Assessment of chronic renal injury in patients with chronic myeloid leukemia in the chronic phase receiving tyrosine kinase inhibitors

We aimed to evaluate the incidence of chronic renal injury in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs) and to identify the associated factors. Data for CML-CP patients with normal estimated glomerular filtration rate (eGFR) at baseline and receiving TKI therapy ≥ 3 months were retrospectively reviewed. The CRAE (chronic renal adverse event, defined as a 30% eGFR reduction from baseline or eGFR < 60 ml/min/1.73 m2 ≥ 90 days whichever occurred first)-free survival rates at 3 years in the imatinib cohort (n = 360) were significantly lower than those in the nilotinib cohort (n = 100) (55% versus 77%, P = 0.001) as a first-line TKI therapy. In multivariate analyses, imatinib, male sex, increasing age, and previous non-TKI treatment were associated with poor CRAE-free survival. In newly diagnosed patients who received imatinib treatment (n = 40), 24-h urine protein levels significantly increased after 6 months, and urinary β2-microglobulin values significantly increased compared to those in the nilotinib cohort (n =15) at 36 months (P = 0.042) and 42 months (P = 0.039). There was no significant difference in CRAE-free survival rates at 3 years between the nilotinib (n = 65) and dasatinib (n = 74) cohorts (67% versus 83%, P = 0.832) as second- or third-line TKI therapies. In multivariate analyses, previous non-TKI treatment was associated with poor CRAE-free survival. We concluded that imatinib was significantly correlated to chronic renal injury, possibly associated with glomerulus and renal tubular injury, compared with nilotinib as a first-line TKI therapy in CML-CP patients. However, nilotinib and dasatinib had similar mild adverse impacts on renal function as second- or third-line therapies.