RELEASE DATE:  May 27, 2004
RFA Number:   RFA-DK-04-011  

EXPIRATION DATE:  March 16, 2005

Department of Health and Human Services (DHHS)
National Institutes of Health (NIH)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) 
invites applications for Interdisciplinary Centers for Polycystic Kidney 
Disease Research (ICPKD) to expand the research infrastructure for both the 
autosomal dominant and autosomal recessive forms of polycystic kidney disease 
(ADPKD and ARPKD). These Centers are intended to attract a partnership of 
interdisciplinary research among investigators with scientific expertise who 
will use complementary and integrated approaches to study polycystic kidney 
A.  Background

PKD is the fourth leading cause of chronic kidney disease (CKD) in America, 
affecting approximately 500,000 people.  A striking feature of PKD is the 
variability with which it affects the patient.  Some develop only a modest 
number of renal cysts during their lifetime and may not be aware of being 
affected by this disorder.  Others develop a massive number of renal cysts 
and may reach renal failure at an early age.  It is not unusual for cysts to 
develop in the liver and within the systemic vasculature.  Evidence also 
indicates that in addition to documented cyst enlargement and interstitial 
fibrosis, apoptotic loss of non-cystic nephrons is a significant component of 
the pathology of PKD and may contribute to the progressive loss of renal 

Much progress has been made since the initial solicitation for PKD centers in 
1999. Examples include: improved animal models of disease due to increased 
understanding of the underlying molecular processes that result in cyst 
formation and growth; progress in understanding the role of the primary 
cilium in kidney tubule cyst formation; progress in understanding aneurysmal 
development in PKD.

The NIDDK has also funded two complementary multicenter clinical studies. In 
1999, the NIDDK funded the Consortium for Radiologic Imaging Studies of 
Polycystic Kidney Disease (CRISP) (RFA-DK-99-003) to determine whether 
changes in anatomic characteristics of the kidneys of patients with PKD will 
be useful in providing surrogate measures for disease progression.  
Preliminary findings from this group over the next several years might inform 
the designs of clinical trials in patients with PKD in the near future. Then, 
in 2001, the NIDDK established the PKD Clinical Trials Network to design and 
implement clinical trials to determine which pharmacologic agents might slow 
the progressive loss of function in PKD. The first large interventional 
clinical trial in this network, called HALT-PKD, will be a randomized trial 
of renin-angiotensin axis blockade in patients with PKD. 

Despite the progress noted above, however, many challenges remain in 
determining the genetic and pathophysiologic mechanisms of PKD.

B.  Research Goals and Scope

Proposed studies should foster and extend the development of new approaches 
into the causes, early diagnoses, and improved treatments for PKD. Therefore 
the following research goals are provided as potential areas of investigation 
that may be considered in developing innovative studies in an ICPKD.  These 
are provided as examples and should not be viewed as restrictive or all 

o Genetic Mechanisms:

Define primary and secondary mutagenic mechanisms of PKD1 & PKD2;

Localize and clone genes for other forms;

Identify genetic loci or genes that modify the PKD disease process;

Develop genomic reagents useful to these goals.

o Biology of Polycystin function

Define cellular and biochemical functions of PKD1-PKD2 and their downstream 

Identify genes responsible for renal cystic development and the progression 
of renal dysfunction in animal models.

o Physiological Studies

Develop physiological measurements in murine models of PKD;

o Pathogenesis and Progression

Define the basis for increased epithelial proliferation;

Define the role of inflammation in disease progression;

Define the role of the renal microvasculature in disease progression;

Develop novel markers or end points to monitor the progression of renal
dysfunction in PKD;

Develop imaging methods and other means to monitor renal dysfunction before 
the decline in GFR;

Further elucidate control of fluid secretion and accumulation in cysts.

o Innovative therapeutic strategies for ameliorating the initiation of cyst 
formation and course of progression of renal dysfunction in humans and in 
animal models

Explore treatments based on new pathogenic insights;

Explore innovative therapies to ameliorate the course of disease using
pharmacologic and gene therapeutic approaches in animal models;

Explore innovative therapies to ameliorate the course of disease using
pharmacologic therapeutic approaches in patients;

Identify and initiate innovative treatments in specific cohorts of patients 
with unusual clinical characteristics (including extra-renal manifestations 
of disease) or rates of progression of renal disease.

Description of a Center

An ICPKD must be an identifiable organizational unit within a single 
university medical center or within a consortium of cooperating institutions 
with a university affiliation.  The overall goal of an ICPKD is to bring 
together, in a cooperative, multidisciplinary and integrative manner, basic 
science and clinical investigators to enrich the effectiveness of research on 

Research Projects

The ICPKD grant consists of a cluster of individual, but interrelated, basic 
and / or clinical research projects, each with high scientific merit and 
clear research objectives. In the aggregate, the projects should be directed 
to the development of fundamental knowledge leading to understanding of the 
disease processes and the design of curative or preventive strategies.  

Core Facilities

Core facilities in an ICPKD are shared resources that enhance productivity or 
in other ways benefit a group of investigators working to accomplish the 
stated goals of the ICPKD.  Cores should be designed to furnish a group of 
investigators with some technique, service, determination, or instrumentation 
in a manner that will enhance the research in progress, consolidate manpower 
effort, and contribute to cost-effectiveness by providing a service at lower 
cost and possibly higher quality than if each investigator were to attempt 
the same activity individually.  

Examples of possible core resources that would be considered within the scope 
of this request for applications include the following:

o  Molecular biology core to supply oligonucleotides and provide automated 
DNA sequencing capability;

o  Animal models core to develop, breed, and maintain animal models for 
diseases of PKD interest, which can be used to improve understanding of the 
human forms of the disease;

o  Tissue culture core for the harvest, cultivation, infection and handling 
of large numbers of cells;

o Imaging core for assessing the ability to tract disease progression;

o  Other cores needed to characterize gene transfer systems.

These cores are not listed in any particular order, nor should they be 
construed to represent a comprehensive list of cores that could be fostered 
under this program.

C.  Pilot and Feasibility (P&F) Program

The Pilot and Feasibility (P&F) program is a vital component of the P50 
Center grant programs. P&F projects can have a major impact on the visibility 
of a Center at an institution and should provide a means of developing new 
ideas and encouraging new members to join the Center. The NIDDK also strongly 
encourages the use of P&F support to foster bench to bedside translation of 
fundamental discoveries. The National Center for Research Resources (NCRR) 
supports approximately 80 General Clinical Research Centers (GCRCs) 
nationwide, which provide services and resources to enhance clinical research 
( By establishing ties with the 
institution's GCRC, the P&F project funds could be leveraged effectively to 
pursue such projects. Each pilot and feasibility study award is intended to 
provide a modest amount of support, not to exceed $50,000 direct costs 
(excluding Fiscal and Administrative costs) 
(, for a 
duration not to exceed two years, which will allow an investigator the 
opportunity to develop sufficient preliminary data to provide the basis for 
an application for independent research support. 

This RFA will use NIH Specialized Centers of Research (P50) award mechanism.  
As an applicant you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project will 
compete with all investigator-initiated applications and will be reviewed 
according to the customary peer review procedures. The anticipated award date 
is October 2005. Applications that are not funded in the competition 
described in this RFA may be resubmitted as NEW investigator-initiated 
applications using the standard receipt dates for NEW applications described 
in the instructions to the PHS 398 application.  

This RFA uses just-in-time concepts.  It also uses the non-modular budgeting 
formats.  This program does not require cost sharing as defined in the 
current NIH Grants Policy Statement at 

The NIDDK intends to commit approximately $1.5 million in FY 2005 to fund two 
new and/or competitive continuation grants in response to this RFA. An 
applicant may request a project period of up to five years and a budget for 
direct costs of up to $750,000 per year (excluding Fiscal and Administrative 
costs) (  
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and duration of 
each award will also vary. Although the financial plans of the IC(s) provide 
support for this program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of meritorious 
You may submit (an) application(s) if your institution has any of the 
following characteristics:
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic institutions/organizations
o Foreign institutions are not eligible to apply. 

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   


Successful applicants, during the second year of the award and each year 
thereafter, may be expected to attend a yearly meeting of PKD Centers 
Directors convened by the NIDDK.  Funds for this activity may be requested in 
the budget proposed for the respective center.

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 

o Direct your questions about scientific/research issues to:

Marva M. Moxey-Mims, M.D.
Pediatric Nephrology & Renal Centers Programs Director
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 639
Bethesda, Maryland 20892-5458
Telephone:  (301) 594-7717
FAX:  (301) 480-3510

o Direct your questions about peer review issues to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes, Digestive, and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, Maryland 20892-5452 
Telephone: (301) 594-8897
Fax:   (301) 480-3505

o Direct your questions about financial or grants management matters to:

Carolyn Kofa
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 727
Bethesda, Maryland 20892-5452
Telephone:  (301) 594-7687
FAX:  (301) 480-3504
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

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 
plan the review.
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone:  (301) 594-8897
FAX:  (301) 480-3505


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a DUN and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 document is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
SUPPLEMENTARY INSTRUCTIONS: Applicants should consult the “Administrative 
Guidelines for Centers for Polycystic Kidney Disease Research” located at:
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  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. The RFA label is also available at:
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
At the time of submission, two additional copies of the application and all 
copies of the appendix material must be sent to:

Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD  20892-5452
(for express/courier service: Bethesda, MD 20817)
APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the applicant 
without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application.  

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIDDK. Incomplete applications will not be reviewed. 
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 the review criteria stated below.  
As part of the initial merit review, all applications will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Diabetes and Digestive and 
Kidney Diseases Advisory Council. 

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application’s overall score, weighting them as appropriate for each 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 

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?

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?

INNOVATION: Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

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)?

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?  

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 

be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  


Sharing Research Data 

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research must include a data sharing plan in their application. The 
reasonableness of the data sharing plan or the rationale for not sharing 
research data will be assessed by the reviewers. However, reviewers will not 
factor the proposed data sharing plan into the determination of scientific 
merit or priority score.
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.


Letter of Intent Receipt Date:          February 15, 2005
Application Receipt Date:               March 15, 2005
Peer Review Date:                       June 2005
Council Review:                         September 2005
Earliest Anticipated Start Date:        October 2005


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained. 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.   (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a 
plan for data sharing or state why this is not possible.  Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research. This policy results from the NIH Revitalization Act of 1993 (Section 
492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
a complete copy of the updated Guidelines are available at  
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 

The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at

policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at and at  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see  
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s) for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 

Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information”, 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 
2010," a PHS-led national activity for setting priority areas. This RFA is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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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