Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-blind, Randomized Placebo-controlled Clinical Trial for the Efficacy and Safety of a Calcineurin Inhibitor, Tacrolimus(Prograf Cap®) in Patients With Non-nephrotic Albuminuric, Normotensive IgA Nephropathy
Brief Summary: This study is to evaluate efficacy and safety of tacrolimus in the patients with non-nephrotic albuminuric, normotensive IgA nephropathy after 16 week treatment with tacrolimus (Prograf) or placebo.


Options:
A: Inclusion Criteria:

1. IgA nephropathy proven on renal biopsy.
2. Proteinuria: \>=1.0g/day while receiving maximum tolerated dose of RAS blockade following the recommended treatment guidelines of each country where the trial is conducted.
3. eGFR: 30 to 120ml/min per 1.73m²(inclusive) while receiving maximum tolerated RAS blockade

Exclusion Criteria:

1. Indication for immunosuppressive therapy with corticosteroids, such as:

   * Minimal change renal disease with IgA deposits Crescents present in \>50% of glomeruli on a renal biopsy within the last 12 months.
2. Contraindication to immunosuppressive therapy with corticosteroids, including:

   * Active infection, including HBV infection or clinical evidence of latent or active tuberculosis (nodules, cavities, tuberculoma, etc)
   * Malignancy within the last 5 years, excluding treated non-melanoma skin cancers (ie. squamous or basal cell carcinoma)
   * Current or planned pregnancy or breastfeeding women of childbearing age who are not able or willing to use adequate contraception.
3. Systemic immunosuppressive therapy in the previous year.
4. Malignant /uncontrolled hypertension (\>160mm systolic or 110mmHg diastolic)
5. Current unstable kidney function for other reasons, e.g. macrohaematuria induced acute kidney injury
6. Age \<18 years old
7. Secondary IgA nephropathy: e.g. due to lupus, liver cirrhosis, Henoch- Schonlein purpura
8. Patients who are unlikely to comply with the study protocol in the view of the treating physician.
B: Inclusion Criteria:

1. underwent renal biopsy within 1 year before start fo trial;
2. 24 hour urinary protein excretion ranged between 1 to 7 g/d;
3. eGFR, evaluated by MDRD formula, should be higher than 30 ml/min

Exclusion Criteria:

1. crescentic glomerulonephritis;
2. steroid therapy subjected within 1 year before trial;
3. malignant hypertension(DBP\> 130 mmHg and/or SBP\> 220mmHg), resistant to anti-hypertensive agents;
4. urinary protein excretion decrease below 1 g/l after run-in period;
5. Myocardial infarction or cerebrovascular accident in 6 months preceding the trial;
6. renovascular disease;
7. diabetes mellitus;
8. Malignancy, severe liver disease, refractory infection;
9. peptic ulcer in active disease phase;
10. pregnancy;
11. other contraindication to the use of ACEi/ ARB or corticosteroid;
12. alcohol abuse or drug addiction
C: Inclusion Criteria:

* Male or female patients from 18-70 years with histologically proven primary IgAN with typical mesangioproliferative features. Diagnosis has to be made by a neuropathologist.
* Proteinuria above 0.75 g/day within 12 weeks prior to or at the first visit in the run-in phase (month -6)and presence of at least one further risk factor for the development of end stage renal disease

  1. arterial hypertension, defined as ambulatory blood pressure \>140/90 mm Hg or the use of antihypertensive medication or
  2. impaired renal function, defined as creatinine clearance or estimated GFR \<90 ml/min.

Exclusion Criteria:

* Known allergy or intolerance to study medication (except in case of ACE-inhibitor, in which case a change to an angiotensin receptor blocker is possible).
* Women who are pregnant or breastfeeding and women without sufficient contraception.
* Any prior immunosuppressive therapy.
* Variants of primary IgAN (e.g. rapidly progressive IgAN with crescents in \>50% of glomeruli or minimal change GN with glomerular IgA deposits).
* Significant liver dysfunction (more than three fold increased GPT compared to norm)
* Contraindication for immunosuppressive therapy, like

  * acute or chronic infectious disease incl. hepatitis and HIV positive patients
  * any malignancy
  * leukocytopenia, thrombocytopenia or known allergy against prednisolone, cyclophosphamide or azathioprine
  * active intestinal bleeding, active gastric or duodenal ulcer
  * Need of permanent immunosuppression, (e.g. transplanted patients, steroid-dependent inflammatory diseases)
* Secondary IgAN or diseases associated with glomerular deposits of IgA.
* Additional other chronic renal disease.
* Creatinine clearance below 30 ml/min (mean of 3 measurements).
* Alcohol or drug abuse
* Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
* Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
* Participation in a parallel clinical trial or participation in another clinical trial within the last 3 months.
* Subjects who are in any state of dependency to the sponsor or the investigators.
* Employees of the sponsor or the investigators.
* Subjects who have been committed to an institution by legal or regulatory order.
D: Inclusion Criteria:

* Patients with IgA nephropathy confirmed by renal biopsy
* Serum creatinine measurement ≤1.5mg/ml or MDRD estimated GFR ≥ 45ml/min/1.73m2 (MDRD: Modification of Diet in Renal Disorder)
* UACR level between 0.3 and 3.0
* Blood pressure measurements \< 130/80mmHg

Exclusion Criteria:

* Use of immunosuppressants for more than two weeks within last one month
* Concomitant use of ACE inhibitor, ARB, steroids or immunosuppressant, NDHP-CCB, diuretics, omega-3 fatty acids and its analogue \& additional dietary to treat igA nephropathy (ACE: Angiotensin Converting Enzyme, ARB: Angiotensin Receptor Blocker, NDHP-CCB: Non-dihydropyridine-type Calcium Channel Blocker
* Pregnant or breast-feeding patients. Patients who plan to bear children or breast-feed during the study and within 6 month after completion of study
* Hypersensitivity to the investigational drug or macrolide agents
* Use of potassium-sparing diuretics
* Persistence of liver function abnormality more than 1 month or presence of acute active hepatitis
* Other investigational drug within last 30 days

Answer: D