PREVALENCE OF RENAL DISFUNCTION IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA USING FIRST AND SECOND-GENERATION TYROSINE KINASE INHIBITORS

Abstract

The use of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it possible for patients to have a life expectancy similar to that of the healthy population. To improve treatment adherence and effectiveness, it is necessary to understand the side effects that the medications may cause. On the other hand, the importance of TKI discontinuation studies are strengthened by recognition of long term adverse events. The primary objective of this study is to assess the prevalence of renal insufficiency in a cohort of CML patients who use first and second-generation tyrosine kinase inhibitors and compare this prevalence between the two generations of the medication. The secondary objective is to identify risk factors for the development of renal alterations secondary to the use of TKIs. Methods: this is an observational, cross-sectional, and analytical clinical study, with a sample consisting of 160 CML patients at the outpatient clinic of a reference hospital in Brazil between October 2000 and January 2023. Clinical and laboratory data available since the start of hospital follow-up were analyzed from the medical records of these patients. Categorical variables were expressed as counts and percentages, and compared using chi-square tests. The Mann-Whitney test was applied for continuous variables. Logistic regression was used for identifying risk factors for renal disfunction. P-values less than 0.05 were considered statistically significant. Data were collected and tabulated in Microsoft Excel® spreadsheets and analyzed using the Statistical Package for the Social Sciences - SPSS® software (IBM® SPSS® Statistics v. 25.0, SPSS Inc, Chicago, USA). Results: The univariate analyses showed a significant relationship between the presence of renal dysfunction and the use of Imatinib (p = 0.0026), advanced age (p = 0.00001), and presence of comorbidities (p = 0.001), particularly systemic arterial hypertension (SAH) (p = 0.0001). With the multivariate analysis, independent variables for renal dysfunction found were, advanced age (p = 0.0023; OR: 2.08; CI: 1.30-3.32), having SAH (p = 0.0142; OR: 1.91; CI: 1.14 – 3.20), and the use of Imatinib (p = 0.0131; OR: 1.89; CI: 1.14 - 3.14). Conclusion: The study findings suggest that the use of Imatinib therapy in patients with chronic myeloid leukemia may be associated with a reduction in glomerular filtration rate and an increase in the occurrence of chronic kidney disease in this population in the long term, especially when combined with other risk factors such as advanced age and the presence of comorbidities, particularly SAH.