Factors affecting change in renal function after contrast-enhanced computed tomography in cancer patients

Objectives. Contrast-enhanced computed tomography (CECT) is the most common form of assessing the effectiveness of cancer patient treatment. However, an injection of an iodine-based contrast agent can cause acute kidney damage (AKI). To determine the frequency and factors affecting post-contrast kidney function deterioration during oncological treatment.  Material and methods. Kidney function in cancer patients with solid tumors undergoing a total of 206 CECTs was retrospectively analyzed.  Results. Two hundred and six CECT procedures in 79 patients (age 68.4 ± 10.6 years) were included in the study. The median eGFR before CECT according to the MDRD was 81 mL/min/1.73m2 (IQR 26). The median time between CECT and kidney function examination was 8 (IQR 8) days. In the whole group, the median eGFR change defined as the difference between eGFR after and before CECT was 0.0 (9.0) mL/min/1.73m2 and was not significant. eGFR decreased in 100/206 (48.5%) CECT procedures with the median difference = –5.0 (6.0) mL/min/1.73m2. However, clinically significant deterioration of renal function (an increase in SCr of > 0.3 mg/dL) was found only in two cases (0.9%). The change in eGFR associated with CECT correlated significantly (p < 0.05) with initial creatinine (r = 0.117) and urea (r = 0.158), but not with age and comorbidities. After dividing the analyzed population according to the median GFR, it turned out that in the group of patients with eGFR < 81 mL/min/1.73m2, the median difference in GFR level was 1 (IQR 10), and in the group with a higher eGFR level the median was –1 (IQR 8.5), which was statistically significant (p = 0.03). The multivariate logistic regression analysis in subsequent reduced models confirmed that SCr, uric acid level, and the use of antimetabolites were the factors independently reducing the risk of deterioration of renal function after CECT.  Conclusions. CECT can be responsible for kidney function deterioration; however, it has no impact on oncological treatment

Influence of Tyrosine Kinase Inhibitors on Hypertension and Nephrotoxicity in Metastatic Renal Cell Cancer Patients

Renal cell carcinoma (RCC) is one of the most common kidney malignancies. An upgraded comprehension of the molecular biology implicated in the development of cancer has stimulated an increase in research and development of innovative antitumor therapies. The aim of the study was to analyze the medical literature for hypertension and renal toxicities as the adverse events of the vascular endothelial growth factor (VEGF) signaling pathway inhibitor (anti-VEGF) therapy. Relevant studies were identified in PubMed and ClinicalTrials.gov databases. Eligible studies were phase III and IV prospective clinical trials, meta-analyses and retrospective studies that had described events of hypertension or nephrotoxicity for patients who received anti-VEGF therapy. A total of 48 studies were included in the systematic review. The incidence of any grade hypertension ranged from 17% to 49.6%. Proteinuria and increased creatinine levels were ascertained in 8% to 73% and 5% to 65.6% of patients, respectively. These adverse events are most often mild in severity but may sometimes lead to treatment discontinuation. Nephrotoxicity and hypertension are related to multiple mechanisms; however, one of the main disturbances in those patients is VEGF inhibition. There is a significant risk of developing hypertension and renal dysfunction among patients receiving anti-VEGF treatment; however, there is also some evidence that these side effects may be used as biomarkers of response to antiangiogenic agents

Oncometabolites—A Link between Cancer Cells and Tumor Microenvironment

The tumor microenvironment is the space between healthy tissues and cancer cells, created by the extracellular matrix, blood vessels, infiltrating cells such as immune cells, and cancer-associated fibroblasts. These components constantly interact and influence each other, enabling cancer cells to survive and develop in the host organism. Accumulated intermediate metabolites favoring dysregulation and compensatory responses in the cell, called oncometabolites, provide a method of communication between cells and might also play a role in cancer growth. Here, we describe the changes in metabolic pathways that lead to accumulation of intermediate metabolites: lactate, glutamate, fumarate, and succinate in the tumor and their impact on the tumor microenvironment. These oncometabolites are not only waste products, but also link all types of cells involved in tumor survival and progression. Oncometabolites play a particularly important role in neoangiogenesis and in the infiltration of immune cells in cancer. Oncometabolites are also associated with a disrupted DNA damage response and make the tumor microenvironment more favorable for cell migration. The knowledge summarized in this article will allow for a better understanding of associations between therapeutic targets and oncometabolites, as well as the direct effects of these particles on the formation of the tumor microenvironment. In the future, targeting oncometabolites could improve treatment standards or represent a novel method for fighting cancer

CD4, CD20 and PD-L1 as Markers of Recurrence in Non-Muscle-Invasive Bladder Cancer

Introduction: A tumor microenvironment plays an important role in bladder cancer development and in treatment response. Purpose: The aim of the study was to assess how the components of the microenvironment affect tumor recurrence and to find the potential biomarkers for immunotherapy in NMIBC. Methods: The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome. Results: Multivariate analysis confirmed that the CD4 (p = 0.001), CD20 (p = 0.008) and PD-L1 expressed on tumor cells (p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4+ cell infiltration (+ infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group also frequently recurs after 12 months (p = 0.0005). Conclusions: The evaluation of CD4+ and CD20+ cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates the determination of a group of patients with a low risk of recurrence