Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: The investigators study will recruit IgA nephropathy patients with proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB. The patients were treated with Hydroxychloroquine 200-400mg/d according to eGFR. The proteinuria will recorded every two months and total four months. Then, the drug will be stopped for two months for observation of change of proteinuria.


Options:
A: Key Inclusion Criteria for the Double-Blind Period:

* Age 18 years or older at screening
* Biopsy-proven primary IgAN
* Proteinuria of ≥1 g/day at screening
* eGFR ≥30 mL/min/1.73 m2 at screening
* Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose)
* Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening
* Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
* Agree to contraception

Key Exclusion Criteria for the Double-Blind Period:

* IgAN secondary to another condition
* Presence of cellular glomerular crescents in \>25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
* Chronic kidney disease (CKD) in addition to IgAN
* History of organ transplantation, with exception of corneal transplants
* Require any prohibited medications
* Treatment of systemic immunosuppressive medications (including corticosteroids) for \>2 weeks within 3 months of screening
* History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
* Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
* Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) \>2 times upper limit of normal at screening
* History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
* Hematocrit value \<27% (0.27 V/V) or hemoglobin value \<9 g/dL (90 g/L) at Screening
* Potassium \>5.5 mEq/L (5.5 mmol/L) at Screening
* History of alcohol of illicit drug use disorder
* History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications
* For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
* Participation in a study of another investigational product within 28 days of screening

Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:

* Completed participation in the double-blind period, including the Week 114 visit
* Did not permanently discontinue study medication during the double-blind period
* Agree to contraception

Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:

* Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
* Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
* Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
* eGFR ≤20 mL/min/1.73 m2 at Week 110
* Female patient is pregnant or breastfeeding

Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

* Participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub study
* A urine protein excretion value of ≥0.3 g/day.
* An eGFR of ≥25 mL/min/1.73m2
* On a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is the maximum tolerated dose.

Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

* Progressed to ESRD requiring RRT
* Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks
* Taking an SGLT2 inhibitor within 12 weeks
B: Inclusion Criteria:

* primary IgA nephropathy
* age 18-75 years
* proteinuria range from 0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB
* eGFR\>30ml/min/1.73m2

Exclusion Criteria:

* immune suppressive agent in recent one years
* crescent glomerulonephritis, might use immune suppressive agent
* chronic hepatic disease
* myocardial infarction
* malignant hypertension
* stroke
* malignant tumor
* retinopathy
* other contraindication of Hydroxychloroquine
* pregnancy and breastfeeding women
* life expectancy for less than 6 months
* in other clinical trials
* not suitable for the study judged by investigator
C: Inclusion Criteria:

1. patients who maintain regular follow-ups at Guang'anmen Hospital, agree to participate, and provide informed consent;
2. biopsy-proven IgA nephropathy, with recent progression to high-risk IgAN\*;
3. eGFR 15 to 60 ml/min/1.73 m2, calculated with the use of CKD-EPI Creatinine Equation 2009.

   * High-risk IgAN: persistent proteinuria ≥ 1 g/d despite at least 8 weeks of optimal supportive care \[maximally tolerated RAS blocker which refers to no symptomatic hypotension, no hyperkalemia, and serum creatinine increased by not more than 30% of baseline, blood pressure control meeting targets (135/85 mmHg or lower), and dietary management (sodium intake less than 6 g/d, protein intake of 0.6-0.8 g/kg/day, and low-fat diet)\], the mean annual eGFR decline rate (eGFR-slope) \>10 ml/min per 1.73 m2 per year, while needing to restart immunosuppressive therapy; or eGFR\<60 ml/min/1.73 m2 at the first diagnosis.

Exclusion Criteria:

1. secondary IgAN;
2. comorbidity of other primary or secondary glomerular diseases;
3. comorbidity of severe primary diseases such as cardiovascular, hepatic, cerebral, and hematopoietic system diseases or mental disorders;
4. allergy or intolerance to the experimental medication (e.g., RAS blockers, prednisolone, cyclophosphamide, YQF compound and its placebo compound);
5. contraindications to immunosuppression therapy-acute and chronic infectious diseases, malignancies, leukopenia, thrombocytopenia, gastrointestinal hemorrhage, ulcers of stomach or duodenum, post-transplantation;
6. pregnant or lactating women;
7. unwilling to participate in this study, failure to accept or tolerate Chinese medicine compound;
8. history of alcohol or drug abuse;
9. poor compliance, loss to follow-up;
10. participation in another clinical investigation.
D: 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.

Answer: B