This document summarizes autosomal dominant polycystic kidney disease (ADPKD). It is the most common inherited kidney disorder, caused by mutations in PKD1 and PKD2 genes. It is characterized by massive cyst growth in the kidneys and other organs. It can lead to end-stage renal disease. Risk factors for faster progression include male sex, early hypertension onset, proteinuria, and PKD1 genotype. Total kidney volume is the strongest predictor of future kidney function decline. Complications include cyst infections, hemorrhage, hypertension, liver cysts, and intracranial aneurysms. Treatment focuses on blood pressure control and vasopressin V2 receptor antagonists to slow disease progression.

1. ‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬

2. Autosomal dominant polycystic
kidney disease(ADPKD)
Dr. Rania Elshal
MNGH

3. Autosomal dominant polycystic kidney
disease(ADPKD)
• ADPKD is the most common inherited kidney
disorder, occurring in 1 of 400 to 1000 live
births.
• It accounts for about 5% of the end-stage
renal disease (ESRD) cases in the United
States.
• ADPKD is a multisystem disorder that affects
almost every organ ; however, its hallmark is
the gradual and massive cystic enlargement of
the kidneys, resulting in kidney failure.

4. Pathogenesis
• Two genes have been implicated in the pathogenesis of
ADPKD.
• PKD1 mutations account for 85% & PKD2 mutations
account for 15%.
• PKD2 mutations impart a milder disease.
• PKD2 mutations develop ESRD at a later age than with
PKD1 mutations (median age of onset of ESRD 74 vs.
54 years, respectively).
• PKD1 is located on the short arm of chromosome 16.
• PKD2 is located on the long arm of chromosome 4.

5. • Most renal cysts develop because of abnormal function of
the primary cilium that resides in all epithelial cells.
• ADPKD, cysts form from all segments of the nephron.
• Less than 5% of all nephrons become cystic in ADPKD.
• Epithelial cell proliferation, fluid secretion, and
alterations in extracellular matrix result in focal out
pouching from the parent nephron.
• Most cysts detach from the parent nephron when cyst size
exceeds 2 cm, and continue to secrete fluid autonomously,
resulting in cyst and kidney enlargement, and progressive
loss of kidney function.

6. Diagnosis
Diagnostic ultrasonographic criteria:
Age Diagnostic criteria
15 to 39 years At least three (unilateral or
bilateral) renal cysts.
40 to 59 years Two cysts in each kidney
Older than 60 Four or more cysts in each
kidney
For patients with no
family history
At least five cysts bilaterally
by the age of 30 and a
phenotype consistent with
ADPKD required

7. CT or MRI:
o For evaluation as a potential kidney donor.
o For family-planning purposes.
o They detect smaller cysts.
Genetic testing:
o Mutation screening using direct sequencing of the
PKD1 or PKD2 genes is commercially available.
o Both the cost of the test and its ability to detect
mutations in only up to 85% of individuals restricts
its use.
o Current mutation detection rates are 75% and 95% for
PKD1 and PKD2 genes, respectively.

8. Manifestations and Complications
• Kidney enlargement:
o A universal feature of ADPKD.
o Kidney enlargement precedes the loss of kidney function by
decades
o Individuals with multiple cysts in small kidneys should be
screened for other cystic diseases.
o Total kidney volume is a good predictive biomarker for the
development of future glomerular filtration rate (GFR) loss,
with potential application in clinical practice.

9. Gross pathology of the autosomal dominant
polycystic kidney disease kidney.

10. • Hematuria:
o Gross or microscopic.
o 35% to 50% of patients.
o Occurs before the loss of kidney function.
o It is associated with increased kidney size and with worse
kidney outcomes.
o Precipitated by trauma, heavy exertion, cyst rupture, lower
UTI, pyelonephritis, cyst infection, or nephrolithiasis.
o ADPKD patients are typically advised to avoid heavy and
high-impact exercise.

11.  Occurs in enlarged kidney.
 Hematuria and fever,
 localized pain is the only presenting complaint.
 The diagnosis of a cyst hemorrhage is based on clinical evaluation and can
be difficult to differentiate from renal cyst infection.
 CT scan can occasionally be helpful in locating hemorrhagic cysts.
 The management for uncomplicated cyst hemorrhage and hematuria is
supportive, and includes hydration, rest, pain control, and often
withholding antihypertensive medications until the acute episode has
resolved.
Cyst hemorrhage

12. Lower
urinary
tract
infection
s:
• Common among ADPKD patients, as in the general population.
• The treatment is the same as in the general population
Pyelonep
hritis&
Renal
cyst
infections
.
.
• Fever and flank pain.
• Blood cultures more identify the pathogen than urine cultures.
• Treatment requires a course of 4 ws with antibiotics that penetrate
into the cyst, such as quinolones, vancomycin, chloramphenicol, or
trimethoprim-sulfamethoxazole.
Nephroli
thiasis
• 5 to 10 higher than general population.
• Anatomic deformities and hypocitraturia.
• Uric acid stone is the most common followed by calcium oxalate.
• NCCT is the modality of choice for diagnosis.
• The medical management is similar to that in non-ADPKD patients

13. • Pain:
• The most common symptom found in ADPKD.
• Acute or chronic.
ACUTE
-Cyst rupture,
cyst infection,
stone.
CHRONIC
-Massive
enlargement,
-lower back.

14. • Hypertension:
• Common and early manifestation of ADPKD affecting more than
60% of patients.
• Age of onset is 29 years.
Pathogenesis:
• Severe among PKD1 versus PKD2 patients.
• Hypertension is also associated with a greater rate of kidney
enlargement.
• A relationship between cyst expansion and elevations in blood
pressure.
• ADPKD kidneys have an attenuated vasculature with evidence of
intrarenal arteriolar tapering.
• Reduction of blood flow correlates inversely with kidney volume.
• All these findings suggest that renal ischemia induced by cyst
expansion plays a role in the etiology of hypertension, and studies
have confirmed the intrarenal activation of the renin-angiotensin-
aldosterone system.

15. • Kidney function:
• Remains normal for decades despite significant cyst expansion
and kidney enlargement.
• After kidney function becomes impaired, progression is
typically universal and rapid, with an average decline in GFR
of 4.0 to 5.0 mL/min/yr.
• Other manifestation:
• Increases thirst.
• Polyuria.
• Nocturia.
• Urinary frequency.
• A decrease in urinary concentrating ability is one of the
earliest manifestations.

16. Predictors for progression to ESRD in
ADPKD
Gender
Male
Onset of
HTN
Early age
Proteinuria
Detectable
Genotype
PKD1

17. Total kidney volume
• It incorporates all of the aforementioned risk
factors.
• The strongest predictor of future GFR loss.
• Total kidney volume of greater than 600 mL/m
accurately predicted the development of CKD
stage 3 within 8 years.
• For each 100 mL/m change in total kidney
volume, there was a 48% increase in the risk of
reaching CKD stage 3.

18. Extrarenal Manifestations
• Polycystic liver disease:
• Hepatic cysts are the most common extrarenal
manifestation in ADPKD.
• Hepatic function is preserved even in the
presence of massive liver cystic disease, and
biochemical tests are normal except for mild
elevation in alkaline phosphatase.
• Cardiovascular manifestations:

19. • Intracranial aneurysms (ICAs)
• Intracranial aneurysms (ICAs) are the most feared
complication of ADPKD.
• Ruptured aneurysms contribute to 4% to 7% of deaths
among ADPKD patients, and they are associated with an
immediate mortality of more than 50% and permanent
morbidity of more than 80%.
• Screening is indicated in asymptomatic patients with a
positive family history for ICA or previous history of
intracranial hemorrhage, those with high-risk
occupations, or before major elective surgery that would
affect intracranial hemodynamics.
• The imaging modality of choice for screening is three-
dimensional MRA.

20. • Elective surgical intervention is recommended
in larger aneurysms (greater than 10 mm).
• For asymptomatic unruptured ICAs between 5
and 10 mm, the management should be
individualized in consultation with the treating
neurosurgeon and neuroradiologist.
• For those with an ICA smaller than 5 mm, the
risk of rupture is relatively small.
• Risk factors for aneurysmal growth include
smoking and hypertension.

21. • Left ventricular hypertrophy (LVH) 48%
• Intracoronary aneurysms, Mitral valve
prolapse and regurgitation 26%
• Aortic insufficiency 11%

22. Therapy
• Current recommendations for target blood-
pressure level and the initial pharmacologic
therapy for ADPKD are targeting blood
pressure below 130/80 mm Hg using ACE
inhibitors or ARB.
• Dietary modifications, including abstinence
from caffeine and increased water intake.

23. • Vasopressin V2 receptor antagonists Tolvaptan
• Sirolimus decrease kidney cyst
• Everolimus use was associated with a high rate
of serious adverse events.

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