Elucidation of the Role of Fat in Abnormally Acidic Urine in Patients with Nephrolithiasis
Study design: a cross-over study to explore whether increasing serum concentration of free fatty acid following oral load with heavy whipping cream will reduce urinary pH concomitant with reduction in ammonium excretion.
The subjects will visit the outpatient Mineral Metabolism research area to obtain past medical history and undergo a physical examination including anthropometric measurements. a fasting blood specimen will be drawn for biochemical analysis including CMP, Mg, P, ua, Lipids, CBC, fasting serum insulin, and free fatty acids.
The study consists of two phases: 1) ammonium chloride load during fat challenge with heavy whipping cream (200 mg/kg body weight) and 2) ammonium chloride load on a control diet which is isocaloric and isovolumic to the fat challenge. The control diet will consist of skim milk and toast. The amounts of heavy whipping cream or skim milk and toast will be calculated using the program on http://cmmcr3.swmed.org/FatChallenge.
Recruited subjects in both groups will undergo a comprehensive metabolic evaluation at the inpatient CTRC, as summarized in Figure 1 in the protocol. During the first 3 days (study days 1-3), the subjects will be maintained at home on a 2000 Kcal frozen metabolic diet (30 % fat, 55% carbohydrate, 15% protein and 300 mg cholesterol per day) with a constant daily intake of 400 mg calcium, 800 mg phosphorus, 100 meq sodium of low acid ash content, and 3000 cc distilled water, provided by the CTRC Metabolic Kitchen. on day 3 at 5:00 pm, subjects will be admitted to the CTRC and will receive metabolic supper at 6:00 pm. on study day 4, subjects will undergo either the fat challenge or the skim milk and toast phase of the study, as well as the ammonium chloride load described below.
Fat challenge / control
During each phase, on day 4, after overnight fast, subjects will empty their bladder at 6:00 am and receive 250 ml of distilled water. a 1 hour fasting urine will be collected under mineral oil from 6:00 - 7:00 am. Starting at 7:00 am and continuing until 4:00 pm, heavy whipping cream/skim milk and toast will be given on an hourly basis. Five 2 hour urines will be obtained between 7:00 am and 17:00 pm. all urines will be collected under mineral oil and analyzed for total volume, pH, Cr, na, K, Ca, Mg, Cl, P, ammonium (nH4+), titratable acidity (Ta), bicarbonate (HCo3-), PCo2 and citrate.
arterialized venous blood will be obtained at 7:00 am for CMP and lipid profile. at 7:00 am, 9:00 am, 11:00 am 1:00 pm, 3:00pm and 5:00pm arterialized venous blood for free fatty acids, glucose ketone bodies, CMP and lipid profile will be obtained.
optional ammonium chloride load
Subjects will be given the opportunity to undergo an optional ammonium chloride load during both phases. The heavy whipping cream (fat challenge phase) or skim milk and toast (control phase) will continue to be given hourly throughout the ammonium chloride load. at 1:00 pm, oral ammonium chloride will be given in the amount of 1 meq/kg body weight, not to exceed 120 meq and not be less than 50 meq. The dose will be rounded to the nearest 5 meq and the capsules will be divided between three time points that are 15 minutes apart starting at 1:00 pm. The maximum number of capsules given at any time point will be 4. Following oral ammonium chloride load, 5 hourly urines will be collected under mineral oil and analyzed as above.
arterialized venous blood will be obtained for CMP, lipid profile and aBG at 1:00 pm, 4:00 pm, and 6:00 pm. arterialized venous blood for free fatty acids, insulin, glucose and ketone bodies will be obtained hourly following ammonium chloride load until the completion of the study at 6:00 pm.
Uric Acid Patients:
All subjects will be age > 21 years of either sex, of any ethnicity. Subjects will be recruited from the UT Southwestern Mineral Metabolism clinic.
Adult subjects, gender-matched, age-matched (within 5 years), and weight-matched (within 10% of body weight) to the uric acid subjects from group 1, with no known history of kidney stones. All subjects will be recruited by campus and community-wide advertising.