Renal Uptake of Fatty Acids (FFA) in Patients With Idiopathic Uric Acid Nephrolithiasis (IUAN)

This is a cross-sectional study of patients with iuan and matched non-stone formers to test
the hypothesis that renal FFa uptake is increased in iuan, using noninvasive 123i-labeled
[MiCRo-SYMBoL]-methyl-p-iodo-phenyl-pentadecanoic acid(123i-BMiPP) SPeCT/CT imaging, an
established FFa analog approved for human studies.

Participants will be placed on an instructed controlled metabolic diet (30% fat, 15% protein,
55% carbohydrate, 300 mg cholesterol per day, 400 mg calcium, 800mg phosphorus, 100 meq
sodium, with low acid ash content, and 3000 cc distilled water) for 5 days to exclude dietary
confounders (3 days as outpatient and the final 2 days as inpatient). On days 4 and 5, two
fasting blood samples will be collected for the measurement of CMP, insulin, FFa and two 24-h
urine samples will be collected under mineral oil to be analyzed for total volume, pH, Cr,
na, K, Ca, Mg, Cl, P, uric acid, nH4+, titratable acidity (Ta), sulfate, HCo3- and citrate.
The morning of day 6, patients will undergo dual 123i-BMiPP and 99mTc-MaG3 (99mTc
mercaptoacetyltriglycine mertiatide) SPeCT/CT imaging after 12 hrs of fasting. 99mTc-MaG3
(8-10mCi) will be injected intravenously for the flow phase of a standard renal scan which
includes dynamic imaging for 2 minutes. an additional 1 minute image will be acquired (the
2-3 minute image on a standard renal scan). acquisition will then stop. immediately afterward
123i-BMiPP (4-5mCi) will be injected intravenously for a 1hour uptake period. after the 1
hour uptake dual isotope (Tc-99m and i-123) SPeCT/CT images of the kidney will be acquired on
a clinical Siemens Symbia dual head SPeCT/CT system. The 99mTc-MaG3 flow image data will be
used to measure renal plasma flow,12 using the Ge Xeleris renal analysis software package
already installed on the clinical SPeCT/CT system. The 123i-BMiPP, a gamma emitter with a
half-life of 13.13 hours, is to measure renal 123i-BMiPP (FFa) uptake 13 123i-BMiPP uptake
will be corrected for effective renal plasma flow (mL/min) measured with 99mTc-MaG3, using
the Ge Xeleris renal analysis software package.

Expected findings: If the hypothesis is correct, the investigators expect increased FFa
uptake as measured by 123i-BMiPP SPeCT/CT corrected for renal effective plasma flow in the
kidney cortex of iuan patients vs. matched controls.

Inclusion Criteria:

- In the IUAN group (N=10), we will include adult subjects with documented IUAN, age >
21 years, either sex, any ethnicity

- In the Control group (N=10), we will include volunteers with no history of stone
disease matched for age (within 5 years), gender, ethnicity, BMI (within 10%) and
diabetes status

Exclusion Criteria:

- Contraindications to SPECT/CT, pregnancy, breastfeeding, chronic renal disease (eGFR <
60 ml/min/1.73m2), proteinuria, genetic diseases of the kidney, inborn defects of
lipid metabolism, alcohol abuse, liver disease (patients with highly elevated total
bilirubin, elevated liver enzymes AST, ALT and alkaline phosphatase and those with an
established liver disease), anemia, and pharmacological treatment with insulin or
insulin-sensitizing drugs such as thiazolidinediones (TZD).

- Patients on antidyslipidemic drugs, alkali therapy or allopurinol will be instructed
to discontinue these drugs 2 weeks prior to the study.