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

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.

Study Overview

• Status: Withdrawn
• Conditions: Uric Acid Nephrolithiasis
• Intervention / Treatment: Other: 123I-BMIPP; Other: 99mTc-MAG3

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75390-8885
      • UT Southwestern Medical Center - Center for Mineral Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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	Other: 123I-BMIPP; Uptake of radioactive isotope by the kidney; Other: 99mTc-MAG3; Uptake of radioactive isotope by the kidney

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Based on preliminary animal study, we anticipate a mean difference of approximately 26% between IUAN and control non-stone forming subjects, but with a higher CV of 20%. For 80% power (=0.05), will be able to detect at 1.5 standardized effect size (%change/CV) with n=10 per group. Comparisons between IUAN and non-stone former groups will be made with two-sample t-tests or Wilcoxon Rank Sum tests.	6 days

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Khashayar Sakhaee, MD, UT Southwestern

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: November 23, 2016
• First Submitted That Met QC Criteria: November 23, 2016
• First Posted (Estimate): November 29, 2016

Study Record Updates

• Last Update Posted (Actual): October 5, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Fatty Acid; Nephrolithiasis, Uric Acid
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Kidney Calculi; Nephrolithiasis; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Technetium Tc 99m Mertiatide
• Other Study ID Numbers: STU 092014-032; R01DK081423-07 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No