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

December 30, 2016 updated by: University of Washington
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

54

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients undergoing hematopoietic cell transplant

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
glomerular filtration rate
Time Frame: Change from baseline in glomeular filtration rate at different time points after hematopoietic cell transplant
Change from baseline in glomeular filtration rate at different time points after hematopoietic cell transplant
Glomerular Filtration Rate (GFR)
Time Frame: Change from Baseline in GFR at 80 to 100 days post transplant
Change from Baseline in GFR at 80 to 100 days post transplant
Glomerular Filtration Rate (GFR)
Time Frame: Change from Baseline in GFR at 1 year post tranplant
Change from Baseline in GFR at 1 year post tranplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Investigators

  • Principal Investigator: Sangeeta R. Hingorani, MD, MPH, Fred Hutchinson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

September 26, 2011

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 6, 2012

Study Record Updates

Last Update Posted (Estimate)

January 4, 2017

Last Update Submitted That Met QC Criteria

December 30, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6726

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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