RELEASE DATE:  March 27, 2003

PA NUMBER:  PA-03-091

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through using 
the electronic SF424 (R&R) application. Accordingly, this funding opportunity 
expires on the date indicated below. Replacement R21 (PA-06-164), R01 (PA-06-163), 
funding opportunity announcements have been issued for the submission date of June 1,
2006 and submission dates thereafter. 

See NOT-OD-06-048 for information on May 1, 2006 Submission Date for AIDS and 
AIDS-related R03 and R21 Applications.

EXPIRATION DATE:  March 2, 2006

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

93.849  NIDDK Kidney Diseases, Urology and Hematology Research


o Purpose of the PA
o Research Objectives
o Mechanisms of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations


The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
invites investigator-initiated research project applications for ancillary 
studies to ongoing or completed clinical trials and epidemiological studies 
of kidney disease as well as clinical trials and epidemiological studies for 
other diseases or populations that lend themselves to the study of kidney 
disease.  These studies may range from new analyses of existing datasets of 
completed studies to additional collection of data and biological specimens 
in ongoing investigations.  The goal of these studies should be to extend our 
understanding of the risk factors for developing kidney disease and their 
associated co-morbid illnesses such as malnutrition and cardiovascular 
disease, factors associated with rapid decline in kidney function among 
persons with chronic kidney disease, and the impact of these diseases on 
quality of life and mental and physical functioning. Studies of biomarkers 
for patients with acute renal failure and other kidney diseases, for example, 
are also appropriate topics for further investigation.  Studies ancillary to 
both government and non-government supported clinical trials and 
epidemiological studies are encouraged.  Analysis of large public access 
databases and other databases is also encouraged.



The public health and economic burden of chronic kidney disease in the United 
States is substantial.  Diabetes and hypertension are the main causes of 
chronic kidney disease in this country.  The number of new cases of end-stage 
kidney disease in 2000 was over 96,000 and the number of patients undergoing 
treatment was over 370,000.  As the United States population continues to age 
it is anticipated that the number of new cases of end-stage kidney disease 
will also increase.  It has been estimated that approximately 20,000,000 
people have chronic kidney disease in this country.  

Acute renal failure in hospitalized patients is also a significant problem in 
the United States, ranging from 1-15% of hospitalized patients.  Medical 
management of acute renal failure has traditionally consisted primarily of 
supportive care, with renal replacement therapy for the most severe cases.  
Despite such interventions in acute renal failure, however, mortality rates 
in affected patients remain very high (>50% in some series).

Over the past two decades the NIDDK has conducted a number of multi-center 
clinical trials studying potential factors that ameliorate the progression of 
chronic kidney disease.  For example, a clinical trial completed in 1994, The 
Modification of Diet in Renal Disease (MDRD) Study examined the effects of a 
low-protein diet and a lower than usual level of blood pressure.  Recently, 
the African American Study of Kidney Disease (AASK) Trial reported the 
results of treatment with a low blood pressure goal and three different anti-
hypertensive drug regimens on the progression of hypertensive kidney disease 
among nearly 1,200 African Americans. (The AASK Trial participants are now 
part of a 5-year prospective cohort study).  Likewise, clinical trials of 
diabetic kidney disease, most recently the Reduction in Endpoints in NIDDM 
with the A2 Receptor Antagonist Losartan (RENAAL) and the Irbesartan Diabetic 
Nephropathy Trial (IDNT), have been supported by the private sector.  Large-
scale multi-center clinical trials supported by the NIDDK with patients with 
end-stage kidney disease have also been completed (The Hemodialysis Study) or 
have been recently initiated (The Dialysis Access Consortium).  A major 
clinical trial of type II diabetes supported by the NIDDK, the Look AHEAD, is 
ongoing whereas the Diabetes Prevention Program, also supported by the NIDDK 
and completed in 2001, continues as a prospective study.  A multi-center 
randomized clinical trial among patients with acute renal failure, co-
sponsored by the Department of Veterans Affairs and the NIDDK, is now 

A number of epidemiological studies conducted among patients with chronic 
kidney disease have focused on patients who have reached end-stage kidney 
disease.  Many of these studies have been conducted through the United States 
Renal Data System (USRDS) supported by the NIDDK.  Some insight about 
selected risk factors for chronic kidney disease prior to end-stage has been 
obtained through epidemiological studies conducted to characterize other 
diseases or examine other populations not selected for chronic kidney disease 
which included measures of kidney function, primarily serum creatinine, or 
permitted the linking of medical records to ascertain death and/or end-stage 
renal disease treatment.  Only recently, the NIDDK established a prospective 
cohort study, the Chronic Renal Insufficiency Cohort (CRIC) Study, to examine 
the risk factors for progression of chronic kidney disease and to identify 
risk factors for cardiovascular disease in adult patients with reduced kidney 
function.  Similarly, the NIDDK plans to establish a prospective cohort study 
of children with chronic kidney disease this year.

The studies noted above and others provide the potential to learn more about 
risk factors for progression of chronic kidney disease and associated co-
morbid illnesses and factors associated with mortality for acute renal 
failure. In many cases these studies have large databases and patient 
samples, lending themselves to new analyses and assays.  While study 
investigators have been actively working on the NIDDK-supported databases and 
samples as well as developing ancillary studies for ongoing studies, this 
Program Announcement seeks to increase the number of ancillary studies and 
stimulate use of existing government supported databases and samples by a 
wider community of investigators.  It is also envisioned that this Program 
Announcement will encourage investigators to conduct ancillary studies in 
non-government supported studies as well as permit analyses of large public 
and private databases.

While it is anticipated that there will be a wide range of opportunities for 
basic and clinical/epidemiological research by accessing data and biological 
samples from these studies at least the following types of investigations are 

1. New analyses of data from completed studies;
2. Assay of archived biological samples from completed and ongoing studies;
3. Collection of new data and samples from ongoing studies;
4. New data collection from completed studies;
5. Combination of data from different studies to perform meta analyses;
6. Analysis of public and other accessible databases.


This Program Announcement will use the NIH research project grant (R01) and 
exploratory/developmental grant (R21) award mechanisms.  The R21 may 
generally not exceed $275,000 direct costs for two years.  However, the 
requested budgets for an R21 can exceed this cap to accommodate F&A costs for 
subcontracts to the project.  The research project (R01) awards provide up to 
five years of funding that is commensurate with the science proposed. 
Responsibility for the planning, direction and execution of the proposed 
research project will be solely that of the applicant.  Awards will be 
administered under the NIH grants policy as stated in the NIH Grants Policy 
Statement, March 2001, available from the internet at

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise follow the instructions for non-
modular research grant applications.  This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at    


You may submit an application(s) if your institution has any of the following 

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 or foreign
o Faith-based or community-based organizations 


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.   


It is required that each applicant provides documentation at the time of 
grant submission that he/she has received approval from the appropriate 
governing body of the respective study to conduct the proposed ancillary 
study.  In cases where large public access databases are proposed for 
investigation, applicants must indicate that the database is available for 
their use.


We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants. Inquiries may fall into two 
areas: scientific/research and financial or grants management issues: 

o Direct your questions about scientific/research issues to:

John W. Kusek, Ph.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 617
Bethesda, Maryland 20892-5458
Telephone:  301-594-7735
Fax:  301-480-3510
E mail: 

Direct your questions about financial or grants management matters to:

Teresa Farris Marquette
Senior Grants Management Specialist
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 728
Bethesda, Maryland 20892-5456
Telephone:  301-594-7682
Fax:  301-4803504
E mail:


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at  Application 
deadlines are also indicated in the PHS 398 application kit.

application instructions outlined in the PHS 398 application kit are to be 
followed, with the following requirements for R21 applications:  

1. R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME" 
concepts, with direct costs requested in $25,000 modules, up to the total 
direct costs limit of $275,000 for the two-year period.  

2. Although preliminary data are not required for an R21 application, they 
may be included.

3. Sections a-d of the Research Plan of the R21 application may not exceed 
15 pages, including tables and figures.  

4. R21 appendix materials should be limited, as is consistent with the 
exploratory nature of the R21 mechanism, and should not be used to circumvent 
the normal page limitations for the research plan.  Copies of appendix 
material will only be provided to the primary reviewers of the application 
and will not be reproduced for wider distribution.  The following materials 
may be included in the appendix:

o  Up to five publications, including manuscripts (accepted for publication), 
abstracts, patents, or other printed materials directly relevant to the 
project.  These may be stapled as sets.

o  Surveys, questionnaires, data collection instruments, and clinical 
protocols.  These may be stapled as sets.

o  Original glossy photographs or color images of gels, micrographs, etc., 
provided that a photocopy (may be reduced in size) is also included within 
the 15 page limit of items a-d of the research plan.

up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at

Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting  $500,000 or more in direct costs must carry out the 
following steps:

1. Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2. Obtain agreement from the IC staff that the IC will accept your 
application; and,
3. Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement (type 3), or any amended or 
revised version of these grant application types.  Additional information on 
this policy is available in the NIH Guide for Grants and Contracts, October 19,
2001 at 

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at  The CSR will 
not accept any application in response to this PA that is essentially the 
same as one currently pending initial review unless the applicant withdraws 
the pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 

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.


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
( will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
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 discuss the following 
aspects of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  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 forward.

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 will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

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.  


BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.


Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program 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.

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 (
NOT-OD-02-001.html); a complete copy of the updated Guidelines are 
available at
_amended_10_2001.htm.  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 
them. This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

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 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). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

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 PA 
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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) - Government Made Easy

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.