Contrast-enhanced Ultrasound of the Kidney

This is an investigator-initiated, prospective study designed to evaluate the accuracy of
contrast-enhanced ultrasound (CEUS) with microbubble contrast agent (perflutren lipid;
Definity®) to identify malignancy in patients with kidney disease, a known risk factor for
kidney malignancy, in whom a conventional ultrasound (US) shows an indeterminate cystic
kidney lesion.

The primary objective of the study is to estimate the sensitivity of CEUS in diagnosing
kidney malignancy in patients with a risk factor for kidney malignancy and compare it to the
current gold standard test in this patient population. Secondary analysis will include more
optimal contrast-enhanced imaging with computed tomography (CT) or magnetic resonance imaging
(MRI) in a subset of patients who can receive these studies. The study outcome will lead to
immediate clinical application in patients with chronic kidney disease. Given the
cost-effectiveness and adverse event profile, it has excellent potential to become
established as first line diagnostics in the general patient population as well.

Inclusion Criteria:

To be eligible for the present study, patients must meet the following criteria:

1. Able to provide written informed consent

2. Willing to comply with protocol requirements

3. At least 18 years of age

4. Have kidney disease, defined as either CKD II-VI, determined by estimated glomerular
filtration rate (GFR) of <90 and derived from serum creatinine measurements, or
albuminuria/proteinuria, determined by albumin to creatinine ratio or protein to
creatinine ratio of >30mg/gm, or having received a kidney transplant

5. Have at least one kidney lesion identified but incompletely characterized on a
non-contrasted US, CT, or MR exam for which the patient's provider recommends
follow-up studies or further evaluation with an additional imaging tests.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded for enrollment:

1. Critically ill or medically unstable and whose critical course during the observation
period would be unpredictable (e.g., chronic obstructive pulmonary disease (COPD)
requiring oxygen)

2. Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid
(Definity®)

3. Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure
>90mmHg), or adult respiratory distress syndrome

4. Active cardiac disease including any of the following:

- Severe congestive heart failure (class IV in accordance with the classification
of the New York Heart Association)

- Unstable angina.

- Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation;
ventricular premature complexes occurring close to the preceding T- wave,
multifocal complexes).

- Myocardial infarction within 14 days prior to the date of proposed Definity®
administration.

- Uncontrolled systemic hypertension (systolic blood pressure (BP) >180 mm Hg
and/or diastolic BP >100 mm Hg despite optimal medical management

5. Is in an intensive care setting

6. Has an unstable neurological disease (e.g cerebrovascular accident (including
transient ischemic attacks (TIAs) within the 3 months before signing of informed
consent

7. Has undergone an invasive procedure on kidney lesion (e.g. tissue biopsy, surgery,
nonsurgical cytoreductive procedure) since identification of lesion via US without
contrast

8. Has any other medical condition or other circumstances that would significantly
decrease the chances of obtaining reliable data or of achieving the study objectives
such as:

- Mental illness

- Drug abuse

9. Female patient who is pregnant or lactating (the possibility of pregnancy has to be
excluded by negative serum or urine beta human chorionic gonadotropin results,
obtained within 24 hours before the perflutren lipid administration, or on the basis
of patient history, e.g.: tubal ligation, hysterectomy or a minimum of 1 year without
menses)

10. Obesity that limits obtainment of acceptable images