Two-Point Measurement of Glomerular Filtration Rate by Iohexol Plasma Disappearance
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
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 Design
Arms and Interventions
| Arm | 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.
|
Outcome Measures
Primary Outcome Measures
- glomerular filtration rate [Change from baseline in glomeular filtration rate at different time points after hematopoietic cell transplant]
- Glomerular Filtration Rate (GFR) [Change from Baseline in GFR at 80 to 100 days post transplant]
- Glomerular Filtration Rate (GFR) [Change from Baseline in GFR at 1 year post tranplant]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- University of Washington
Investigators
- Principal Investigator: Sangeeta R. Hingorani, MD, MPH, Fred Hutchinson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
- Al-Tonbary YA, Hammad AM, Zaghloul HM, El-Sayed HE, Abu-Hashem E. Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase? J Pediatr Hematol Oncol. 2004 Jun;26(6):336-41.
- Beddhu S, Samore MH, Roberts MS, Stoddard GJ, Pappas LM, Cheung AK. Creatinine production, nutrition, and glomerular filtration rate estimation. J Am Soc Nephrol. 2003 Apr;14(4):1000-5.
- Demirtaş S, Akan O, Can M, Elmali E, Akan H. Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin Biochem. 2006 Feb;39(2):115-8. Epub 2005 Dec 6.
- Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002 Aug;40(2):221-6.
- Fliser D, Franek E, Joest M, Block S, Mutschler E, Ritz E. Renal function in the elderly: impact of hypertension and cardiac function. Kidney Int. 1997 Apr;51(4):1196-204.
- Holweger K, Bokemeyer C, Lipp HP. Accurate measurement of individual glomerular filtration rate in cancer patients: an ongoing challenge. J Cancer Res Clin Oncol. 2005 Sep;131(9):559-67. Epub 2005 Oct 20. Review.
- Kleber M, Cybulla M, Bauchmüller K, Ihorst G, Koch B, Engelhardt M. Monitoring of renal function in cancer patients: an ongoing challenge for clinical practice. Ann Oncol. 2007 May;18(5):950-8. Epub 2007 Mar 9.
- Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, Powe NR, Rossert J, Wheeler DC, Lameire N, Eknoyan G. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007 Aug;72(3):247-59. Epub 2007 Jun 13.
- Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70.
- Perkins BA, Nelson RG, Ostrander BE, Blouch KL, Krolewski AS, Myers BD, Warram JH. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J Am Soc Nephrol. 2005 May;16(5):1404-12. Epub 2005 Mar 23.
- Ross EA, Wilkinson A, Hawkins RA, Danovitch GM. The plasma creatinine concentration is not an accurate reflection of the glomerular filtration rate in stable renal transplant patients receiving cyclosporine. Am J Kidney Dis. 1987 Aug;10(2):113-7.
- Séronie-Vivien S, Toullec S, Malard L, Thomas F, Durrand V, Chatelut E. Contribution of the MDRD equation and of cystatin C for renal function estimates in cancer patients. Med Oncol. 2006;23(1):63-73.
- Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C. Cystatin C and the risk of death and cardiovascular events among elderly persons. N Engl J Med. 2005 May 19;352(20):2049-60.
- Visvardis G, Griveas I, Zilidou R, Papadopoulou D, Mitsopoulos E, Kyriklidou P, Manou E, Ginikopoulou E, Meimaridou D, Pavlitou A, Sakellariou G. Glomerular filtration rate estimation in renal transplant patients based on serum cystatin-C levels: comparison with other markers of glomerular filtration rate. Transplant Proc. 2004 Jul-Aug;36(6):1757-9.
- 6726