Comparison of Markers of Kidney Function

Sponsor

University of California, Los Angeles (Other)

Overall Status

Completed

CT.gov ID

NCT01403766

Collaborator

Gentian (Other)

Enrollment

Location

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Glomerular filtration rate (GFR) is the best known measurement of kidney function. Serum creatinine (blood test) is the most commonly used marker to predict GFR. It is a convenient, inexpensive test that involves a single blood draw with rapid results. However, creatinine has several limitations because its blood level is dependent on age, body mass, and sex. One of the gold standards for measuring GFR is plasma clearance of an IV injected agent, iohexol. It has been found to be safe and nontoxic in prior studies, but is not practical in the clinical setting due to the need for several timed blood draws. Recent studies have investigated the use of cystatin C as an alternative marker to predict GFR. Cystatin C also involves only a single blood draw, and has less confounding factors than creatinine since it is independent of age, body mass, and sex. Currently, it remains controversial whether cystatin C is a significantly better biomarker of estimated GFR than creatinine. To date, there has not been a large prospective cohort study to compare cystatin C and creatinine in pediatric kidney transplant patients who are on maintenance immunosuppression (anti-rejection drugs). Accurate measurement and early detection of deterioration of GFR is critical in the care of this patient population. The purpose of this study is to assess the accuracy of estimating GFR by using cystatin C versus creatinine clearance equations when compared to the surrogate gold standard of iohexol GFR in pediatric renal transplant patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease Renal Insufficiency

Detailed Description

Study patients will come in for their surveillance biopsy done as standard of care post-transplant. They we be made NPO at midnight prior to the biopsy per routine. On arrival, they will have standard of care pre-biopsy bloods drawn along with baseline study labs including serum enzymatic creatinine (1mL of blood), cystatin C (1.5 mL of blood), and 1mL of blood collected pre-iohexol infusion. Two IV's will be started, one for iohexol administration and fluids, and the other for blood draws. Study patients will be started on 1x maintenance intravenous fluids. The patient will then have their standard of care protocol biopsy in the ultrasound suite. After the biopsy 5 mL Iohexol (Omnipaque 300) will be administered over 1-2 minutes, with epinephrine, solumedrol, and diphenhydramine on hand in the event of a reaction although this is very unlikely. The patient will be observed and vital signs will be taken 10 minutes post-infusion. After biopsy, maintenance fluids will be continued until completion of the study. Blood for determination of Iohexol levels (1mL) will be drawn at 10, 30, 120, and 300 minutes post iohexol infusion when patient is being observed post biopsy. At completion of the study at 300 minutes post iohexol infusion, serum creatinine (1mL of blood), cystatin C (1.5 mL of blood) will be drawn again. The total volume of blood drawn for the study will be 10mL.

Creatinine (enzymatic method) will be determined on the Olympus system, and Cystatin C (Gentian assay) will be determined on the AU400 Olympus System at the UCLA Department of Pathology and Laboratory Medicine Outreach Laboratory. Iohexol GFR will be determined at the University of Rochester Medical Center in Dr. Schwartz's laboratory. Kidney biopsies will be graded by updated Banff criteria, and reviewed by blinded pathologist.

Study Design

Study Type:

Observational

Actual Enrollment :

17 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Comparison of Estimated GFR Using Cystatin C Versus Creatinine in Pediatric Renal Transplant Patients

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Pediatric post-kidney transplant Patients having standard of care surviellance biopsies.

Outcome Measures

Primary Outcome Measures

The primary outcome measure is a comparison of determination of GFR through three methods: cystatin C (Gentian assay), creatinine (Schwartz and update Schwartz) and iohexol disappearance [Participants will be followed for the duration of the Iohexol GFR measurement (approximately 8 hours) that will take place at the time of surveillance biopsy at either 6 months, 1 or 2 years post-transplant..]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Renal transplant patient aged 1 to <19 years old
Stable allograft function (no history of biopsy proven acute rejection or increase of creatinine of > 10% from baseline in the past 6 months)
No changes in maintenance immunosuppression in the month before the protocol biopsy
Subject and/or parent must be able to understand and provide informed consent

Exclusion Criteria:

Biopsy proven acute rejection in the past 6 months
Change in maintenance immunosuppression in the month before the protocol biopsy
Known diabetes mellitus
Known thyroid dysfunction
Allergy to Iohexol or other contrast media
Inability or unwillingness of a participant or their legal guardian to give written informed consent or comply with the study protocol