Albuminuria
Conditions
Keywords
proteinuria
Brief summary
Phosphorus-based food additives are commonly used by food manufacturers for many applications, such as enhancing flavor, in ready-to-eat foods and beverages. While these additives can significantly increase an individual's daily phosphorus intake, little is known about the effect of dietary phosphorus on kidney health. In this study, the investigators will first lower baseline phosphorus intake to about 1000mg/d by educating participants to avoid foods with phosphorus additives. Then, participants will be randomized to a higher phosphorus period (\ 2gm/d) and a lower phosphorus period (\ 1gm/d) by providing unaltered, commercially-available food/beverage products with and without phosphorus additives. The investigators hypothesize that participants will have higher urine albumin excretion and fibroblast growth factor-23 (FGF-23) during the higher phosphorus period compared to the lower phosphorus period.
Detailed description
The Study of Dietary Additive Phosphorus on Proteinuria and FGF-23 (SODA-POP) was a single-center, randomized, double-blind, two-period cross-over study that examined the effect of higher vs. lower phosphorus intake for 3 week periods, achieved by addition of commercially available diet beverages and breakfast bars to diet on albuminuria and fibroblast growth factor 23, in adults with presumed early chronic kidney disease (estimated glomerular filtration rate \>= 45 ml/min/1.73m2; and urine albumin/creatinine ratio \>=17 mg/g for men or \>=25 mg/g for women).
Interventions
OTHERHigher phosphorus period
Commercially-available unaltered food/beverage products containing phosphorus additives (\ 1gm/d of phosphorus) will be given for 3 weeks. All participants at the beginning of the study will receive dietary education to reduce their baseline consumption of phosphorus to a goal of \ 1gm/d by receiving education on avoiding phosphorus-based additives.
OTHERLower phosphorus period
Commercially-available unaltered food/beverage products without phosphorus additives (\<10mg/d of phosphorus) will be given for 3 weeks. All participants at the beginning of the study will receive dietary education to reduce their baseline consumption of phosphorus to a goal of \ 1gm/d by receiving education on avoiding phosphorus-based additives.
Sponsors
Johns Hopkins University
Geisinger Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults at least 21 years of age with at least microalbuminuria
Exclusion criteria
Estimated glomerular filtration rate \<45ml/min/1.73m2, poorly controlled diabetes or hypertension, nephrotic syndrome, hyperparathyroidism, Paget's Disease, multiple myeloma, uncontrolled thyroid disease, chronic antacid use, use of phosphorus binders, phosphorus supplements, or high-dose vitamin D, inability to complete feeding study, investigator discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Urine Albumin Excretion | 3 weeks | Two 24-hour urine collections will be collected during the 3rd week of each period |
| Fibroblast Growth Factor-23 (FGF-23) | 3 weeks | Plasma FGF-23 will be measured at the end of each 3 week period in the morning after an overnight fast. As this is a small pilot study, we will not adjust for multiple comparisons. A p value\<0.05 will be considered statistically significant for both outcomes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | 2-3 weeks | Blood pressure was measured at the end of weeks 1, 2, and 3. At each visit, 3 readings were obtained in the seated position by trained and certified observers after 5 minutes of rest with an Omron HEM-907 device (Omron Healthcare Inc, Bannockburn, Ill) using a standardized protocol. We used the average of all blood pressure measurements at the end of weeks 1, 2, and 3 for each period. |
| Diastolic Blood Pressure | 2-3 weeks | Blood pressure measured at the end of weeks 1, 2, and 3. At each visit, 3 readings were obtained in the seated position by trained and certified observers after 5 minutes of rest with an Omron HEM-907 device (Omron Healthcare Inc, Bannockburn, Ill) using a standardized protocol. We used the average of all these readings taken during end of weeks 1, 2, and 3 for each period. |
Countries
United States
Participant flow
Recruitment details
Primary recruitment strategies included mass mailing of study brochures to individuals with self-reported type 2 diabetes in neighboring zip codes and to past and current participants of other research studies.
Participants by arm
| Arm | Count |
|---|---|
| Higher Phosphorus Period Then Lower Phosphorus Period Randomized to higher phosphorus period first, then lower phosphorus period second.
Commercially-available unaltered food/beverage products containing phosphorus additives (\
1gm/d of phosphorus) will be given for 3 weeks
At the beginning of the study participants receive dietary education to reduce their baseline consumption of phosphorus to a goal of \
1gm/d by receiving education on avoiding phosphorus-based additives
Higher phosphorus period: Commercially-available unaltered food/beverage products containing phosphorus additives (\
1gm/d of phosphorus) given for 3 weeks
Lower phosphorus period: Commercially-available unaltered food/beverage products without any phosphorus additives given for 3 weeks | 15 |
| Lower Phosphorus Period Then Higher Phosphorus Period Randomized to higher phosphorus period first, then lower phosphorus period second.
Commercially-available unaltered food/beverage products containing phosphorus additives (\
1gm/d of phosphorus) will be given for 3 weeks
At the beginning of the study participants receive dietary education to reduce their baseline consumption of phosphorus to a goal of \
1gm/d by receiving education on avoiding phosphorus-based additives
Lower phosphorus period: Commercially-available unaltered food/beverage products without any phosphorus additives given for 3 weeks
Higher phosphorus period: Commercially-available unaltered food/beverage products containing phosphorus additives (\
1gm/d of phosphorus) given for 3 weeks | 16 |
| Total | 31 |
Baseline characteristics
| Characteristic | Higher Phosphorus Period Then Lower Phosphorus Period | Lower Phosphorus Period Then Higher Phosphorus Period | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Continuous | 68.0 years STANDARD_DEVIATION 7.3 | 64.2 years STANDARD_DEVIATION 9.9 | 66.0 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 16 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 14 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Male | 9 Participants | 4 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 22 / 31 | 23 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
Primary
24-hour Urine Albumin Excretion
Two 24-hour urine collections will be collected during the 3rd week of each period
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Higher Phosphorus Period | 24-hour Urine Albumin Excretion | 86.2 mg/day |
| Lower Phosphorus Period | 24-hour Urine Albumin Excretion | 76.4 mg/day |
Comparison: Sample size for this study was calculated using the xsampsi module in STATA, based on a previous study with repeat 24-hour urine collections (standard deviation, 1.04). At an α level of 0.05, we anticipated that a sample size of 30 participants with mean albuminuria of 100 mg/d would result in \>80% power to detect a 13% difference in log- transformed albuminuria between the higher and lower phosphorus additive periods.p-value: 0.0595% CI: [-0.025, 0.34]Mixed Models Analysis
Primary
Fibroblast Growth Factor-23 (FGF-23)
Plasma FGF-23 will be measured at the end of each 3 week period in the morning after an overnight fast. As this is a small pilot study, we will not adjust for multiple comparisons. A p value\<0.05 will be considered statistically significant for both outcomes
Time frame: 3 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Higher Phosphorus Period | Fibroblast Growth Factor-23 (FGF-23) | 132.6 Relative units/ml |
| Lower Phosphorus Period | Fibroblast Growth Factor-23 (FGF-23) | 128.2 Relative units/ml |
p-value: 0.0595% CI: [-0.059, 0.136]Mixed Models Analysis
Secondary
Diastolic Blood Pressure
Blood pressure measured at the end of weeks 1, 2, and 3. At each visit, 3 readings were obtained in the seated position by trained and certified observers after 5 minutes of rest with an Omron HEM-907 device (Omron Healthcare Inc, Bannockburn, Ill) using a standardized protocol. We used the average of all these readings taken during end of weeks 1, 2, and 3 for each period.
Time frame: 2-3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Higher Phosphorus Period | Diastolic Blood Pressure | 69.3 mmHg | Standard Deviation 10.8 |
| Lower Phosphorus Period | Diastolic Blood Pressure | 70.2 mmHg | Standard Deviation 11.4 |
p-value: 0.0595% CI: [-2.7, 1]Mixed Models Analysis
Secondary
Systolic Blood Pressure
Blood pressure was measured at the end of weeks 1, 2, and 3. At each visit, 3 readings were obtained in the seated position by trained and certified observers after 5 minutes of rest with an Omron HEM-907 device (Omron Healthcare Inc, Bannockburn, Ill) using a standardized protocol. We used the average of all blood pressure measurements at the end of weeks 1, 2, and 3 for each period.
Time frame: 2-3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Higher Phosphorus Period | Systolic Blood Pressure | 126.9 mmHg | Standard Deviation 13.5 |
| Lower Phosphorus Period | Systolic Blood Pressure | 128 mmHg | Standard Deviation 15.6 |
p-value: 0.0595% CI: [-4.1, 1.9]Mixed Models Analysis