AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY
DISEASE.
DR. ABIRA KHAN
INTRODUCTION
• Multisystem disorder characterized by multiple bilateral renal cysts
associated with cysts in other organs such as liver, pancreas and arachnoid
membranes.
• Occurs in all races.
• Occurs approximately in 1 in every 400-1000 live births.
• Only one half of patients with ADPKD are estimated to be diagnosed during
their lifetime since the disease is often clinically silent.
• Among most patients, kidney function remains intact until 4th decade of life.
• Once the GFR starts to decline, average reduction is 4.4-5.9ml/min per year.
GENETICS
• Mutations in one of two genes account for most of the cases of ADPKD.
• PKD1 gene (which encodes polycystin-1) is located on chromosome 16p13.
• The PKD2 gene(which encodes polycystin-2) is located on 4q21 chromosome.
RISK
FACTORS
CLINICAL PRESENTATION
Clinical presentation includes :
1. Renal manifestations.
2. Extra renal manifestations.
1. HEMATURIA : Grossly visible. Occurs in 35-
CLINICAL 50% of patients. Occurs due to rupture of cyst into the
PRESENTATIO collecting system. Usually resolves within 2-7 days with
hydration, bedrest and analgesics.
N 2. CONCENTRATING DEFECT : Patients
most often complaint of increased thirst, Polyuria,
nocturia and urinary frequency.
3. NEPHROLITHIASIS : Occcurs in 25% of
patients. More than half of stones are uric acid stones.
RENAL 4. FLANK AND ABDOMINAL PAIN :
MANIFESTATIONS. Acute pain maybe caused by Infections(cystic or
parenchymal), nephrolithiasis or cyst hemorrhage.
5. RECURRENT UTI.
6. HYPERTENSION.
CLINICAL
PRESENTATIO 1. HEPATIC & PANCREATIC CYSTS.
N 2. IntraCranial Aneurysms.
3. Cardiac valve defects.
4. Colonic diverticula.
EXTRA RENAL 5. Abdominal wall hernias.
MANIFESTATIONS.
DIAGNOSIS
Involves 3 subgroups.
1. Asymptomatic patients with positive family history.
2. Symptomatic patients with positive family history.
3. Patients without family history of ADPKD.
• An ULTRASOUND is usually sufficient
DIAGNOSI to diagnose or rule out the presence of
S disease.
• An MRI maybe needed if USG findings
are equivocal or to evaluate incidentally
detected complications.
ASYMPTOMATIC
PATIENTS WITH
• If MRI results are equivocal, GENE
POSITIVE FAMILY
TESTING is performed to confirm the
HISTORY
diagnosis.
• CT/MRI is preferred over initial USG.
DIAGNOSIS
• In addition to diagnoses, CT/MRI can
serve as a baseline image for future
comparison and can identify
complications and disease in other
organs.
SYMPTOMATIC
PATIENTS WITH • The choice between CT amd MRI
POSITIVE FAMILY depends upon patient’s kidney function,
HISTORY given the risk of contrast exposure with
CT.
• No established imaging criteria.
DIAGNOSIS
• These patients are diagnosed with
ADPKD if they have 10 or more
cysts(>5mm) in each kidney particularly
if kidneys are enlarged of liver cysts are
present.
PATIENTS WITHOUT
A HISTORY OF
ADPKD • Genetic testing should be performed in
patients with equivocal imaging results.
DIAGNOSIS Genetic testing is performed in the
following scenarios.
1. Imaging results uncertain.
2. Atypical presentations
• Early and severe ADPKD.
• Kidney failure without significant enlargement of
kidneys.
SPECIFIC ROLE • Marked asymmetry in disease severity between
kidneys.
OF GENETIC
3. Sporadic ADPKD without family history.
TESTING 4. PKD with syndromic features.
TREATMENT
Treatment involves :
1. Initial management for all patients.
2. Identifying HIGH-RISK patients.
3. Additional management of HIGH-RISK patients.
• MANAGEMENT OF BP : In the absence of
TREATMENT contraindications, ACEi/ARBs are recommended to
target BP of 110/75 in young healthy individuals.
• DIETARY SODIUM RESTRICTION : Restrict
dietary sodium with a goal of 2grams intake per day
or less.
• INCREASED FLUID INTAKE : Patients with
INITIAL ADPKD are advised to take >3L fluid per day unless
MANAGEMENT OF the eGFR Is less than 30 or there us risk of
ALL PATIENTS hyponatremia.
The identification of high risk individuals is necessary for
prognostic reasons and to identify patients who may benefit
from specific therapies.
TREATMENT PREFERRED METHOD : MAYO CLASSIFICATION
SYSTEM.
• Categorizes patients into 5 classes from the lowest to highest risk
of disease progression (1A, 1B, 1C,1D,1E)
• Requires patient’s age, height and Total Kidney Volume(TKV).
IDENTIFYING HIGH
RISK • TKV can be calculated using TKV calculator which uses coronal
and sagittal length and width and depth measurements of both
PATIENTS kidneys
• Provides an age adjusted assessment of progression risk for those
with typical ADPKD.
TOLVAPTAN
TREATMENT • New drug approved by FDA for patients
with high risk of progression of kidney
disease.
• Vasopressin V2 receptor (V2R) antagonist.
ADDITIONAL
MANAGEMENT FOR • Slows the rate of cyst growth and decline in
HIGH-RISK eGfR.
PATIENTS
• The major expected but still unproven
benefit is Delaying the need of RRT.
THANKYOU!
