Update on the Genetics of Kidney Disease

Kenneth V. Lieberman, MDChief, Division of Pediatric Nephrology

The Joseph M. Sanzari Children’s HospitalHackensack University Medical Center

Professor of PediatricsUMDNJ – New Jersey Medical School

Goals

• Educate• Enlighten• Energize• Empower• Entertain

Genetics Practice• Traditional

– Inheritance patterns– Syndrome recognition

• Modern– Mutation finding– Ameliorating therapy– Diagnostic tools – substrate testing, genetic

testing• Future

– Gene therapy– Human genome project

Central Dogma

Autosomal Dominant

Autosomal Recessive

X-Linked

Lyonization

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

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

KDW

• Survey data: ESRD of unknown etiology– 10-30%– Glomerulosclerosis – “scarred”– Hypoplasia/dysplasia – “small”– Inadequate/incomplete diagnosis

• glomerulonephritis• hypertension

Importance• Patient’s 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

Genetic testing

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

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)

Examples (2)

• Fabry’s Disease– X-linked– Specific treatment available– Transplant implications (extra benefit)

• Atypical Hemolytic-Uremic Syndrome– Different inheritance patterns– Transplant implications (liver as well as

kidney)

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

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?