Approach

The goal is to confirm autosomal-dominant PKD (ADPKD) diagnosis and to then classify the patient’s risk of progression to kidney failure on the basis of the combination of clinical, genetic, and imaging factors.[35] Extrarenal manifestations and evidence of long-term complications of ADPKD also need to be ascertained.

  • A positive family history of ADPKD, with signs and symptoms of renal and/or extrarenal manifestations, is highly suggestive of ADPKD. Definitive diagnosis is from imaging studies of the kidneys, or genetic testing if imaging is inconclusive.[4]

  • A likely diagnosis may be considered in patients without a positive family history, and the presence of renal cysts, with or without hepatic cysts, in the absence of other manifestations is suggestive of a different renal cystic disease.[11] However, genetic testing is indicated for a definitive diagnosis in these patients.[1] At least 10% to 15% of patients with a negative family history will have a new mutation.[1]

Appropriate counseling should be done before testing (imaging or genetic) for PKD.[21] Potential discrimination, in terms of insurability and employment, associated with a positive diagnosis should be discussed.[1]

History

Family history may include ADPKD, end-stage renal disease (ESRD), intracranial aneurysm, hemorrhagic stroke, or subarachnoid hemorrhage. For adults with a family history of ADPKD, diagnosis may be made presymptomatically by abdominal imaging.[1] 

Common presenting symptoms include flank/abdominal pain, renal colic, and gross hematuria, and, less commonly, headaches.[1][11][36] Urinary tract infections (UTIs) occur in 30% to 50% of adult patients with PKD.[1] Patients with lower tract UTIs present with a history of dysuria, urgency, and suprapubic pain. UTIs involving the renal parenchyma or cysts typically present with flank pain and fever. Patients with kidney stones may present with flank pain, hematuria, dysuria, and fever. Heartburn, reflux, nausea, dyspnea, early satiety, or increased abdominal girth may occur with severe hepatic disease.[37] There is an association between ADPKD and diverticulosis in the presence of ESRD.[38]

Physical exam

Abdominal examination often reveals a palpable renal or hepatic mass. ADPKD is characterized by progressive enlargement of innumerable renal cysts and kidney size, which increases exponentially with age.[26] Kidneys become massively enlarged and may be associated with significant morbidity from the additional mass and weight.[39] Polycystic liver disease is present in over 90% of individuals with ADPKD ages older than 35 years.[4][37] Hepatomegaly is commonly present even before detection of liver cysts by imaging.[38]

Hypertension is common and often occurs at a relatively young age with an average age of onset of between 30 to 34 years.[7] Detection of hypertension before any of the other clinical manifestations is often how the disease is first detected in young patients.[1] 

Inguinal, incisional, or paraumbilical hernias are often present.[31][38] A cardiac murmur may be present, suggestive of mitral valve prolapse, mitral regurgitation, aortic regurgitation, or dilated aortic root.[1]

Laboratory tests

Serum electrolytes, blood urea nitrogen, creatinine, and fasting lipid profile should be ordered initially. Creatinine can be used to estimate glomerular filtration rate.[31] Elevated lipids may be associated with a higher likelihood of progressive renal insufficiency.[40]

Urinalysis should be ordered in all patients to detect presence of increased urinary albumin excretion or proteinuria. If increased urinary albumin excretion or proteinuria are found, this indicates a higher likelihood of progression to chronic kidney disease.[31][40] Microscopic or macroscopic hematuria is common. Leukocyturia can be seen in people with PKD, but it does not always indicate UTI, and a urine culture should be obtained in that situation. Urine culture should always be obtained at initial evaluation if there are symptoms of UTI or fever.[1] Urine culture may be negative even with serious urine infection, because cysts do not communicate with the urinary tract. In patients with abdominal or flank pain and/or tenderness and fever, a C-reactive protein should be requested.[1] All patients with metabolically active stone disease should have 24-hour urine collection for urine biochemistry (urine volume, pH, oxalate, uric acid, citrate, phosphate, sodium, and calcium, as well as creatinine to assess the completeness of the collection), and supersaturation should be calculated. Low urine citrate and urine pH are the main metabolic factors predisposing to stone formation in ADPKD.[41]

Renal imaging

Imaging shows the presence of renal cysts with, or without, hepatic cysts. Ultrasonography is the most common initial test to order because of low cost, wide availability, and safety.[4][31] Unified ultrasound diagnostic criteria for the diagnosis of ADPKD in at-risk people (those from families with ADPKD of unknown genotype) have been developed.[42] The presence of at least three (unilateral or bilateral) renal cysts and two cysts in each kidney is sufficient for diagnosis of at-risk individuals ages 15 to 39 and 40 to 59 years, respectively; in those over 60 years, four or more cysts in each kidney is required.[42] These criteria should not be applied to magnetic resonance imaging (MRI) or computed tomography (CT) scans as could lead to false-positive results.

Contrast-enhanced CT scan or MRI detect cysts of 2 to 3 mm in diameter and are particularly useful for diagnosis in younger patients.[4] In patients at risk of ADPKD younger than 30 years of age, a test criterion of a total of >10 renal cysts seen on MRI is considered sufficient for diagnosis.[43] The use of CT needs to be weighed against the radiation dose. 

Imaging by CT scan or MRI should be part of the initial evaluation of ADPKD, as it provides precise, standardized measurement of maximum kidney length, width, and depth measurements, and an estimate of total kidney volume.[31] These quantitative data are of prognostic value.[1] An image-based classification system based on total kidney volumes from CT scan or MRI has been used to identify potential cases of more rapidly progressive disease. This classification system optimizes patient selection for specific disease therapy.[44]

In patients with a negative family history, imaging-based diagnosis is not sufficient because criteria were developed in individuals who had a 50% risk of ADPKD.[4] A likely diagnosis of ADPKD can be considered if, despite no family history, there are >10 cysts in each kidney, and there is no evidence of renal or extrarenal manifestations of another cystic renal disease that could explain the phenotype; however, genetic testing is indicated to confirm diagnosis.[1][11]

A positron emission tomography scan is more sensitive than CT or MRI for detecting cyst infections.[1]

[Figure caption and citation for the preceding image starts]: CT scan of abdomen and pelvis of patient with mild diseaseFrom collection of Dr M. Hogan [Citation ends].com.bmj.content.model.Caption@192d64f6[Figure caption and citation for the preceding image starts]: MRI of abdomen and pelvis of patient with symptomatic polycystic kidney diseaseFrom collection of Dr M. Hogan [Citation ends].com.bmj.content.model.Caption@4885cd74 

Investigation of extrarenal manifestations

Cardiovascular abnormalities include hypertension, left ventricular hypertrophy, aortic root dilatation, arterial aneurysms, heart valve abnormalities, and intracranial aneurysms.[1] ECG and echocardiogram are used for the initial assessment of cardiovascular complications such as left ventricular hypertrophy (can be present without hypertension), cardiac function (e.g., ejection fraction, diastolic dysfunction), and valvular abnormalities.[45]

CT scan and MRI may also provide evidence of extrarenal cysts. Hepatic cysts are the most common extrarenal manifestation.[1] Pancreatic cysts (prevalence 9% on ultrasound screening, 36% on MRI) are almost always asymptomatic with rare occurrences of recurrent pancreatitis.[38] Pancreatic cysts are rarely associated with intraductal papillary mucinous tumor or carcinoma.[38] Additionally, if nephrolithiasis is suspected, CT or MRI imaging can differentiate stone disease from cyst wall calcification or parenchymal calcifications. About 20% of patients have kidney stones, and the composition of these is typically uric acid or calcium oxalate.[41][46]Dual-energy CT is a useful method to discriminate uric acid stones from other (non-uric acid) renal stones.[31]

The presence of intracranial aneurysms is four times higher in patients with ADPKD than in the general population.[4] Identification of sentinel headaches and prompt diagnosis and treatment of a leaking aneurysm is an important determinant of outcome.[34] If subarachnoid hemorrhage is suspected, a noncontrast head CT is performed, which, if nondiagnostic, should be followed by lumbar puncture.[47]​ If these tests are positive, the patient should be admitted immediately to a neurosurgical intensive care unit for vessel imaging, usually a CT angiogram, and treatment of the leaking intracranial aneurysm.[48] See our topics Cerebral aneurysm and Subarachnoid hemorrhage.

Diagnostic lumbar puncture in adults: animated demonstration
Diagnostic lumbar puncture in adults: animated demonstration

How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.

Genetic testing

Genetic testing can be used in the following cases:[21]

  1. The imaging results are equivocal or inconclusive

  2. To confirm a presumed diagnosis in the absence of family history of the disease (conclusive proof of the diagnosis in these patients relies on mutation analysis)

  3. When a definite diagnosis is required in a younger patient, such as a potential living related kidney donor

  4. For prenatal and preimplantation genetic testing.

Mutations in the PKD1 gene cause more severe disease than those in the PKD2 gene.[2] Genetic testing for PKD1 mutation screening is expensive and challenging due to its large size and complexity.[21] It can be done by linkage or sequence analysis; however, sequence analysis is preferred. Despite comprehensive screening, 10% to 15% of patients suspicious of ADPKD have no mutation detected in either PKD1 or PKD2.[21] Patients can be rescreened for mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism.[20] If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[55]​ All published mutations and other variants are publicly available in the ADPKD variant database. PKD Foundation: ADPKD variant database Opens in new window If a mutation is known in one family member, this mutation can be confirmed in other family members at a considerably lower cost.

An emerging approach is whole-exome sequencing. In one validation study, whole-genome sequencing was able to overcome pseudogene homology and identify all types of variants in the PKD1 gene.[19]

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