Approach Considerations
Ultrasonography is the procedure of choice in the workup of patients with autosomal dominant polycystic kidney disease (ADPKD). It is also ideal for screening patients' family members. Computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) are useful in selected cases. Other studies to perform include the following:
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Serum chemistry profile, including calcium and phosphorus
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Complete blood cell count
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Uric acid determination
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Intact parathyroid hormone assay
An increased hematocrit may result from increased erythropoietin secretion from cysts. A decrease in urine-concentrating ability is an early manifestation of the disease. Microalbuminuria occurs in 35% of patients with ADPKD. However, nephrotic-range proteinuria is uncommon.
Urinary proteomic biomarkers may have the potential for diagnosis and prognosis of ADPKD. In a large clinical proteomic study, Kistler et al reported that the performance of urinary peptidomic biomarker scores in ADPKD is superior to that of other biochemical markers in young patients with this disease and that proteomic profiling is potentially useful in the diagnosis and risk stratification of ADPKD. In the study, urine samples from 1048 patients were analyzed to characterize the urinary peptidomic pattern of patients with early-stage ADPKD. [33]
Genetic testing
Genetic testing may be performed. Genetic testing can accurately differentiate ADPKD, autosomal recessive polycystic kidney disease (ARPKD), and autosomal dominent polycystic liver disease (ADPLD). In ADPKD, the presence of either PKD1 or PKD2 subtypes changes the prognosis and may help guide clinical management. [3]
Genetic testing by means of DNA linkage analysis has an accuracy rate greater than 95% for ADPKD1 and ADPKD2. Mutation screening is commercially available.
A major indication for genetic screening is in young adults with negative ultrasonographic findings who are being considered as potential kidney donors. [6]
Staging by glomerular filtration rate
Staging of kidney failure is as follows:
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Stage 1 – Glomerular filtration rate (GFR) >90 mL/min
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Stage 2 - GFR 60-90 mL/min
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Stage 3 - GFR 30-60 mL/min
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Stage 4 - GFR 15-30 mL/min
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Stage 5 - GFR < 15 mL/min
Other studies
Intravenous urography was once widely used in the diagnosis of ADPKD. Among its disadvantages are that it involves contrast medium and it is diagnostic only in advanced-stage ADPKD when distortion of calyces has developed. It is no longer indicated to establish a diagnosis of the disease.
Barium enema may be used to help diagnose colonic diverticula. Doppler studies and 2-dimensional echocardiography are used to exclude mitral prolapse, which is often associated with ADPKD.
Screening for intracranial aneurysm
Intracranial aneurysms are at least twice as common in patients with ADPKD as in the general population. [34] On screening, intracranial aneurysms are found in approximately 10% of asymptomatic patients with ADPKD. [35] Indications for screening, which is done with time-of-flight MRA, include the following [34] :
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Before major elective surgery
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Central nervous system signs or symptoms (eg, nausea and vomiting, lethargy, photophobia, focal signs, seizure, transient ischemic attack, loss of consciousness)
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Family history of intracranial aneurysm or intracranial hemorrhage
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High-risk occupation (eg, airline pilot)
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New-onset severe headache
Ultrasonography
Ultrasonography is the most widely used imaging technique to help diagnose ADPKD. [36] It can detect cysts from 1-1.5 cm. This study avoids the use of radiation or contrast material, is widely available, and is inexpensive. The sensitivity of ultrasonography for ADPKD1 is 99% for at-risk patients older than 20 years; however, false-negative results are more common in younger patients. Sensitivity for ADPKD2 is lower and is still not well defined.
Ultrasonography is also useful for exploring abdominal extrarenal features of ADPKD (eg, liver cysts, pancreatic cysts).The presence of hepatic or pancreatic cysts supports the diagnosis of ADPKD.
Ultrasonographic diagnostic criteria for ADPKD1 were established by Ravine et al in 1994 and are as follows [7] :
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At least 2 cysts in 1 kidney or 1 cyst in each kidney in an at-risk patient younger than 30 yearsAt least 2 cysts in each kidney in an at-risk patient aged 30-59 years
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At least 4 cysts in each kidney for an at-risk patient aged 60 years or older
Ultrasonographic diagnostic criteria for ADPKD in patients with a family history but unknown genotype were established by Pei et al in 2009 and are as follows [8] :
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Three or more (unilateral or bilateral) renal cysts in patients aged 15-39 years
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Two or more cysts in each kidney in patients aged 30-59 years
The presence of fewer than 2 renal cysts provides a negative predictive value of 100% and can be considered sufficient for ruling out disease in at-risk individuals older than 40 years of age.
CT, MRI, and MRA
CT is more sensitive than ultrasonography and can detect cysts as small as 0.5 cm. However, it exposes the patient to radiation and is more expensive; therefore, it is not used routinely for diagnosis or for follow-up studies of ADPKD. CT may be useful in doubtful cases in children or in complicated cases (eg, kidney stone, suspected tumor).
MRI is more sensitive than either ultrasonography or CT scanning. It may be more helpful in distinguishing renal cell carcinoma from simple cysts.
MRI is the best imaging tool for monitoring kidney size after treatment to assess progress, and it is the criterion standard to help determine renal volume for clinical trials of drugs for ADPKD. However, it is not routinely used because it is expensive and tedious. It should not be used unless the patient is in a protocol or similar situation.
Spithoven et al reported that determining measured total kidney volume (TKV) by MRI and manual tracing took an average of 55 minutes, but a recently proposed MRI method for estimating TKV, eTKVellipsoid, required an average of only 5 minutes. In their comparison study, eTKVellipsoid performed relatively well compared with mTKV and could detect change in TKV over time. [37]
Magnetic resonance angiography (MRA) is the preferred imaging technique for diagnosing intracranial aneurysms (ICAs). It is used selectively rather than routinely. Indications for this study are as follows [9, 10] :
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Family history of stroke or ICA
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Development of symptoms suggesting an ICA
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Job or hobby in which a loss of consciousness may be lethal
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Past history of ICA
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Polycystic kidney.
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Polycystic kidney disease and massive polycystic liver disease.
