Please select the eligibility criteria that correspond to the clinical trial below.
Title: South Danish Hypertension and Diabetes Study
Brief Summary: The purpose of this study is to estimate the effect of spironolactone on blood pressure resistant to therapy in type-2 diabetics.


Options:
A: Inclusion Criteria:

* Age \< 75 years
* Type-2 diabetes
* Therapy resistant hypertension (by ABPM)
* Treatment with at least 3 antihypertensives

Exclusion Criteria:

* HbA1c \> 10.0
* BP \> 180/110 mmHg
* Secondary hypertension
* Intolerance to spironolactone
* Permanent treatment with nonsteroidal antiinflammatory drugs or systemic glucocorticoids
* Total cholesterol 10 mmol/l
* New York Heart Association class III and IV
* Pregnancy or planned pregnancy
* Psychiatric disease
* Malignant disease
* Insufficient adherence
B: Inclusion Criteria:

1. Written informed consent must be provided before participation. Patient information and consent form must be approved by relevant independent ethical committee. Specifically, all participating patients will be asked to give informed consent for long-term follow-up and collection of follow-up data
2. Male or female patients ≥ 18 years and \< 75 years of age at Screening visit
3. Type 2 DM (WHO criteria)
4. Persistent normoalbuminuria (at least 2 of 3 UACR \< 30 mg/g samples from "run in"-period)
5. Estimated GFR \>45 ml/min/1.73m2 (MDRD formula) at Screening visit
6. The patient must be willing and able to comply with the protocol for the duration of the study
7. Female without child-bearing potential at the screening visit. Defined as one or more of following:

7.1) Female patients ≥ 50 years of age at the day of inclusion, who have been postmenopausal for at least 1 year 7.2) Female patients \< 50 years of age at the day of inclusion, who have been postmenopausal for at least 1 year and serum follicle stimulating hormone levels \> 40 milli International unit / mL as well as serum estrogen levels \< 30 pg/ml or a negative estrogen test.

7.3) 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral ovariectomy with or without hysterectomy.

OR a negative urine pregnancy test at the Screening visit AND one or more of following:

7.4) Correct use of reliable contraception methods. This includes one or more of the following: hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring or oral) or an intrauterine device (IUD) OR correct use of double barrier with one of the following: barrier methods (diaphragm, cervical cap, Lea contraceptive or condom) AND in combination with a spermicide.

7.5) General sexual abstinence from the time of screening/ baseline, during the study until a minimum of 30 days after the last administration of study medication if this is already established as the patient's preferred and usual lifestyle.

7.6) Having only female sexual partners. 7.7) Sexual relationship with sterile male partners only

Exclusion Criteria:

1. Average of systolic BP\< 110 or \>160 mm Hg at baseline
2. Average of diastolic BP \> 100 mm Hg at baseline
3. Type 1 DM (WHO criteria)
4. HbA1c \<6.5% (48 mmo l/ mol) AND \> 5 years of known duration of diabetes type 2 AND never treated with an antidiabetic drug of any kind.
5. Current in treatment with more than one RAAS blocking agent (Angiotensin Converting Enzyme inhibitor, Angiotensin Receptor Blocker or Direct Renin Inhibitor)
6. Current lithium treatment
7. Known or suspected hypersensitivity to Spironolactone or to any of its excipients.
8. Current use of potassium sparing diuretics, such as: Spironolactone, Eplerenone or Amiloride etc.
9. Screening (week -6) plasma (or serum) potassium level \>5.0 mmol/L
10. Low plasma sodium determine by the investigator
11. Current cancer treatment or within five years from baseline (except basal cell skin cancer or squamous cell skin cancer)
12. Any clinically significant disorder, except for conditions associated with type 2 DM history, which in the Investigators opinion could interfere with the results of the trial
13. Cardiac disease defined as: Heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial ischemia, stroke, cardiac re-vascularisation or coronary artery bypass within the last 3 months
14. Diagnosis of non-Diabetic CKD current or in the past
15. Diagnosis of liver cirrhosis with current impaired liver function within the last 3 years.
16. Diagnosis of Addison's disease.
17. Being lactating.
18. Intend to become pregnant within the duration of the study or not use adequate birth control.
19. Known or suspected abuse of alcohol or narcotics
20. Not able to understand informed consent form
21. Participation in any other intervention trial than PRIORITY or a related sub-study is not allowed within 30 days before inclusion or concurrent to this study
C: Inclusion Criteria:

* Men aged 18 years and older or postmenopausal women aged 55 years and older or women aged 18 years and older without childbearing potential based on surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy
* Clinical diagnosis of CHF (chronic heart failure), either ischemic or non-ischemic, NYHA (New York Heart Association) class II - III, treated with evidenced-based therapy for CHF, e.g. beta-blockers and ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blocker) as well as diuretics, unless contraindicated or not tolerated
* Known kidney damage for \>/= 3 months, as defined by structural or functional abnormalities of the kidney, and

  * Part A: 60 mL/min/1.73 m\*2 \</= eGFR (estimated Glomerular Filtration Rate) \< 90 mL/min/1.73 m\*2 (MDRD, Modification of Diet in Renal Disease) at the screening visit
  * Part B: 30 mL/min/1.73 m\*2 \</= eGFR \<= 60 mL/min/1.73 m\*2 (MDRD) at the screening visit
* Serum potassium \</= 4.8 mmol/L at the screening visit
* Systolic blood pressure \>/= 90 mmHg without signs or symptoms of hypotension at the screening visit

Exclusion Criteria:

* Known hypersensitivity to the study drug (active substance or excipients) or spironolactone and respective excipients (Part B only)
* Subjects with anuria, acute renal failure, or Addison's disease
* Acute coronary syndrome or unstable coronary artery disease within 30 days prior to randomization
* Valvular heart disease requiring surgical intervention during the course of the study
* History of hospitalization for hyperkalemia or acute renal failure induced by previous aldosterone antagonist treatment
D: Inclusion Criteria:

* Adult male and female subjects aged 20-65 of all ethnic backgrounds.
* Type I diabetes mellitus defined as sudden onset of insulin requiring diabetes prior to age 20 and at least 5 years duration
* Type 2 diabetes mellitus defined as onset \> 20 years of age and treatment with oral hypoglycemic agent and/or insulin and increased C-peptide level.
* Seated SBP \> 130 mmHg documented at one screening visit or treated SBP \< 130 mmHg with a documented history of SBP \> 130 mmHg on more than one previous occasion
* Proteinuria defined as a 24-hour urine albumin/creatinine ratio \> 300 mg/g while on an ACE inhibitor with or without non-ARB, non-aldosterone antagonist treatment
* Ongoing treatment (\> 3 months) with an ACE inhibitor or ARB with or without additional antihypertensive therapy (e.g. CCB, a-blocker, b-blocker, clonidine).

Exclusion Criteria:

* BMI \> 45 kg/m2
* Baseline serum creatinine \> 3.0 mg/dl in females and \> 4.0 mg/dl in males or creatinine clearance \<20 ml/min estimated by Cockcroft-Gault equation (based on age, fasting serum creatinine concentration and ideal body weight in kilograms).
* Secondary cause of kidney disease other than diabetic nephropathy
* Serum potassium concentration \>5.5 mEq/L on ACE inhibitor therapy 7-10 days prior to randomization
* Poorly controlled diabetes, i.e. HgbA1C \> 11 mg/dl 7-10 days prior to randomization
* History of allergy to iothalamate or history of renal failure due to contrast nephropathy
* Stroke or myocardial infarction within the preceding 12 months prior to randomization
* Coronary revascularization procedure within past 6 months
* Clinically apparent congestive heart failure defined as clinical signs of heart failure or an ejection fraction of \< 40% (and/or depressed LV systolic function by echocardiogram).
* Terminal disease including cancer and AIDS
* Documented increase in serum creatinine \> 50% of baseline within 3 months prior to the run-in period
* Renal disease known or in the opinion of the investigator caused by a condition other than diabetes
* Known adverse reaction to study medications including ACE inhibitors, ARB and spironolactone
* History of chronic or intermittent gross hematuria
* Spontaneous 24-hour urine sodium excretion rate exceeding 350 mEq/day
* AST or ALT greater than 2.5 the upper limit of normal for the laboratory
* Pregnancy
* History of autoimmune disease, connective tissue disease or multiple drug allergies
* Anticipated need for renal replacement therapy within 12 months Inclusion criteria for normal subjects
* Adult male and female subjects aged 20-65 of all ethnic backgrounds Exclusion criteria for normal subjects
* Chronic medical conditions, including but not limited to diabetes mellitus, hypertension, chronic kidney disease, and hyperlipidemia.
* Use of medications for antihypertensive
* Inability to follow study protocol for any reason

Answer: A