NIH GUIDE, Volume 23, Number 21, June 3, 1994

PA NUMBER:  PA-94-071

P.T. 34





  Membrane Structure/Function 

  Biology, Cellular 

  Biology, Molecular 

National Institute of Diabetes and Digestive and Kidney Diseases


The National Institute of Diabetes and Digestive and Kidney Diseases

(NIDDK) encourages research grant applications for support of studies

on the identification, description and characterization of renal

tubular epithelial ion transport mechanisms that may underlie

pathophysiological states.  The objective is to promote research at

the molecular and cellular level to better understand aberrations in

renal epithelial transport mechanisms that may lead to disease


The NIDDK, through its Division of Kidney, Urologic and Hematologic

Diseases is the principal agency that supports fundamental and

applied research directed at normal renal structure, function and

regulation.  These studies provide the basis for studies on the

underlying mechanisms of kidney disease.  This program includes

studies utilizing whole kidney and/or the selected segments of the

kidney or individual cells or any of their subcellular components as

models.  Those studies involving individual tubular segments,

isolated cells and their component membranes have extended our

knowledge of ion transport processes in the normal kidney, but still

lacking is a comprehensive understanding of the many factors that

govern body electrolyte balance and associated disease states.

Nevertheless, the interactive play among receptors, modulatory

proteins, phospholipid metabolites and second messengers is now

becoming more clear in the modulation of ion transport, cytoskeletal

organization, and growth and differentiation of the kidney.  There

are cellular and molecular biologic techniques that make it possible

to identify and clone genes and proteins within renal epithelial

cells responsible for anionic and cationic transport processes.


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.  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



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

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, units of State or local

governments, and eligible agencies of the Federal government.

Foreign institutions are not eligible for First Independent Research

Support and Transition (FIRST) (R29) awards.  Applications from

minority individuals and women are encouraged.


This PA will use the National Institutes of Health (NIH) individual

research grant (R01) and FIRST (R29) award mechanisms.

Responsibility for planning, direction, and execution of the proposed

project will be solely that of the applicant.  Because the nature and

scope of the research proposal in response to this PA may vary, it is

anticipated that the size of an award will vary also; however, the

support of requests exceeding the NIDDK average grant size of

$160,000 direct cost for R01 grants would be unusual and require

ample justification.  FIRST (R29) awards are limited to $350,000 over

the five year period.


Investigations are needed that will lead to functional connections

between existing fundamental knowledge gained from physiological

studies and, information yet to be obtained by directly addressing

the pathophysiology in various renal tubular epithelial diseases.

Examples of diseases with disorders of epithelial transport include:

renal tubular acidosis, gout, cystinuria, nephrogenic diabetes

insipidus, polycystic kidney disease and Fanconi and Bartters


Responding applications should emphasize mechanisms rather than mere

descriptions of processes.  State-of-the-art biochemistry, and

molecular and cellular biological techniques should be utilized in

such investigations.

The following are examples of projects/topics that would be

responsive, but are not meant to present the full range of


o  The mechanisms underlying the involvement of specific ion solute

and water transporters in hereditary kidney disease, such as

polycystic kidney disease, cystinuria, nephrogenic diabetes insipidus

or hereditary disorders of urinary proton, phosphorous, calcium and

uric acid excretion.

o  The mechanisms underlying the involvement of specific ion solute

and water transporters in acquired kidney disease, such as

obstructive nephropathy, hyperaldosteronism, or drug-induced


o  The aberrant regulation by systemic hormones, intracellular second

messengers, phospholipid metabolites, or ions in the expression and

activities of different renal ion and solute transport systems.

o  Role and mechanism of action of analogs and/or antagonists of

specific transport systems or hormones/growth factors/cytokines or

their receptors in treatment of kidney disease.

o  Studies of immunohistochemistry and in situ hybridization in human

biopsies of the pathophysiological basis of abnormal urinary K+, Na+,

Cl-, PO4, and H2O excretion.

o  Identification and functional significance of mutated genes whose

expression is regulated by signal transduction through systemic

hormones, growth factors, or other modulators in dysregulated

endocrine or transport function.

o  The mechanisms underlying hypertrophy and upregulation of

transport mechanisms in the renal response to partial loss of

functioning nephrons.




It is the policy of the NIH that women and members of minority groups

and their subpopulations must be included in all NIH supported

biomedical and behavioral research projects involving human subjects,

unless a clear and compelling rationale and justification is provided

that inclusion is inappropriate with respect to the health of the

subjects or the purpose of the research.  This new policy results

from the NIH Revitalization Act of 1993 (Section 492B of Public Law

103-43) and supersedes and strengthens the previous policies

(Concerning the Inclusion of Women in Study Populations, and

Concerning the Inclusion of Minorities in Study Populations), which

have been in effect since 1990. The new policy contains some

provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should

read the "NIH Guidelines For Inclusion of Women and Minorities as

Subjects in Clinical Research," which have been published in the

Federal Register of March 9, 1994 (FR 59 11146-11151) and reprinted

in the NIH Guide for Grants and Contracts, Volume 23, Number 11,

March 18, 1994.

Investigators also may obtain copies of the policy from the program

staff listed under INQUIRIES.  Program staff may also provide

additional relevant information concerning the policy.


Investigators are encouraged to consider alternative methods and

approaches in their research grant applications that do not require

the use of whole animals, use alternative species such as nonmammals

or invertebrates, reduce the number of animals required, and

incorporate refinements to procedures that will result in the

elimination or further minimization of pain and distress in animals.


Applications are to be submitted on the grant application form PHS

398 (rev. 9/91) and will be accepted at the regular application

deadlines for new research grant applications.  Application kits are

available at most institutional offices of sponsored research and may

be obtained from the Office of Grants Information, Division of

Research Grants, National Institute of Health, Westwood Building,

Room 449, Bethesda, MD 20892, telephone 301/435-0714. The title and

number of this program announcement must be typed in Section 2a on

the face page of the application.  The earliest possible award dates

will be approximately nine months after the respective receipt dates.

Applications received too late for one review cycle will be held

until the next receipt date.

Applications for FIRST awards (R29) must include at least three

sealed letters of reference attached to the face page of the original

application.  First award (R29) applications submitted without the

required number of reference letters will be considered incomplete

and will be returned without review.  Applications will be received

by the NIH Division of Research Grants (DRG) and referred to an

appropriate study section for scientific and technical merit review.

Institute assignment decisions will be governed by normal

programmatic considerations as specified in the NIH referral

guidelines.  Following scientific-technical review, the applications

will receive a second-level review by an appropriate national

advisory council.

The completed original application and five legible copies must be

sent or delivered to:

Division of Research Grants

National Institute of Health

Westwood Building, Room 240

Bethesda, MD  20892**


The review criteria customarily employed by the NIH for research

grant applications and FIRST awards will prevail.  Following the

initial scientific review, those applications recommended for further

consideration will be evaluated by the appropriate National Advisory



Applications assigned to the National Institute of Diabetes and

Digestive and Kidney Diseases will compete for available funds with

all other approved applications assigned to the Institute.  The

following will be considered in making funding decisions:

o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement


Written, email, and telephone inquiries are encouraged.  The

opportunity to clarify any issues or questions from potential

applicants is welcome.

Direct inquiries regarding programmatic issues to:

M. James Scherbenske, Ph.D.

Division of Kidney, Urologic and Hematologic Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 3A-04A

Bethesda, MD  20816

Telephone:  (301) 594-7522

Inquiries regarding fiscal matters may be directed to:

Helen Y. Ling

Division of Extramural Activities

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 639

Bethesda, MD  20816


This program is described in the Catalog of Federal Domestic

Assistance No. 93.849.  Awards are made under authorization of the

Public Health Service Act, Title IV, Part A (Public Law 78-410, as

amended by Public Law 99-158, 42 USC 241 and 285) and administered

under PHS grants policies and Federal Regulations 42 CFR 52 and 45

CFR Part 74.  This program is not subject to the intergovernmental

review requirements of Executive Order 12372 or Health Systems Agency



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