The Management of Resistant Hypertension in Kidney Transplant Patients Using Chlorthalidone
The Management of Resistant Hypertension in Kidney Transplant Patients Using Chlorthalidone
Chlorthalidone might offer an effective, safe and inexpensive anti-hypertensive treatment for
 kidney transplant patients who have resistant hypertension on multi-drug therapy. We will
 collect initial data on the safety and efficacy of Chlorthalidone in the treatment of
 patients with resistant hypertension.

 To Examine the efficacy of chlorthalidone as an anti-hypertensive agent in the treatment of
 resistant hypertension among stable kidney transplant recipients
The study involves transplant recipients presenting to the transplant Clinic Gateway 7th
 floor with resistant hypertension. The initial contact will take place in the transplant
 clinic study consist of approximately eight out patient visits over a 8 week period:
 Screening, and follow-up visits will be conducted at the Clinical Research Services (CRS)
 Unit. The Baseline (Week 1), Visit 1 Enrollment (Week 1) Day 1 and 2, Visit 2, (Week 3) Day 1
 and 2, and Visit 3 End of Study, (Week 7) Day 1 and 2. Additional visits maybe required to
 accommodate adverse reactions. The study will require approximately four (4) time points
 where blood pressure, pulse and weight is obtained, safety blood collections approximately
 2-3 tablespoons drawn by venipuncture and 24 hour urine collection periods. Home blood
 pressure readings will be required at two (2) time points during the study. The subject will
 be required to stop taking current medications for seven weeks, take study medication for 6
 weeks and report adverse reactions and concomitant medications at each visit.

 During the Enrollment visit, the subject will be identified, informed consent obtained,
 demographic characteristics, past medical history, co-morbid illnesses, current medications,
 and home and office blood pressures will be recorded to assess for eligibility criteria. This
 data will be collected prospectively by the investigators.

 Initial clinical assessment at the time of the patient's screening visit will be performed at
 the outpatient testing center in the transplant clinic. A three day window will be allowed
 for all visits. The following measurements will occur at this visit: Biometric measurements:
 vitals ( blood pressure and pulse) body weight, EKG, Arm circumference, confirmation of
 hypertension by 24-h ABPM , urine studies: 24 hour urine collection and evaluation, safety,
 8-10AM sitting upright Plasma Aldosterone/Renin Ratio, clinical safety laboratory test: bone
 morphogenetic protein, Mg/phosphorus level, Parathyroid hormone, vitamin D level and HbA1c,
 review and document concomitant medications, including current furosemide prescription.
 Subjects who meet the inclusion criteria and none of the exclusion criteria will start
 Baseline (Week 1) Measurements.

 At Baseline (Week 1) the current furosemide prescription will be documented and discontinued.
 This will begin the washout period. The washout period will continue for one week. At the end
 of the washout period the subject will be instructions to return to the CRS unit for Visit 1
 Enrollment measurements.

 Visit 1 Enrollment Measurements Week 1, Day 1, include the following measurements: Biometric
 measurements: Body Weight, confirmation of hypertension by 24-h ABPM Urine studies: start 24
 hour Urine collection, safety laboratory evaluations: bone morphogenetic protein , document
 concomitant medications, and adverse reactions. Visit 1 Enrollment Measurements Week 1 Day 2
 the subject will return the 24-hour urine collection and the 24 hour ABPM will be removed.
 The study medication chlorthalidone will be started. The subject will take study medication
 for 3 weeks before returning for the next study visit: Visit 2 (Week 3) Day 1 . A three day
 window will be allowed.

 At Visit 2 (Week 3) Day 1 and 2. Biometric measurements: Body Weight and home B/P recordings,
 start 24 hour Urine collection. Review pill count for compliance, concomitant medications and
 adverse reactions will be obtained. Day 2: the subject will return the 24-hour urine
 collection. Review study removal criteria After taking the study medication for three weeks,
 the subject will return to the CRS unit for Visit 3 End of Study, (Week 7) Day 1 and 2 Visit
 3 End of Study, (Week 7) Day 1 and 2. On day 1, Biometric measurements: Body Weight, start
 24-h ABPM , Urine studies: start 24 hour Urine collection, safety laboratory evaluations:
 8-10AM sitting upright Plasma Aldosterone/Renin Ratio, collect safety labs: bone
 morphogenetic protein, Mg/phosphorus level, parathyroid hormone, vitamin D level and HbA1c,
 document pill count, concomitant medications, home blood pressure readings and adverse
 Reactions. Day 2: the subject will return the 24-hour urine collection and the 24 hour ABPM
 will be removed If blood pressure is adequately controlled on study medication subject may
 continue study medication. If blood pressure not adequately controlled on study medication
 the subject may return to pre-study medication or a medication prescribed by physician.
Inclusion Criteria:

 1. Agree to participate in study

 2. Patients after kidney transplantation> 6 months post-transplant.

 3. Age>18 years

 4. Home or office Systolic Blood pressure >140 confirmed with daytime 24-h ABPM of
 average systolic blood pressure >140.

 5. Tacrolimus/Cyclosporine therapy with therapeutic trough level based upon historical
 values

 6. Stable renal function for at least 3 months before enrollment.

 7. Historical Baseline estimated Glomerular Filtration Rate >30mL/min

 8. No more than trace edema on physical examination at time of initial assessment.

 9. Receiving optimal doses of ≥ 3 anti-hypertensive medications including furosemide at
 ≤80mg/d.9.

 10. 8-10 in morning sitting Plasma aldosterone Concentration < 15ng/dL and Plasma Renin
 Activity <0.6ng/mL/h

 Exclusion Criteria:

 1. Serum sodium<135meq/L based upon historical values

 2. Serum potassium<3.5meq/L based upon historical values

 3. Poorly controlled diabetes mellitus with HbA1c>9% based upon historical values

 4. Already on thiazide

 5. Arm circumference >42cm

 6. Clinically significant hepatic dysfunction based upon medical history or historical
 values

 7. Two (2) Unsuccessful baseline ABPMs

 8. Poor adherence in run-in period as suggested by an unsuccessful 24-h urine collection.

 9. DBP≥110 or SBP≥200

 10. Allergy to Chlorthalidone