Vermassen Tijl, Geboes Karen, Lumen Nicolaas, Van Praet Charles, Rottey Sylvie, Delanghe Joris
Department of Medical Oncology, University Hospital Ghent, Ghent, Belgium.
Biomarkers in Cancer, Ghent University, Ghent, Belgium.
Clin Kidney J. 2024 Jan 12;17(1):sfae006. doi: 10.1093/ckj/sfae006. eCollection 2024 Jan.
Tyrosine kinase inhibitors (TKIs) are associated with kidney function deterioration. A shift is ongoing towards glomerular filtration rate (GFR) equations based on other protein markers, such as cystatin C (CSTC) and β-trace protein (BTP). We evaluated various GFR equations for monitoring of kidney function in actively treated oncology patients.
We monitored 110 patients receiving a TKI. Blood and urine were collected during therapy. Serum analysis included creatinine (Cr), CSTC and BTP; for consequent GFR determination. Urine was analysed for protein, albumin, immunoglobulin G, and α-1-microglobulin. A similar analysis was done in a patient subgroup receiving immune checkpoint inhibitors (ICI) as prior or subsequent line of therapy.
Cr remained constant during TKI treatment (= 0.7753), whereas a significant decrease in CSTC (from week 2 onward, < 0.0001) and BTP (at weeks 2 and 4, = 0.0100) were noticed. Consequently, GFR estimations, using CSTC and/or BTP as a biochemical parameter, showed an apparent increase in GFR, whereas this was not observed for Cr-related GFR estimations. As a result, the GFR gap (ΔGFR) was significantly different from week 2 onward between Cr-based and CSTC-based GFR and between BTP-based and CSTC-based GFR. Glomerular damage was noticed with significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio and immunoglobulin G (all < 0.0001). No change in α-1-microglobulin was seen. ICI treatment had no effect on Cr (= 0.2262), CSTC (= 0.7341), and BTP concentrations (= 0.3592).
GFR equations, in which CSTC is incorporated, fail to correctly estimate the GFR in oncology patients treated with TKIs. As TKI-treated patients show clear signs of glomerular injury, further assessment is needed on how to correctly monitor the kidney function in actively treated oncology patients.
酪氨酸激酶抑制剂（TKIs）与肾功能恶化有关。目前正朝着基于其他蛋白质标志物的肾小球滤过率（GFR）方程转变，如胱抑素C（CSTC）和β-微球蛋白（BTP）。我们评估了各种GFR方程在积极治疗的肿瘤患者中监测肾功能的情况。
我们监测了110名接受TKI治疗的患者。在治疗期间采集血液和尿液。血清分析包括肌酐（Cr）、CSTC和BTP，用于随后的GFR测定。对尿液进行蛋白质、白蛋白、免疫球蛋白G和α-1-微球蛋白分析。对接受免疫检查点抑制剂（ICI）作为先前或后续治疗方案的患者亚组进行了类似分析。
在TKI治疗期间Cr保持恒定（=0.7753），而CSTC（从第2周起，<0.0001）和BTP（在第2周和第4周，=0.0100）显著下降。因此，使用CSTC和/或BTP作为生化参数的GFR估计显示GFR明显增加，而基于Cr的GFR估计未观察到这种情况。结果，从第2周起，基于Cr的GFR与基于CSTC的GFR之间以及基于BTP的GFR与基于CSTC的GFR之间的GFR差距（ΔGFR）有显著差异。观察到肾小球损伤，尿蛋白与肌酐比值、白蛋白与肌酐比值和免疫球蛋白G显著增加（均<0.0001）。α-1-微球蛋白未见变化。ICI治疗对Cr（=0.2262）、CSTC（=0.7341）和BTP浓度（=0.3592）无影响。
纳入CSTC的GFR方程未能正确估计接受TKIs治疗的肿瘤患者的GFR。由于接受TKI治疗的患者显示出明显的肾小球损伤迹象，需要进一步评估如何正确监测积极治疗的肿瘤患者的肾功能。
