Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, Multi-center, Open-label Study to Determine Long-term Safety, Tolerability and Efficacy of Split-dose Oral Regimens of Tolvaptan Tablets in a Range of 30 to 120 mg/d in Patients With Autosomal Dominant Polycystic Kidney Disease
Brief Summary: This study's purpose is to evaluate the long-term safety of open-label tolvaptan regimens to determine the maximally-tolerated dose and acquire pilot efficacy data in patients with autosomal dominant polycystic kidney disease (ADPKD).


Options:
A: 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
B: Inclusion Criteria:

* Prior participation in designated tolvaptan ADPKD studies (156-04-248, 156-04-249).
* Able to give Informed Consent.

Exclusion Criteria:

* Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
* In the opinion of the study investigator or sponsor may present a safety risk.
* Patients who are unlikely to adequately comply with study procedures.
* Patients who at Day 1 have an estimated glomerular filtration rate (GFR) below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry.
* Patients having contraindications to magnetic resonance imaging (MRI) or gadolinium contrast will be eligible but will not be able to participate in MRI.
* Patients taking a diuretic within 1 week of enrollment or likely to need diuretic therapy prior to Month 2.
C: 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
D: Inclusion Criteria:

* Age\>18 years
* Clinical and ultrasound diagnosis of ADPKD
* GFR \>40 ml/min/1-73 m2 (estimated by the 4 variable MDRD equation)
* Written informed consent

Exclusion Criteria

* Diabetes
* Overt proteinuria (urinary protein excretion rate \>1g/24 hours) or abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease
* Urinary tract lithiasis, infection or obstruction
* Cancer
* Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
* Pregnancy, lactation or child bearing potential and ineffective contraception (estrogen therapy in post menopausal women should not be stopped)

Answer: B