Please select the eligibility criteria that correspond to the clinical trial below.
Title: HALT Progression of Polycystic Kidney Disease Study A
Brief Summary: The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two multicenter randomized clinical trials targeting different levels of kidney function: 1) early disease defined by GFR \>60 mL/min/1.73 m2 (Study A); and 2) moderately advanced disease defined by GFR 25-60 mL/min/1.73 m2 (Study B; NCT01885559). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study A will be followed for at least 5 years, while those enrolled in Study B will be followed for five-to-eight years, with the average length of follow-up being six and a half years. The two concurrent randomized clinical trials differ by eligibility criteria, interventions and outcomes to be studied.


Options:
A: Inclusion Criteria:

* Diagnosis of ADPKD.
* Age 15-49 (Study A); Age 18-64 (Study B).
* GFR \>60 mL/min/1.73 m2 (Study A); GFR 25-60 mL/min/1.73 m2 (Study B).
* BP ≥130/80 or receiving treatment for hypertension.
* Informed Consent.

Exclusion Criteria:

* Pregnant/intention to become pregnant in 4-6 yrs.
* Documented renal vascular disease.
* Spot urine albumin-to-creatinine ratio of \>0.5 (Study A) or ≥1.0 (Study B) and/or findings suggestive of kidney disease other than ADPKD.
* Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of \>126 mg/dl / random non-fasting glucose of \>200 mg/dl.
* Serum potassium \>5.5 milliequivalent per liter (mEq/L) for participants currently on ACE-I or ARB; \>5.0 mEq/L for participants not currently on ACE-I or ARB.
* History of angioneurotic edema or other absolute contraindication for ACE-I or ARB. Intolerable cough associated with ACE-I is defined as a cough developing within six months of initiation of ACE-I in the absence of other causes and resolving upon discontinuation of the ACE-I.
* Indication (other than hypertension) for β-blocker or calcium channel blocker therapy (e.g. angina, past myocardial infarction, arrhythmia), unless approved by the site principal investigator. (PI may choose to accept an individual who is on only a small dose of one of these agents and would otherwise be eligible.)
* Systemic illness necessitating nonsteroidal antiinflammatory drugs (NSAIDs), immunosuppressant or immunomodulatory medications.
* Systemic illness with renal involvement.
* Hospitalized for acute illness in past 2 months.
* Life expectancy \<2 years.
* History of non-compliance.
* Unclipped cerebral aneurysm \>7mm diameter.
* Creatine supplements within 3 months of screening visit.
* Congenital absence of a kidney (also total nephrectomy for Study B).
* Known allergy to sorbitol or sodium polystyrene sulfonate.
* Exclusions specific to magnetic resonance imaging (Study A).
B: Inclusion Criteria:

* Male or female ADPKD patient between 18 and 40 years of age
* measured GFR higher than 70 ml/min 1.73m2
* documented kidney volume progression
* informed consent

Exclusion Criteria:

* Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
* increased liver enzymes (2-fold above normal values)
* hypercholesterolemia (fasting cholesterol \> 8 mmol/l) or hypertriglyceridaemia (\> 5 mmol/l) not controlled by lipid lowering therapy
* granulocytopenia (white blood cell \< 3,000/mm3) or thrombocytopenia (platelets \< 100,000/mm3),
* infection with hepatitis B or C, HIV
* any past or present malignancy
* mental illness that interfere with the patient ability to comply with the protocol
* drug or alcohol abuse within one year of baseline
* co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
* co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
* known hypersensitivity to macrolides or Rapamune
C: Inclusion Criteria:

1. Diagnosis of ADPKD, based upon the modified Ravine criteria
2. Age between 18 and 60 years.
3. eGFR (MDRD) between 30 and 60 ml/min/1.73 m2.
4. Providing informed consent.

Exclusion Criteria:

1. Patients who, in the opinion of the study investigator may present a safety risk.
2. Patients who are unlikely to adequately comply with the trial's procedures \[due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or noncompliance).
3. a. Patients taking medications or having concomitant illnesses likely to confound endpoint assessments (e.g. nephrotoxic medications such as chronic NSAID, cyclosporine, lithium immunosuppressant use) b. Patients having concomitant illnesses likely to confound endpoint assessments (e.g. diabetes mellitus for which medication is needed and patients with proteinuria \> 1 g /24hr).
4. Patients who underwent surgical or drainage interventions for cystic kidney disease the year before study-entry or are likely candidates for these procedures within 2 years of start of the study.
5. Patients taking other experimental (i.e.,non approved by FDA/EMA or indication of ADPKD) therapies.
6. Patients having used Lanreotide (or another somatostatin analogue) in the 3 months before study start.
7. Patients with known intolerance for Lanreotide (or another somatostatin analogue).
8. Unwillingness to comply with reproductive precautions. Women who are capable of becoming pregnant must be willing to comply with approved birth control from two-weeks prior to, and for 60 days after taking investigational product.
9. Women, who are pregnant or breastfeeding.
10. Patients, who suffer from cardiac arrhythmias, that are thought to be dangerous in combination with lanreotide administration.
11. Patients, who ever suffered from symptomatic gallstones and did not undergo cholecystectomy.
12. Patients, who have a medical history of pancreatitis.
13. Patients, who have a medical history of infected liver cysts.

In addition:

* Patients, who underwent liver cyst drainage or surgery in the year before, can enter the study, but will not be assessed for change in liver volume.
* Patients having contraindications to, or interference with MRI assessments, as dictated by local regulation, will not be allowed to undergo MR imaging. However, these patients can enter the study, but will not be assessed for change in kidney and/or liver volume.
D: Inclusion Criteria:

* ADPKD, as confirmed by history, ultrasound, computed- or magnetic resonance tomography
* Eighteen years of age, or older
* Baseline eGFR below 60 mL/min per 1.73m2
* Negative serum pregnancy test prior to administration of sirolimus and agreement to use contraception throughout the study and three months after
* Written informed consent

Exclusion Criteria:

* Need for renal replacement therapy
* Pregnancy/lactation
* Plans to become pregnant in the near future
* Refusal to use sufficient contraception
* Proteinuria as defined as protein:creatinine ratio \>1000 or \>1g/d, respectively
* History of life threatening complications of ADPKD
* Evidence of active systemic- or localized major infection
* Evidence of infiltrate or consolidation on chest X-ray
* Use of any investigational drug or -treatment up to 4 weeks prior to enrolment and during the study
* Known allergy/hypersensitivity to sirolimus and its derivatives
* Medication that will interfere with the cytochrome P450 (CYP3A4/CYP3A5) system
* Total white blood cell count below or equal to 3000/mm3
* Platelet count below or equal to 100.000/mm3
* Fasting triglycerides above or equal to 400 mg/dL
* Fasting total cholesterol above or equal to 300 mg/dL
* Concomitant glomerular diseases
* Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
* History of malignancy, with the exception of adequately treated basal cell- and squamous cell carcinoma of the skin
* HIV positivity

Answer: A