Full Text DK-96-003


NIH GUIDE, Volume 24, Number 33, September 22, 1995

RFA:  DK-96-003

P.T. 04

  Children (Patients) 
  Diagnosis, Medical 
  Disease Prevention+ 
  Treatment, Medical+ 

National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  May 23, 1996
Application Receipt Date:  July 23, 1996


This Request for Applications (RFA) invites investigators to submit
research applications for a Pediatric Research Center of Excellence
in Nephrology and Urology.  The purpose of the research center is to
attract scientific expertise into the study of urological and kidney
diseases of the pediatric population.  Studies designed to foster and
extend the development of new approaches into the causes, early
diagnoses, improved treatment, and where possible, prevention of
these diseases and disorders are appropriate.

Individual institutions with nephrology and urologic research
capabilities are eligible to apply.  Interinstitutional collaborative
research arrangements are also appropriate and encouraged.
Coordination for such arrangements must be evident and clearly
meaningful and appropriate for the research proposed.


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. This RFA,
Research Center of Excellence in Pediatric Nephrology and Urology, is
related to the priority area of debilitating childhood diseases.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202/512-1800).


Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and
eligible agencies of the Federal government.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.  Foreign institutions are not
eligible to apply.


Support of this program will be through the NIH specialized center
(P50) award.  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the
applicant.  Awards will be administered under PHS grants policy as
stated in the PHS Grants Policy Statement.

This RFA is a one-time solicitation.  The total requested project
period for an application submitted in response to this RFA may not
exceed five years.  The earliest anticipated award date is April 1,


The NIDDK expects to award up to two center grants (P50) for research
into pediatric nephrology and urologic disorders in fiscal year 1997.
The anticipated awards are for five years and are contingent upon the
availability of appropriated funds.  The total amount of available
funds to support this program is anticipated to be no more than $1.2
million per year.  No applicant may request more than $750,000 in
total costs (including both direct and indirect costs) in the initial
budget period.  A standard escalation factor may be used for
subsequent budget periods.

Two competing continuation applications are anticipated in response
to this RFA.  The budget for the first year of a competing
continuation application may be increased by 10 percent above the
last issued non-competing (Type 5) award.  In all cases, budgets are
not to exceed the $750,000 total cap.


Kidney and urologic diseases account for substantial and increasing
morbidity and financial burden in the United States.  They threaten
the health and well being of over 13 million Americans and accounted
for an estimated cost of at least $50 billion in 1990.  Although
considerable progress has been made in understanding the basic
physiology and pathophysiology of the normal renal and urinary
systems, there has been only limited progress in unraveling the
mechanisms of disease processes that have their origins in infancy
and childhood.  Developmental disorders of the kidney account for
about one-third of all childhood diseases.  These disorders are often
of such severity that renal dialysis or renal transplantation are
often required during infancy or childhood.  Examples of these
disorders in the very young patient include dysplasia(s) and
hypoplasia(s), cystic malformations, PKD, and congenital structural
abnormalities i.e., obstructive uropathy, vesicoureteral reflux and
the resulting reflux nephropathy.  Older children, more often,
develop end-stage renal failure from conditions such as immune
complex disease, hereditary nephropathy, focal segmental
glomerulosclerosis, IgA nephropathy, and the hemolytic uremic
syndrome.  The basic cellular and molecular mechanisms of the
majority of these disorders are poorly understood.  Progression often
occurs, even when the primary disease process have been thought to
have been adequately treated and the disorder appears to have become
inactive.  Therefore, a great need exists to better understand the
pathogenesis of these conditions, with the ultimate aim of improving

In pediatric nephrology, representative areas of research appropriate
for investigation include:

(1) studies of renal disorders of genetic and congenital origin that
may lead to progressive loss of renal function or cause severe
metabolic imbalances in children,

(2) further identification and study of genes and molecular events
involved in renal and urogenital morphogenesis and differentiation,
with a focus on the biology of maturation of the renal and urogenital

(3) studies of events involved in cellular signaling in renal
morphogenesis in health and disease, including the definition of
events involved in cellular communication and mechanisms by which
growing cells influence and are influenced by extracellular matrix
(the focus of these studies should include renal disorders),

(4) studies to understand the molecular mechanisms underlying the
renal hypertension in infants and children.  More specifically,
investigations addressing the development of renal, endocrine,
neurogenic, cardiogenic, and vascular mechanisms involved in blood
pressure control during fetal and post-natal development,

(5) studies addressing the use of gene targeting and transgenic
technologies to understand the cause of hypertension during

(6) studies addressing the relation of ethnicity, age and
hypertension in the pediatric population,

(7) studies addressing the short and long-term effects of
anti-hypertensive agents in infants and children,

(8) identification of risk factors and predisposing factors
contributing to renal disease progression in infants and children,

(9) studies addressing the etiology, pathophysiology, and treatment
strategies for end-stage renal disease in infants and young children,
including determinants of abnormal growth and development, the
development of animal models to quantitate the contribution of
selective variables on growth retardation in chronic renal failure,
the effects of exogenous recombinant hormones, and the role of uremia
in protein synthesis in young growing infants,

(10) cellular and molecular studies underlying the development and
progression of glomerulonephritis in children, including the
molecular changes affecting the glomeruli, alterations of the
basement membrane, mechanisms leading to proteinuria, and the
biochemistry of the nephron during pathological states.

In pediatric urology, representative areas of research investigation
include, but are not limited to:

(1) molecular, cellular and morphological studies on the development
of the genitourinary tract,

(2) in utero and fetal urological developmental abnormalities; the
effects of early vs. delayed intervention,

(3) the developmental immunobiology of the urinary tract,

(4) long term effects of early outlet obstruction on the developing

(5) environmental and maternal effects on the developing urogenital

(6) the relationship between pediatric bladder disorders, such as
enuresis, infections, etc. and adult bladder function,

(7) stromal and epithelial interactions, and the identification of
stem cells in urological system development,

(8) the neurobiology of the developing genitourinary tract.

The development of animal or cellular models which can elucidate the
basic molecular events in these disorders is encouraged.  The
ontogeny of bladder and ureteral function, prostate development, and
penile erectile function should also be investigated at the genetic,
biochemical and cellular levels.  The effects of urological surgical
procedures on subsequent developmental processes could also be


Successful applicants are expected to attend a yearly meeting of
Center Directors convened by the NIDDK.  Funds to support travel to
this meeting may be requested in the budget proposed for the center.


It is the policy of the NIH that women and members of minority groups
and their sub-populations 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 28, 1994 (FR 59 14508-14513), and reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS  Volume 23, Number 11,
March 18, 1994.

Investigators may also obtain copies from these sources or from the
program staff or contact person listed under INQUIRIES.  Program
staff may also provide additional relevant information concerning the


Prospective applicants are asked to submit, by May 23, 1996, a letter
of intent that includes a descriptive title of the proposed research,
the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of a subsequent application, the
information that it contains allows NIDDK staff to estimate the
potential review workload and avoid conflict of interest in the

The letter of intent is to be sent to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS.37F - MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7515


The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Grants Information, Division of Research Grants,
National Institutes of Health, 6701 Rockledge Drive, Room 3034, MSC
7762, Bethesda, MD 20892-7762, telephone 301/710-0267, email:

Applications must include the following items:

o  A Table of Contents;

o  A Rationale for the Proposed Center and a Statement of Objectives;

o  Institutional Environment and Resources;

o  Organization and Administrative Structure of the Center;

o  Specific Managerial Responsibilities for the Center;

o  Travel funds in the proposed budget for an annual meeting of
Center Directors;

o  A description of the method for the replacement of the Center
Director (should the need arise);

o  A description of the proposed research projects;

o  A description of the proposed cores;

o  A description of the procedure to be used for the
addition/deletion of cores and projects during the proposed period of

o  A description of the administrative relationship of the Center to
the applicant institution.

The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title and number must be typed on
line 2 of the face page of the application form and the YES box must
be marked.

Submit a signed, typewritten original of the application, including
the Checklist, plus three signed photocopies, in one package to:

6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At time of submission, two additional copies of the application must
be sent  to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, MSC 6600
Bethesda, MD  20892-6600

Applications must be received by July 23, 1996.  If an application is
received after that date, it will be returned to the applicant
without review.  Unsolicited material received after July 23, 1996
will not be accepted.


Upon receipt, applications will be initially reviewed for
completeness and responsiveness.  Incomplete and/or non-responsive
applications will be returned to the applicant without further
consideration.  Evaluation for responsiveness to the program
requirements and criteria stated in the RFA is an NIDDK staff

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIDDK 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 will
be discussed, assigned a priority score, and receive a second level
review by the National Diabetes and Digestive and Kidney Advisory

The review criteria for individual research projects include:

o  The scientific, technical or medical significance and originality
of the proposed research;

o  The feasibility and adequacy of the experimental design;

o  The qualifications and research experience of the proposed

o  The availability of resources necessary for the research;

o  The appropriateness of the budget and timetable in relation to the
scope of 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

The review criteria for scientific cores include:

o  The appropriateness and utility of the core to the proposed

o  Each core unit must provide facilities or services to at least two
research projects recommended for approval;

o  The quality of the proposed facilities or services including
administrative arrangements for utilizing the core;

o  The qualifications, experience, and commitment of the personnel
involved in the core;

o  The appropriateness of the budget.

The review criteria for the overall Center program include:

o  The scientific merit of the program as a whole;

o  The significance of the overall goals of the Center;

o  The cohesiveness and multi disciplinary scope of the Center and
the coordination and interrelationship of the projects and cores to
the common theme of the Center;

o  The leadership, scientific expertise, and commitment of the
proposed Center Director.

Administrative Considerations

o  The institutional environment for and resources available to
Center investigators;

o  The institutional commitment to the proposed Center;

o  The administrative leadership necessary to provide for the quality
control of supported projects in the Center, the allocation of funds,
and the ability to foster communication and cooperation among Center

o  The appropriateness of the budget in relation to the proposed
activities of the Center;

o  The adequacy of addressing the protection of human subjects,
animal welfare, and biohazard issues.

For the purposes of this RFA a distinction between a P50 grant and a
P01 grant is made as follows:

Research projects supported by the P50 center award are of uniformly
high scientific merit, and are generally related to central issues in
pediatric nephrologic and urologic diseases and disorders.  Each
project should be directed to the development of fundamental
knowledge leading to understanding disease processes and the design
of curative or preventative strategies.  The P50 grant mechanism
provides an opportunity to approach multi disciplinary basic research
in a synergistic fashion. Close cooperation, communication, and
collaboration among all center personnel of many professional
disciplines are characteristics of a successful P50 center.

In comparison, each research project of the P01 Program Project
Grant, also of uniformly high scientific merit must contribute to or
be directly related to a clearly defined central unifying theme of
the total research effort.  The projects should demonstrate essential
elements of unity and interdependence.


The earliest anticipated date of award is April 1, 1997.  Factors
that will be taken into consideration in making awards include the
scientific merit of the proposed Center as determined by peer review
and the availability of funds.


Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Ralph L. Bain, Ph.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-19 - MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7717
FAX:  (301) 480-3510
Email:  bainr@ep.niddk.nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Ms. Helen Ling
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive - MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8857
FAX:  (301) 480-3504
Email:  lingh@ep.niddk.nih.gov


This program is described in the Catalog of Federal Domestic
Assistance No. 93.849.  Awards are made 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

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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