Please select the eligibility criteria that correspond to the clinical trial below.
Title: Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?
Brief Summary: Patients with kidney failure have a poor survival rate that is due to a much higher than average rate of heart and vascular disease. The reason that kidney failure causes heart disease is unknown but recent research suggests that a hormone called aldosterone, which is increased in patients with kidney disease may damage the heart and blood vessels.

The investigators propose, using a randomized blinded trial, to find out whether drugs that inhibit the actions of aldosterone have beneficial effects on the cardiovascular system in patients with kidney failure


Options:
A: 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
B: Inclusion Criteria:

* Men and women aged 18 years and older. The lower age limit may be higher if legally required in the participating country
* Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active
* Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital
* Subjects with clinical diagnosis of chronic heart failure (CHF) either ischemic or non ischemic, New York Heart Association (NYHA) functional class II-IV
* Subjects with type 2 diabetes mellitus and / or
* Subjects with 30 mL/min/1.73m\^2 \</= eGFR \</= 60 mL/min/1.73m\^2 (MDRD, Modification of Diet in Renal Disease Study Group) at screening
* Left ventricular ejection fraction (LVEF) \</= 40%
* Blood potassium \</= 5.0 mmol/L at screening
* Systolic blood pressure \>/= 90 mmHg without signs and symptoms of hypotension at the screening visit

Exclusion Criteria:

* Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
* Acute coronary syndrome (ACS) in last 30 days prior to screening
* Cardiogenic shock
* Valvular heart disease requiring surgical intervention during the course of the study
* Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit
* Concomitant treatment with any mineralocorticoid receptor antagonist (MRA), renin inhibitor, or potassium-sparing diuretic
C: Inclusion Criteria:

* Men and women aged 18 years and older.The lower age limit may be higher if legally required in the participating country
* Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active.
* Subjects with type 2 diabetes mellitus fulfilling at least 1 of the following criteria

  * are on oral antidiabetics and / or insulin,
  * have a documented fasting glucose \>/= 7.0 mmol/L in the medical history,
  * have a 2 hour plasma glucose \>/=11.1 mmol/L during an oral glucose tolerance test in the medical history, or
  * have a glycated hemoglobin (HbA1c) \>/=6.5% \[National Glycohemoglobin Standardization Program (NGSP) / Diabetes Control and Complications Trial (DCCT)\] in the medical history or at the run-in visit
* Subjects with a clinical diagnosis of diabetic nephropathy (DN) based on at least 1 of the following criteria:

  * Persistent very high albuminuria defined as urinary albumin-to-creatine ratio (UACR) of \>/=300 mg/g ( \>/= 34 mg/mmol) in 2 out of 3 first morning void samples and estimated glomerular filtration rate (eGFR) \>/=30 mL/min/1.73 m² but \< 90 mL/min/1.73m² (Chronic Kidney Disease Epidemiology Collaboration, CKD EPI) (mL = milliliter; min = minute; m2 = square meter; g = gram; mmol = millimole) or
  * Persistent high albuminuria defined as UACR of \>/=30 mg/g but \<300 mg/g in (\>/=3.4mg/mmol but \<34 mg/mmol) in 2 out of 3 first morning void samples and eGFR \>/=30 mL/min/1.73 m² but \< 90 mL/min/1.73m²
* Subjects treated with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) for at least 3 months without any adjustments to this therapy for at least 4 weeks prior to the screening visit
* Serum potassium \</= 4.8 mmol/L at both the run-in visit and the screening visit

Exclusion Criteria:

* Non-diabetic renal disease
* Glycated hemoglobin (HbA1c) \>12% at the run-in visit or the screening visit
* UACR \>3000 mg/g (339mg/mmol) in any of the urinary first morning void samples at the run-in visit or screening visit
* Hypertension with mean sitting systolic blood pressure (SBP) \>/=180 mmHg or mean sitting diastolic blood pressure (DBP) \>/=110 mmHg at the run-in visit or mean supine SBP \>/=160 mmHg or mean sitting DBP \>/=100 mmHg at the screening visit
* Subjects with a clinical diagnosis of heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the run-in visit
* Concomitant therapy with eplerenone, spironolactone, any renin inhibitor, or potassium-sparing diuretic
* Dialysis for acute renal failure within the previous 6 months prior to the run-in visit
D: Inclusion Criteria:

* Mild-moderate chronic kidney disease (glomerular filtration rate \[GFR\] 40-80 mls/min calculated by Cockroft-Gault equation)
* Controlled blood pressure (\< 130/80 mmHg)
* On established (\> 6 weeks) treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).

Exclusion Criteria:

* Diabetes mellitus
* Clinical evidence of fluid overload or hypovolaemia
* Recent (\< 2 months) acute myocardial infarction
* Left ventricular (LV) dysfunction (ejection fraction \< 40% by echocardiography).

Answer: D