FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology, Orthopedic, Metabolic |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Pharmacology / Toxicology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 2 - 24 |
| Updated: | 3/16/2019 |
| Start Date: | December 6, 2018 |
| End Date: | February 2022 |
| Contact: | Andrew M South, MD MS |
| Email: | asouth@wakehealth.edu |
| Phone: | 336-716-9640 |
Interplay of FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)
Hereditary hypophosphatemia encompasses rare genetic conditions characterized by renal
phosphate wasting. Increased circulating levels of fibroblast growth factor 23 (FGF23), a key
regulator of phosphorus metabolism, are critical to the pathophysiology of these diseases,
most notably in X-linked hypophosphatemia (XLH). Increased FGF23 induces hypertrophy and
scarring in the heart in part via stimulating the traditional renin-angiotensin system (RAS)
pathway, angiotensin-converting enzyme (ACE)/angiotensin (Ang ll), particularly in patients
with chronic kidney disease, but the effect of FGF23 on the heart in patients with
FGF23-related hypophosphatemic diseases is unknown. In addition, the relationship between
FGF23 and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7) pathway of
the RAS is unknown.
The objective of this study is to describe the relationship between FGF23, which causes low
phosphorus levels, and components of the RAS in the blood and urine to help the investigators
understand why the disease occurs and how to better treat it.
Subjects will be identified by querying the Electronic Medical Record according to medical
diagnosis. Thirty subjects, 2-24 years of age, will be recruited from the tertiary care
Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital.
Inclusion criteria include a confirmed diagnosis of hereditary FGF23-related
hypophosphatemia. Clinical data will be obtained from the Electronic Medical Record. Each
subject will undergo study assessments at baseline, 6 months and 1 year that include blood
work, an echocardiogram, and blood pressure measurements.
The primary hypothesis is that subjects with higher Ang-(1-7) levels have lower rates of
cardiac hypertrophy and thus are protected against high FGF23 levels. The secondary
hypothesis is that subjects with higher Ang-(1-7) levels have lower systolic blood pressure.
phosphate wasting. Increased circulating levels of fibroblast growth factor 23 (FGF23), a key
regulator of phosphorus metabolism, are critical to the pathophysiology of these diseases,
most notably in X-linked hypophosphatemia (XLH). Increased FGF23 induces hypertrophy and
scarring in the heart in part via stimulating the traditional renin-angiotensin system (RAS)
pathway, angiotensin-converting enzyme (ACE)/angiotensin (Ang ll), particularly in patients
with chronic kidney disease, but the effect of FGF23 on the heart in patients with
FGF23-related hypophosphatemic diseases is unknown. In addition, the relationship between
FGF23 and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7) pathway of
the RAS is unknown.
The objective of this study is to describe the relationship between FGF23, which causes low
phosphorus levels, and components of the RAS in the blood and urine to help the investigators
understand why the disease occurs and how to better treat it.
Subjects will be identified by querying the Electronic Medical Record according to medical
diagnosis. Thirty subjects, 2-24 years of age, will be recruited from the tertiary care
Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital.
Inclusion criteria include a confirmed diagnosis of hereditary FGF23-related
hypophosphatemia. Clinical data will be obtained from the Electronic Medical Record. Each
subject will undergo study assessments at baseline, 6 months and 1 year that include blood
work, an echocardiogram, and blood pressure measurements.
The primary hypothesis is that subjects with higher Ang-(1-7) levels have lower rates of
cardiac hypertrophy and thus are protected against high FGF23 levels. The secondary
hypothesis is that subjects with higher Ang-(1-7) levels have lower systolic blood pressure.
Clinical data will be collected from the Electronic Medical Record, including age, sex,
parent-reported race, past medical and family histories, and current medications. The
investigators will calculate body mass index and define overweight/obesity as a body mass
index ≥85% percentile for age and sex. The investigators will calculate the estimated
glomerular filtration rate to measure renal function based on serum creatinine standardized
to age, sex, and height.
Blood (less than 5 mL) and urine samples will be collected at each study visit at the same
time as routine clinical labs. Ang ll and Ang-(1-7) will be measured in the plasma and urine
using radioimmunoassays in a CLIA-certified laboratory within the Hypertension and Vascular
Research Biomarker Analytical Core at Wake Forest School of Medicine. The investigators will
calculate the ratio of the two peptides and, in the urine, standardize their values to urine
creatinine. In the blood, creatinine, calcium, phosphorus, and vitamin D will be collected
and in the urine, albumin, calcium, phosphorus, and creatinine will be collected all per
standard of care. FGF23 and klotho will be analyzed in the Core via commercially available
ELISA's.
All patients receive baseline and, if abnormal, follow-up echocardiograms to evaluate for
left ventricular hypertrophy.
Blood pressure will be measured at clinic visits. Because age, sex, and height define
normative pediatric values, the investigators will standardize blood pressure with z scores.
parent-reported race, past medical and family histories, and current medications. The
investigators will calculate body mass index and define overweight/obesity as a body mass
index ≥85% percentile for age and sex. The investigators will calculate the estimated
glomerular filtration rate to measure renal function based on serum creatinine standardized
to age, sex, and height.
Blood (less than 5 mL) and urine samples will be collected at each study visit at the same
time as routine clinical labs. Ang ll and Ang-(1-7) will be measured in the plasma and urine
using radioimmunoassays in a CLIA-certified laboratory within the Hypertension and Vascular
Research Biomarker Analytical Core at Wake Forest School of Medicine. The investigators will
calculate the ratio of the two peptides and, in the urine, standardize their values to urine
creatinine. In the blood, creatinine, calcium, phosphorus, and vitamin D will be collected
and in the urine, albumin, calcium, phosphorus, and creatinine will be collected all per
standard of care. FGF23 and klotho will be analyzed in the Core via commercially available
ELISA's.
All patients receive baseline and, if abnormal, follow-up echocardiograms to evaluate for
left ventricular hypertrophy.
Blood pressure will be measured at clinic visits. Because age, sex, and height define
normative pediatric values, the investigators will standardize blood pressure with z scores.
Inclusion Criteria:
- Confirmed diagnosis of hereditary FGF23-related hypophosphatemia
Exclusion Criteria:
- Acquired FGF23-related hypophosphatemia
- Age less than 2 years
- Inability to provide urine sample
We found this trial at
1
site
1 Medical Center Blvd
Winston-Salem, North Carolina 27157
Winston-Salem, North Carolina 27157
336-716-2011
Principal Investigator: Andrew M South, MD
Phone: 336-716-7541
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