Renal deterioration of patients with metastatic cancer is a frequently occurring complication after chemotherapy. The IRMA(The Renal Insufficiency and Cancer Medications) study showed that kidney injury is common in people receiving anticancer therapy and that dose adjustment is required in these patients . Since there is no significant difference in the therapeutic efficacy of chemotherapy regimens in mCRC, it is critical to preserve adequate organ function and avoid excessive toxicity when selecting the first chemotherapy regimen. There are few studies that predict the long-term toxicity by considering the patient’s basic characteristics and risk factors at the time of first chemotherapy regimen selection.
We investigated real-world data based on the effects of chemotherapy on renal dysfunction in patients with mCRC. Our findings demonstrated that the AKI incidence over 1 year was 9.1%. Among chemotherapy regimens, the FOLFIRI + bevacizumab showed the most decrease in eGFR and the highest AKI incidence. The significant prognostic factors for AKI were old age, BMI, proteinuria at baseline, and bevacizumab-containing regimens, especially FOLFIRI + bevacizumab.
The anticancer drugs used among patients with mCRC are relatively less toxic to the kidneys. Oxaliplatin, a platinum complex anticancer drug, has lower renal toxicity than other platinum agents [15, 16]. Furthermore, irinotecan, a semi-synthetic derivative of camptothecin, has fewer renal complications because it is extensively subjected to hepatic metabolism and excreted into the bile [17, 18]. 5-FU, a pyrimidine antimetabolite, is also safe for renal function and does not require dose reduction due to renal dysfunction [19, 20]. There is still no worldwide consensus on renal dose adjustment for the use of 5-FU; however, some studies are aiming to standardize drug dose reduction in patients with renal dysfunction, including those on hemodialysis [19, 21]. Bevacizumab, a VEGF ligand inhibitor, can damage vascular endothelial cells. Its renal toxicity is mainly renovascular, including hypertension and proteinuria, which causes nephrotic syndrome and subsequently, decreased GFR . Cetuximab, a monoclonal antibody targeting EGFR, is known to promote the progressive development of hypomagnesemia due to renal magnesium wasting [7, 23].
In our study, FOLFIRI + bevacizumab regimen was identified to worsen the most renal function. Irinotecan could induce diarrhea, with an incidence of 80–90%, among which grades 3 and 4 accounted for 39% , and intravascular volume depletion could induce pre-renal AKI. The combination of bevacizumab, which causes hypertension and proteinuria, could affect renal dysfunction more.
Some study has addressed the risk factors for AKI in gastrointestinal cancer. Li et al.  reported that diabetes, cancer type, anti-tumor treatment, ALT, serum creatinine, eGFR, serum uric acid, hypoalbuminemia, anemia, and abnormal sodium and potassium levels in patients with gastrointestinal cancers were risk factors for AKI; however, since it is an analysis of gastrointestinal cancers, risk factors for AKI in mCRC were unknown.
Our study has several limitations. It was a retrospective study performed at a single institute, and we did not follow the exact AKI definition of KDIGO with respect to the 7-day window period. The incidence of AKI in our study was 9.1%, which was lower than the previously reported incidences of AKI in patients with mCRC (9.2%, 20.3%, 22.5%, and 34.9%) [10, 26–28]. This may be due to the criteria used in our study pertaining to exclusion of patients who experienced disease progression during chemotherapy, the different definitions of AKI used, and the heterogeneity of the study population.
Nevertheless, we collected renal function serial eGFR data for 1 year after the initiation of chemotherapy and provided information about renal dysfunction as well as comorbidities and co-prescriptions to evaluate AKI risk factors in this population. Compared with previous studies that analyzed renal complications using a specific regimen [10, 28], this study analyzed the risk factors for renal dysfunction after the initiation of chemotherapy, focusing on the widely used 4 chemotherapy regimens of mCRC, i.e., FOLFIRI or FOLFOX combined with bevacizumab or cetuximab. We hope that it could be helpful for physicians to select 1st line chemotherapeutic agents based on patients’ risk factors in terms of renal protection.; in mCRC patients with high-risk factors, more careful monitoring is necessary when applying the first-line palliative chemotherapy to avoid or alleviate renal deterioration. These results provide useful information regarding toxicity and efficacy when selecting a first-line regimen for patients with mCRC.