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

NCT ID: NCT02975986

Last Updated: 2020-10-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2021-12-31

Brief Summary

The investigators will test the hypothesis that renal uptake of free (i.e. non-esterified) fatty acids (FFa) is increased in iuan. To accomplish this goal the investigators will measure renal FFa uptake FFa uptake in vivo in patients with iuan and matched non-stone forming subjects via single-photon emission computed tomography (SPeCT)/CT imaging.

The definitive proof of the hypothesis rests on whether increased renal FFa uptake is demonstrable in humans with iuan.

Detailed Description

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.

Conditions

Uric Acid Nephrolithiasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Controlled metabolic diet

All study patients will be placed on an instructed controlled metabolic diet. Intervention: Uptake of radioactive isotope by the kidney Radiotracer: 123I-BMIPP, 99mTc-MAG3

Group Type: OTHER

123I-BMIPP

Intervention Type: OTHER

Uptake of radioactive isotope by the kidney

99mTc-MAG3

Intervention Type: OTHER

Uptake of radioactive isotope by the kidney

Interventions

123I-BMIPP

Uptake of radioactive isotope by the kidney

Intervention Type: OTHER

99mTc-MAG3

Uptake of radioactive isotope by the kidney

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Khashayar Sakhaee, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern

Locations

UT Southwestern Medical Center - Center for Mineral Metabolism

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

R01DK081423-07

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU 092014-032

Identifier Type: -

Identifier Source: org_study_id