• About Us
  • Company Overview
  • Leadership
  • Investors
  • Strategic Alliances
  • Contacts
  • FibroGen Europe
• Clinical
  • Current Trials
• Research & Development
  • Hypoxia-Inducible Factor
    HIF Biology

     

    HIF-PHI Therapy

     

    Anemia

     

    Cytoprotection/Inflammation
  • Connective Tissue Growth Factor
    CTGF Biology

     

    Anti-CTGF Therapy

     

    Chronic Kidney Disease

     

    Fibrotic Disease

     

    Cancer
  • Recombinant Human Collagen & Gelatin
• News
  • Publications
  • Email Sign up
  • Press Releases
• Careers
  • Job Search
  • Notice to Search Firms and Recruiters

Unmet Need

Diabetes Epidemic

The Centers for Disease Control and Prevention reports there the number of Americans with diabetes has grown to about 24 million people, or roughly 8 percent of the U.S. population (based on data from 2007). Recent estimates indicate that the number of newly diagnosed diabetics has been growing at a compounded annual rate of 4.2%. The CDC estimates another 57 million people have blood sugar abnormalities called pre-diabetes, which puts people at increased risk for the disease. Worldwide, there are 171 million people with diabetes. Accompanying this worldwide epidemic of diabetes are reports of dramatic increases in diabetic kidney disease (DKD), a progressive deterioration of the kidneys that can lead to end-stage renal disease (ESRD), necessitating dialysis or transplant.

Kidney disease is a common complication of diabetes

During the initial stages of DKD, hyperglycemia and hypertension damage the main structures of the kidney causing hyperfiltration, hypertrophy (increased kidney weight) and elevated urinary albumin excretion. A diagnosis of DKD is based in part of the finding of elevated amounts of protein, mainly albumin, in the urine (a condition termed proteinuria). According to the guidelines of the Kidney Disease Quality Initiatives Outcome (KDOQI ), microalbuminuria (defined as an albumin to creatinine ratio (ACR) between 30-300 mg/g) is associated with stable kidney function but a greater risk of disease progression and kidney failure. In the US, approximately 3.4 million patients with diabetes have microalbuminuria. KDOQI also describes a portion of the patient population exhibiting higher elevations of albumin, referred to as macroalbuminuria (ACR between > 300 mg/g). Macroalbumniuria is associated with progressive decline in kidney function (measured as glomerular filtration rate (GFR)), an increase in systemic blood pressure, and a high risk of kidney failure. Approximately 1.1 million people with diabetes in the US have macroalbuminuria.

Epithelial to Mesenchymal Transition (EMT) and Progression of DKD

DKD worsens as a result of increased permeability of the glomeruli (filtering units) and the excessive production and build up of extracellular matrix components, which leads to pathological scarring or chronic fibrosis. Fibrosis is a major factor in the late-stage progression of DKD, and, without specific interventions, causes a decline in GFR and ultimately leads to end-stage renal disease (ESRD). Fibrosis is a result of a cellular process called epithelial to mesenchymal transition (EMT). In kidney disease, EMT occurs when normal functioning tubular epithelial cells incur repeated insults and injury and consequently morph into scar-producing mesenchymal cells. Persistent and excessive scarring in the kidney as a result of EMT leads to tubulointerstitial fibrosis, disease progression, and ultimately ESRD. Traditionally, fibrosis has been considered irreversible; however, data are emerging that EMT can be reversed.

Diabetes is the leading cause ESRD

From 1993 to 2003, the rate of ESRD due to diabetes increased by 86%. Since 1980, diabetes has become the single largest contributor to ESRD-contributing 45% of the prevalent population and 53% of the incident population. While some patients may survive more than 5 years after reaching this point, most die from cardiovascular complications before or soon after progressing to the need for dialysis or transplantation.

Unmet Need

Current management of DKD aims at controlling hyperglycemia and hypertension. The only approved therapy demonstrating clinical benefit in reducing the rate of progression of DKD is angiotensin receptor blocker (ARB) therapy. Losartan and irbesartan are approved for patients with type 2 diabetes mellitus, macroalbuminuria, elevated serum creatinine and hypertension. Patients receiving ARB treatment and/or angiotensin converting enzyme inhibitors (ACEi) continue to suffer declining renal function. There is no currently approved standard therapy that reduces or ameliorates the progressive renal functional decline beyond treatment with ACEi and/or ARB medications. Multiple factors may propel the continued progressive decline, including hypertension, hyperglycemia, and possibly hyperlipidemia.

These factors dictate a significant need for novel approaches to treat DKD and to prevent ESRD. Underscoring a compelling unmet medical need in delaying dialysis is the fact that total Medicare ESRD costs reached $18.5 billion in 2004, with $16.3 billion spent on dialysis. Cardiovascular mortality in diabetic individuals also remains a medical catastrophe and the primary cause of death in patients with diabetic kidney disease.