Accurate measurement of individual glomerular filtration rate in cancer patients: an ongoing challenge

Abstract

A narrow therapeutic index is a characteristic feature of cytotoxic agents. Some of these agents are almost entirely eliminated renally in unchanged active form. As a consequence, assessment of the individual glomerular filtration rate (GFR) may help to predict the pharmacokinetic behaviour of cytotoxic agents in plasma more precisely. In addition, GFR-adapted individualization of cancer chemotherapy may have an enormous impact on the severity of side effects. Several methods are available to determine GFR or creatinine clearance (CrCl). GFR-measurement based on experimental methods with radiolabelled isotopes, contrast media or inulin helps to reflect the real situation very closely. In addition, 24-h urine collection is a convenient and feasible method to measure creatinine clearance. Finally, several mathematical equations exist to estimate GFR or CrCl based on serum creatinine and other parameters. Only a few of these equations have been developed in oncologic patients. However, some of these equations are routinely used in clinical practice, because they allow a rapid estimation of GFR. Based on the fact that clinically relevant differences have been assessed between calculated values and the real situation, mathematical calculation of GFR or CrCl does not seem to be appropriate to assess individual renal function precisely enough over a broad range of individual GFR or CrCl. Whether the measurement of low-molecular-weight proteins, such as cystatin C and ss-trace protein, may help to reflect the real situation more precisely is a matter of controversial debate.

Estimating GFR in Adult Patients with Hematopoietic Cell Transplant

“…Studies comparing serum CysC with eGFR measurements in patients with cancer have reported conflicting results but generally found CysC to perform better than serum Cr (7,8,(29)(30)(31). One adult HCT study evaluated CysC as a measure of renal function (31), finding that elevations in CysC did not correlate with serum Cr or Cr clearance.…”

Cystatin C: A Marker of Renal Function

“…48 There is some evidence that cystatin C concentrations are not affected by the presence of malignancies or inflammation. 49 On the other hand Kos et al have observed in their study a significant correlation between increased serum cystatin C and malignant progression in melanoma and colorectal cancer. 50 Demirtas et al conducted a study on 19 leukemic patients to evaluate the influence of malignancy and the impact of nephrotoxic drugs used in bone marrow transplantation (BMT) on the circulating levels of cystatin C in leukemia.…”

Estimation of renal function and its potential impact on carboplatin dosing in children with cancer

“…Although creatinine clearance is a reliable marker in day-to-day practice in adults, its use in paediatrics has been questioned and there are situations where a more accurate measure of GFR is preferred Holweger et al, 2005). This information may be particularly important in clinical situations where potentially nephrotoxic drugs are administered, in addition to allowing for accurate renal function-based dosing of anticancer drugs such as carboplatin (Calvert et al, 1989;Holweger et al, 2005). It has been well established that the use of radioisotope tracers, such as 51 Cr-EDTA and 99m Tc-DTPA, are reliable methods for the accurate estimation of GFR (Rehling et al, 1984;Fawdry et al, 1985).…”