Megan T. Bing, MD
James A. Brown, MD, FACS
BASICS
DESCRIPTION
• Inherited disease characterized by bilateral development of renal and extrarenal cysts with variable progression to ESRD, requiring either dialysis or transplantation
• Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of genetic kidney disease leading to chronic kidney disease
EPIDEMIOLOGY
Incidence
• 1–2:1,000 live births
– Occurs worldwide and in all races
– 4.4% of patients with renal replacement therapy have ADPKD
Prevalence
• 1:400 to 1:1,000
– Renal volume increases 5.27% per year as cysts grow
RISK FACTORS
• Having a family member with ADPKD
– Inherited in autosomal dominant fashion
– Ages range from infant to elder
Genetics
• 1:1,000 carry mutant gene
• Autosomal dominant with 100% penetrance
• Genetically heterogenous: 2 genes
– PKD1 (16p13.3) (Type 1 ADPKD)
Accounts for 85% of cases
More severe disease
Encodes polycystin-1 (PC1)
– PKD2 (4q21) (Type 2 ADPKD)
Accounts for 15%
Less severe disease
Encodes polycystin-2 (PC2)
PATHOPHYSIOLOGY
• Loss of PC1 or PC2 results in inability of tubular cells to maintain polarity, increased rate of proliferation and apoptosis, increased cellular secretion and remodeling of extracellular matrix (ECM)
– Epithelial cell growth
– ECM remodeling
– Na+-K+ ATPase found apically which leads to abnormal flow of fluid
ASSOCIATED CONDITIONS
• Abdominal wall hernia
• Cardiac valvular abnormalities
• Colon diverticula
• Hepatic cysts from 29–73%
• Splenic and pancreatics in a small percentage
• Intracranial aneurysms
– Only screen if patient has previous rupture
– Saccular “berry” aneurysm of cerebral arteries in 3–13%
• Pancreatic cysts
• Polycystic liver disease
GENERAL PREVENTION
Genetic and prenatal counseling
DIAGNOSIS
HISTORY
• Typical presentation is 30- to 50-yr-old patient with HTN, hematuria, flank pain
• Calculi may also be present
• Family history: 3 generations with cystic renal disease
PHYSICAL EXAM
• HTN, hypertensive retinopathy
• Heart murmur
• Enlarged kidneys on abdominal exam
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum Cr may be elevated
• BUN may be elevated
• Hematuria on UA
– In up to 50% and often the initial presenting symptom
Imaging
• Imaging is the main diagnostic tool
• Plain abdominal radiographs: Limited in early-stage disease; later may indicate displacement of organs with or without calcifications
• US
– With unknown genotype, the presence of 3 or more (unilateral or bilateral) renal cysts establishes the diagnosis in 15–39 yo, 2 or more cysts in each kidney is sufficient if aged 40–59 yr, and 4 or more cysts in each kidney is required for individuals ≥60 yr
– Conversely, <2 renal cysts in at-risk individuals aged ≥40 yr are sufficient to exclude the disease
• CT and MRI methods have greater sensitivity compared to US for detecting cysts <1 cm and in evaluating individual cysts for hemorrhage or malignancy
– Hemorrhagic renal cysts are fairly common
– On MRI uncomplicated cysts resemble simple cortical cysts
Homogeneous low signal intensity on T1 and high signal intensity on T2
• Echocardiography
– Evaluate for mitral prolapse
Diagnostic Procedures/Surgery
Cytogenetic analysis: May be needed when FH or imaging is equivocal
Pathologic Findings
• Gross pathology
– Bilaterally enlarged kidneys with multiple colored and fluid-filled cysts
• Histopathology
– Multicystic renal dysplasia in cortex and medulla
– Sclerosis
DIFFERENTIAL DIAGNOSIS
• Patients >10 yr old
– Simple cysts
Simple cyst not common <30 yr of age
>4 simple cysts in each kidney is rare
– Localized renal cystic disease
– Medullary sponge kidney
– Bilateral parapelvic cysts
– Autosomal recessive polycystic kidney disease (ARPKD)
– Tuberous sclerosis complex
– Von Hippel–Lindau disease
– Medullary cystic disease
– Orofaciodigital syndrome type I
– Autosomal dominant polycystic liver disease: Liver lesions predominate but also have renal cysts; genetic testing may be needed to differentiate
• Patients <10 yr of age
– Contiguous PKD1–TSC2 deletion syndrome
– ARPKD
– Meckel–Gruber syndrome
TREATMENT
GENERAL MEASURES
• Increase fluid intake
• Coordinated care with nephrology
• Protein-restricted diet is controversial
• Neurosurgery consult if intracranial aneurysm is present (1)
MEDICATION
First Line
• Hypertension:
– Angiotensin-converting enzyme (ACE) inhibitors (ie, captopril, enalapril, lisinopril) or
– Angiotensin II receptor blockers (ARBs) such as telmisartan, losartan, irbesartan, and candesartan
• Hyperlipidemia: Statin
Second Line
• Somatostatin (2)
• Inhibitors of mTOR
SURGERY/OTHER PROCEDURES
• Renal replacement therapy (2,4)
– Renal transplantation
– Hemodialysis/peritoneal dialysis
• Percutaneous cyst aspiration
– <200 mL
– Sclerosing agent should be used
• Cyst decortication—typically for pain with large dominant cysts(s)
– 95–100% success rate for relieving pain
– Initial improvement in lowering HTN, but not sustained
• Nephrectomy
– Disabling symptoms due to massively enlarged kidneys
– Worsening or development of ventral (abdominal wall) hernias
– Nephrectomy may be considered before renal transplant
Suspected malignancy
Recurrent infection
Extension of the polycystic kidney into the potential pelvic surgical transplant location
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Infection: Lipid soluble antibiotic (sulfamethoxazole and trimethoprim or ciprofloxacin)
• Chronic pain: Avoid NSAIDs
• A small, randomized, placebo-controlled trial found that intramuscular octreotide slowed progression of renal cystic disease
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Renal function usually normal until the 4th decade of life
• Disease diagnosed in utero carries a poor prognosis
• Patients on RRT carry the same or better prognosis than non-ADPKD patients on RRT
• Risk factors for progression:
– Genetic factors (PKD1 vs. PKD2)
– Hypertension
– Early onset of symptoms including proteinuria and hematuria
– Male gender
– Increased kidney size (kidney size is greater with PKD1 mutations)
– Increased left ventricular mass index
– Dipstick detectable proteinuria
– Low birth weight
– Decreased renal blood flow
– Increased urinary sodium excretion
– Increased LDL cholesterol
– Increased plasma copeptin (surrogate marker for vasopressin)
• With more advanced renal disease, ACE inhibitors and ARBs can cause hyperkalemia or worsen renal failure. Monitoring of serum chemistries is essential
• When screening family members with a family history of ADPKD data suggests that individuals >40 yr with a family history but without renal cysts are unlikely to develop ADPKD
COMPLICATIONS
• Cerebral hemorrhage
• Chronic kidney disease
• Renal cell carcinoma risk is not elevated; but when present is often bilateral and multicentric
– Often present with fever
• Proteinuria
• Chronic pain
– Nephrolithiasis in 25% of patients
• Pyelonephritis
• Cyst rupture
• Rarely portal HTN, cholangiocarcinoma
FOLLOW-UP
Patient Monitoring
• Follow BUN and Cr
• Prenatal testing for ADPKD is clinically available if the mutation has been identified in an affected family member or if linkage has been established in the family
Patient Resources
• www.pkdcure.org
• www.pkdinternational.org
REFERENCES
1. Agarwal MM, Hemal AK. Surgical management of renal cystic disease. Curr Urol Rep. 2011;12:3–10.
2. Caroli A, Perico N, Perna A, et al. Effect of long-acting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): A randomised, placebo-controlled, multicentre trial. Lancet. 2013;382(9903):1485–1495.
3. Harris PC, Torres VE. Polycystic kidney disease. Ann Rev Med. 2009;60:321–337.
4. Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: The last 3 years. Kidney Int. 2009;76:149–168.
ADDITIONAL READING
• Grantham JJ. The etiology, pathogenesis, and treatment of autosomal dominant polycystic kidney disease: Recent advances. Am J Kidney Dis. 1996;28:788–803.
• Helal I, Reed B, Schrier RW, et al. Emergent early markers of renal progression in autosomal-dominant polycystic kidney disease patients: Implications for prevention and treatment. Am J Nephrol. 2012;36:162–167.
• Steinman TI. Polycystic kidney disease: A 2011 update. Curr Opin Nephrol Hypertens. 2012;21:189–194.
See Also (Topic, Algorithm, Media)
• Acquired Renal Cystic Disease
• Polycystic Kidney Disease, Autosomal Dominant Images 
• Polycystic Kidney Disease, Autosomal Recessive
• Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
• Renal Mass
• Retroperitoneal Mass and Cysts
CODES
ICD9
• 585.9 Chronic kidney disease, unspecified
• 753.13 Polycystic kidney, autosomal dominant
ICD10
• N18.9 Chronic kidney disease, unspecified
• Q61.2 Polycystic kidney, adult type
CLINICAL/SURGICAL PEARLS
• Lipid soluble antibiotics are needed for treatment of renal cyst infection.
• Abdominal pain and flank pain is common and may be due to infection, nephrolithiasis, or cyst hemorrhage.
• Cyst decortication is useful for large painful cysts.
• Patients with a personal or family history of cranial bleed need surveillance by neurosurgery.
• Acute cyst rupture usually best treated with pain control and observation.