Neither creatinine- nor cystatin C-estimated glomerular filtration rate is optimal in oncology patients treated with targeted agents

Abstract

Cystatin C concentrations were decreased during targeted therapy due to cathepsin D-mediated proteolysis. Cystatin C-eGFR is therefore not considered a suitable marker for assessing kidney function in oncology patients, and other techniques to estimate the GFR have to be applied in this patient population.

KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancer

“…Therefore, universal use of cystatin C-based equations is not recommended. 29 Use of the Cockcroft-Gault formula in determining dosing of chemotherapeutic agents is problematic because it may underestimate creatinine clearance, leading to inappropriate dose reductions of cancer treatments. 30 Better methods for estimating GFR are needed, as are point-of-care tests that can rapidly measure GFR.…”

Prävention der akuten Nierenschädigung beim kritisch kranken Patienten

“…Noch ist unklar wie die Ausgangsnierenfunktion für die Dosisberechnung ermittelt werden soll. Schätzformeln, die auf der Messung von Kreatinin oder Cystatin C beruhen, versagen bei diesem Patientenkollektiv [80] ebenso wie die Cockfort-GaultFormel [9], sodass einige Autoren eine Messung z. B. mit Iohexol für unabdingbar erachten [30].…”

Serum cystatin C level can be used to estimate GFR in patients with solid tumors: Moderator Commentary

“…The authors noted a significant decrease in cystatin C (1.03 vs 0.90 mg/L, p < 0.001) and corresponding increase in cystatin C-eGFR (71 vs 89 mL/min/1.73 m², p < 0.001) during treatment, while serum creatinine and creatinine-eGFR remained unchanged, leading to an increasing ΔGFR (creatinine-eGFR minus cystatin C-eGFR). 47 Importantly, these changes were only present in patients treated with TKIs, not in those treated with bevacizumab and adjuvant chemotherapy. 47 It was shown that tumor release of cathepsin D and subsequent cleavage of cystatin C was responsible.…”

“…46 Finally, in a recent study of 80 solid patients with cancer (74% renal cell carcinoma, 19% colorectal carcinoma), who were treated with tyrosine-kinase inhibitors (TKIs, 74%), bevacizumab (20%) and everolimus (6%), a treatment-related decrease in cystatin C levels was reported. 47 In this study, the applicability of cystatin C for estimation of GFR in patients with cancer under treatment with targeted agents was investigated with respect to their well-known potential for nephrotoxicity. The authors noted a significant decrease in cystatin C (1.03 vs 0.90 mg/L, p < 0.001) and corresponding increase in cystatin C-eGFR (71 vs 89 mL/min/1.73 m², p < 0.001) during treatment, while serum creatinine and creatinine-eGFR remained unchanged, leading to an increasing ΔGFR (creatinine-eGFR minus cystatin C-eGFR).…”

“…47 Importantly, these changes were only present in patients treated with TKIs, not in those treated with bevacizumab and adjuvant chemotherapy. 47 It was shown that tumor release of cathepsin D and subsequent cleavage of cystatin C was responsible. 47 These cancer-related and GFR-independent abnormalities in cystatin C serum levels should be taken into account when evaluating suitability of cystatin C as a marker of kidney function in these patients.…”