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

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.