Synergy HT muli-mode microplate reader for ELISA analysis, and Meso Scale
Discovery (MSD) MESO QuickPlex SQ 120 instrument for electrochemiluminescence
detection of biomarkers in singleplex and multiplex assay formats. Additionally,
the laboratory operates an automated Rx Daytona clinical chemistry analyzer from
Randox Laboratories capable of measuring electrolytes, creatinine, albumin,
cystatin C, and a variety of other analytes listed below. The laboratory employs
Sorvall legend X1R bench top centrifuges, refrigerators, and freezers (-20°C and
-80°C) for processing and temporary storage of samples and reagents. Long term
sample storage is also offered through our biorepository.
Automated clinical chemistry analyzer assays
 * Electrolytes
 * Albumin
 * Urine albumin
 * Creatinine
 * Urea
 * Cystatin C
 * Full list of analytes


MESO QuickPlex SQ 120 instrument assays
 * 4-plex (IL-18, KIM-1, MCP-1, YKL-40)
 * 2-plex (Ang-1, Ang-2)
 * 2-plex (Eotaxin, Eotaxin-2)
 * 2-plex (IL-5, IL-9)
 * 2-plex (TNFR-1, TNFR-2)
 * 7-plex Kidney Injury Panel-5 (Albumin, B2M, Cystatin C, EGF, NGAL/LCN2,
   Osteopontin, Uromodulin)
 * 10-plex Proinflammatory Panel (IL-10, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8,
   TNF-α, IFN-γ, IL-12p70)
 * 7-plex Angiogenesis Panel (bFGF, Flt-1,PIGF, Tie-2, VEGF, VGEF-C,VGEF-D)
 * 3-plex (Galectin-3,NT-proBNP,ST-2)
 * Singleplex (NT-proBNP, Follistatin, Tie-1, NGAL)
 * Full list of analytes


INSTRUCTIONAL VIDEOS







METHODOLOGY WORK FOR BIOMARKER DEVELOPMENT

Novel biomarkers have great potential in preventing, detecting, and guiding
treatment of diseases. We have collaborated to develop methodologies that meet
the analytic demands for evaluating novel biomarkers.



PUBLICATIONS



PROGNOSTIC ENRICHMENT OF BIOMARKERS FOR CLINICAL TRIALS

We have developed an online tool which can be found here. This tool allows
investigators to evaluate biomarkers for prognostic enrichment of clinical
trials. Enriching clinical trials with prognostic biomarkers can help trials to
better evaluate an intervention in a patient population with a higher rate of
the unwanted event than the broader patient population. This higher event rate
translates to a lower sample size for the clinical trial. More details regarding
this tool can be found in the Clinical Trials paper: Evaluating biomarkers for
prognostic enrichment of clinical trials, which is available here.


SOMALOGIC INFORMATION

We have worked with SomaLogic, a protein biomarker discovery and clinical
diagnostics company. We have compared several blood and urine proteins by
immunoassay method and aptamer method (SomaLogic), the results of which can be
found here (see updated supplementary figures). Further details regarding the
assays and measurements can be found here.


CAREERS


 * We are seeking candidates with experiences in fields such as epidemiology and
   biostatistics. Persons interested in working in a dynamic translational
   research environment are encouraged to contact us to discuss career
   opportunities.
      
      
    * Postdoctoral Fellowship positions are available at Johns Hopkins
      University in translational research, biomarker development, clinical
      epidemiology, and biostatistics. Postdoctoral fellows are supported by NIH
      T32 Training Grants restricted to U.S. citizens and permanent residents.
      Please send curriculum vitae, statement of research training interest and
      email addresses of three references to: alindem1@jhmi.edu
      
      
    * Junior Faculty positions are available at the Division of Nephrology at
      the Johns Hopkins University School of Medicine. Please send curriculum
      vitae, statement of research training interest and email addresses of
      three references to: alindem1@jhmi.edu
      
      
    * Postgraduate research positions are available for 1-2 years in the
      Division of Nephrology. The position involves direct patient interaction,
      collection and processing of human blood and urine specimens, medical
      chart abstraction using electronic health records, study database entry,
      literature review, and reporting at team meetings. Requirements for the
      position include BA/BS in the life sciences or completion of the
      pre-medical track. Interested applicants should send a cover letter,
      resume and unofficial transcript to: alindem1@jhmi.edu
      
      

Gallery News

GALLERY

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2019 American Transplant Congress

Chirag Parikh receiving an Honorary Master of Arts Privatim, from President
Salovey

Chirag Parikh receiving the Young Investigator Award at the 2017 American
Society of Nephrology Kidney Week

Chirag Parikh’s Young Investigator Plenary Talk at the 2017 American Society of
Nephrology Kidney Week

2017 Deceased Donor Study Annual PI Meeting

Dr. Isaac Hall receives the 2nd Annual Iva Dostanic Award

Chirag Parikh with Kathleen F Kerr, PhD, Assoc. Professor, Biostats, University
of Washington

Jason Greenberg at the 2016 American Society of Nephrology Kidney Week

Sherry Mansour and Mark Perazella at the 2016 American Society of Nephrology
Kidney Week

Chirag Parikh receives the Jeff Gray Translating to Management Award at the 22nd
AKI & CRRT meeting in San Diego, March 2017.

Chirag Parikh receives the Young Investigator Award at the 2017 American Society
of Nephrology Kidney Week.

Chirag Parikh receives the 2018 ANIO Academic Excellence Award

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NEWS

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 * Dr. Parikh Named Director of Nephrology
 * Dr. Parikh Received Academic Excellence Award
 * Dr. Parikh Awarded the American Society of Nephrology 2017 Young Investigator
   Award
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 * Marathon Running and Kidney Damage: What Runners Should Know

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