Two-Point Measurement of Glomerular Filtration Rate by Iohexol Plasma Disappearance

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Washington
Sponsor:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01545531
First received: September 26, 2011
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to measure glomerular filtration rate (GFR) by iohexol plasma disappearance (gold standard) and measure serum Cystatin C levels (surrogate marker) in patients enrolled in our prospective study at baseline, day 100 and 1 year after hematopoietic cell transplant and determine if these levels correlate with serum creatinine and an estimated GFR using the Modification of Diet in Renal Disease (MDRD) equation and Schwartz formula in children.


Condition Intervention
Renal Disease
Renal Insufficiency
Drug: Iohexol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • glomerular filtration rate [ Time Frame: Change from baseline in glomeular filtration rate at different time points after hematopoietic cell transplant ] [ Designated as safety issue: No ]
  • Glomerular Filtration Rate (GFR) [ Time Frame: Change from Baseline in GFR at 80 to 100 days post transplant ] [ Designated as safety issue: No ]
  • Glomerular Filtration Rate (GFR) [ Time Frame: Change from Baseline in GFR at 1 year post tranplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2008
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Iohexol GFR Drug: Iohexol
Iohexol, a non-ionic, low osmolar, X-ray contrast medium (OmnipaqueR) that is safe and non-toxic and used for angiographic and urographic procedures, is eliminated from plasma exclusively by glomerular filtration [13]. Study subject will receive 5 ml of iohexol solution (Omnipaque 300, corresponding to 647 mg iohexol per ml or 300 mg iodine per ml) through peripheral IV or central Line infusion over 1-2 minutes followed by 10 ml of saline solution at baseline, day 100 and 1 year after HCT.

Detailed Description:

Serum creatinine does not accurately measure kidney function in patients with mild renal insufficiency or in certain other patient populations (for example, individuals with malnutrition, muscle wasting, cancer, or the elderly) [8, 9]. The serum creatinine level and related estimating equations, routinely used clinical measures to estimate kidney function, are dependent on muscle mass, and influenced by age, race, gender, and weight.[10, 11]. Patients undergoing hematopoietic cell transplant may have large fluctuations in their nutritional status, muscle mass and weight that will influence glomerular filtration rates based on estimation equations or serum creatinine levels. In fact, a recently published position paper recommends that research be done specifically to evaluate the accuracy of golemular filtration rate estimating equations in cancer patients "with a particular focus on reducing the influence of confounding factors such as muscle wasting, malnutrition and extracellular fluid volume expansion [12]." Cystatin C is a cysteine protease inhibitor that is expressed by all nucleated cells and is freely filtered by the glomerulus. Serum Cystatin C correlates well with measured glomerular filtration rate and more accurately measures kidney function than does serum creatinine in the elderly, cancer patients, diabetics and renal transplant recipients[9, 13-15]. It is also linearly associated with all cause mortality, cardiovascular mortality and heart failure risk[16]. The gold standard measurements of Golemular filtration rate using inulin or radioisotope-labeled or nonlabeled trace quantities of EDTA, technetium-99-diethylenetriamine pentaacetic acid, iothalamate or iohexol are expensive and time intensive which limits their clinical usefulness. Although the studies done using cystatin C in patients with cancer have reported some conflicting results when comparing cystatin C to estimated GFR measurements, they have generally found it to perform better than serum creatinine [14, 17-20]. Only one study has been done in the HC population to evaluate cystatin C as a measure of renal function and the authors did not include a gold standard measurement for GFR for comparison with cystatin C levels [20]. The authors found elevations in cystatin C in patients after HCT compared to the control group. However, these elevations did not correlate with serum creatinine or creatinine clearance. A plausible conclusion is that serum cystatin C is a more sensitive marker of renal function than the other measures they employed. These authors also did not look at area under the curve, receiver operator characteristic curves or 1/cystatin C curves all of which have been shown to be more accurate and to correlate better with other measures of GFR[21]. Moreover, no long-term studies have been done in this patient population using cystatin C to assess renal function or to define CKD prevalence.

Iohexol, a non-ionic, low osmolar, X-ray contrast medium (OmnipaqueR) that is safe and non-toxic and used for angiographic and urographic procedures, is eliminated from plasma exclusively by glomerular filtration[13]. Iohexol has a molecular weight of 821 daltons, a plasma elimination half-time of ~90 min, is distributed into the extracellular space and has less than 2% plasma protein binding [13, 17]. Iohexol is excreted completely unmetabolized in the urine with 100% recovery within 24 hours after injection [14]. Since iohexol can be quantified in small samples, capillary, as well as venous, sampling can be employed [15]. Extrarenal elimination of iohexol in a setting of reduced GFR is negligible[16]. Iohexol is measured in deproteinized plasma or serum by HPLC. The commercially available preparations contain two isomers of iohexol, both of which are handled similarly by the body [15, 18].

An accurate measure of kidney function is important for clinical management of medications, choice of conditioning regimen, prognosis, and study of treatment toxicities. Establishment of the precise prevalence is needed to design clinical intervention trials.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age > 2 years
  • follow-up at Seattle cancer care alliance

Exclusion Criteria:

  • age <2 years
  • history of diabetes mellitus
  • inability to return to the SCCA for follow-up at 1 year
  • allergy to iodine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545531

Contacts
Contact: Sangeeta R. Hingorani, MD, MPH 2069873120 sangeeta.hingorani@seattlechildrens.org
Contact: Emily C. Pao, BS 2066676614 epao@fhcrc.org

Locations
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Sangeeta R. Hingorani, MD, MPH Fred Hutchinson Cancer Research Center
  More Information

Publications:

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01545531     History of Changes
Other Study ID Numbers: 6726
Study First Received: September 26, 2011
Last Updated: April 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
glomerular filtration rate
iohexol
hematopoietic cell transplant
kidney function
gold standard measure
cystatin C.

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Iohexol
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014