#1726 Effect of tyrosine kinase inhibitors on hyperfiltration response and renal functions in nephrectomized renal cell carcinoma patients

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Abstract Background and Aims Renal cell carcinoma (RCC) is a disease that is resistant to classical cancer treatments such as systemic chemotherapy and radiotherapy and is instead treated with surgery, ablative methods, immunotherapy, and targeted agents. Nephrectomy is frequently used and causes dramatic nephron loss. The hyperfiltration response that occurs after nephron loss appears as a compensatory mechanism. In this study, the effects of Tyrosine Kinase Inhibitors (TKIs), used in the treatment of RCC, on the hyperfiltration response and renal functions were investigated. Method A total of 248 patients who were either followed up without treatment or received TKI within 12 months post-operatively, among those who underwent surgery for RCC at Hacettepe University Hospitals between January 2015 and June 2023, were included in the study. Five-year follow-ups of the patients were examined. To investigate the effect of the timing of TKI initiation on the hyperfiltration response, the patient group who started the medication was divided into two subgroups: early (0–3 months) and late (0–12 months). The inclusion and exclusion processes of the patients are shown in the flowchart (Fig. 1). Results Basic clinical and demographic data of the patients are summarized in Fig. 2. No difference was observed between the preoperative estimated glomerular filtration rate (eGFR) and proteinuria values of the groups that did not receive TKI and those that received early or late treatment (P = 0.24, P = 0.145). The postoperative eGFR course was similar in patients who received and did not receive TKI. In the group that started TKI early, following the decrease in eGFR in the first month postoperatively, it was observed that the eGFR values stabilized between the 1st and 6th months with the initiation of TKI. In the late-start group, after a rapid decrease between the 0th and 3rd months, the eGFR values were found to be clinically and statistically lower than the other group at the 3rd month (P = 0.03). In this group, it was observed that eGFR values increased after the 3rd month with the initiation of TKI, and the difference between the two groups became statistically significant at the 24th month (P = 0.04) (Fig. 3). When proteinuria values were compared between the three groups, proteinuria values in the group that started early treatment at the 1st, 6th, 12th, 18th, and 24th months were found to be statistically significantly higher than in the other groups (P < 0.05). It was shown that the presence of hypertension before diagnosis was associated with lower eGFR in the preoperative period and up to the 24th month postoperatively, independent of TKI use (Fig. 4). Conclusion Although eGFR loss was observed in all patients after nephrectomy, no significant difference was shown between the groups that received and did not receive TKI (Fig. 5). In the group that started TKI after nephrectomy, regardless of whether the drug was initiated early or late, no negative impact of starting the drug on the hyperfiltration response could be demonstrated. It was determined that the decreased eGFR after nephrectomy remained stable or did not decrease further with early treatment in advanced-stage patients and with late treatment in low-stage patients. In light of these findings, it is suggested that TKIs may be safe and beneficial for renal survival in the presence of the necessary indications, even in patients with low eGFR.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.