Transcript Autosomal Dominant Polycystic Kidney Disease.

HPI
• 34 year old White female who presented to
the hospital with a complaint of abdominal
pain and fever x 2 days.
• (+) Decreased appetite
• (-) Nausea, vomiting, diarrhea
• Internal medicine was consulted and initially
started her on Rocephin 1g qd and did urine
and blood cultures
• Patient continued to have fever on Rocephin
so a CT of the abdomen and pelvis was
ordered
• Dx: Autosomal dominant polycystic kidney disease(ADPK)
• Renal cyst infection secondary to UTI was suspected
• IR placed a catheter into a cyst and drained purulent and
bloody fluid.
• Fluid culture grew E. Coli sensitive to ciprofloxacin
• Patient was then started on IV ciprofloxacin and her fever
and abdominal pain resolved
Autosomal Dominant Polycystic Kidney Disease
(ADPKD)
• Most common inherited renal disorder
• Characterized by the formation and progressive
enlargement of renal cysts which which are
destructive to renal parenchyma and often lead to
renal failure (ESRF) in late middle age
• Autosomal dominant!!!!!!!
• Affects 1/400-1000 people in the US
• Accountable for 10-12% all ESRD patients receiving
hemodialysis
• 200-400 thousand persons with ADPKD in US
• ~ 600 new cases per year
Autosomal Dominant Polycystic Kidney Disease
(ADPKD)
• Cyst formation probably begins in utero and
symptoms may rarely be present in newborns
• Cysts initially involve only portions of the
nephrons
• Asymptomatic and renal function is retained
until 4th- 5th decade of life
• Almost all patients experience renal failure by
80 years of age
Clinical Presentation
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Palpable mass
Abdominal pain
Gross hematuria
Hypertension
Renal failure
Complications
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Intracystic hemorrhage
Renal stones
Chronic pain symptoms
UTI
Cyst infection
Extrarenal Manifestations of ADPKD
• Cerebral aneurysms (20%)
• Hepatic cysts (60%)
• From biliary epithelium
• Pancreatic cysts (10%)
• Cardiac
• Mitral valve prolapse, bicuspid aortic valve, aortic
aneurysms, aortic dissections
• Colonic diverticula
• Abdominal wall and inguinal hernia
Causes of death
The main causes of death in ADPKD are:
• Uremia (ESRD)
• Atherosclerosis affecting coronary, intracranial
arteries
• Sudden rupture of intracranial aneurysms
• Sepsis
Gross appearance
Pathophysiology
• Caused by mutations of PKD1 and PKD2 genes on
chromosomes 16 and 4 respectively
• PKD1 codes for Polycystin-1 protein – function not
known; thought to be involved in cell-cell, cellmatrix interactions.
• PKD2 codes for Polycystin-2 protein – cation
channel involved in regulation of intracellular Ca2+
level.
Pathophysiology
• These defects result in altered tubular epithelial growth
and differentiation
– Abnormal extracellular matrix
– Increased cell proliferation
– Increased fluid secretion
• Formation of cysts
• PKD1 mutations are more common and account for 90%
of all ADPKD cases
• PKD1 associated with earlier onset renal failure
Differentials
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Autosomal recessive polycystic kidney disease
Multiple simple cysts
Von Hippel-Lindau (VHL) disease
Tuberous sclerosis
Acquired uremic cystic kidney disease
(hemodialysis)
• Medullary sponge kidney
• Multicystic dysplastic kidney
Diagnosis: Ultrasonography
• Ultrasonography is the most widely used technique
to diagnose ADPKD
• Findings: Diffuse hyperechogenicity, enlarged
kidneys, and cysts, usually bilateral
• Can detect cysts 1 – 1.5 cm
• 99% sensitivity for at risk patients >20 yo
– Higher false negatives in people < 20yo
• Not recommended as a routine diagnostic
procedure in patients < 14yo
Diagnosis: Ultrasonography
• No exposure to radiation or contrast material
• Inexpensive
• Also useful for evaluating extra-renal cysts in
the abdomen (liver, pancreas)
FIGURE 36.48. Autosomal Dominant Polycystic Disease. The kidney of a 57-year-old patient with
a family history of cystic renal disease shows replacement of the renal parenchyma with
innumerable cysts of varying size. Both kidneys were greatly enlarged.
Diagnosis: Computed tomography (CT)
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More sensitive than US
Can detect smaller cysts (0.5cm)
Involves radiation exposure
More expensive
Not used routinely for diagnosis or follow up
studies
• More useful in unclear or more complicated
cases in children
Diagnosis: MRI
• More sensitive than either US or CT
• More useful in distinguishing renal cell
carcinoma from cyst
• Used to monitor kidney size after treatment to
assess progress
• Not routinely used due to its high cost
Diagnosis: Intravenous Urography
• Used to be a widely used technique to
diagnosed ADPKD
• Involves contrast (nephrotoxic)
• Only helpful in the diagnosis of advanced
ADPKD with distortion of renal calyces
• No longer indicated
Diagnostic criteria
• At risk patients <30 yo
– at least 2 renal cysts (unilateral or bilateral)
• 30-59 yo
– At least 2 cysts in each kidney
• 60+ yo
– At least 4 cysts in each kidney
Treatment
• Treatment is primarily supportive care
• Control of HTN is important to slow disease
progression
– ACE-I, ARB
• Treating complications of renal failure
– Hyperkalemia, hyperphosphatemia, hypocalcemia,
acidosis
• Treating UTI and renal cyst infections
• Avoidings nephrotoxic agents (NSAIDS)
Treatment
• Surgical drainage and decompression of large
cysts is effective for pain relief
• ESRD patients require hemodialysis or renal
transplantation
References
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E., William, and Clyde A. Fundamentals of diagnostic radiology. 3rd ed. Lippincott
Williams & Wilkins, 2007. 949-950
D. Ravine, et al. Evaluation of ultrasonographic diagnostic criteria for autosomal
dominant polycystic kidney disease 1. The Lancet. Volume 343, Issue 8901, 2
April 1994, Pages 824-827.
Alkis M. Pierides, et al. Autosomal dominant polycystic kidney disease—type 2.
Ultrasound, genetic and clinical correlations. Nephrol. Dial. Transplant. (2000)
15 (2): 205-211.
Emedicine.com. (2010). Polycystic kidney disease. Retrieved: October 10, 2010
from http://emedicine.medscape.com/article/244907-overview
Emedicine.com. (2008). Autosomal Dominant Polycystic Kidney Disease. Retrived:
October 9, 2010 from http://emedicine.medscape.com/article/376995imaging
Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease.
Lancet. 2007;369(9569):1287-1301.
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