Full Text PA-97-108
 
STUDIES OF MOLECULAR MECHANISMS OF RENAL INJURY AND RECOVERY
 
NIH GUIDE, Volume 26, Number 31, September 19, 1997
 
PA NUMBER: PA-97-108
 
P.T.


Keywords: 

 
National Institute of Diabetes and Digestive and Kidney Diseases
 
PURPOSE
 
The Division of Kidney, Urologic and Hematologic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases
announces a continuing interest in receiving research project
applications on the above subject.
 
The need for this initiative was recognized, in part, as a result of
the recommendations emanating from the conference held at the NIH in
May, 1996, organized and sponsored by the DKUHD, titled "Acute Renal
Failure in the 21st Century."   A report from the meeting summarized
recommendations from the participants, which included a set of
published recommendations for patient management and outcomes
assessment (AJKD, Vol. 29, # 5, 793-799, 1997).  Also advocated was
the development and establishment of a multi-center database as one
mechanism to facilitate cooperative multi-center studies.  It was
further recommended that research initiatives be undertaken to
enhance the transfer of new body of knowledge derived from basic
studies and laboratory investigation (including cellular and
molecular aspects of tissue injury, changes in cell differentiation,
cell repair mechanisms, cell death and organ recovery) to the
clinical management of ARF.  With a more complete understanding of
these fundamental aspects of the pathophysiological response by the
kidney to ARF, it is anticipated that new therapies and potentially
novel uses of replacement therapies may emerge.  Additional insight
in this field will likely emerge from another conference convened by
the American Society of Nephrology, with support from the NIDDK
("Mechanisms of Tissue Injury and Repair") that will be convened
November 1997.
 
HEALTHY PEOPLE 2000
 
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas. Potential
applicants may obtain a copy of "Healthy People 2000 (Full Report:
Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, D.C. 20402-9325 (telephone
202-783-3238).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic for-profit and nonprofit
organizations, public and private, such as universities, colleges,
hospitals, and laboratories, units of State and local governments,
and eligible agencies of the Federal Government.   Although
applications from foreign laboratories are excluded, collaborative
efforts with foreign laboratories may be expedited as subcomponents
(subcontracts) of applications submitted through domestic
institutions.  Racial/ethnic minority individuals, women, and persons
with disabilities are encouraged to apply as principal investigators.
 
MECHANISM OF SUPPORT
 
Support for this program will be through the grant-in-aid and will be
governed by the current policies of grant programs of the National
Institutes of Health.  New applications may be submitted for the
traditional, investigator-initiated research project grant (R01),
First Independent Research Support and Transition [FIRST (R29)]
awards.  On a limited basis, and only following extensive
consultation with NIDDK Program Staff will program project (P01) and
the NIH Investigator-Initiated Interactive Research Project Grants
(IRPG) submissions be entertained.  Within the framework of the above
support mechanisms, the applicants are expected to plan, direct, and
conduct the research programs.  The project periods during which the
research will be conducted should adequately reflect the time
required to accomplish the stated goals and be consistent with the
policies for the respective support mechanisms.  Support will be
provided for up to 5 years (renewal for subsequent periods) subject
to the availability of funds and progress achieved.
 
FUNDS AVAILABLE
 
There are no set aside funds for this solicitation and therefore all
applications submitted in response to this PA compete for the dollars
available during any current or subsequent fiscal year.  New
applications in response to this announcement are to be submitted at
the regularly published receipt dates of February 1, June 1 and
October 1 (exceptions are IRPGs, which have receipt dates of February
15, June 15 and October 15).
 
RESEARCH OBJECTIVES
 
The purpose of this initiative is to stimulate research into the
pathophysiological response by the kidney to acute renal failure
(ARF), which can lead to new therapies and novel uses of replacement
therapies in the clinical setting.  To that end, the following are
some of the objectives of this solicitation that are being
encouraged, which are examples only and should not be viewed as all
inclusive:
 
o  Studies addressing the effect on function of renal cells of
ischemia/hypoxia induced alterations in cytoskeletal proteins and ATP
depletion;
 
o   Studies to determine the role of integrins and protein kinases in
the cascade of events leading to acute tubular obstruction/necrosis;
 
o  Studies to evaluate the role of blood pressure maintenance in
recovery from ARF;
 
o  Studies on nephrotoxins, including antibiotics, heavy metals,
oxidants, and halogenated hydrocarbons;
 
o  Clinical studies to evaluate the effects of  hormones (e.g., ANP,
a-MSH, prostaglandins, nitric oxide, endothelin) and growth factors
or their inhibitors on prevention and recovery from ARF;
 
o  Post-transplantation ARF: Studies to protect renal allografts and
to evaluate the relationship between delayed graft function and long-
term outcome;
 
o  Studies that will identify the regulatory mechanism(s) in
regeneration of the kidney following ischemic or toxic insults and
identify regeneration-specific gene pathways;
 
o  Studies to evaluate the effects of intermittent hemodialysis (IHD)
and continuous hemodialysis on residual kidney function in critically
ill patients with ARF;
 
o  Studies to ascertain the role of ARF in multiorgan dysfunction
syndrome (MOD);
 
o  Studies that will determine appropriate nutritional support in the
ARF patient;
 
o  Studies to identify appropriate characteristics of dialysis
membranes for renal replacement in ARF;
 
o  Proposals that will lead to the development of a cooperative
multicenter database for coordination of studies in ARF;
 
o  Studies that will identify methods to enhance endogenous pathways
within the kidney that protect against injury or stimulate repair;
 
o  Studies that will lead to the development and validation of
severity of illness scores in ARF patients;
 
o  Studies that will lead to markers for early detection of renal
injury.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
Whenever human subjects may be used in research proposed in
applications in response to this PA, the following language is
required:
 
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 20, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Application kits are
available at most institutional offices of sponsored research, or may
be obtained from the Grants Information Office, Office of Extramural
Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
301-710-0267, email: asknih@odrockm1.od.nih.gov.
 
The program announcement title and number must be typed on line 2 of
the face page of the application form and the YES box must be marked.
 
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award applications submitted without the required
number of reference letters will be considered incomplete and will be
returned without review.
Prospective applicants considering the submission of a
program project applications should contact the program official
listed under INQUIRIES to obtain the booklet "Guidelines for NIDDK
Program Project Grants."  Those considering the submission of
Interactive Investigator- Initiated Research Project Grants should
refer to the publication "Guidelines: NIH Investigator-Initiated
Interactive Research Project Grant" (NIH Guide for Grants and
Contracts, Volume 24, Number 35, October 6, 1995, PA-96-001).
 
Mail the signed, original, single-sided application, along with five
exact, single-sided copies and five collated sets of appendix
materials to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040-MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
 
REVIEW CONSIDERATIONS
 
Applications will be assigned on the basis of established Public
Health Service referral guidelines.  Applications that are complete
will be evaluated for scientific and technical merit by an
appropriate peer review group convened in accordance with NIH peer
review procedures. As part of the initial merit review, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.
 
Review Criteria
 
o Significance:  Does this study address an important problem?  If
the aims of the application are achieved, how will scientific
knowledge be advanced?  What will be the effect of these studies on
the concepts or methods that drive this field?
 
o Approach:  Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to
the aims of the project?  Does the applicant acknowledge potential
problem areas and consider alternative tactics?
 
o Innovation:  Does the project employ novel concepts, approaches or
method? Are the aims original and innovative?  Does the project
challenge existing paradigms or develop new methodologies or
technologies?
 
o Investigator:  Is the investigator appropriately trained and well
suited to carry out this work?  Is the work proposed appropriate to
the experience level of the principal investigator and other
researchers (if any)?
 
o Environment:  Does the scientific environment in which the work
will be done contribute to the probability of success?  Do the
proposed experiments take advantage of unique features of the
scientific environment or employ
 
useful collaborative arrangements?  Is there evidence of
institutional support?
 
o  Appropriateness of the proposed budget and duration in relation to
the proposed research.
 
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects, and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other approved
applications assigned to the National Institute of Diabetes and
Digestive and Kidney Diseases. The following will be considered in
making funding decisions:
 
o Quality of the proposed project as determined by peer review
o Availability of funds
o Program priority.
 
INQUIRIES
 
Inquiries are encouraged.  The opportunity to clarify any
issues or questions from potential applicants is welcome.
 
Inquiries regarding programmatic issues may be directed
to:
 
M. James Scherbenske, Ph.D.
Division of Kidney, Urologic and Hematologic Diseases
NIDDK
Natcher Building, Room 6AS.19E
45 CENTER DR MSC 6600
BETHESDA, MD 20892-6600
Telephone:  (301) 594-7719
FAX:  (301) 480-3510
E-mail:  scherbensk@extra.niddk.nih.gov
 
Direct inquiries regarding fiscal and administrative
matters to:
 
Mrs. Helen Y.S. Ling
Grants Management Specialist
Division of  Extramural Activities
NIDDK
Natcher Building, Room 6AN.44F
45 CENTER DR MSC 6600
BETHESDA, MD 20892-6600
Telephone:  (301) 594-8857
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.XXX (insert 93.847 for DEM, 93.848 for DDN and
93.849 for KUH).  Awards are under authorization of the Public Health
Service Act, Title IV, Part A (Public Law 78-410, as amended by
Public Law 99-158, 42 USC 241 and 285) and administered under PHS
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74.
This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children. This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
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