Comparison of Markers of Kidney Function
Condition: Chronic Kidney Disease; Renal Insufficiency
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
Study type: Observational

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.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited from UCLA pediatric kidney transplant patients with stable
        allograft function that come in for routine surveillance biopsy. Patients will be induced
        with either daclizumab, basiliximab, or thymoglobulin and maintained on tacrolimus,
        mycophenolate mofetil, and steroid-free or steroid-based immunosuppression.
      
Keywords: pediatric; kidney; transplant; GFR; creatinine; cystatin C; iohexol