Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration
Brief Summary: Background:

Obesity is associated with a high prevalence of chronic kidney disease.The glomerular hyperfiltration associated with obesity may play a role in the pathogenesis of obesity associated chronic kidney disease. Attenuation of hyperfiltration by pharmacological means may slow down the development and progression of chronic renal failure. The investigators have previously shown that acetazolamide, a proximally acting diuretic that activates tubuloglomerular feedback(TGF) by increasing solute delivery to the Macula DENSA, abates glomerular hyperfiltration. The present study was designed to test the hypothesis that this decrease in hyperfiltration is specific to acetazolamide and not due to a non specific diuretic effect. The aim of the present study is to compare the effects of furosemide and acetazolamide on glomerular hemodynamics in subjects with severe obesity.

Methods:

A randomized double-blind crossover controlled design will be used. Fifteen obese subjects and ten subjects with normal body weight will participate in the study. Obese subjects will undergo measurement of glomerular filtration rate (GFR)(inulin clearance), renal plasma flow (RPF) (p-aminohippuric acid clearance), filtration fraction, fractional excretion of lithium (FE LI) and blood pressure, before and after intravenous administration of furosemide 2 mg. and acetazolamide 5 mg/kg BW. Ten subjects with normal body weight will undergo measurement of renal function without administration of diuretics.


Options:
A: Inclusion Criteria:

* Biopsy-proven IgA nephropathy
* body mass index more than 23 Kg/m2
* 24 hours urine protein more than 1 g
* estimated GFR more than 20 ml/min

Exclusion Criteria:

* pregnancy and lactation
* rapidly renal function decline
* crescent formation in renal biopsy more than 10%
B: Inclusion Criteria:

* 15 obese men (BMI\>30), aged 18 to 55, with glomerular hyperfiltration (creatinine clearance\>130 ml/min)) and 10 normal body weight men (BMI\<25), aged 18 to 55.

Exclusion Criteria:

* Heart failure, CKD, COPD
* Known allergy to furosemide, acetazolamide, inulin or amino-hippurate
* Pharmacologic treatment for hypertension, cardiac disease, diabetes mellitus
* Treatment with corticosteroids, antiepileptics or NSAID
C: Inclusion Criteria:

1. The subject is a recipient of a living donor or deceased donor kidney only transplant
2. Subject is \> 18 years of age
3. BMI≥30 on POD 0

Exclusion Criteria:

1. Multi-organ transplant
2. Subjects taking tacrolimus pre-transplant (i.e. positive crossmatch transplants or re-transplants)
3. Patients undergoing simultaneous sleeve gastrectomy at the time of transplant.
D: Inclusion Criteria:

1. Screening eGFR ≥ 15.0 and \< 30.0 mL/min/1.73 m2;
2. A history of type 2 diabetes; diagnosis should have been made at ≥ 30 years of age;
3. Male or female at least 18 years of age;
4. Treatment with an angiotensin converting enzyme (ACE)inhibitor and/or an angiotensin II receptor blocker (ARB)for at least 6 weeks prior to and during screening. Stable dose 2 weeks prior to and during screening. Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication must have discontinued treatment at least 8 weeks prior to Screening Visit A;
5. Mean systolic blood pressure (SBP) must be ≤ 160 mmHg and ≥ 105 mmHg and mean diastolic blood pressure (DBP) must be \< 90 mm Hg during screening; both mean SBP and mean DBP (determined as the average of three readings) must be within this range at two separate time points measured at least 4 days apart during the screening period (blood pressure may be re-evaluated once during an unscheduled visit);
6. Willing to practice methods of birth control (both male and female patients) during the entire study period and for at least 30 days after the last dose of the study drug is ingested;
7. Serum magnesium level must be ≥ 1.3 mEq/L (0.65 mmol/L) at Screening Visit B or during subsequent unscheduled visit during screening (serum magnesium level may be re-evaluated once during an unscheduled visit);
8. Willing and able to cooperate with all aspects of the protocol;
9. Willing and able to give written informed consent for study participation and provide consent for access to medical data according to appropriate local data protection legislation, allowing authorization to access medical records and describe events captured in the endpoints

Exclusion Criteria:

1. Type 1 diabetes mellitus (juvenile onset). If a history of diabetic ketoacidosis exists, a C-peptide level must confirm type 2 diabetes;
2. Known non-diabetic renal disease (e.g., polycystic kidney disease, focal segmental glomerulosclerosis) \[nephrosclerosis superimposed on diabetic kidney disease is acceptable\];
3. Ongoing clinical evidence suggesting non-diabetic renal disease other than nephrosclerosis;
4. History of a renal transplant or a planned transplant from a living donor during the study;
5. Albumin to creatinine ratio (ACR) greater than 3500 mg/g (395.5 mg/mmol);
6. Hemoglobin A1c level \> 11.0% (97 mmol/mol) during screening;
7. Acute dialysis or acute kidney injury within 12 weeks prior to screening or during screening;
8. Clinical signs and/or symptoms of uremia and expected need for renal replacement therapy within 12 weeks following randomization, as assessed by the investigator;
9. Recently active cardiovascular disease defined as: a. Unstable angina pectoris within 12 weeks before study randomization; b. Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeks before study randomization; c. Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization; d. Current diagnosis of Class III or IV New York Heart Association (NYHA) congestive heart failure;
10. Clinical diagnosis of severe obstructive valvular heart disease or severe obstructive hypertrophic cardiomyopathy;
11. Atrioventricular block, 2o or 3o, not successfully treated with a pacemaker;
12. DAdministration of a contrast agent that may induce nephropathy within 30 days prior to study randomization or planned during the study;
13. Systemic immunosuppression for a total of \> 2 weeks, cumulatively, within the 12 weeks prior to randomization or planned during the study;
14. Total bilirubin, aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) levels greater than the upper limit of normal (ULN), or alkaline phosphatase level greater than two times the ULN on ANY screening laboratory test result;
15. Female patients who are pregnant, intend to become pregnant during the study, or are nursing;
16. BMI \< 18.5 g/m2
17. Known hypersensitivity to any component of the study drug;
18. Current history of drug or alcohol abuse as assessed by the investigator;
19. Clinically significant infection requiring intravenous administration of antibiotics or hospitalization within 6 weeks of screening or during screening;
20. Hepatitis B surface antigen positive;
21. Diagnosis or treatment of a malignancy in the past 5 years, excluding non-melanoma skin cancer and carcinoma in situ of the cervix or a condition highly likely to transform into malignancy during the course of the study;
22. A clinical condition that in the judgment of the investigator could potentially pose a health risk to the patient while involved in the study;
23. Participation in a clinical study involving any intervention within 30 days prior to randomization, concurrent participation in such a study, or participation in a prior clinical study involving bardoxolone methyl in any form;
24. Unable to communicate or cooperate with the investigator due to language problems, poor mental development or impaired cerebral function.

Answer: B