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ARRA Investments in Kidney Diseases

Public Health Burden
An estimated 23 million Americans have chronic kidney disease (CKD),1 and over 525,000 people with kidney failure are undergoing dialysis or living with a kidney transplant.2 People with chronic kidney disease are at an increased risk of death from cardiovascular disease.

Genetics of Chronic Kidney Disease
Several ARRA-funded projects are aimed at improving our understanding of genetic factors that contribute to chronic kidney disease:
  • A project to generate mouse models to better understand how variants of the MYH9 gene contribute to the development of kidney disease.3
  • Adding a comprehensive genotyping study to the Chronic Renal Insufficiency Cohort (CRIC) study, to provide additional information in the context of progressive chronic kidney disease.4
  • The first genome-wide association study of the kidney disease IgA nephropathy.5
  • A study to identify novel genetic causes of the rare disease steroid-resistant nephrotic syndrome (SRNS).6
Pathophysiology of Chronic Kidney Disease
ARRA-funded projects are investigating the functional changes that accompany chronic kidney disease, in hope of developing better protective or restorative therapies:
  • A study to characterize the role of the pericyte—the support cell for small blood vessels—in development of kidney fibrosis and vascular regeneration following injury of the kidney.7
  • An investigation to define the factors, such as the protective factor Ngal that is highly expressed in acute kidney injury, that convert undifferentiated tissue called mesenchyme into nephrons.8
  • Generation of mouse lines of diabetic kidney disease that more closely resemble the human condition in order to study abnormal blood vessel growth in the kidney.9
Cardiovascular Complications of Chronic Kidney Disease
Most patients with chronic kidney disease die of cardiovascular disease. Projects to enhance our understanding of the cardiovascular complications in CKD include:
  • The potential role of inflammation and insulin resistance in the progression of cardiovascular disease in patients who have undergone kidney transplantation.10
  • An assessment of the potential role of endogenous hormones, ouabin and marinobufagenin, in the progression of CKD to cardiovascular disease in African Americans with hypertensive kidney disease.11
  • A study investigating whether patients who have chronic renal insufficiency are at increased risk of developing an eye condition called retinopathy.12
Treatment of Kidney Disease
Several ARRA-funded projects take novel approaches that either attempt to restore lost kidney function through stem cells, or detect disease at an early stage to preserve kidney function in people with kidney disease.
  • A project will develop a stepwise protocol for the differentiation of human inducible pluripotent stem (iPS) cells into renal progenitor cells for the treatment of chronic kidney disease.13
  • One study will use an innovative approach to develop cell therapeutic agents from human umbilical cord blood-derived hematopoietic stem cells (UCB-HSC) to treat acute kidney injury.14
  • A project will identify small-molecule inhibitors of a chloride ion channel to prevent cyst growth in autosomal dominant polycystic kidney disease (PKD) for further pre-clinical development.15
Diagnosis and Pathophysiology of Polycystic Kidney Disease (PKD)
PKD is a genetic disorder characterized by the growth of numerous large, fluid-filled cysts in the kidneys that can, over time, cause the kidneys to fail.
  • A project will use metabolomics to discover a novel pattern of urinary and plasma metabolite biomarkers for the most common form of PKD, autosomal dominant PKD.16
  • A study will characterize small membrane bound exosome vesicles in the urine of people with the more common form of PKD, with a goal of developing an assay to permit early diagnosis of PKD.17
  • A project will identify novel kidney signaling pathways relevant to cyst growth in PKD.18

  1. Levey AJ et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med 150: 604-612, 2009.
  2. U.S. Renal Data System Annual Data Report, 2009.
  3. 5RC1DK087220-02 -- Genetic Determinants of Susceptibility to Kidney Disease in African Americans -- COFFMAN, THOMAS M (NC)
  4. 3U01DK060990-09S1 -- Genome Wide Association of Renal Progression in the CRIC Study -- FELDMAN, HAROLD I (PA)
  5. 5RC1DK087445-02 -- A GWAS for IgA Nephropathy, the Most Common form of Glomerulonephritis -- GHARAVI, A (CT)
  6. 5RC1DK086542-02 -- Exon capture and large-scale sequencing for disease-cause identification, early detection and drug discovery in nephrotic syndrome -- HILDEBRANDT, FRIEDHELM (MI)
  7. 1RC1DK087389-021 -- Kidney Pericytes in Vascular Regeneration after Injury -- DUFFIELD, JEREMY S (MA)
  8. 3R01DK058872-09S1 -- Cytokines Convert Epithelial Precursors to Nephrons -- BARASCH, JOHNATHAN (NY)
  9. 3U01DK076136-04S1 -- Angiogenic Signals in Diabetic Complications -- COFFMAN, THOMAS M (NC)
  10. 3R01DK069919-04S1 -- Vascular Risk after Kidney Transplantation -- LARSEN, JENNIFER L (NE)
  11. 1R21DK078218-01A1 -- Endogenous Cardiac Glycosides in AASK -- ASTOR, BRAD C (MD)
  12. 3R01DK074151-04S1 -- Retinopathy in Chronic Renal Insufficiency -- GRUNWALD, JUAN E (PA)
  13. 5RC1DK086406-02 -- Inducible Pluripotent Stem Cells and Kidney Regeneration -- BONVENTRE, JOSEPH V (MA)
  14. 5RC1DK086886-02 -- Use of Umbilical Cord Blood derived HSC to Treat Acute Kidney Injury -- LIN, FANGMING (TX)
  15. 5RC1DK086125-02 -- CFTR inhibitors for therapy of polycystic kidney disease -- VERKMAN, ALAN S (CA)
  16. 5R01DK082690-02 -- A Metabolomic Approach to Discovering Biomarkers for ADPKD -- WEISS, ROBERT H (CA)
  17. 5RC1DK086161-02 -- Analysis of the proteome of PKD-ELVs in polycystic kidney disease and controls -- HOGAN, M (MN)
  18. 1RC1DK086738-01 -- A forward genetic screen for PKD pathways in mice using the PiggyBac transposon -- SOMLO, STEFAN (CT)

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