Subject: RFA DK-9l-07 NIH Guide l/25/9l
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Thu, 24 Jan 91 10:55 EST

Hi Paul,
   The third of five.  Please post to the listserver as:
      RFADK-91-07.910125
        Thanks.    dottie
 ---------------------------- Text of forwarded message -----------------------
 
RESEARCH CENTER OF EXCELLENCE IN PEDIATRIC NEPHROLOGY AND
UROLOGY
 
RFA AVAILABLE:  DK-91-07
 
P.T. 04; K.W. 0785095, 0785220, 0770005
 
National Institute of Diabetes and Digestive and Kidney Diseases
 
Application Receipt Date:  April 2, 1991
 
The Division of Kidney, Urologic and Hematologic Diseases
(DKUHD) of the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) invites applications for a
pediatric kidney and urology research center grant (P50) to
be awarded in fiscal year 1991.  NIDDK anticipates the award
of one pediatric kidney and urology center grant from this
solicitation.
 
BACKGROUND
 
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.  Renal failure is more
frequent in adults, but the majority have their onset in
childhood.  A significant proportion of disorders that lead
to end-stage renal disease (ESRD) or cause severe metabolic
imbalances in children are inherited (or are presumed to be)
renal diseases.  The majority of inherited diseases seem to
result from single gene defects, providing an opportunity to
identify and study genes integral to normal renal and
urinary tract development and differentiation of normal
function.  Alport syndrome is an X-linked, dominant disorder
leading to end-stage glomerular disease and is due to
alterations in basement membrane collagen.  Polycystic
kidney disease, inherited as an autosomal recessive or
autosomal dominant trait, results in a gross distortion of
renal architecture and progressive renal insufficiency,
representing the single most common inherited renal disease
leading to ESRD.  Vitamin D resistant rickets, congenital
nephrogenic diabetes insipidus, and inherited forms of renal
tubular acidosis are manifestations of abnormalities in
specific renal tubular transport mechanisms and result in
severe metabolic disturbances.
 
To date, investigations have provided only detailed
morphologic descriptions of basement membrane abnormalities
in only a few of the inherited glomerular disorders and have
characterized the tubular pathology in the various inherited
cystic diseases.  However, at present, the understanding of
the molecular, cellular, and biochemical basis of these
disorders is lacking.
 
Developmental disorders of the kidney account for about one
third of all childhood diseases.  These disorders are often
of such severity that renal replacement therapy with
dialysis or renal transplantation is required during infancy
or childhood.  Examples of these disorders include renal
tubular cystic disease, dysplasia/hypoplasia, and congenital
obstructive uropathy.  They represent a most important group
of disorders because they constitute a major preventable cause
of chronic renal failure.  Vesicoureteral reflux and reflux
nephropathy, posterior urethral valves, prune belly
syndrome, and dysfunctional voiding and neurogenic bladder,
are the lower urinary tract diseases most commonly
encountered in the pediatric population.  These problems
affect different structures within the kidney and urinary
tract causing renal function derangements.  They often lead
to chronic renal disease and renal insufficiency resulting
ultimately in ESRD.  Previous studies have elucidated the
anatomical components of these disorders, however, the basic
mechanisms at the cellular and molecular levels resulting in
these disorders are not understood.
 
The many basic aspects of the renal and urinary tract
development have been defined only at the structural and
immunohistochemical level.  The cell and molecular biologic
aspects of the development of the glomerular, tubular, and
lower urinary tract system are incompletely defined.
Examples include the cellular derivation of the glomerular
mesangium, composition and characteristics of the embryonic
mesangial matrix and endothelial cells, events involved in
cellular communication and transformation, and mechanisms by
which differentiating and growing cells influence and are
influenced by the extracellular matrix.  Further definition
of those events occurring at the cellular and subcellular
levels during normal renal and urinary tract development
will greatly facilitate our understanding of renal and
urologic developmental disorders and may provide insights
into disease processes.
 
Very little is known about the control of normal kidney and
urologic function in the small pre-term or normal newborn
infant.  Similarly, the response of these systems to stress
or disease is not fully understood.  Enhanced understanding
of the biology of maturation and differentiation and the
developmental physiology of the kidney and urinary tract
should result in a better understanding of the management of
infants and children with renal/urological disease.  It is
reasonable to expect that further understanding of these
processes will result in the elucidation of the causes and
many of the important consequences of renal diseases that
affect both children and adults.
 
Chronic renal insufficiency and ESRD in children represents
a significant problem.  The needs and requirements and the
risks and complications associated with chronic renal
insufficiency in infants and children are very different
from those in the adult.  Growth retardation for example, is
seen in more than half the children with reduced renal
function.  Other serious complications include impaired
development, marked central nervous system dysfunction,
severe bone disease, presence of metabolic derangements,
early severe anemia leading to limited energy and exercise
capacity, hypertension, cardiovascular complications leading
to morbidity and mortality, and enhanced clinical response
to infection and stress.
 
Added risks directly associated with dialysis include blood
access related problems, recurrent infections such as
peritonitis, sepsis, and death.  Risks associated with
transplantation include graft loss due to acute or chronic
rejection and graft loss due to recurrent or de novo
disease, complications of the immunosuppressive therapy such
as infections, hypertension and cataracts, hypoglycemia,
which may be severe in children leading to seizures,
multiple technical problems, and even death.  Enhancing the
understanding of the basic mechanisms responsible for these
serious complications of renal insufficiency should result
in the greatest benefits for affected infants and children,
their families, and society in general.
 
The proposed multidisciplinary Research Center of Excellence
in Pediatric Nephrology and Urology should: (a) provide the
necessary expertise to investigate topical areas of research
related to the pathogenesis of pediatric kidney and urologic
diseases, some of which were referred to above; (b) represent
a stimulating scientific environment designed to secure
the appropriate exposure to a new generation of
investigators who should, in a continuum, enhance the scope of
the investigations initiated by the Center; and (c) bring
together the strength of multiple basic and clinical
disciplines to unravel the problems of kidney and urinary
tract disease processes that affect the pediatric patient
population or have their origins in childhood.
 
OBJECTIVES AND SCOPE
 
The emphases of this initiative are threefold:  (1) to
attract new scientific expertise into the study of the basic
mechanisms of pediatric kidney and urological diseases;  (2)
to encourage interdisciplinary research in this area; and
(3) to extend these basic investigations into areas that
will provide the background for future innovative clinical
and epidemiologic studies of the causes, therapy, and
prevention of pediatric kidney and urologic diseases and
disorders.  In approaching the study of these disease
processes, it is anticipated that extensive collaboration
will be required between  clinical and basic scientists such
as those in cell biology, molecular biology, immunology,
genetics, epidemiology, biochemistry, physiology, and
pathology.  Individual institutions with both basic and
clinical research capabilities are eligible to apply.
Interinstitutional collaborative research arrangements are
permitted and encouraged whenever appropriate.
 
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) identification and study of genes integral
to normal renal and urinary tract development and to
differentiation of renal function, including studies of
cellular derivation of the glomerular components,
composition, and characteristics of the embryonic
extracellular matrix and endothelial cells; (3) definition
of the events involved in cellular communication and
mechanisms by which differentiating and growing cells
influence and are influenced by the extracellular matrix;
(4) studies of the ontogeny of the glomerulus and various
nephron segments, growth, and renal function adaptation seen
as a continuum; (5) studies of neonatal risk factors
contributing to renal disease in children and identification
of early determinants and predisposing factors for renal
diseases initiated in childhood and expressed in adult life;
(6) investigation of the pathophysiology of progressive
nephron loss in renal diseases most frequently observed in
children, including primary glomerulopathies, congenital
nephrotic syndrome, polycystic kidney disease, IgA
nephropathy, hypertension, renal tubulopathies, and
pyelonephritis; (7) studies of the pathophysiology of renal
growth in children with renal disease and factors affecting
sex maturation and fertility, prior to and after
transplantation; (8) modulation of growth and development in
children receiving exogenous recombinant hormones, and
development of animal models to quantitate the contribution
of selective variables on growth retardation, (9) improved
methods for measuring renal function including glomerular
filtration rate in the pediatric population.
 
PEDIATRIC UROLOGY
 
Examples of representative areas of research appropriate for
investigation include:  (1) the pathophysiology of bladder
function and dysfunction in the pediatric population; (2)
the development of diagnostic methodology for the evaluation
of these defects; (3) the relationship between the
pathogenesis of dysfunction and the development of sequelae
in the adolescent and adult; (4) clinical studies of pre-
and neonatal bladder obstruction, enuresis, its
pathogenesis, treatment, and adult sequelae; (5) the effects
of urethral obstruction, such as posterior urethral valves
and meatal stenosis, on subsequent bladder function; (6) the
effect of bladder dysfunction on ureteral and renal
development and function; and the pathogenesis, treatment,
and sequelae of vesicoureteral reflux.
 
This initiative encourages applicants to utilize
technologies that explore the basic genetic, biochemical,
and cellular mechanisms involved in the development of
pediatric urological disorders.  Also encouraged are studies
of the basic physiology and pathophysiology of neonatal and
pediatric urological disorders.  The development of animal
or cellular models that can elucidate the basic mechanisms
in these disorders is also an area for potential
exploration.  The ontogeny of bladder function, penile
erectile function, renal and ureteral musculature function
should also be investigated at genetic, biochemical, and
cellular levels.  The association between pediatric
urological disorders and adult disorders is a fertile area
for investigation.  These studies would determine a
molecular or cellular basis for such adult disorders as
bladder dysfunction that have their origin in a pediatric
event.
 
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
 
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them.  This policy is intended to apply
to males and females of all ages.  If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
 
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group.  In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups.  However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
 
The rationale for studies on single minority population groups
should be provided.
 
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
 
The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
 
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
 
If the required information is not contained within the
application, the application will be returned.
 
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies.  If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
 
All applications for clinical research submitted to NIH are
required to address these policies.  NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
 
MECHANISM OF SUPPORT
 
NIDDK expects to award one pediatric kidney and urology
research center grant (P50) in fiscal year 1991 on a
competitive basis.  Foreign institutions are not eligible to
apply.  The anticipated award is for five years and is
contingent upon the availability of appropriated funds.  The
total amount of available funds to support this program is
anticipated to be no more than $750,000 per year.  No
applicant may request more than $750,000 in total costs
(both direct and indirect costs) in the initial budget
period.  Subsequent budget periods may include a standard
escalation factor.
 
Applications should include the following items:
 
A Table of Contents;
 
Rationale for the proposed Center and Statement of
Objectives;
 
Institutional Environment and Resources;
 
Organization and Administrative Structure of the Center;
 
Specific Managerial Responsibilities for the Center;
 
Travel funds in the proposed budget for an annual meeting of
Center Directors;
 
A description of the method for the replacement of the
Center Director (should the need arise);
 
A description of the procedure to be used for the
addition/deletion of cores and projects during the proposed
period of operation;
 
A description of the administrative relationship of the
Center to the Applicant Institution.
 
Consultation relating this Request for Applications (RFA) and
suggested guidelines for
preparation of applications may be obtained from:
 
Dr. Ralph L. Bain
Kidney and Urology Research Centers Program Director
DKUHD/NIDDK
Federal Building Room 102
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-8218
 
All potential applicants are strongly encouraged to consult
with the Program Director.
 
REVIEW PROCEDURES
 
Applications for an award of a research center grant will be
evaluated in a national competition by the NIH peer review
process.  Applications will be reviewed initially by a
special review committee convened by the NIDDK and reviewed
subsequently by the National Diabetes and Digestive and
Kidney Diseases Advisory Council.
 
Applications are unlikely to be reviewed by a site visit
team; therefore, the written application should be complete
so as to facilitate review without a site visit.  Extensive
additional material submitted subsequent to the stated
receipt date will not be accepted.
 
Receipt Date:              April 2, 1991
 
Council Review:    September 12-13, 1991
 
Earliest Award Date:  September 30, 1991
 
In cases where the number of applications is large compared
to the number of awards to be made, the NIH may conduct a
preliminary scientific peer review to eliminate those
applications that are clearly not competitive.  The NIH
will administratively withdraw from competition those
applications judged to be noncompetitive and so notify the
applicant and the institutional business official.  Those
applications judged to be both competitive and responsive to
the RFA will be further evaluated according to the review
criteria stated below.
 
REVIEW CRITERIA
 
A. The review criteria for individual research projects
include:
 
The scientific, technical, or medical significance and
originality of the proposed research;
 
The feasibility and adequacy of the experimental design;
 
The qualifications and research experience of the proposed
personnel;
 
The availability of resources necessary for the research;
 
The appropriateness of the budget and timetable in relation
to the scope of the proposed research.
 
B. The review criteria for scientific cores include;
 
The appropriateness and utility of the core to the proposed
Center; each core unit must provide facilities or services
to at least two research projects recommended for approval;
 
The quality of the proposed facilities or services including
administrative arrangements for utilizing the core;
 
The qualifications, experience, and commitment of the
personnel involved in the core;
 
The appropriateness of the budget.
 
C. The review criteria for the overall Center program include:
 
The scientific merit of the program as a whole;
 
The significance of the overall goals of the Center;
 
The cohesiveness and multidisciplinary scope of the Center
and the coordination and interrelationship of the projects
and cores to the common theme of the Center;
 
The leadership, scientific expertise, and commitment of the
proposed Center Director.
 
D. Administrative Considerations
 
For all Center applications the review will assess:
 
The institutional environment for and resources available to
Center investigators;
 
The institutional commitment to the proposed Center;
 
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 investigators;
 
The appropriateness of the budget in relation to the
proposed activities of the Center;
 
The adequacy of addressing the protection of human subjects,
animal welfare, and biohazard issues.
 
METHOD OF APPLYING
 
Potential applicants are urged to submit a letter of intent
to the Program Director by February 15, 1991, regarding their
application.  The letter of intent is nonbinding and is not
a precondition for an award.  The letter of intent should
include the name(s) of the Principal Investigator(s),
principal collaborators, a descriptive title of the proposed
research center, and the organization(s) involved.
Applications must be submitted using PHS Form 398 (Rev.
10/88).  The RFA label contained in the application kit must
be affixed to the bottom of the face page of the original
copy of the application.  Failure to use this label could
result in delayed processing and review of the application.
Complete line 2 of the application face page by inserting the
title and number of this RFA.
 
Mail the completed application (original and four copies)
to:
 
Application Receipt Office
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, MD  20892**
 
Simultaneously submit two copies under separate cover to:
 
Review Branch, NIDDK
5333 Westbard Avenue
Westwood Building Room 406
Bethesda, MD  20892
 
The special single receipt date for submissions in response
to this announcement is April 2, 1991, with earliest funding
September 30, 1991.
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.849, Kidney, Urologic, and Hematologic
Diseases Research.  Awards will be made under the authority
of the Public Health Service Act, Title III,Section 301
(Public Law 78-410, as amended; 42 USC 241) and administered
under PHS grant policies and Federal Regulations 42 CFR Part
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.