NIH GUIDE, Volume 21, Number 44, December 11, 1992

PA:  PA-93-29

P.T. 34





  Risk Factors/Analysis 


National Institute of Diabetes and Digestive and Kidney Diseases


The National Institute of Diabetes and Digestive and Kidney Diseases

(NIDDK) invites research applications for studies related to Kidney

Disease of Diabetes Mellitus (KDDM).  This Program Announcement (PA)

invites submission of individual research grant applications focusing

primarily on basic research into the pathogenetic mechanisms of KDDM.


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 PA,

Kidney Disease of Diabetes Mellitus:  Pathogenic Mechanisms, is related

to the priority area of diabetes and chronic disabling diseases.

Potential applicants may obtain a copy of "Healthy People 2000" (Full

Report:  Stock No. 017-001-00474-0) or Healthy People 2000" (Summary

Report:  Stock No. 017-001-00473-1) through the Superintendent of

Documents, Government Printing Office, Washington, DC 20402-9325

(telephone (202) 783-3238).


Applications may be submitted by domestic and foreign for-profit or

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.  Minority

individuals and women are encouraged to apply.  Foreign institutions

are not eligible for the First Independent Research Support and

Transition (FIRST) (R29) awards.


Support of this program will be through the traditional NIH

grant-in-aid research project grant (R01) and First Independent

Research Support and Transition (FIRST) award (R29).  Responsibility

for the planning, direction, and execution of the proposed project will

be solely that of the applicant.  Except as otherwise stated in this

announcement, awards will be administered under PHS grants policy as

stated in the PHS Grants Policy Statement.  It should be noted that

FIRST (R29) awards are restricted to domestic institutions only.

A maximum of three years may be requested for foreign awards.  FIRST

award applications should request five years.  Annual awards will be

made, subject to continued availability of funds and progress achieved.

Although this program is provided for in the financial plans of the

NIDDK, the award of grants pursuant to this PA is contingent upon the

availability of funds for this purpose.  It is anticipated that the

average size of an award made in response to this PA will be about

$180,000 per year including both direct and indirect costs; however,

considerable variability around this average is expected.


This PA is intended to encourage new fundamental studies of KDDM.  The

aim is to stimulate investigator-initiated research protocols designed

to further the understanding of the pathogenetic mechanisms and genetic

determinants of KDDM, as well as to address issues concerning risk

factors, co-morbidity, and causes of excess incidence of diabetic

end-stage renal disease (ESRD) in certain minority populations.

Kidney disease of diabetes mellitus (KDDM) continues to be the most

frequent cause of ESRD in the USA and the largest single cause of renal

disease.  This is true for Caucasians, African Americans, Hispanics,

and Native Americans.  Even though progress has been made in

understanding some of the mechanisms leading to the development of KDDM

and its progression to ESRD, the pathogenesis of KDDM still remains

largely undefined.

Examples of representative research topics that would be considered

responsive to this solicitation include the following:

o  Characterization of the pathogenetic mechanisms and the genes

associated with KDDM, including the role of the genes in the immune

response in insulin-dependent diabetes mellitus (IDDM), and genetic and

environmental determinants in non-insulin dependent diabetes mellitus


o  Identification of the role, pathways, and interaction of biochemical

and metabolic factors in KDDM.

o  Comparison of KDDM in IDDM vs NIDDM.

o  Biochemical characterization of the changes observed in glomerular

basement membrane.

o  Morphologic and morphometric studies of, e.g., the glomeruli,

including basement membrane thickening, extent of mesangial expansion,

and quantitation of capillary surface area with disease progression.

o  Studies addressing risk factors and co-morbidity in KDDM.

o  Studies of the pathophysiology of hyperfiltration and its linkage to

subsequent morphologic injury.

o  Investigation of the possible causes of the excess incidence of KDDM

in Blacks, Hispanics, and Native Americans, including genetic and

environmental factors.

o  Studies examining the etiology of KDDM including non-enzymatic

glycation, aldose reductase activity, hyperinsulinemia, and

hyperglycemia, that may serve as a model for understanding KDDM and

other complications of diabetes.


Interdisciplinary approaches may be needed and are encouraged for these

studies.  For example, collaborations among the following disciplines

may be productive:  molecular and cell biology, genetics, immunology,

pathology, biochemistry/metabolism, nephrology, endocrinology,

physiology, and pharmacology.




NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are 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 must be placed on the need for inclusion of minorities

and women in studies of diseases, disorders and conditions which

disproportionally 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 must be


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 must be addressed in developing a research design

and sample size appropriate for the scientific objectives of the study.

This information must be included in the form PHS 398 (rev. 9/91) in

Item 4 (Research Design and Methods) of the Research Plan and

summarized in Item 5, Human Subjects.  Applicants 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 is defined as 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


If the required information is not contained within the application,

the application will be returned without review.

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 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.


The research grant application form PHS 398 (rev.9/91) is to be used in

applying for these grants.  The form is available from most

institutional offices of sponsored research and from the Office of

Grants Inquiries, Division of Research Grants, National Institutes of

Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone

(301) 496-7441.

The PA title and number must be typed on line 2a of the face page of

the application form and check the YES box.

Submit a signed, typewritten original of the application, including the

Checklist, and five signed, exact photocopies, in one package to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**

FIRST (R29) award applications must include at least three sealed

letters of reference attached to the face page of the original

applications.  FIRST (R29) award applications submitted without the

required numbered of reference letters will be considered incomplete

and will be returned without review.

The Division of Research Grants (DRG) will not accept any application

in response to this announcement that is essentially the same as one

currently pending initial review, unless the applicant withdraws the

pending application.  However, it is allowable to submit the same

project as both an R01 and as a component project of a program project.

The DRG will not accept any application that is essentially the same as

one already reviewed.  This does not preclude the submission of

substantial revisions of applications previously reviewed.  Such

applications must not only include an introduction addressing the

previous critique, but also be responsive to this PA.


Applications received in response to this PA will be assigned to an

initial review group and to an awarding Institute/Center for possible

funding on the basis of established PHS referral guidelines.  A review

for scientific and technical merit will be conducted by an initial

review group convened by the DRG in accordance with the standard NIH

peer review procedures.  Following this review, the applications will

be given a secondary review by the National Diabetes and Digestive and

Kidney Diseases Advisory Council or the corresponding Advisory

Council/Board of another funding component (unless the application is

not recommended for further consideration by the initial review group).

Review criteria for application submits in response to a PA are

generally the same as those for unsolicited research grant

applications.  Review criteria include:

o  Scientific, technical, or medical significance and merit specific to

the objectives of the PA and originality of the proposed research

o  Appropriateness and adequacy of the experimental approach and

methodology proposed to carry out the research

o  Qualifications and research experience of the Principal Investigator

and staff, particularly but not exclusively in the area of the proposed


o  Availability of resources necessary to perform the research

o  Appropriateness of the proposed budget and duration in relation to

the proposed research


Applications received in response to this PA will compete for available

funds with other applications recommended for funding.  The following

will be considered in making funding decisions:

o  quality of the proposed project as determined by peer review,

o  availability of funds, and

o  program balance among research areas of the announcement.


NIDDK staff are available for consultation concerning application

development before or during the process of preparing an application.

Potential applicants are advised to contact NIDDK staff as early as

possible for information or assistance in initiating the application

process and developing an application.

Direct inquiries regarding programmatic issues to:

Gladys H. Hirschman, M.D.

Director, Chronic Renal Diseases Program

Division of Kidney, Urologic and Hematologic Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 3A-07

Bethesda, MD  20892

Telephone:  (301) 496-8218


Charles A. Wells, Ph.D.

Director, Diabetes Complications Program

Division of Diabetes, Endocrinology and Metabolic Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 622

Bethesda, MD  20892

Direct inquiries regarding fiscal matters to:

Aretina D. Perry

Grants Management Specialist

Division of Extramural Activities

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 639

Bethesda, MD  20892

Telephone:  (301) 496-7467


This program is described in the Catalog of Federal Domestic Assistance

Nos. 93.849 and 93.847.  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 review.


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