Update on the Genetics of Kidney Disease

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Update on the Genetics of Kidney Disease

• Kenneth V. Lieberman, MD
• Chief, Division of Pediatric Nephrology
• The Joseph M. Sanzari Childrens Hospital
• Hackensack University Medical Center
• Professor of Pediatrics
• UMDNJ New Jersey Medical School

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Goals

• Educate
• Enlighten
• Energize
• Empower
• Entertain

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Genetics Practice

• Traditional
• Inheritance patterns
• Syndrome recognition
• Modern
• Mutation finding
• Ameliorating therapy
• Diagnostic tools substrate testing, genetic
  testing
• Future
• Gene therapy
• Human genome project

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Central Dogma
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Autosomal Dominant
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Autosomal Recessive
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X-Linked
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Lyonization
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Family history

• The lack of a history is not a negative history
• Consanguinity autosomal recessive
• Maternal uncles X-linked
• Children presence, state of health
• Update
• Update
• Update

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Questions for patient

• Health problems other than ESRD and its related
  complications
• Diseases in the family, outside of the usual
  (i.e., MI, strokes, DM, HTN) map out
• Update
• Update
• Update

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KDW

• Survey data ESRD of unknown etiology
• 10-30
• Glomerulosclerosis scarred
• Hypoplasia/dysplasia small
• Inadequate/incomplete diagnosis
• glomerulonephritis
• hypertension

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Importance

• Patients own care
• Piece of mind
• Missing other disease manifestation
• Transplant recurrence
• Treatment
• Finding pre-symptomatic relatives (kids)
• Prophylactic treatment
• Counseling of young couples
• Prenatal diagnosis
• Carrier detection

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Genetic testing

• Diagnostic testing
• Predictive testing
• Prognostic testing
• Carrier testing
• Preimplantation testing
• Prenatal testing
• Newborn screening

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Examples (1)

• Medullary Cystic Kidney Disease (UMOD)
• Autosomal dominant high transmission risk
• Gout
• FSGS
• Might be autosomal recessive
• High transplant recurrence risk
• Alport
• Mostly X-linked
• Mothers (female carriers are variably
  symptomatic, mostly minimal)

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Examples (2)

• Fabrys Disease
• X-linked
• Specific treatment available
• Transplant implications (extra benefit)
• Atypical Hemolytic-Uremic Syndrome
• Different inheritance patterns
• Transplant implications (liver as well as kidney)

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Examples (3)

• Polycystic Kidney Disease
• Distinguish AR from AD (other organ involvement)
• Early detection treatment available
• Distinguish from Von Hippel-Lindau
• Nephrogenic Diabetes Insipidus
• X-linked
• Early detection
• Dehydration risk

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Put the nephrologist on the spot

• Did you consider
• I found out that
• Do you want to consider a referral to
• Do you want to consider genetic testing?