AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE

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AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
CONGENITAL HEPATIC FIBROSIS

• PLANNING STRATEGY
• Physician/scientist feedback

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PURPOSE

• To create and accelerate interest and awareness
  of ARPKD/CHF specifically through aggressive
  research and medical education programs.

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ARPKD

• Autosomal Recessive Polycystic Kidney Disease is
  a severe genetic disease caused by cysts and
  dilated tubules impacting kidney function. The
  highest impact is at the neonate/infant level.

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CONGENITAL HEPATIC FIBROSIS

• Congenital Hepatic Fibrosis is a rare hereditary
  disorder characterized by periportal fibrosis
  with irregularly shaped bile ducts, intrahepatic
  portal hypertension and esophageal varices.

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CONGENITAL HEPATIC FIBROSIS

• CHF is most commonly linked to ARPKD patients.
• Always present to some degree with ARPKD
• Complications from CHF can be life threatening

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DISEASE IMPACT

• ARPKD/CHF affects approximately 1 in 20,000 live
  births.
• Almost 50 of infants with ARPKD die at birth or
  shortly thereafter primarily due to kidney
  failure or failure of the lungs to develop.
• As many as 25 die of renal failure in early
  infancy - with significant mortality the first
  month of life.

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DISEASE IMPACT

• Neonates and infants are the groups most severely
  affected.
• High Blood Pressure is present in most cases of
  ARPKD by age 1
• After survival of the newborn period,
  approximately 33 experience ESRD by age 15
• Cholangitis contributes significantly to the
  morbidity and mortality rates in CHF

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SYMPTOMS

• Hematemesis or melena is the presenting symptom
  in up to 70 of patients with CHF.
• Nephromegaly is a common finding upon physical
  examination
• High Blood Pressure
• Kidney failure
• Ductal plate malformation and biliary disease
• Portal hypertension associated with splenomegaly
  and esophageal varices.

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ASSOCIATIONS

• Most severe form of PKD
• CHF progresses with age
• CHF is not well understood, even within the
  medical community.
• Care varies widely and depends on who your doctor
  is, and where you live
• Systemic and portal hypertension are common
• The inheritance pattern, onset, cyst
  formation/location differ between ADPKD and ARPKD
  

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MEDICAL RESEARCH

• Limited focus on disease
• No coordination of studies/results
• Individual studies at various universities
• Lack of clinical patients/awareness
• (Approximately 5,700 NIH clinical studies.
  1,074 kidney related/1 is on ARpkd. 578 liver
  related studies/1 is on CHF.)

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NIH MEDICAL RESEARCH

• LANDMARK NIH STUDY (5-10 YR STUDY PERIOD)
• ARPKD/CHF Medical Workshop
• NIH, Liver Action Plan calls for CHF research

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KNOWLEDGE GAPS

• Identification of all conditions, mutations, and
  genes causing CHF
• Stages of CHF development
• PKD vs. ARpkd gene impact
• Characterize fibrosis (vs. cirrhosis)
• Physician/scientist feedback

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KNOWLEDGE GAPS

• Determine specifically how ductal plate
  malformation affects CHF
• EGFR receptor impact and other factors affecting
  CHF
• Clinical management for this disease
• Physician/scientist feedback

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PROMISING ADVANCES

• Angiotensin blockade
• Lipid lowering medications
• Dietary modifications
• (ADPKD related)

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PROMISING ADVANCES

• EGFR-TK1s have been shown to retard the
  progression of liver and kidney disease by
  reducing cyst size and preserving renal function.
• (FOR ADPKD, in animals)

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PROMISING ADVANCES

• V2RA therapy is currently in phase 3 trials and
  holds great promise. This class of drug reduces
  AMP levels, cyst volume, kidney weight, BUN and
  renal fibrosis volume.
• (FOR ADPKD, in animals)

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PLANNING DIRECTION

• ARPKD/CHF is BOTH a rare kidney and liver
  disease.
• CHF is unappreciated
• Identification of CHF genes
• Accurate and current information needs to be
  communicated to physicians..quickly
• PHYSICIAN/SCIENTIST FEEDBACK

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PLANNING DIRECTION

• Involvement of top ARPKD/CHF specialists.worldwid
  e
• Dont spread patients too thin
• Create ARPKD/CHF Research Consortium and NIH
  sources of funding.
• PHYSICIAN/SCIENTIST FEEDBACK

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MAJOR GOALS

• Increase interest among medical community and
  patients affected.
• Dramatically increase revenues for ARPKD/CHF
  funding.
• Solve key knowledge gaps regarding the disease,
  conditions and treatments.

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NEXT STEPS

• Attract more patients to studies
• Pinpoint critical study areas
• Involve promising drug therapies
• Share data quickly
• Generate interest in medical community

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ABOUT THEARPKD/CHF ALLIANCE

• Only organization worldwide solely dedicated to
  this disease
• Guided by Scientific Board
• Helped sponsor NIH, ARPKD/CHF Workshop
• Instrumental in generating NIH Clinical Study
• Extensive website and patient list
• Central patient voice for research and support