TY  - CHAP
M1  - Book, Section
TI  - Autosomal Dominant Polycystic Kidney Disease
A1  - Germino, Gregory G.
A1  - Chapman, Arlene B.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/ommbid.250
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Autosomal  dominant  polycystic  kidney  disease  (ADPKD)  (MIM  173900)  is  the  most  common  inherited  renal  disease,  accounting  for  4.8  percent  of  the  end-stage  renal  disease  (ESRD)  population  in  the  United  States  and  is  a  systemic  disorder  involving  the  heart,  liver,  cerebral  vasculature,  and  connective  tissue.  Clinical  manifestations  of  this  disorder  are  highly  variable  within  and  between  families.  The  average  age  of  presentation  is  in  the  fourth  decade  of  life  with  invariable  penetrance  by  the  age  of  70  years.Diagnosis  of  ADPKD  relies  on  multiple  sources  of  information  including  medical  history,  physical  examination,  laboratory  evaluation,  renal  imaging,  and  genetic  analysis.  Gene  linkage  analysis  provides  no  information  concerning  the  clinical  severity  of  the  disorder  and  is  used  primarily  for  screening  potentially  eligible  renal  donors.  Ultrasound  in  the  imaging  procedure  of  choice  used  to  make  a  phenotypic  diagnosis  of  ADPKD  due  to  its  sensitivity  as  well  as  cost  and  lack  of  invasiveness.  Individuals  from  autosomal  dominant  polycystic  kidney  disease  type  1  gene  and  gene  symbol  (PKD1)  families  with  a  negative  ultrasound  after  30  years  of  age  have  a  less  than  5  percent  chance  of  being  carriers  of  the  disease.Polycystic  liver  disease  is  a  common  manifestation  in  ADPKD  and  is  useful  in  differentiating  ADPKD  from  other  renal  cystic  disorders  of  the  kidney.  Polycystic  liver  disease  presents  approximately  10  years  after  renal  cystic  disease  with  women  more  severely  affected  than  men.  Birth  control  pill  use,  pregnancy,  and  postmenopausal  estrogen  use  are  associated  with  more  progressive  polycystic  liver  disease.  Although  liver  cystic  involvement  can  be  massive,  liver  function  continues  to  remain  normal.Intracranial  aneurysms  (ICA)  occur  in  8  percent  of  ADPKD  individuals  as  opposed  to  2  percent  of  the  general  population.  ICA  cluster  in  families  with  a  family  history  of  ICA  and  are  often  multiple.  Smoking  and  hypertension  are  not  risk  factors  for  ICA  development  in  ADPKD.  Individuals  with  a  positive  family  history  of  ICA  should  be  screened  using  time-of-flight  three-dimensional  magnetic  resonance  angiography.  Reoccurrence  of  ICA  is  common  in  ADPKD  individuals  with  a  previous  ICA,  usually  at  least  3  years  after  the  initial  observation,  and  occurs  more  often  in  those  individuals  where  rupture  has  occurred.Hypertension  is  the  most  common  renal  complication  in  ADPKD  occurring  in  60  percent  of  individuals  with  normal  renal  function  and  is  associated  with  a  faster  rate  of  progression  to  renal  failure.  Activation  of  the  renin-angiotensin-aldosterone  system  plays  an  important  role  in  the  pathogenesis  of  hypertension  in  this  disorder.  Preliminary  results  from  long-term  studies  suggest  that  angiotensin  converting  enzyme  inhibition,  in  contrast  to  conventional  diuretic  therapy,  may  be  beneficial  in  preventing  progression  to  renal  failure  in  this  disorder.Multiple  therapies  have  been  prescribed  in  experimental  animal  models  of  ADPKD  and  have  shown  success  in  slowing  functional  and  structural  progression  of  the  disease.  These  therapies  have  not  yet  been  successfully  applied  to  man.  Specifically,  protein  restriction  has  not  demonstrated  a  significant  impact  on  slowing  progression  to  renal  failure  in  human  ADPKD.  However,  study  design  may  not  have  been  adequate  to  demonstrate  a  true  benefit  of  this  intervention.Genetic  linkage  studies  suggest  there  are  at  least  three  forms  of  ADPKD.  The  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/ommbid.250
Y2  - 2024/04/19
UR  - ommbid.mhmedical.com/content.aspx?aid=1181476776
ER  -