Study of Vitamin D and Uric Acid Lowering on Kidney and Blood Vessel Function
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Obesity Weight Loss, Renal Impairment / Chronic Kidney Disease, Hematology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology, Hematology, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | March 2011 |
| End Date: | June 2015 |
Modifiable Effectors of Renin System Activation: Treatment Evaluation (MODERATE)
The investigators hypothesize that, among non-hypertensive overweight and obese individuals,
treatment of vitamin D deficiency and lowering uric acid concentrations (by either xanthine
oxidase inhibition or increased renal excretion) will attenuate renin angiotensin system
(RAS) activation, improve endothelial function, and lower blood pressure.
treatment of vitamin D deficiency and lowering uric acid concentrations (by either xanthine
oxidase inhibition or increased renal excretion) will attenuate renin angiotensin system
(RAS) activation, improve endothelial function, and lower blood pressure.
We have demonstrated that lower levels of 25-hydroxyvitamin D (25[OH]D) and higher
concentrations of uric acid are both potentially modifiable factors that are independently
associated with an increased risk of developing hypertension (high blood pressure) in
humans. Other investigators have shown that vitamin D supplementation, or lowering uric acid
with allopurinol, may reduce blood pressure. Animal experiments suggest that activation of
both the systemic and local kidney-specific renin angiotensin systems (RAS) may be the
principal mechanism linking 25(OH)D and uric acid with hypertension. In human parallels to
these animal studies, we have shown in cross-sectional analyses that non-hypertensive
individuals with lower 25(OH)D and higher uric acid levels have increased activation of
their systemic and kidney-specific RAS, independent of other factors. However, whether
vitamin D supplementation or uric acid lowering attenuates RAS activation has never been
demonstrated in humans. Both lower 25(OH)D and higher uric acid concentrations are also
associated with endothelial dysfunction in humans, and endothelial function may modulate the
RAS and provide an alternate mechanism for the development of hypertension. It remains
unclear, however, whether an intervention to increase 25(OH)D or decrease uric acid levels
among non-hypertensive adults improves endothelial function; furthermore, it is unknown
whether treatment of these individuals would lower blood pressure. Determining whether
treatment of 25(OH)D and uric acid concentrations, per se, can attenuate RAS activation,
improve endothelial function, and lower blood pressure among nonhypertensive individuals is
critically important, with implications stretching beyond hypertension prevention, since RAS
activation, endothelial dysfunction, and blood pressure are also implicated in the pathology
of cardiovascular and chronic kidney disease. Individuals who are overweight and obese
(two-thirds of US adults) represent an important population who are known to have lower
25(OH)D levels, higher uric acid concentrations, activation of the RAS, endothelial
dysfunction, and an increased risk of hypertension, cardiovascular disease, and chronic
kidney disease. Interestingly, our preliminary data demonstrate that among overweight and
obese individuals with normal 25(OH)D or low uric acid levels, adiposity is no longer
associated with activation of the RAS, suggesting that low 25(OH)D and high uric acid
concentrations might be mediators of the adverse consequences of overweight and obesity.
concentrations of uric acid are both potentially modifiable factors that are independently
associated with an increased risk of developing hypertension (high blood pressure) in
humans. Other investigators have shown that vitamin D supplementation, or lowering uric acid
with allopurinol, may reduce blood pressure. Animal experiments suggest that activation of
both the systemic and local kidney-specific renin angiotensin systems (RAS) may be the
principal mechanism linking 25(OH)D and uric acid with hypertension. In human parallels to
these animal studies, we have shown in cross-sectional analyses that non-hypertensive
individuals with lower 25(OH)D and higher uric acid levels have increased activation of
their systemic and kidney-specific RAS, independent of other factors. However, whether
vitamin D supplementation or uric acid lowering attenuates RAS activation has never been
demonstrated in humans. Both lower 25(OH)D and higher uric acid concentrations are also
associated with endothelial dysfunction in humans, and endothelial function may modulate the
RAS and provide an alternate mechanism for the development of hypertension. It remains
unclear, however, whether an intervention to increase 25(OH)D or decrease uric acid levels
among non-hypertensive adults improves endothelial function; furthermore, it is unknown
whether treatment of these individuals would lower blood pressure. Determining whether
treatment of 25(OH)D and uric acid concentrations, per se, can attenuate RAS activation,
improve endothelial function, and lower blood pressure among nonhypertensive individuals is
critically important, with implications stretching beyond hypertension prevention, since RAS
activation, endothelial dysfunction, and blood pressure are also implicated in the pathology
of cardiovascular and chronic kidney disease. Individuals who are overweight and obese
(two-thirds of US adults) represent an important population who are known to have lower
25(OH)D levels, higher uric acid concentrations, activation of the RAS, endothelial
dysfunction, and an increased risk of hypertension, cardiovascular disease, and chronic
kidney disease. Interestingly, our preliminary data demonstrate that among overweight and
obese individuals with normal 25(OH)D or low uric acid levels, adiposity is no longer
associated with activation of the RAS, suggesting that low 25(OH)D and high uric acid
concentrations might be mediators of the adverse consequences of overweight and obesity.
Inclusion Criteria:
- 25(OH)D < 20 ng/mL OR Uric acid ≥ 5 mg/dL
- Age ≥ 18, ≤ 75 years
- BMI ≥ 25
Exclusion Criteria:
- Hypertension, or on BP-lowering medicine
- Diabetes
- Coronary Heart Disease
- estimated glomerular filtration rate (EGFR) <60 mL/min
- Kidney stones
- Active cancer (except non-melanoma skin cancer)
- Pregnant
- Taking vitamin D supplements and unwilling to stop
- Osteoporosis
- Hypo- or hypercalcemia
- Hypo- or hyperphosphatemia
- Known allergy to ACE-inhibitors
- Taking medication for hyperuricemia
- Gout, anemia, cirrhosis, active/chronic hepatitis, abnormal aspartate
aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin levels, or
anemia
- Known allergy to either allopurinol or probenecid
- Current use of didanosine, azothioprine, methotrexate, ketoprofen, ketorolac,
mycophenolate, or ACE-inhibitors
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